Acute interstitial diseases are usually due to sensitivity to drugs, including antibiotics (penicillin, sulfonamides), nonsteroidal anti-inflammatory drugs, and phenytoin. The pathologic hallmark of acute interstitial nephritis is the infiltration of inflammatory cells in the interstitium.
A typical presentation is a rapid deterioration in renal function associated with a recent introduction of a new drug. The finding of eosinophiluria is very suggestive of allergic interstitial nephritis. Recovery may be complete, especially if the offending drug is withdrawn. A short course with corticosteroids may hasten the recovery.
Chronic interstitial nephritis is characterized by focal or diffuse interstitial fibrosis accompanied by infiltration, with inflammatory cells ultimately associated with extensive tubular atrophy. It represents a nonspecific reaction to a variety of causes: analgesic abuse, lead and cadmium toxicity, nephrocalcinosis, urate nephropathy, radiation nephritis, sarcoidosis, Balkan nephritis, and some instances of obstructive uropathy.
Analgesic nephropathy typically occurs in patients with chronic and recurrent headaches or with chronic arthritis who habitually consume large amounts of the drugs. Phenacetin was implicated initially, but with elimination of phenacetin from the mixtures, the incidence of analgesic nephropathy has not decreased. Chronic use of nonsteroidal anti-inflammatories is a frequent cause of this condition. The ensuing damage to the kidneys usually is detected late, after renal insufficiency has developed. Careful history taking or the detection of analgesic metabolites in the urine can lead to this diagnosis. The history of excessive use of analgesics may be concealed by the patient.
The kidney lesion is pathologically nonspecific, consisting of peritubular and perivascular inflammation with degenerative changes of the tubular cells (chronic interstitial nephritis). There are often no glomerular changes.
Renal papillary necrosis extending into the medulla may involve many papillae.
Hematuria can be a common presenting complaint but it is usually microscopic. Renal colic occurs when necrotic renal papillae slough away. Polyuria may be prominent.
Signs of acidosis (hyperpnea), dehydration, and pallor are common. Infection is a frequent complication. The urine usually is remarkable only for the presence of blood and small amounts of protein. Elevated blood urea nitrogen and creatinine and the electrolyte changes characteristic of metabolic acidosis and renal failure are typically present.
Urinary concentrating impairments are usually present.
Urograms show cavities and ring shadows typical of areas of destruction of papillae.
Uric Acid Nephropathy
Crystals of urate produce an interstitial inflammatory reaction. Urate may precipitate out in acid urine in the calyces to form uric acid stones. Patients with myeloproliferative disease under treatment are subject to occlusion of the upper urinary tract by uric acid crystals. Alkalinization of the urine and a liberal fluid intake help prevent crystal formation. Allopurinol is a useful drug to prevent hyperuricemia and hyperuricosuria. Recently, it has been suggested that many instances considered to be chronic “gouty nephropathy” are instead related to chronic lead renal injury and not due to primary uric acid depositions.
Interstitial nephritis due to obstruction may not be associated with infection. Tubular conservation of salt and water is impaired. Partial to full renal recovery follows relief of the obstruction but is inversely related to the duration of obstruction.
Features of myelomatosis that contribute to renal disease include proteinuria (including filtrable Bence-Jones protein and κ and &lamda; chains) with precipitation in the tubules leading to accumulation of abnormal proteins in the tubular lumen. A Fanconi-like syndrome may develop.
Plugging of tubules, tubular atrophy, and, occasionally, the accumulation of amyloid may also be present. Renal failure may occur acutely or develop slowly. Hemodialysis may rescue the patient during efforts to control the myeloma with chemical agents.
A primary renal disorder that is related is termed light chain nephropathy. Patients have nephrosis and usually progressive renal failure. In contrast to multiple myeloma, there is no malignant hematopoietic process. Either k or l light chains are measurable in the urine and light chain deposits are seen in the glomeruli. There is no effective treatment.