Category Archives: Renal disease

Renal disease in the elderly

Renal disease and renal failure are common in the elderly. Acceptance of patients aged 65 years and over for renal replacement therapy approximately doubles the number of such patients in whom renal replacement is initiated. Renal failure in the elderly more often results from renal vascular disease or urinary tract obstruction than in younger age groups. In males, obstruction is most often due to benign or malignant prostatic enlargement, while in females it results from pelvic cancer. Progressive sclerosis of glomeruli occurs with ageing and this, together with the development of atheromatous renal vascular disease, accounts for the progressive reduction in GFR seen with advancing years. A GFR of 50-60 rnl min ” (about half the normal value for a young adult) may be regarded as ‘normal’ in patients in their eighties. The reduction in muscle mass often seen with ageing may mask this deterioration in renal function in that the serum creatinine concentration may be less than 0.12 mmol litre ” in an elderly patient whose GFR is 50 rnl min’ or lower. The use of serum creatinine as a measure of renal function in the elderly must take this into account. This is especially important in the elderly when prescribing drugs whose excretion is in whole or in part by the kidney.
URINARY TRACT INFECTIONS are more common in the elderly, in whom impaired bladder emptying due to prostatic disease in males and neuropathic bladderespecially common in females-is frequently found. Symptoms may be atypical, the major complaints being incontinence, nocturia, smelly urine or vague change in well-being with little in the way of dysuria. Demonstration of significant bacteriuria in the presence of such symptoms requires treatment.
URINARY INCONTINENCE is one of the major disabilities of the elderly. Correctable factors, such as chronic constipation, infections and treatable bladder outflow impairment need to be excluded. An expert and committed incontinence advisory and treatment service combining nursing and medical skills is invaluable in elderly patients with this distressing problem. Home visits to ensure the availability of commodes and toilets is essential. For established incontinence, catheterization may be necessary.

Further reading

Cameron JS, Davison AM, Grunfeld JP, Kerr DNS & Ritz E (eds) (1991) Oxford Textbook of Clinical Nephrology . Oxford: Oxford University Press. Coe FL, Parks JH & Asplin JR (1992) Medical progress: The pathogenesis and treatment of kidney stones. New England Journal of Medicine 327, 1141-1152. Feehally J (1988) Immune mechanisms in glomerular IgA deposition. Nephrology Dialysis Transplantation 3, 361-378. Jacobson HS (1991) Chronic renal failure: pathophysiology. Lancet 338, 419—423.

Klahr S (1991) Chronic renal failure: management. Lancet 338, 423—427. Lee DBN, Goodman WG & Coburn JW (1988) Renal osteodystrophy: some new questions on an old disorder. American Journal of Kidney Diseases XI, 365- 376.
Lewis EJ, Hunsicker LG, Bain RP & Rohde RD (1993) The effect of angiotensin-converting enzyme inhibition on diabetic nephropathy. New England Journal of Medicine 329: 1456—1462. Nolph KD, Lindblad AS & ovak JW (1988) Current concepts: Continuous ambulatory peritoneal dialysis. New England Journal of Medicine 318, 1595-1600. Robinson AJ (1994) Antineutrophil cytoplasmic antibodies (ANCA) and the systemic vasculitides. Nephrology, Dialysis, Transplantation 9, 119-126. Weatherall DJ, Ledingham JGG & Warrell JDA (eds) (1994) Oxford Textbook of Medicine, 3rd edn, section on nephrology. Oxford: Oxford University Press. Current Opinions in Nephrology and Hypertension, ed Brenner BM. Current Science. Monthly journal with review articles: each issue devoted to one or two topics.
Nephrology, Dialysis, Transplantation. Oxford University Press. This is the major European journal devoted to the subject, with review articles, editorial comments and original papers.


Benign enlargement of the prostate gland

Benign prostatic enlargement occurs most often in men over the age of 60 years. Such enlargement is much less common in African and Asian individuals. It is unknown in eunuchs. The aetiology of the condition is unknown. Microscopically, hyperplasia affects the glandular and connective tissue elements of the prostate. Enlargement of the gland stretches and distorts the urethra, obstructing bladder outflow. The bladder musculature hypertrophies so that a higher than usual pressure is generated within the bladder in order to overcome the obstruction and allow voiding of urine. Bands of muscle fibre are seen at cystoscopy (trabeculation). Eventually the bladder becomes dilated and the muscle hypotonic. The sphincter mechanism at the vesicoureteric junction may be impaired and reflux of urine from the bladder into the ureters and upper urinary tract may occur.


Frequency of urination, usually first noted as nocturia, is a common early symptom. Difficulty or delay in initiating urination, with variability and reduced forcefulness of the urinary stream and post-void dribbling are often present. Suprapubic pain occurs if bladder bacteriuria is present, if a bladder calculus has formed as a result of stagnation of urine within the bladder, or in acute retention of urine. Flank pain may accompany dilatation of the upper tracts. Acute retention of urine (see below) or retention with overflow incontinence may occur. Occasionally, severe haematuria results from rupture of prostatic veins or as a consequence of bacteriuria or stone disease. Some patients present with severe renal failure. Abdominal examination for bladder enlargement together with examination of the rectum are essential. A benign prostate feels smooth. An accurate impression of prostatic size cannot be obtained on rectal examination.


This should include urine culture, assessment of renal function by measuring the serum urea and creatinine concentrations, measurement of prostate-specific antigen (markedly raised in prostatic cancer), a plain abdominal X-ray, and renal ultrasonography to define whether upper tract dilatation is present. Excretion urography is not usually necessary. The completeness of bladder emptying after an act of voiding can be assessed by ultrasonography or by inspection of the after-voiding radiograph carried out during excretion urography. Cystourethroscopy is essential.


Patients with moderate prostatic symptoms can be treated medically. A number of drugs have been tried including a-blockers. Finasteride is a competitive inhibitor of Sa-reductase, which is the enzyme involved in the conversion of testosterone to dihydrotestosterone. This is the androgen primarily responsible for prostatic growth and enlargement. Finasteride decreases prostatic volume with an increase in urine flow. This new treatment must be compared with transurethral resection which is quick and safe.
Deterioration in renal function or the development of upper tract dilatation requires surgery. Transurethral resection is usually successful unless the gland is very large. It carries a lower morbidity and mortality with a shorter stay in hospital than open prostatectomy. Microwave hyperthermia, balloon dilatation and prostatic stents are all being tried, but long-term results are unavailable as yet. Very large glands require open transvesical prostatectomy.

In acute retention or retention with overflow, the first priorities are to relieve pain and to establish urethral catheter drainage. The bladder should be decompressed slowly to prevent bleeding from the mucosa. If urethral catheterization is impossible, suprapubic catheter drainage should be carried out. The choice of further management is then between immediate prostatectomy, a period of catheter drainage followed by prostatectomy, or the acceptance of a permanent indwelling suprapubic or urethral catheter.
Prostatic carcinoma Prostatic carcinoma accounts for 7% of all cancers in men and is the fourth commonest cause of death from malignant disease in men in England and Wales. Malignant change within the prostate becomes increasingly common with advancing age. By the age of 80 years, 80% of men have malignant foci within the gland, but most of these appear to lie dormant. Histologically, the tumour is an adenocarcinoma. Hormonal factors are thought to playa role in the aetiology.


Presentation is usually with symptoms of lower urinary tract obstruction or of metastatic spread, particularly to bone. The diagnosis may be made by the incidental finding of a hard irregular gland on rectal examination or as an unexpected histological result after prostatectomy for what was believed to be benign prostatic hypertrophy.


Investigation is as for benign enlargement of the prostate gland, with in addition measurement of prostate-specific antigen level, supplemented by transrectal ultrasound of the prostate and prostatic biopsy. A histological diagnosis is essential before treatment is  considered. This may be obtained by:

CYTOLOGICAL STAINING of biopsy material from the prostate
HISTOLOGICAL EXAMINATION of biopsy material or material obtained at transurethral or open prostatectomy If metastases are present, serum acid phosphatase and serum prostate-specific antigen are usually elevated; it is a myth that elevated levels occur as a result of rectal examination.
Ultrasonography and transrectal ultrasonography are of value in defining the size of the gland and staging any tumour present. The upper renal tracts can be examined  by ultrasonography for evidence of dilatation. Bone metastases may appear as osteosclerotic lesions on X-ray or may be detected by isotopic bone scans.


Microscopic, not clinically palpable turnour can be managed by watchful waiting. Treatment for disease confined to the gland is radical prostatectomy or radiotherapy, both resulting in an 80–90% 5-year survival. There have, however, been no controlled trials of this therapy and survival may be good without therapy. Locally extensive disease is managed with radiotherapy. Metastatic disease can be treated with orchidectomy, but many men refuse. Luteinizing hormone-releasing hormone (LHRH) analogues such as buserelin or goserelin are equally effective and preferred by many. The addition of an antiandrogen, e.g. cyproterone or flutarnide, seems to increase median survival. Non-hormonal chemotherapy is unhelpful.


The duration of survival depends on the age of the patient and the degree of differentiation and extent of the tumour.


A yearly rectal examination for men over 40 years of age remains a reasonable screening technique. Transrectal ultrasonography and measurement of serum prostatespecific antigen are being evaluated.


