Renal disease is suspected if there are:
• Symptoms referable to the urinary tract
• An elevated blood urea or creatinine concentration
• Abnormalities on urinalysis
This is of little value in the differential diagnosis of renal disease except in the diagnosis of haematuria. Overt ‘bloody’ urine is usually unmistakable but should be checked using dipsticks (Stix testing). Very concentrated urine may also appear dark or smoky. Other causes of discoloration of urine include cholestatic jaundice, haemoglobinuria, drugs such as rifampicin, use of fluorescein or methylene blue, and ingestion of beetroot. Discoloration of urine after standing for some time occurs in porphyria, alkaptonuria and in patients ingesting the drug L-dopa. In patients with frequency or dysuria the passage of crystal clear urine usually indicates that significant bacteriuria is absent.
In health, the volume of urine passed is primarily determined by diet and fluid intake. In temperate climates it lies within the range 800-2500 ml per 24 hours. The minimum amount passed to stay in fluid balance is determined by the amount of solute-mainly urea and electrolytes- being excreted and the maximum concentrating power of the kidneys. On a normal diet, some 800 mosmol of solute are passed daily. Since the maximum urine concentration is approximately 1200 mosmollitre-1, the minimum volume of urine obligated by excretion of 800 mosmol of solute would thus be approximately 650 ml. Fluid intake is generally greater than this, so that larger volumes of more dilute urine are passed. A diet rich in carbohydrate and fat and low in protein and salt results in a lower solute excretion and as little as 300 ml of urine per day may be required. Conversely, a high-salt, high-protein intake obligates a larger urine flow and, via the thirst mechanism, a higher fluid intake. The appropriateness of a given daily urine output must therefore be related to factors such as diet, body size and fluid intake. In disease, impairment of concentrating ability requires increased volumes of urine to be passed, given the same daily solute output (Table 9.3). An increased solute output, e.g. in glycosuria or increased protein catabolism following surgery or associated with sepsis, also demands increased urine volumes.
The maximum urine output depends on the ability to produce a dilute urine. Intakes of 10 or even 20 litres daily can be tolerated by normal humans but, given a daily solute output of 800 mosmol, require the ability to dilute to 80 and 40 mosmol litre “, respectively. Where diluting ability is impaired, the ability to excrete large volumes of ingested water is also impaired.
Oliguria, usually defined as the excretion of less than 300 ml of urine per day, may be ‘physiological’, e.g. in patients with hypotension and hypovolaemia, where urine is maximally concentrated in an attempt to conserve water. More often, it is due to intrinsic renal disease or obstructive nephropathy. Anuria (no urine) suggests urinary tract obstruction until proved otherwise; bladder outflow obstruction must always be considered first.
Polyuria is a persistent, large increase in urine output, usually associated with nocturia. It must be distinguished from frequency of micturition with the passage of small volumes of urine. Documentation of fluid intake and output may be necessary. Polyuria is the result of an excessive (hysterical) intake of water, an increased excretion of solute (as in hyperglycaemia and glycosuria), or a defective renal concentrating ability or failure of production of ADH.
Specific gravity and osmolality
Urine specific gravity is a measure of the weight of dissolved particles in urine, whereas urine osmolality reflects the number of such particles. Usually the relationship between the two is close. An exception exists when a relatively small number of relatively large particles are present in urine, as occurs in multiple myeloma. Measurement of urine specific gravity or osmolality is only required under limited circumstances, such as the differential diagnosis of oliguric renal failure or the investigation of polyuria or inappropriate ADH secretion.
Measurement of urinary pH is unnecessary except in the investigation and treatment of renal tubular acidosis.
Chemical (Stix) testing
Routine Stix testing of urine for blood, protein and sugar is obligatory in all patients suspected of having renal disease. Blood Haematuria may be overt, with bloody urine, or microscopic and found only on chemical testing. A positive Stix test must always be followed by microscopy of fresh urine to confirm the presence of red cells and so exclude the relatively rare conditions of haemoglobinuria or myoglobinuria. Bleeding may come from any site within the urinary tract:
OVERT BLEEDING FROM THE URETHRA is suggested when blood is seen at the start of voiding and then the urine becomes clear.
BLOOD DIFFUSELY PRESENT THROUGHOUT THE URINE comes from the bladder or above.
BLOOD ONLY AT THE END OF MICTURITION suggests bleeding from the prostate or bladder base. Careful urine microscopy is mandatory as the presence of red-cell casts is diagnostic of bleeding from the kidney, most often due to glomerulonephritis. In the absence of red-cell casts, further investigations, such as urine cytology, intravenous urography and cystoscopy, are required to define the site of bleeding. Renal biopsy may be required.
Proteinuria is one of the most common signs of renal disease. Detection is now primarily by Stix testing. Most reagent strips can detect a concentration of 150 mg litre-1 or more in urine. They react primarily with albumin and are relatively insensitive to globulin and Bence-lones proteins.
If proteinuria is confirmed on repeated Stix testing, protein excretion in 24-hour urine collections should be measured. Normal values for urinary protein excretion are dependent on the laboratory methods used and in particular whether or not the method measures Tamm-Horsfall glycoprotein, which is a normal constituent of urine. Results must therefore take account of the laboratory’s normal reference range. Given this caveat, healthy adults excrete approximately 60-100 mg of protein daily but up to 150-200 mg daily is within the acceptable range. Slightly higher values-up to 300 mg daily-may be excreted by adolescents. Pyrexia, exercise and adoption of the upright posture all increase urinary protein output. Proteinuria, while occasionally benign, always requires further investigation.
particular whether or not the method measures Tamm- Horsfall glycoprotein, which is a normal constituent of urine. Results must therefore take account of the laboratory’s normal reference range. Given this caveat, healthy adults excrete approximately 60-100 mg of protein daily but up to 150-200 mg daily is within the acceptable range. Slightly higher values-up to 300 mg daily-may be excreted by adolescents. Pyrexia, exercise and adoption of the upright posture all increase urinary protein output. Proteinuria, while occasionally benign, always requires further investigation.
POSTURAL PROTEINURIA. This term is used to refer to proteinuria present on dipstick testing which becomes undetectable after a period of hours lying flat. Typically, a negative dipstick result is obtained on the first urine passed on rising in the morning, whereas subsequent specimens give a positive result. This is regarded by many-including some insurance companies-as a benign condition. Renal biopsy sometimes discloses glomerular abnormalities but progressive renal failure is rare.
Renal glycosuria is uncommon, so that a positive test for glucose always requires exclusion of diabetes mellitus.
Dipsticks are available for testing for bacteriuria based on detection of nitrite produced from the reduction of urinarynitrate by bacteria. Unfortunately, there is an unacceptable false-negative detection rate and urine culture is still required.
The term microalbuminuria is an unfortunate one since the albumin referred to is of normal molecular size and weight. Normal urine contains albumin in a concentration of less than 20 mg litre-I. Dipsticks, however, only detect albumin in a concentration around 150 mg litre – I. An increase in albumin between these two levels-socalled microalbuminuria-is now known to be an early indicator of diabetic glomerular disease. It is now widely used as a predictor of the development of nephropathy in diabetics and may be extended to other conditions. Measurement is done by radioimmunoassay. Timed 24-hour urinary excretion may be measured. Microalbuminuria is then defined as an excretion rate between 30 and 150 p.g min-I. Equally reliable results may be more conveniently obtained using random samples in which albumin concentration is related to urinary creatinine concentration (normal range <0.2-2.8 mg of albumin per mmollitre-I creatinine).