Interstitial inflammation with tubular damage is a regular feature of bacterial pyelonephritis but, contrary to former belief, it rarely, if ever, leads to chronic renal damage in the absence of reflux, obstruction or other complicating factors. However, there is growing concern that tubulointerstitial disease due to other causes is more common than was previously diagnosed. The major stimulus for this interest came from recognition that it could be due to analgesic abuse. Subsequently, tubulo-interstitial disease due to a variety of drugs has been recognized and this condition should be considered in all patients presenting with otherwise unexplained renal failure. Presentation may be with acute, often oliguric renal failure or more commonly as chronic slowly progressive renal disease.
Acute tubulo-interstitial nephritis is most often due to a hypersensitivity reaction to drugs, most commonly drugs of the penicillin family and nonsteroidal anti-inflammatory drugs (NSAIDs). Patients present with fever, arthralgia, skin rashes and acute oliguric or non-oliguric renal failure. Many have eosinophilia and eosinophiluria. Renal biopsy shows an intense interstitial cellular infiltrate, often including eosinophils, with variable tubular necrosis.
Treatment involves withdrawal of offending drugs. High-dose steroid therapy (prednisolone 60 mg daily) is commonly given but its efficacy has not been proved. Patients may require dialysis for management of the acute renal failure. Most patients have good recovery of kidney function, but some may be left with significant interstitial fibrosis.
The major causes of chronic tubulo-interstitial nephritis are set out. In many cases no cause is found. The patient usually either presents with polyuria and nocturia, or is found to have proteinuria or uraemia. Proteinuria is usually slight (less than 1 g daily). Papillary necrosis with ischaemic damage to the papillae occurs in a number of interstitial nephritides, e.g. in analgesic abuse, diabetes mellitus, sickle cell disease or trait. The papillae can separate and be passed in the urine. Chronic tubulointerstitial nephritis may be associated with microscopic or overt haematuria or sterile pyuria, and occasionally a sloughed papilla may cause ureteral colic or produce acute ureteral obstruction. The radiological appearances must be distinguished from those of chronic pyelonephritis .
Tubular damage to the medullary area of the kidney leads to defects in urine concentration and sodium conservation with polyuria and salt wasting. Fibrosis progressing into the cortex leads to loss of excretory function and uraemia.
The chronic consumption of large amounts of analgesics (especially those containing phenacetin) leads to chronic tubulo-interstitial nephritis and papillary necrosis. This also seems to be true of NSAIDs. In Australia, the incidence of end-stage renal failure due to analgesic nephropathy has declined as ‘over-the-counter’ purchase of nephrotoxic analgesics has been reduced by legislation.
Analgesic nephropathy is twice as common in women as in men and presents typically in middle-age. Patients are often depressed or neurotic. Presentation may be with anaemia, chronic renal failure, symptoms of urinary infection (which may be difficult to eradicate), haematuria, or urinary tract obstruction (due to sloughing of a renal papilla). Salt and water-wasting renal disease may occur.
Chronic analgesic abuse also predisposes to the development of uroepithelial tumours.
The consumption of analgesics should be discouraged. If necessary, dihydrocodeine or paracetamol are reasonable alternative choices. This may result in the arrest of the disease and even in improvement in function. UTI, hypertension (if present) and saline depletion will require appropriate management. The development of flank pain or an unexpectedly rapid deterioration in renal function should prompt ultrasonography or urography to screen for urinary tract obstruction due to a sloughed papilla.
This is a chronic tubulo-interstitial nephritis endemic in the central Danube basin in the former Yugoslavia, Bulgaria and Rumania. Primarily restricted to rural areas, its cause is unknown. The disease is insidious in onset, with mild proteinuria progressing to renal failure in 3 months to 10 years. Patients exhibit a high incidence of uroepithelial tumours.
There is no treatment. Other forms of chronic tubulo-interstitial nephritis are rare . Diagnosis of all forms depends on a careful history being taken, with special attention to drug-taking and industrial exposure to nephrotoxins. In patients with unexplained renal impairment with normalsized kidneys, renal biopsy must always be undertaken to exclude a treatable interstitial nephritis.