Testicular turnours, though uncommon, are the commonest malignant disease in men between the ages of 29 and 34 years  All such turnours should nowadays be regarded as curable. Patient survival depends upon early diagnosis, accurate staging of the turnour and appropriate treatment and follow-up. The expertise of a specialist centre is invaluable.
More than 96% of testicular tumours arise from germ cells. Two main types of tumour exist: 1 Seminomas (about one-third) 2 Teratomas (about two-thirds)


The aetiology is unknown. The risk of malignant change is much greater in undescended testes and there is a history of orchidopexy in about 10% of patients.


Common presenting symptoms are:
• Testicular swelling, which may be painless or painful
• Symptoms from metastases


The differential diagnosis includes:
• Epididymo-orchitis
• Torsion
• Chronic infection, e.g. tuberculosis, syphilitic gumma


Diagnosis may only be possible after surgical explorationof the testis through the groin. Scrotal exploration and scrotal testicular biopsy should be avoided owing to the high incidence of tumour implantation. Staging of the tumour will require:
• Chest X-ray to look for metastases
• Estimation of o-fetoprotein and f3-human chorionic gonadotrophin concentrations (tumour markers)
• Abdominal CT scanning


Seminomas are radiosensitive, so turnours confined to the testis or with metastases below the diaphragm only are treated by radiotherapy. More widespread tumours require chemotherapy.
Teratomas are treated by orchidectomy if the growth is confined to the testis. Chemotherapy is required for more widespread disease.

Turnours Of the kidney and genitourinary tract


These comprise 1-2% of all malignant tumours, and the male/female ratio is 2 : 1.

Renal cell carcinoma

Renal cell carcinomas (previously called hypernephromas or Grawitz tumours) arise from proximal tubular epithelium. They are the commonest renal tumour in adults. They rarely present before the age of 40 years, the average age of presentation being 55 years.


The tumours may be solitary, multiple or occasionally bilateral. The tumour lies within the kidney but it may eventually penetrate the capsule. Macroscopically, its cut surface appears as a yellow mass, sometimes containing areas of haemorrhage and cystic degeneration. Local invasion of renal veins and spread to the opposite kidney may occur, as may metastasis to lymph nodes, liver, bone and lung (often as an apparently solitary metastasis). Renal cell carcinomas are highly vascular tumours. Microscopically the tumour is composed of large cells  containing clear cytoplasm.


Patients present with haematuria, loin pain and a massin the flank. Malaise, anorexia and weight loss may occur,  and occasionally patients present with polycythaemia . Pyrexia is present in about one-fifth of patients and approximately one-quarter present with metastases. Rarely, a left-sided varicocele may be associated with leftsided tumours that have invaded the renal vein and caused obstruction to drainage of the left testicular vein.


Excretion urography will reveal a space-occupying lesion in the kidney; 10% of these show calcification. Ultrasonography is used to demonstrate the solid lesion and to examine the patency of the renal vein and inferior vena cava. CT scanning can also be used to identify the renal lesion and involvement of the renal vein or inferior vena cava. MRI is proving to be better than CT for tumour staging. Renal arteriography will reveal the tumour’s circulation. Urine cytology for malignant cells is of no value. The ESR is usually raised.


Treatment is by nephrectomy unless bilateral tumours are present or the contralateral kidney functions poorly, in which case conservative surgery such as partial nephrectomy may be indicated. If metastases are present, nephrectomy may still be warranted since regression of metastases has been reported after removal of the main tumour mass. Severe flank pain may also demand nephrectomy despite the presence of metastases. Radiotherapy has no proven value. Medroxyprogesterone acetate is of some value in controlling metastatic disease. Treatment with interferon-a produces up to a 20% response rate in the short term.


The prognosis depends upon the degree of differentiation of the tumour and whether or not metastases are present. The 5-year survival rate is 60-70% with tumours confined to the renal parenchyma, 15-35%, with lymph node involvement, and only approximately 5% in those who  have distant metastases.

Nephroblastoma (Wilms’ tumour)

This tumour is seen mainly within the first 3 years of life and may be bilateral. It presents as an abdominal mass, rarely with haematuria. Diagnosis is established by excretion urography followed by arteriography. A combination of nephrectomy, radiotherapy and chemotherapy as much improved survival rates, and the majority of children, even those with metastatic disease, are cured.

Renal arteriogram in a patient with renal carcinoma. Note the abnormal tumour circulation.

Renal arteriogram in a patient with renalcarcinoma. Note the abnormal tumour circulation.


Renal adenoma

Benign adenomas are usually an incidental finding, presentingas a space-occupying lesion on excretion urography.  They seldom cause symptoms. On urography they may be difficult to distinguish from a renal cell carcinoma.
• Simple cysts
Simple cysts are common. They are discussed III
Differentiation of benign renal cyst from malignant tumour If a space-occupying lesion is a chance finding on excretion urography in a patient with no relevant symptoms and no haematuria, ultrasonography should be carried out. If the lesion is transonic with no features suggesting a tumour, no further investigation is required. If haematuria has been present, a needle should be inserted into the transonic lesion and cyst fluid aspirated and examined for malignant cells. Contrast medium may be injected to delineate the walls of the cyst. Lesions shown to be solid or non-homogeneous on ultrasonography require further investigation by CT or arteriography.


The calyces, renal pelvis, ureter, bladder and urethra are lined by transitional cell epithelium. Transitional cell tumours account for about 3% of deaths from all forms of malignancy. Such tumours are uncommon below the age of 40 years, and the male/female ratio is 4 : 1. Bladder tumours are about 50 times as common as those of the ureter or renal pelvis.


These include:


EXPOSURE TO INDUSTRIAL CARCINOGENS such as f3- naphthylamine and benzidene. Workers in the chemical, cable and rubber industries are at particular risk. EXPOSURE TO DRUGS, e.g. phenacetin, cyclophosphamide. CHRONIC INFLAMMATION, e.g. schistosomiasis (usually associated with squamous carcinoma).


Painless haematuria is the commonest presenting symptom of bladder malignancy, although pain may occur owing to clot retention. Symptoms suggestive of UTI may develop in the absence of significant bacteriuria. In patients with bladder cancer, pain may also result from local nerve involvement.
Presenting symptoms may result from local metastases. Transitional cell carcinomas in the kidney and ureter may present with haematuria. They may also give rise to flank pain, particularly if urinary tract obstruction is present.


Investigation includes:

CYTOLOGICAL EXAMINATION of urine for malignant cells


CYSTOSCOPY if no evidence of upper urinary tract pathology has been found
Cystoscopy may be omitted in men under 20 and women under 30 years if significant bacteriuria accompanies the haematuria and both cease following control of the infection, and if urine cytology and excretion urography are normal. With these exceptions, it is essential that haematuria is always investigated.
In cases where the tumour is not clearly outlined on excretion urography, abdominal CT scanning and/or retrograde ureterography may be helpful.


Pelvic and ureteric tumours

These are treated by nephroureterectomy. Radiotherapy and chemotherapy appear to be of little or no value. Subsequently cystoscopy should be regularly carried out, since about half the patients will develop bladder tumours.

Bladder tumours

Treatment depends upon the stage of the tumour (in particular whether it has penetrated the bladder muscle) and its degree of differentiation. Treatment options include local cystodiathermy and/or resection with follow-up check cystoscopies, cytological examination of urine/cystoscopy, cystectomy, radiotherapy, or local and systemic chemotherapy.


The prognosis ranges from a 5-year survival rate of 80% for lesions not involving bladder muscle to 5% for those presenting with metastases.

Cystic, congenital and familial disease

Cystic renal disease

Solitary or multiple renal cysts are common, especially with advancing age: 50% of those aged 50 years or more have one or more such cysts. They have no special significance except in the differential diagnosis of renal tumours . Such cysts are often asymptomatic and are found on excretion urography or ultrasound examination performed for some other reason. Occasionally they may cause pain and/or haematuria due to their large size or bleeding may occur into the cyst.

Adult polycystic renal disease

Adult polycystic renal disease (APeD) is an important cystic disease of the kidney that is relatively common. In the large majority of cases, inheritance is in an autosomal dominant manner as a single gene defect linked to the ahaemoglobin gene locus on the short arm of chromosome 16. It is manifested in infancy as tiny cystic lesions distributed throughout both kidneys and should be distinguished from juvenile nephronophthisis (see below). The precise mechanism for cyst formation is disputed. With advancing age the cysts enlarge at a variable rate, often at the same rate within family groups but at different rates between different families. There is progressive asymmetric renal enlargement, with compression of intervening renal tissue and progressive loss of excretory function.
Clinical presentation may be at any age from the second decade. Presenting symptoms include:
• Acute loin pain and/or haematuria due to haemorrhage into a cyst
• Vague loin or abdominal discomfort due to the increasing size of the kidneys
• Development of hypertension or symptoms of uraemia The natural history of the disease is one of progressive renal impairment, sometimes punctuated by acute episodes ofloin pain and haematuria and commonly associated with the development of hypertension. It is popularly believed that there is an increased incidence of UTI in patients with APeD. There is little evidence to support this, but if such patients do develop infection it may be more difficult to eradicate. As mentioned earlier, the rate of progression to renal failure is variable but tends to follow the same pattern in families. Some may reach endstage renal failure at 40 years but others survive to 70 years or more.
Approximately 30% of patients with APeD have hepatic cysts; these rarely cause liver dysfunction. Cysts may more rarely develop in the pancreas, spleen, ovary and other organs. Berry aneurysms of the cerebral vessels (10- 30%) are not infrequent and may result in subarachnoid or cerebral haemorrhage. Renal neoplasms may develop in polycystic kidneys and are difficult to diagnose. Polycythaemia and mitral valve prolapse are not uncommon associations.


