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143 RENAL TUBULAR DISEASE

143 RENAL TUBULAR DISEASE
Harrison’s Manual of Medicine

143

RENAL TUBULAR DISEASE

Acute (Allergic) Interstitial Nephritis (AIN)
Chronic Interstitial Nephritis (IN)
Polycystic Kidney Disease
Renal Tubular Acidosis (RTA)
Bibliography

Tubulointerstitial diseases constitute a diverse group of acute and chronic, hereditary and acquired disorders involving renal tubules and supporting structures (Table 143-1). Functionally, they may result in nephrogenic diabetes insipidus (DI) with polyuria, nocturia, non-anion-gap metabolic acidosis, salt-wasting, and hypo- or hyperkalemia. Azotemia is common, owing to associated glomerular fibrosis and/or ischemia. Compared with glomerulopathies, proteinuria and hematuria are less dramatic, and hypertension is less common. Functional consequences of tubular dysfunction are outlined in Table 143-2.

Table 143-1 Principal Causes of Tubulointertitial Disease of the Kidney

Table 143-2 Transport Dysfunction of Tubulointerstitial Disease

Acute (Allergic) Interstitial Nephritis (AIN)
Drugs are a leading cause of this type of renal failure, usually identified by a gradual rise in the serum creatinine at least several days after the institution of therapy, occasionally accompanied by fever, eosinophilia, rash, and arthralgias. In addition to azotemia, there may be evidence of tubular dysfunction (e.g., hyperkalemia, metabolic acidosis). Drugs that commonly cause AIN include: anti-staphyloccal (i.e., methicillin, oxacillin, or nafcillin) and other penicillins, cephalosporins, sulfonamides, quinolones, rifampin, allopurinol, and cimetidine; NSAIDs may cause AIN with or without nephrotic syndrome. UA shows hematuria, pyuria, and eosinophiluria on Hansel’s or Wright’s stain.
Renal dysfunction usually improves after withdrawal of the offending drug, but complete recovery may be delayed and incomplete. In uncontrolled studies, glucocorticoids have been shown to promote earlier recovery of renal function. Other than kidney biopsy, no specific diagnostic tests are available. Acute pyelonephritis may also cause AIN, although it is rarely associated with renal failure, unless bilateral (or present in a single functioning kidney) or complicated by urinary tract obstruction, sepsis syndrome, or volume depletion.
Chronic Interstitial Nephritis (IN)
Analgesic nephropathy is an important cause of chronic renal failure (CRF) that results from the cumulative (in quantity and duration) effects of combination analgesic agents, usually phenacetin and aspirin. It is thought to be a more common cause of end-stage renal disease in Australia/New Zealand than elsewhere owing to the larger per capita ingestion of analgesic agents in that region of the world. Transitional cell carcinoma may develop. Analgesic nephropathy should be suspected in pts with a history of chronic headache or back pain with CRF that is otherwise unexplained. Manifestations include papillary necrosis, calculi, sterile pyuria, and azotemia. Metabolic causes of chronic IN include: hypercalcemia (with nephrocalcinosis), oxalosis (primary or secondary, e.g., with intestinal malabsorption, leading to nephrocalcinosis), hypokalemia, and hyperuricemia or hyperuricosuria. Chronic IN can occur in association with several systemic diseases, including sarcoidosis, Sjögren’s syndrome, and tuberculosis, and following radiation or chemotherapy exposure (e.g., ifosfamide, cisplatin).
Polycystic Kidney Disease
Autosomal dominant polycystic kidney disease (ADPKD) is the most important hereditary renal disease (except perhaps for “essential” hypertension). It is characterized clinically by episodic flank pain, hematuria (often gross), hypertension, and/or urinary infection in the third or fourth decade. The kidneys are often palpable and occasionally of very large size. Hepatic cysts and intracranial Berry aneurysms may also be present.
The expression of ADPKD is variable. Some persons discover the disease incidentally in late adult life, having had mild to moderate hypertension earlier. More often, azotemia is progressive and unfortunately does not appear to respond as favorably to ACE inhibition or to the restriction of dietary protein intake as other causes of renal disease. The diagnosis is usually made by ultrasonography. Renal cysts are common (50% of persons >50 years have at least one cyst), and multiple renal cysts do not necessarily indicate the presence of ADPKD.
Renal Tubular Acidosis (RTA)
This describes a number of pathophysiologically distinct entities of tubular function whose common feature is the presence of a non-anion-gap metabolic acidosis. Diarrhea and RTA together constitute the vast majority of cases of non- anion-gap metabolic acidosis.
DISTAL (TYPE 1) RTA   Pts are unable to acidify the urine despite acidosis; it may be inherited (autosomal dominant) or acquired due to autoimmune and inflammatory diseases (e.g., Sjögren’s syndrome, sarcoidosis), urinary tract obstruction, or amphotericin B therapy. Type I RTA may be associated with hypokalemia, hypercalciuria, and osteomalacia.
PROXIMAL (TYPE II) RTA   There is a defect in bicarbonate reabsorption, usually associated with glycosuria, aminoaciduria, phosphaturia, and uricosuria (indicating proximal tubular dysfunction); it may be inherited or acquired due to myeloma, renal transplantation, or drugs (e.g., ifosfamide, L-lysine). Treatment requires large doses of bicarbonate, which may aggravate hypokalemia, and repletion of phosphorus to prevent bone disease.
TYPE IV RTA   Due to a defect in ammonium excretion, acidosis is accompanied by hyperkalemia and usually with low renin and aldosterone levels (and minimal response to exogenous mineralocorticoid). It is associated with diabetes, other forms of glomerulosclerosis, and many forms of advanced CRF (especially with tubulointerstitial component).

TREATMENT
Tubulointerstitial diseases associated with exogenous toxins (e.g., analgesic nephropathy, lead and other heavy metal nephropathy) should be treated by withdrawal of the offending toxin. Primary oxalosis may require liver (or combined liver-kidney) transplantation, but secondary oxalosis can be improved with a low-oxalate diet, generous fluid intake, and supplemental calcium salts (calcium carbonate or calcium citrate) with meals to bind intestinal oxalate and prevent hyperoxalemia/hyperoxaluria. Calcium citrate affords additional protection against nephrolithiasis (correcting hypocitraturia). Hypercalcemia due to multiple causes (e.g., primary hyperparathyroidism, vitamin D excess, thiazide therapy, milk-alkali syndrome) can usually be corrected once recognized. Pts with pyelonephritis due to reflux or recurrent UTI with ADPKD may benefit from suppressive antibiotic therapy. The treatment of RTA depends on type but focuses on correction of the acidosis and prevention of nephrolithiasis (type I), vitamin D deficiency and other metabolic complications (type II), and severe hyperkalemia (type IV).

Bibliography

For a more detailed discussion, see Yu ASL, Brenner B: Tubulointerstitial Diseases of the Kidney, Chap. 277, p. 1606, in HPIM-15.

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