Physical examination commonly reveals large, irregular kidneys and possibly hepatomegaly. Definitive diagnosis was previously based on excretion urography, but is now more easily established by ultrasound examination . However, such renal imaging techniques may be equivocal, especially in subjects under the age of 20 years.


The disease is always progressive. The most important aspect of management is regular blood pressure recording in affected patients, with control of hypertension as it develops. Uncontrolled hypertension accelerates the loss of kidney function. Some patients may develop salt and water wasting as the disease advances, when salt replacement with Slow Sodium can improve excretory function. Many patients will require renal replacement by dialysis and/or transplantation.


The children and siblings of patients with established APeD should be routinely offered screening. We believe that this should be offered to identify patients with this disorder, who must then have regular blood pressure checks and should be offered genetic counselling in respect of family planning. Screening should not be carried out before the age of 20 years, as excluding the condition may be difficult and hypertension is unusual before this age. Even at this age, renal ultrasonography may give a false-negative result. Gene linkage analysis can be utilized in many families.

Medullary cystic disease (‘juvenile nephronophthisis’)

Developing early in childhood, juvenile nephronophthisisis commonly inherited in an autosomal recessive manner.  A similar condition developing later in childhood (medullary cystic disease) is inherited as an autosomal dominant trait, but sporadic cases occur in both conditions. Despite its name, the dominant histological finding is interstitial inflammation and tubular atrophy, with later development of medullary cysts. Progressive glomerular failure is a secondary consequence. The dominant features are polyuria, polydipsia and growth retardation. Diagnosis is based on the family history and renal biopsy, the cysts rarely being visualized by imaging techniques.

Ultrasound scan of a polycystic kidney showing an enlarged kidney with many cysts of varying size

Ultrasound scan of a polycystic kidney showing an
enlarged kidney with many cysts of varying size

Medullary sponge kidney

Medullary sponge kidney is an uncommon but not rare condition that usually presents with renal colic or haem aturia. Although it is most often sporadic, a few affected families have been reported. The condition is characterize by dilatation of the collecting ducts in the papillae, sometimes with cystic change. In severe cases the medullary area has a sponge-like appearance. The condition may affect one or both kidneys or only part of one kidney. Cyst formation is commonly associated with the development of small calculi within the cyst. In about 20% of patients there is associated hypercalciuria or renal tubular acidosis. Hemihypertrophy of the skeleton has been described in this condition. The diagnosis is made by excretion urography, which shows small calculi in the papillary zones with an increase in radio density around these following injection of contrast medium as the dilated or cystic collecting ducts are filled with contrast.
The natural history is one of intermittent colic with passage of small stones or haematuria. Renal function is usually well maintained and renal failure is unusual, except where obstructive nephropathy develops owing to the growth of stones in the pelvis or ureters.



Agenesis may be bilateral or unilateral. Unilateral agenesis (‘solitary kidney’) occurs in 1 in 1000 of the population. It is usually associated with compensatory hypertrophy of the single kidney and normal renal function. Save for the potential hazard of trauma to this solitary kidney, it has no clinical significance.


Renal hypoplasia (failed development) of one kidney is uncommon, and hypoplasia of both kidneys is rare. It may be difficult to distinguish unilateral renal hypoplasia from a small kidney due to renal artery stenosis, obstruction or reflux nephropathy in early life. Clinical interest in the condition most often arises in patients with hypertension, where the small kidney may be considered the cause. If the small kidney is shown by radioisotope studies to contribute no useful renal function and if the hypertension has developed in a young subject or is difficult to control by medical treatment, nephrectomy should be undertaken.

Ectopic kidneys

Defects in embryological renal development may lead to ectopic or maldeveloped renal systems. At the risk of oversimplification, the kidneys may be thought of as developing in the embryo as one structure in the ‘pelvic’ area, migrating upwards and separating with growth. Failure in normal development may result in failure of the kidneys to migrate normally and indeed they may fail to separate. This results in a ‘pelvic kidney’ when one or both remain in the pelvis, a ‘crossed ectopic kidney’ when both have moved to the same side of the spine, a horseshoe or discoid kidney when there is partial (usually fusion of the lower poles) or total failure of separation. In clinical practice the main problem associated with ectopic kidneys usually relates to impaired urinary drainage with secondary obstruction or stone formation. This may be compounded if infection supervenes, the poor drainage making eradication of infection difficult and predisposing to stone formation. Pelvic kidneys may interfere with parturition.



Familial renal disease is in general rare, but there are anumber of familial conditions that, among other things, can affect the kidneys.
Alport’s syndrome  Alpert’s syndrome is a rare condition characterized by hereditary nephritis with haematuria, progressive renal failure and high-frequency nerve deafness. It is principally expressed in males and both X-linked and dominant modes of inheritance have been postulated. Some 15% of cases may have ocular abnormalities such as cataract, conical cornea and dislocated small lens. The disease is progressive and accounts for some 5% of cases of endstage renal failure in childhood or adolescence. Anti- GBM antibody does not adhere normally to the glomerular basement membrane of affected individuals.

Congenital nephrotic syndrome

This syndrome is rare.

Renal tubular transport defects

Renal tubular transport defects include cystinuria, X-linked hypophosphataemia, Hartnup’s disease, adult Fanconi syndrome, galactosaemia and fructosaemia. They are discussed.

Renal glycosuria

Renal glycosuria, in which there is glucose in the urinein subjects demonstrated to have normal blood glucose  levels, who are not starved and who have no other urinary bnormality, is uncommon. Such patients have either a defect in the tubular threshold for reabsorption of glucose in the proximal tubule (a ‘splayed’ reabsorption curve) or a defect in the maximal tubular reabsorption of glucose. Both autosomal dominant and recessive inheritance have been postulated. It has no clinical significance except in the differential diagnosis of patients with diabetes mellitus or other tubular disorders such as the Fanconi syndrome.

Complications of long-term dialysis

Cardiovascular disease and sepsis are the leading causes of death in long-term dialysis patients. Causes of fatal sepsis include peritonitis complicating peritoneal dialysis and Staph. aureus infection (including endocarditis) complicating the use of indwelling access devices for haemodialysis.

DIALYSIS AMYLOIDOSIS is caused by the accumulation of amyloid protein as a result of failure of clearance of f32-microglobulin, a molecule of 11.8 kDa. This protein is the light chain of the class I HLA antigens and is normally freely filtered at the glomerulus but is not removed by cellulose-based haemodialysis membranes. Complement activation resulting from the use of cellulose-based membranes may increase the generation rate of the protein. The protein polymerizes to form amyloid deposits, which may cause median nerve compression in the carpal tunnel or a dialysis arthropathy-a clinical syndrome of pain and disabling stiffness in the shoulders, hips, hands, wrists and knees. f32-Microglobulin-related amyloid may be demonstrated in the synovium. There is little inflammation and the pathogenesis is ill understood. Rapid improvement after renal transplantation is probably due to steroid therapy. Low-dose prednisolone alone can also cause an improvement. A change to a biocompatible synthetic membrane has also been reported to be of benefit: again, the mechanism for this improvement is not clear. Amyloid deposits can also cause pathological bone cysts and fractures, pseudotumours and gastrointestinal bleeding caused by amyloid deposition around submucosal blood vessels.
The extent of amyloid deposition is best assessed by nuclear imaging, either using [99ffiTclDMSA, or, more specifically, by the use of radiolabelled serum amyloid P component.


Successful renal transplantation offers the potential for complete rehabilitation in end-stage renal failure. It allows freedom from dietary and fluid restriction, anaemia and infertility are corrected and the need for parathyroidectomy is reduced.
The technique involves the anastomosis of an explanted human kidney, either from a cadaveric donor or, less frequently, from a living close relative, on to the iliac vessels of the recipient. The donor ureter is placed into the recipient’s bladder. Unless the donor is genetically identical (i.e. an identical twin), immunosuppressive treatment is needed, for as long as the transplant remains in place, to prevent rejection. Eighty per cent of grafts now survive for 5-10 years in the best centres, and 60% for 10-30 years.
Success of transplantation is affected by numerous factors:
DR matching appears to have the most impact on survival, followed by the B and, least importantly, the A loci. Complete compatibility at A, B and DR offers the best chance of success, and this has led to nationwide matching schemes for kidneys retrieved from cadaver donors.

The anatomy of a renal transplant operation

The anatomy of a renal transplant operation

PREOPERATIVE BLOOD TRANSFUSION appears to exert a non-specific immunosuppressive effect, decreasing the incidence of rejection; however this effect is modest compared to the immunosuppressive effects of cyclosporin, and blood transfusion carries a risk of HLA sensitization.
THE ‘CENTRE EFFECT’: graft survival is higher in those entres with extensive experience of medical management of transplant recipients.

Donor kidney

CADAVERIC DONATION. Most countries allow the removal of kidneys and other organs from patients who have suffered irretrievable brain damage (‘brain stem death’) while their hearts are still beating.
LIVING RELATED DONA TION. Occasionally a close relative may volunteer as a potential donor. A sibling donor may be HLA identical or share one or no haplotypes with the potential recipient. Most transplant centres accept one haplotype matches as well as HLA-identical donors. Most avoid using child-to-parent donation unless the circumstances are exceptional.
Potential living related donors are subjected to an intensive preoperative evaluation, including clinical examination and measurement of renal function, tests for carriage of hepatitis B, C, HIV and cytomegalovirus, and detailed imaging of renal anatomy with IVU and then arteriography, to be sure that transplantation will be technically feasible.

Immunosuppression for transplantation

Long-term drug treatment for the prevention of rejectionis employed in all cases apart from living related donation  from an identical twin. Some degree of immunological tolerance does develop, and the risk of rejection is highest in the first 3 months after transplantation. A combination of immunosuppressive drugs is usually used. CORTICOSTEROIDS have a non-specific immunosuppressive action. High-dose methylprednisolone is used as the primary treatment for acute rejection.
AZATHIOPRINE prevents cell-mediated rejection by interfering with nucleic acid synthesis and preventing replication of lymphocytes. Adverse effects include suppression of red cell and platelet production and an increased incidence of infections (particularly viral).
CYCLOSPORIN prevents the activation ofT lymphocytes in response to new antigens and is highly effective in preventing rejection, while leaving the function of the rest of the immune system largely intact. Its introduction has revolutionized organ transplantation. Disadvantages include variable bioavailability, high cost and nephrotoxicity. Even with careful adjustment of the dose in response to trough blood levels, renal function may be adversely affected due to renal vasoconstriction which may result in irreversible interstitial fibrosis.
NEW IMMUNOSUPPRESSIVE AGENTS such as FKS06 and rapamycin are becoming available and are undergoing clinical trials.
ANTIBODIES AGAINST T CELLS are potent and relatively specific immunosuppressive agents whose role is increasing. Antibodies may be polyclonal or monoclonal, derived from mouse, rabbit, horse, or ‘humanized’, and directed against any of a number of lymphocycte surface marker proteins, enabling neutralization or killing oflymphocytes with certain functions, e.g. T cells, activated T cells, cells expressing adhesion molecules, cells expressing the interleukin-2 receptor. These antibodies may be used both in the prevention and the treatment of rejection, but are highly immunosuppressive; some may increase the risk of virus-associated malignancy, e.g. lymphomas.
IN FUTURE attention will turn increasingly to the induction of immunological tolerance to grafted organs and to the use of organs from genetically modified animals. Complications of renal transplantation These include:


OPPORTUNISTIC INFECTIONS, e.g. Pneumocystis, cytomegalovirus.
LIPID ABNORMALITIES and a high risk of cardiovascular events.
HYPERTE sION-often attributable to cyclosporin.
RECURRENCE OF THE DISEASE WHICH CAUSED RENAL FAILURE-this is uncommon but may occur in specific diseases, e.g. primary oxalosis, mesangiocapillary glomerulonephritis, focal segmental glomerulosclerosis, Goodpasture’s syndrome.
DE NOVO GLOMERULO EPHRITIS in the grafted kidney.

MALIGNANCY, particularly lymphomas and skin cancers- these are often attributable to viral induction of malignancy.
ASEPTIC NECROSIS OF BONE resulting from high-dose corticosteroid treatment.

Choice of renal replacement therapy

For the majority of patients with end-stage renal failure a renal transplant is the treatment of choice, but because of the limited availability of donor organs many patients remain on dialysis for years while waiting for a transplant. Sensitization to HLA antigens, for instance by pregnancy, blood transfusion or a previous failed transplant, makes finding a compatible organ more difficult. In addition, there are a number of patients who are thought unsuitable for transplantation, e.g.
• Previous malignancy
• Severe non-renal disease likely to limit survival and the degree of rehabilitation after transplantation
• Elderly patients
The choice between CAPD and haemodialysis is influenced by medical, social, psychological and. financial factors. Nearly all renal units offer a choice of modalities.


Prevention of chronic renal failure.

Prevention of chronic renal failure.

Peritoneal dialysis

Peritoneal dialysis utilizes the peritoneal membrane as a semi-permeable membrane, avoiding the need for extracorporeal circulation of blood. This is a very simple, low technology treatment compared to haemodialysis. The principles are simple :
1 A tube is placed into the peritoneal cavity through the anterior abdominal wall.
2 Dialysate is run into the peritoneal cavity, usually under gravity.
3 Urea, creatinine, phosphate, and other uraemic toxins pass into the dialysate down their concentration gradients.
4 Water (with solutes) is attracted into the peritoneal cavity by osmosis, depending on the osmolarity of the dialysate. This is determined by the dextrose content of the dialysate .
5 The fluid is changed regularly to repeat the process. For acute peritoneal dialysis a stiff catheter is inserted under local anaesthetic in the midline, one-third of the way down between the umbilicus and the symphysis pubis.
Chronic peritoneal dialysis requires insertion of a soft catheter, with its tip in the pelvis, exiting the peritoneal cavity in the midline and lying in a skin tunnel with an exit site in the lateral abdominal wall. This form of dialysis can be adapted in several ways.

Range of concentrations (mmol litre:") in routinely available CAPO dialysate.

Range of concentrations (mmol litre:”) in routinely available CAPO dialysate.


Dialysate is present within the peritoneal cavity continuously, apart from when dialysate is being exchanged. Dialysate exchanges are performed three to five times a day, using a sterile no-touch technique to connect 1.5-3 litre bags of dialysate to the peritoneal catheter; each exchange takes 20-40 min. This is the technique most often used for maintenance dialysis in patients with endstage renal failure.


Dialysate is exchanged every 60-120 min, requiring the patient to remain in bed during the treatment. This form of treatment is often used for acute renal failure and as maintenance treatment for end-stage renal failure when 20-40 hours’ treatment per week is given as two or more overnight sessions.

The siting of a Tencknoff

The siting of a Tencknoff


(N I P D). An automated device is used to performexchanges each night while the patient is asleep. Sometimes  dialysate is left in the peritoneal cavity during the day in addition, to increase the time for which biochemical exchange is occurring.
TIDAL DIALYSIS. A residual volume is left within the peritoneal cavity with continuous cycling of smaller volumes in and out.
FLUID BALANCE CONTROL. Ultrafiltration, i.e. removal of excess plasma water and solutes, is achieved using hypertonic dialysate, which exerts an osmotic ‘drag’. Depending on the patient’s fluid intake and residual urine output, it may be necessary to use one or more hypertonic dialysate bags daily to achieve fluid balance in CAPD. Fluid overload is a relatively common problem in CAPD, and is due to failure of transport across the peritoneal membrane.

Complications of peritoneal dialysis

PERITONITIS. Bacterial peritonitis is the commonest serious complication of CAP D and other forms of peritoneal dialysis. Clinical presentations include abdominal pain of varying severity (guarding and rebound tenderness are unusual), and a cloudy peritoneal effluentwithout which the diagnosis cannot be made. Microscopy reveals a neutrophil count of >100 cells/rnl. Nausea, vomiting, fever and paralytic ileus may be seen if peritonitis is severe.
CAPD peritonitis must be investigated with culture of peritoneal effluent. Empirical antibiotic treatment must be started immediately, with a spectrum which covers both Gram-negative and Gram-positive organisms, e.g. third generation cephalosporin intravenously. Antibiotics may be given by the oral, intravenous or intraperitoneal route; most centres rely on intraperitoneal antibiotics. Common causative organisms are listed.
Staph. aureus peritonitis should lead to a search for nasal carriage of this organism and Staph. epidermidis peritonitis usually indicates contamination from the patient’s (or helper’s) skin. Relapsing Staph. epidermidis peritonitis with an organism with the same antibiotic sensitivity pattern on each occasion may indicate that the Tenckhoff catheter has become colonized: often this is difficult to eradicate without replacement of the tube under antibiotic cover.
Gram-negative peritonitis may complicate septicaemia from urinary or bowel infection. A mixed growth of Gram-negative and anaerobic organisms strongly suggests bowel perforation, and is an indication for formallaparotomy. Fungal peritonitis often follows antibacterial treatment but may occur de novo. Clinical presentation is very variable. It is rare to be able to cure fungal peritonitis without catheter removal as well as antifungal treatment. Intraperitoneal amphotericin has been associated with the formation of peritoneal adhesions.
INFECTION AROUND THE SITE where the catheter exits through the skin is relatively common. It should be treated aggressively (with systemic and/or local antibiotics) to prevent spread of the infection into the subcutaneous tunnel and the peritoneum; the commonest causative organisms are staphylococci.
Other complications CAPD is often associated with constipation, which in turn may impair flow of dialysate in and out of the pelvis. Occasionally dialysate may leak through a diaphragmatic defect into the thoracic cavity, causing a massive pleural ‘effusion’. The glucose content of the effusion is usually diagnostic or the diagnosis may be made by instillation of methylene blue with dialysate and the demonstration of a blue colour on pleural tap. Dialysate may also leak into the scrotum down a patent processus vaginalis. Failure of peritoneal membrane function is a predictable complication of long-term CAPD, resulting in worsening biochemical exchange and decreased ultrafiltration with hypertonic dialysate. It is thought that this problem may be accelerated by excessive reliance onhypertonic dialysate to remove fluid.
Sclerosing peritonitis is a rare but potentially fatal complication of CAPD. The causes are often unknown, but recurrent peritonitis, contamination of the peritoneal cavity with chlorhexidine, and some drugs have been implicated. Progressive thickening of the peritoneal membrane occurs in association with adhesions and strictures, turning the small bowel into a mass of matted loops and causing repeated episodes of small bowel obstruction. There is no known way of reversing the process. CAPD should be abandoned.

Some causes of CAPD peritonitis.

Some causes of CAPD peritonitis.

Contraindications to peritoneal dialysis There are few absolute contraindications apart from unwillingness or inability on the patient’s part to learn the technique.
Previous peritonitis causing peritoneal adhesions may make peritoneal dialysis impossible: but the extent of adhesions is difficult to predict, and it may be worth an attempted surgical placement of a dialysis catheter. The presence of a stoma (colostomy, ileostomy, ileal urinary conduit) makes successful placement of a dialysis catheter extremely unlikely. Active intra-abdominal sepsis, for instance due to diverticular abscesses, is an absolute contraindication to peritoneal dialysis although diverticular disease per se is not.
Abdominal hernias may often expand during CAPD as a result of increased intra-abdominal pressure, and should ideally be repaired before or at the time of CAPD catheter insertion.
Visual impairment may make it difficult for a patient to perform dialysate exchanges, but completely blind patients can be trained in the technique if adequately motivated.
Severe arthritis makes it difficult to perform the exchanges, but a large number of mechanical aids are available. Sterilization of connections by heat or ultraviolet light reduces the risk of peritonitis. Adequacy of peritoneal dialysis No consensus yet exists on how the adequacy of peritoneal dialysis should be measured. Symptoms of underdialysis (see p. 486) should be noted. A protein intake of at least 1.1 g kg-i ideal body weight together with dialysis adequate to keep peak or average blood urea concentration below 25 mrnol litre'” probably indicates adequate dialysis. Renal function declines less rapidly in CAPD patients than in those receiving intermittent haemodialysis, but with total renal failure it is often difficult to maintain adequacy of dialysis with CAPD alone, necessitating conversion to haemodialysis. CAPD is an excellent treatment or those patients likely to receive a renal transplant or for elderly patients with limited life expectancy, but is probably not the treatment of choice in the small minority in whom long-term dialysis is contemplated.

Patient education

Involvement at an early stage in various aspects of treatment helps prepare the way for the complicated training that may lie ahead. Dietary and drug therapy should be explained. As dialysis and/or transplantation may be required in the future, forward planning may be necessary. The patient’s home may need to be assessed and converted to take dialysis equipment. Job prospects and economic resources need to be considered.


Approximately 100 individuals per million population reach end-stage renal failure per annum. The aim of all renal replacement techniques is to mimic the excretory functions of the normal kidney, including excretion of nitrogenous wastes, e.g. urea, maintenance of normal electrolyte concentrations, and maintenance of a normal extracellular volume.

Changes across a semi-permeable dialysis membrane.

Changes across a semi-permeable dialysis


Basic principles

In haemodialysis blood from the patient is pumped through an array of semi-permeable membranes (the dialyser, often called an ‘artificial kidney’) which bring the blood into close contact with dialysate, flowing countercurrent to the blood. The plasma biochemistry changes towards that of the dialysate due to diffusion of molecules down their concentration gradients.
THE DIALYSIS MACHINE comprises a series of blood pumps, with pressure monitors and bubble detectors and a proportionating unit, also with pressure monitors and blood leak detectors. Blood flow during dialysis is usually 200-300 ml min “! and dialysate flow usually 500 ml min~l. The efficiency of dialysis in achieving biochemical change depends on blood and dialysate flow and the surface area of the dialysis membrane. Dialysate is prepared by a proportionating unit which mixes specially purified water with concentrate, resulting in fluid with the composition described. A large number of semi-permeable membranes are now available. Cellulose-based membranes are the most widely used and cheapest. The total surface area of the dialyser is about 1 m? while the thickness is about 10 /-Lm. Numerous configurations have been invented; the one in most common use is the hollow fibre dialyser, in which blood from the patient is distributed to thousands of hollow fibres made from a semi-permeable material, with the dialysate flowing around the outside of the fibres . Newer highly permeable synthetic membranes allow more rapid haemodialysis than with cellulose-based membranes (high-flux haemodialysis).

Range of concentrations (mmol litre:") in routinely available final dialysates used for haemodialysis.

Range of concentrations (mmol litre:”) in routinely available final dialysates used for haemodialysis.

Access for haemodialysis

Adequate dialysis requires a blood flow of at least 200 ml min’. The most reliable long-term way of achieving this is surgical construction of an arteriovenous fistula, using the radial or brachial artery and the cephalic vein. This results in distension of the vein and thickening (‘arterialization’) of its wall, so that after 6-8 weeks largebore needles may be inserted to take blood to and from the dialysis machine. Arteriovenous shunts are large-bore plastic cannulae surgically tied into a superficial artery and adjacent vein. These allow direct flow of arterial blood into the dialysis machine, which is returned directly into a vein. Between dialysis sessions flow between artery and vein is restored by a plastic connector between the two cannulae, which lie outside the body, usually on the forearm. Disadvantages include a high rate of infection, thrombosis and the potential for disconnection which could result in exsanguination. If dialysis is needed immediately, a large-bore doublelumen cannula may be inserted into a central vein-usually the subclavian, jugular or femoral. Semi-permanent dual-lumen venous catheters may also be inserted with a skin tunnel to lessen the risk of infection.

Dialysis prescription

Dialysis must be tailored to an individual patient to obtain optimal results.
DRY WEIGHT is the weight at which a patient is neither fluid overloaded nor depleted. Patients are weighed at the start of each dialysis session and the transmembrane pressure adjusted to achieve fluid removal equal to the amount by which they exceed their dry weight.

A hollow fibre dialyser

A hollow fibre dialyser

THE DIALYSATE BUFFER is usually acetate or bicarbonate. The sodium and calcium concentration of the dialysate buffer are carefully monitored. A high dialysate sodium causes thirst and hypertension. A high dialysate calcium causes hypercalcaemia, whilst a low calcium dialysate combined with poor compliance of medication with oral calcium carbonate and vitamin D may result in hyperparathyroidism.

FREQUENCY AND DURATION of dialysis is adjusted to achieve adequate removal of uraemic metabolites and to avoid excessive fluid overload between dialysis sessions. An adult of average size usually requires 4-5 hours’ treatment three times a week if standard Cuprophane dialysers are used. Twice weekly dialysis is only adequate if the patient has considerable residual renal function. All patients are anticoagulated (usually with heparin) during treatment as contact with foreign surfaces activates the clotting cascade. In the UK, many patients have selfsupervised home haemodialysis.

Complications of haemodialysis

Hypotension during dialysis is the major complication. Contributing factors include: an excessive removal of extracellular fluid, inadequate ‘refilling’ of the blood compartment from the interstitial compartment during fluid removal, abnormalities of venous tone, autonomic neuropathy, acetate intolerance (acetate acts as a vasodilator) and left ventricular hypertrophy.
Very rarely patients may develop anaphylactic reactions to ethylene oxide, which is used to sterilize most dialysers. Patients receiving ACE inhibitors are at risk of anaphylaxis if polyacrylonitrile dialysers are used. Other potential, rare, complications include the hard water syndrome (caused by failure to soften water resulting in a high calcium concentration prior to mixing with dialysate concentrate), haemolytic reactions and air embolism.

Adequacy of dialysis

Morbidity and mortality in dialysis patients are influenced by the adequacy of dialysis and nutrition of the patient. Symptoms of underdialysis are non-spec ific and include insomnia, itching, fatigue despite adequate correction of anaemia, restless legs and a peripheral sensory neuropathy. Full assessment of the adequacy of dialysis demands a computerized calculation of urea kinetics, requmng measurement of the residual renal urea clearance, the rate of rise of urea concentration between dialysis sessions and the reduction in urea concentration during dialysis. Machine haemodialysis is the most efficient way of achieving rapid biochemical improvement, for instance in the treatment of acute renal failure or severe hyperkalaemia. This advantage is offset by disadvantages such as haemodynamic instability, especially in acutely ill patients with multi-organ disease, and over-rapid correction of uraemia can lead to ‘dialysis disequilibrium’. This is characterized by nausea and vomiting, restlessness, headache, hypertension, myoclonic jerking, and in severe instances seizures and coma due to rapid changes in plasma osmolality leading to cerebral oedema. These problems have led to the increasing adoption of gentler continuous methods for the treatment of acute renal failure

Principles of haemofiltration.

Principles of haemofiltration.


This removes plasma water and its dissolved constituents, e.g. K+, Na”, urea, phosphate, by convective flow across a high-flux semi-permeable membrane, and replacing it with a solution of the desired biochemical cmposition . Lactate is used as buffer in the replacement solution because rapid infusion of acetate causes vasodilatation and bicarbonate may cause precipitation of calcium carbonate. Haemofiltration can be used for both acute and chronic renal failure. High volumes need to be exchanged in order to achieve adequate small molecule removal; typically a 22-litre exchange three times a week for maintenance treatment and 1000 ml hour-l in acute renal failure.

Haemod iafi Itration

This is a combination of high-flux haemodialysis, using dialysate made from highly purified water for countercurrent dialysis, plus haemofiltration combined with infusion of replacement fluid. Advantages include a better small molecule clearance than with haemofiltration alone, a good clearance of middle molecules and an excellent haemodynamic stability. However, it is expensive.

Continuous treatments

Continuous treatments are used in acute renal failure and have the advantage of slow continuous correction of metabolic and fluid balance. They are particularly suitable for patients with haemodynamic instability. Blood flow may be achieved either by using the patient’s own blood pressure to generate flow through a dialyser (continuous arteriovenous treatment, CA VH) or by the use of a blood pump to draw blood from the ‘arterial’ lumen of a duallumen catheter placed in the jugular, subclavian or femoral vein, through the dialyser, and back to the ‘venous’ lumen (continuous venovenous treatment, CVVH).
CONTINUOUS HAEMOFILTRATION (CAVH, CVVH) refers to the continuous removal of ultra filtrate from the patient, usually at rates of up to 1000 ml hour-I, combined with simultaneous infusion of replacement solution. For instance, in a fluid-overloaded patient one might remove filtrate at 1000 ml hour-I and replace at a rate of 900 ml hour-I, achieving a net fluid removal of 100 ml hour-I. Haemofiltration may have an advantage over continuous haemodialysis of removing cardiodepressant substances which appear to accumulate in acute renal failure and septic shock.
CONTINUOUS HAEMODIALYSIS (CAVHD, CVVHD) involves the continuous passage of dialysate countercurrent to the flow of blood. Dialysate is pumped (using an intravenous fluid pump) through the dialysate compartment of a synthetic membrane hollow fibre dialyser at a rate of around 1000 ml hour-I.
CONTINUOUS HAEMODIAFILTRATION (CAVHDF, CVVHDF) is a combination of haemofiltration and haemodialysis, involving both the net removal of ultrafiltrate from the blood and its replacement with a replacement solution, together with the countercurrent passage of dialysate (which may be identical to the replacement solution). Both the ultrafiltrate and the spent dialysate appear as ‘waste’.

SLOW CONTINUOUS ULTRAFILTRATION (SCUF) is the removal of ultrafiltrate from the patient by convection across the dialyser without infusion of replacement fluid or dialysate flow. Fluid is normally removed at a rate of 100-200 ml hour-I. This results in a gradual reduction in plasma volume and is useful for the treatment of severe volume overload, for instance in severe cardiac failure prior to definitive treatment. No biochemical improvement occurs, and this is not really a renal replacement technique, but is mentioned here for completeness.

The principles of peritoneal dialysis.

The principles of peritoneal dialysis.


The principles of management are outlined in Information box 9.2 and Practical box 9.4. Obviously, treatment should be directed at the underlying disease. However, many causes of acute renal failure result in the ‘final common path’ of acute tubular necrosis.

No treatment has been shown to affect the natural history of acute tubular necrosis. Clearly as many of the factors leading to hypoperfusion should be controlled as quickly as possible. Often this requires fluid replacement, guided by measurements of central venous pressure or pulmonary capillary wedge pressure. The polyuric phase of acute tubular necrosis requires extremely careful clinical care in order to avoid further renal injury from hypovolaemia. Inotropic support is rational treatment in patients with cardiac disease and poor renal perfusion; low-dose dopamine selectively improves renal perfusion.

The role of loop diuretics and mannitol remain controversial. Theoretically these agents may help to flush out tubular debris, prevent reflex vasoconstriction in response to tubular injury, and decrease renal work and oxygen consumption. Controlled trials have shown that loop diuretics in very high doses may increase urine volumes in acute tubular necrosis without much effect on GFR or the subsequent need for dialysis. This marginal benefit must be weighed against the risk of exacerbating hypovolaemia if they are used without adequate monitoring, the risk of auditory toxicity, and (with mannitol) the risk of causing volume expansion and pulmonary oedema if an adequate diuresis is not achieved.

Acute renal failure can be treated by dialysis. Particular care should be used to avoid haemodynamic disturbance and because of this continuous haemofiltration, haemodialysis or peritoneal dialysis are often preferred to intermittent haemodialysis, particularly in patients with persistent cardiovascular instability.

Information box 9.2 General management of acute renal failure. Practical box 9.4 Practical management of acute renal failure

Information box 9.2 General management of acute renal failure. Practical box 9.4 Practical management of acute renal failure

Chronic renal failure
The underlying cause of renal disease should be treated aggressively wherever possible, e.g. tight metabolic control in diabetes.

Blood pressure control

Antihypertensive treatment is thought to decrease the rate of deterioration of renal function in chronic progressive renal disease, whatever the initiating cause. Blood pressure should probably be reduced to around 140/80 mmHg. Captopril (an ACE inhibitor) has been proven to slow the rate of deterioration in GFR in diabetic nephropathy to a greater extent than with other hypotensive agents inducing the same degree of blood pressure reduction. ACE inhibitors are under investigation for other renal disease but are now the drugs of choice for hypotensive therapy. ACE inhibitors must be used with caution in the presence of coexistent renal vascular disease. Adequate blood pressure control may require a combination of drugs together with large doses of diuretics to correct sodium and water retention. In patients receiving regular dialysis blood pressure can often be controlled by removal of sodium and water during dialysis.


Hyperkalaemia often responds to dietary restriction of potassium intake. Drugs which cause potassium retention should be stopped. Occasionally it may be necessary to presribe ion-exchange resins to remove potassium in the gastrointestinal tract.


Correction of acidosis helps to correct hyperkalaemia in chronic renal failure, and may also decrease muscle catabolism. Sodium bicarbonate supplements are often effective, but may cause oedema and hypertension due to extracellular fluid expansion. Calcium carbonate, also used as a calcium supplement and phosphate binder, also has a beneficial effect on acidosis.

Calcium and phosphate

Hypocalcaemia and hyperphosphataemia should be aggressively treated, preferably with regular (e.g. 3- monthly) measurements of serum PTH to assess how effectively hyperparathyroidism is being suppressed. Dietary restriction of phosphorus is seldom effective alone, because so many important foods contain it. Oral calcium carbonate acts as a calcium supplement and also reduces bioavailability of dietary phosphorus. la-Cholecalciferol and 1,25-(OH)2D3 increase calcium absorption and also directly suppress parathyroid activity, but must be used with great caution to avoid hypercalcaemia. They have the disadvantage that they also increase phosphorus absorption and may therefore exacerbate hyperphosphataemia. H2 antagonists decrease the effectiveness of phosphate binders.

Dietary restrictions

In advanced renal disease, reduction of protein intake lessens the amount of nitrogenous waste products generated, and this may delay the onset of symptomatic uraemia. There is some evidence to suggest that dietary protein restriction may slow the rate of progression towards end-stage disease but this remains controversial.

Fluid and salt intake

A high fluid intake is probably beneficial in chronic renalfailure, allowing excretion of metabolites despite poor  concentrating ability, and suppressing vasopressin (which may contribute to progressive renal disease). Fluid restriction is sometimes necessary in patients with oedema, but is less important than sodium restriction.


The treatment of lipid abnormalities in chronic renal failure is controversial. Reducing excessive dietary fat intake is sensible. Many lipid-lowering drugs are unsafe in renal failure.


The anaemia of erythropoietin deficiency can be treated with synthetic (recombinant) human erythropoietin, starting at a dose of 25-50 U kg” three times a week; subcutaneous administration is more effective than intravenous. Blood pressure, haemoglobin concentration and reticulocyte count are measured every 2 weeks and the dose adjusted to maintain a target haemoglobin of 10-l2 g dl”. Failure to respond to 300 U kg” weekly, or a fall in haemoglobin after a satisfactory response, may be due to iron deficiency, bleeding, malignancy or infection. Partial correction of anaemia with erythropoietin has been clearly shown to improve quality of life, exercise tolerance, sexual function and cognitive function in dialysis patients, and to result in regression of left ventricular hypertrophy. Avoidance of blood transfusion also lessens the chance of sensitization to HLA antigens, which may otherwise be a barrier to successful renal transplantation. The disadvantages of erythropoietin therapy are that it is expensive and causes a rise in blood pressure in up to 30% of patients, particularly in the first 6 months. Peripheral resistance rises in all patients, due to loss of hypoxic vasodilatation and to increased blood viscosity. A rare complication is encephalopathy with fits, transient cortical blindness and hypertension. Other causes of anaemia should be looked for and treated appropriately.



Anaemia is present in the great majority of patients with chronic renal failure. Several factors have been implicated:

ERYTHROPOIETIN DEFICIENCY is the most important BONE MARROW TOXINS such as polyamines, aluminium, arsenic, copper, lead BONE MARROW FIBROSIS secondary to hyperparathyroidism HAEMATINIC DEFICIENCy-iron, vitamin B12′ folate INCREASED RED CELL DESTRUCTION due to mechanical, oxidant and thermal damage during haemodialysis ABNORMAL RED CELL MEMBRANES causing increased osmotic fragility

INCREASED BLOOD Loss-occult gastrointestinal bleeding, blood sampling, blood loss during haemodialysis or due to platelet dysfunction

ACE inhibitors may cause anaemia in chronic renal failure, probably by interfering with the control of endogenous erythropoietin release.

Bone disease

RENAL OSTEODYSTROPHY. The term renal osteodystrophy embraces the various forms of bone disease that develop in chronic renal failure, i.e. osteomalacia and osteoporosis, secondary and tertiary hyperparathyroidism  and osteosclerosis (Fig. 9.32). Covert renal osteodystrophy is present in most patients with severe renal failure. Phosphate retention results in hyperphosphataemia, which lowers the concentration of ionized serum calcium. Other effects include decreased renal production of 1,25(OH)2D3′ which leads to decreased calcium absorption and a fall in serum calcium. This in turn stimulates the release of PTH, which may already be increased due to the loss of the normal inhibitory effect of 1,25(OH)2D3


HYPERPARATHYROIDISM. Poor absorption of dietary calcium and phosphate retention lowers the serum calcium. PTH is released in response to hypocalcaemia and promotes resorption of calcium from bone and increased proximal tubular reabsorption of calcium in the kidney in an attempt to correct the low serum calcium. Over months or years, this ‘secondary’ hyperparathyroidism can lead to severe decalcification of the skeleton associated with the classical radiological appearances listed in Fig. 9.32.

A common, but not inevitable, sequel to long-standing secondary hyperparathyroidism is hyperplasia of the glands, leading to autonomous or ‘tertiary’ hyperparathyroidism. In this condition PTH is released inappropriately, resulting in hypercalcaemia and severe bone disease. Hyperparathyroidism causes bone and joint pains and a high serum alkaline phosphatase. Histologically there is
increased osteoclastic activity, cyst formation and bone marrow fibrosis (osteitis fibrosa cystica or von Recklinghausen’s disease of bone).

OSTEOSCLEROSIS. This literally means ‘hardening of bone’ and may be a direct result of excess PTH. Alternate bands of sclerotic and porotic bone in the vertebrae produce the characteristic ‘rugger-jersey spine’ X-ray appearance.

Skin disease

Itching is a common and frequently intractable problem in dialysis patients. The cause is multifactorial and includes:

• Elevated calcium x phosphate product-the most important remediable cause
• Hypermagnesaemia
• Hyperparathyroidism (even if calcium and phosphate levels are well controlled)
• Iron deficiency
• Inadequate dialysis
• Dry skin-simple aqueous creams are helpful Chronic renal failure may also cause pseudoporphyria, a blistering photosensitive skin rash. The pseudoporphyria is due to suppression of hepatic uroporphyrin decarboxylase combined with a decreased clearance of porphyrins in the urine or by dialysis.

Gastrointestinal complications

These include:

DECREASED GASTRIC EMPTYING and increased risk of reflux oesophagi tis.


INCREASED RISK OF ACUTE PANCREATITIS-particularly in continuous ambulatory peritoneal dialysis (CAPD) (see p.488). However, elevations of serum amylase of up to three times normal may be found in chronic renal failure without any evidence of pancreatic disease, due to retention of high-molecular-weight forms of amylase normally excreted in the urine. In patients on CAPD, presence of amylase in the peritoneal effluent is diagnostic of pancreatitis.

CONSTIPATION-particularly in patients on CAPD.

Metabolic abnormalities

GOUT. Urate retention is a common feature of chronic renal failure, particularly in renal vascular disease. Treatment of asymptomatic hyperuricaemia does not (as once thought) protect against further deterioration in renal  function. Treatment of clinical gout is complicated by the nephrotoxic potential of NSAIDs. Colchicine is useful in treatment of the acute attack, and allopurinol should be introduced later under colchicine cover to prevent further attacks. The dose of allopurinol should be reduced in renal impairment.

INSULIN RESISTANCE is a feature of advanced renal impairment, and may contribute to hypertension and lipid abnormalities, but rarely causes clinically significant hyperglycaemia.

Pathogenesis and radiological features of renal osteodystrophy.

Pathogenesis and radiological features of renal osteodystrophy.

LIPID METABOLISM ABNORMALITIES are common In renal failure and include:

• Impaired clearance of triglyceride-rich particles
• Hypercholesterolaemia (particularly in advanced renal failure)

The situation is further complicated in end-stage renal cisease, excessive glucose absorption (in CAPD) and immunosuppressive drugs (in transplantation) may all contribute to lipid abnormalities.

Endocrine abnormalities

These include:

HYPERPROLACTINAEMIA, which may present with galactorrhoea in men as well as women.

INCREASED LUTEINIZING HORMONE (LH) LEVELS in both sexes, and abnormal pulsatility of LH release.

DECREASED SERUM TESTOSTERONE LEVELS (only rarely below the normal levels). Impotence and decreased spermatogenesis are common.

ABSENCE OF NORMAL CYCLICAL CHANGES IN FEMALE SEX HORMONES, resulting in oligomenorrhoea or amenorrhoea.

COMPLEX ABNORMALITIES OF GROWTH HORMONE SECRETION AND ACTION, resulting in impaired growth in uraemic children. Pharmacological treatment with recombinant growth hormone and insulinlike growth factor is being studied.

ABNORMAL THYROID HORMONE LEVELS, partly due to altered protein binding. Sensitive assays for thyroidstimulating hormone are the best way to assess thyroid function. True hypothyroidism occurs with increased frequency in renal failure. Function of the posterior pituitary is normal in renal failure.

Muscle dysfunction

Uraemia appears to interfere with muscle energy metabolism, but the mechanism for this interference is uncertain. Decreased physical fitness (cardiovascular deconditioning) also contributes; exercise training programmes are of benefit in uraemic patients.

Nervous system

CENTRAL. Severe uraemia causes an unusual combination of depressed cerebral function and decreased seizure threshold. However, convulsions in a uraemic patient are much more commonly due to other causes such as accelerated hypertension, TTP, or drug accumulation.

Asterixis, tremor and myoclonus are also features of severe uraemia.

Rapid correction of severe uraemia by haemodialysis leads to ‘dialysis disequilibrium’ due to osmotic cerebral swelling; this can be avoided by correcting uraemia by short, repeated haemodialysis or by the use of peritoneal dialysis.

‘Dialysis dementia’ is a syndrome of progressive intellectual deterioration, speech disturbances, myoclonus and fits which is now known to be due to aluminium intoxication; it may be accompanied by aluminium bone disease and by microcytic anaemia. Low-grade aluminium exposure may also cause more subtle, subclinical deterioration in intellectual function.

AUTONOMIC. Reversible autonomic dysfunction is common in renal impairment. Findings include:

• Increased circulating catecholamine levels associated with down-regulation of a-receptors

• Impaired baroreceptor sensitivity
• Impaired efferent vagal function

All of these abnormalities improve to some extent after institution of regular dialysis and resolve completely after successful renal transplantation.

PERIPHERAL. Median nerve compression in the carpal tunnel is common, and usually due to J32-microglobulinrelated amyloidosis .

Restless legs syndrome is common in uraemia. Patients complain of an irresistible need to move their legs, often interfering with sleep. The syndrome is difficult to treat.

Iron deficiency should be treated if present. Attention should be paid to adequacy of dialysis. Symptoms may improve with the correction of anaemia by erythropoietin.

Clonazepam and codeine phosphate are sometimes useful. Renal transplantation cures the problem. A polyneuropathy occurs in patients who are inadequately dialysed.

Cardiovascular disease

Life expectancy remains severely reduced compared to the normal population due to a greatly increased incidence of cardiovascular disease, particularly myocardial infarction, cardiac failure, sudden cardiac death and stroke.

Hypertension is a frequent complication of renal failure.

Cardiac hypertrophy is common, even in patients without hypertension. Causative factors include anaemia, causing increased cardiac work, hyperparathyroidism, hypertension, sympathetic overactivity, recurrent volume overload and possibly uraemia per se.

Systolic and diastolic dysfunction are also common. Diastolic dysfunction is largely attributable to left ventricular hypertrophy and contributes to hypotension during fluid removal on haemodialysis. Systolic dysfunction may be due to:

• Myocardial fibrosis
• Abnormal myocyte function due to uraemia
• Calcium overload and hyperparathyroidism
• Carnitine and selenium deficiency

Successful renal transplantation improves some, but not all, of these abnormalities. Left ventricular hypertrophy is a risk marker for early death in renal failure, as in the general population, but it is not yet known whether treatments which result in regression of left ventricular hypertrophy reduce mortality. Systolic dysfunction is also an important marker for early death in renal failure. Vascular calcification is frequent in all sizes of vessel in renal failure. In addition to the classical risk factors for atherosclerosis, a raised calcium x phosphate product causes medial calcification. Hyperparathyroidism may also contribute independently to the pathogenesis by increasing intracellular calcium. Diffuse calcification of the myocardium is also common; the causes are similar.

There is no good evidence that dialysis per se results in accelerated atherosclerosis; the excess risk of cardiovascular death is highest in the predialysis phase of chronic renal failure.

Pericarditis is common and occurs in two clinical settings:

URAEMIC PERICARDITIS is a feature of severe, preterminal uraemia or of underdialysis. Haemorrhagic pericardial effusion and atrial arrhythmias are often associated. There is a danger of pericardial tamponade and anticoagulants should be used with caution. Pericarditis usually resolves with intensive dialysis.

DIALYSIS PERICARDITIS occurs as a result of an intercurrent illness or surgery in a patient receiving apparently adequate dialysis.


A list of causes of chronic renal failure, together with their relative frequencies in European patients starting dialysis, is given in Table 9.23. In the early stages, a specific diagnosis is often possible but with near end-stage renal failure with small kidneys a specific diagnosis is often impossible even with a renal biopsy. Hypertension is frequently found, but whether this is the cause or the result of the renal disease is often impossible to determine.

Causes of end-stage renal failure

Causes of end-stage renal failure


At first presentation it is often impossible to determine whether a uraemic patient has acute or chronic renal disease.


Particular attention should be paid to:


DRUG INGESTION, including non-prescnption medications or dietary supplements

PREVIOUS MEDICAL AND SURGICAL HISTORY, e.g. previous chemotherapy, multisystem diseases such as SLE
PREVIOUS OCCASIONS on which urinalysis or measurement of urea and creatinine might have been performed, e.g. pre-employment or insurance medical examinations, new patient checks
FAMILY HISTORY of renal disease


The early stages of renal failure are often completely asymptomatic, despite the accumulation of thousands of metabolites. Symptoms are common when the blood urea concentration is over 40 mmol litre “, but many patients develop uraemic symptoms at lower levels of blood urea. It is not the accumulation of urea itself which causes symptoms, but a combination of many different metabolic abnormalities. Symptoms include:
• Malaise, loss of energy
• Loss of appetite
• Insomnia
• Nocturia and polyuria due to impaired concentrating ability
• Bed-wetting in children may be due to nocturia rather than to emotional disturbance
• Itching
• Nausea and vomiting
• Paraesthesiae due to polyneuropathy
• Restless legs syndrome
• Bone pain due to metabolic bone disease
• Paraesthesiae and tetany due to hypocalcaemia
• Symptoms due to salt and water retention-peripheral or pulmonary oedema
• Symptoms due to anaemia
• Amenorrhoea in women; erectile impotence in men
In more advanced uraemia (blood urea >50- 60 mrnol litre “), these symptoms become more severe, and eNS symptoms are common:
• Mental slowing, clouding of consciousness, and seizures
• Myoclonic twitching Severe depression of glomerular filtration can result in oliguria. This can occur with either acute renal failure or the terminal stages of chronic renal failure. However, even if the GFR is profoundly depressed, failure of tubular reabsorption may lead to very high urine volumes. For instance, a GFR of 5 ml rnin ” without any tubular reabsorption would produce a urine output of 300 ml hour-lor over 7litres a day! Because tubular dysfunction always accompanies glomerular disease to some extent, the urine output is therefore not a useful guide to renal function.


There are few specific physical signs of uraemia per se. Findings may include:
SHORT STATURE-in patients who have had chronic renal failure in childhood
PALLOR-due to anaemia
INCREASED PHOTOSE SITIVE PIGMENTATION which may make the patient look misleadingly healthy BROWN DISCOLORATION of the nails
SCRATCH MARKS due to uraemic pruritis
FLOW MURMURs-mitral regurgitation due to mitral annular calcification; aortic and pulmonary regurgitant murmurs due to volume overload
The kidneys themselves are usually impalpable unless grossly enlarged due to polycystic disease, obstruction or tumour. Rectal and vaginal examination may disclose evidence of an underlying cause of renal failure, particularly urinary obstruction and should always be performed. In addition to these findings, there may be physical signs of any underlying disease which may have caused the renal failure, for instance:
• Cutaneous vasculitic lesions in systemic vasculitides
• Retinopathy in diabetes
• Evidence of peripheral vascular disease
• Evidence of spina bifida or other causes of neurogenic bladder
An assessment of the central venous pressure, skin turgor, blood pressure both lying and standing, and peripheral circulation should also be made. The major symptoms and signs of chronic renal failure are shown.



HAEMATURIA may indicate glomerulonephritis but other sources must be considered. Haematuria should not be assumed to be due to the presence of an indwelling catheter.
PROTEINURIA is strongly suggestive of glomerular disease, but may occur with tubular disease. Urinary infection may also cause proteinuria.
GLYCOSURIA with normal blood glucose indicates tubular disease (failure of tubular reabsorption of glucose).

Urine microscopy

WHITE CELLS in the urine usually indicate active bacterial urinary infection, but this is an uncommon cause of acute renal failure; sterile pyuria suggests papillary necrosis (see p. 461) or renal tuberculosis. EOSINOPHILURIA is strongly suggestive of allergic tubulo-interstitial nephritis.

Symptoms and signs of chronic renal failure.

Symptoms and signs of chronic renal failure.

GRANULAR CASTS are formed from abnormal cells within the tubular lumen, and indicate active renal disease.
RED CELL CASTS are highly suggestive of glomerulonephritis. RED CELLS in the urine may be from anywhere between the glomerulus and the urethral meatus.

Urine biochemistry

24-HoUR CREATININE CLEARANCE IS useful III assessing the severity of renal failure.
MEASUREMENTS OF URINARY ELECTROLYTES are unhelpful in chronic renal failure. The use of urinary sodium in the distinction between prerenal and intrinsic renal disease is discussed.
URINE OSMOLALITY is a measure of concentrating ability. A low urine osmolality is normal in the presence of a high fluid intake but indicates renal disease when the kidney should be concentrating urine, e.g. in hypovolaemia or hypotension.
URINE ELECTROPHORESIS is necessary for the detection of light chains, which can be present without a detectable serum paraprotein.

Plasma biochemistry


SERUM ELECTROPHORESIS should be performed for myeloma.
SERUM LDH -acute elevation occurs in renal infarction due to embolism.

EXTREME ELEVATIONS OF CREATINE KINASE and a disproportionate elevation in serum creatinine compared to urea suggest rhabdomyolysis.


EOSI NOPHILIA suggests vasculitis, allergic tubulointerstitial nephritis, or cholesterol embolism.

RAISED VISCOSITY OR ESR suggests myeloma or vasculitis.

FRAGMENTED RED CELLS AND/OR THOMBOCYTOPENIA suggests intravascular haemolysis due to accelerated hypertension or haemolytic uraemic syndrome.

TESTS FOR SICKLE CELL DISEASE should be performed when relevant.


COMPLEMENT COMPONENTS may be low in active renal disease due to SLE, mesangiocapillary glomerulonephritis, poststreptococcal glomerulonephritis, and

AUTOANTIBODY SCREENING is useful in detection of SLE , scleroderma (see p. 403), Wegener’s granulomatosis and microscopic polyarteritis and Goodpasture’s syndrome (see p. 451).
CRYOGLOBULINS should be sought in patients with unexplained glomerular disease, particularly mesangiocapillary glomerulonephritis.


URINE CULTURE should always be performed.

EARLY-MORNING URINE SAMPLES should be cultured if tuberculosis is possible.

ANTIBODIES TO STREPTOCOCCAL ANTIGENS (ASOT, antiDNAase B) should be sought if post streptococcal glomerulonephritis is possible.

ANTIBODIES TO HEPATITIS BAND C may point to polyarteritis nodosa or membranous nephropathy (hepatitis B) or to cryoglobulinaemic renal disease (hepatitis C).

ANTIBODIES TO HIV raise the possibility of HIVassociated glomerulonephritis.

MALARIA is an important cause of glomerular disease in the tropics.

Radiological investigation

ULTRASOUND. Every patient should undergo ultrasonography (for renal size and to exclude hydronephrosis), and plain abdominal radiography and renal tomography to exclude low-density renal stones or nephrocalcinosis, which may be missed on ultrasound.

INTRAVENOUS UROGRAPHY is seldom diagnostic in advanced renal disease.

C T is useful for the diagnosis of retroperitoneal fibrosis and some other causes of urinary obstruction, and may also demonstrate cortical scarring.

Renal biopsy

This should be considered in every patient with unexplained renal failure and normal-sized kidneys, unless there are strong contraindications. If rapidly progressive glomerulonephritis is possible, this investigation must be performed within 24 hours of presentation if at all possible, to guide immunosuppressive treatment.


Distinction between acute and chronic renal failure depends on the history, duration of symptoms and previous urinalyses or measurements of renal function.

The rapid rate of change of urea and creatinine with time suggests an acute process. A normochromic normocytic anaemia suggests chronic disease, but anaemia may complicate many of the diseases which cause acute renal failure, due to a combination of haemolysis, bleeding, and deficient erythropoietin production.

The ultrasound estimation of renal echogenicity and size is helpful. Small kidneys of increased echogenicity are diagnostic of a chronic process, although the reverse is not always true: the kidneys may remain normal in size in diabetes and amyloidosis, for instance. Renal osteodystrophy suggests chronic disease.

The measurement of carbamylated haemoglobin (product of non-enzymatic reaction between urea and haemoglobin, cf. glycosylated haemoglobin) is not yet widely available.