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For further information, see CMDT Part 22-24: Chronic Tubulointerstitial Diseases

Key Features

Essentials of Diagnosis

  • Kidney size is small and contracted

  • Decreased urinary concentrating ability

  • Hyperchloremic metabolic acidosis

  • Reduced glomerular filtration rate (GFR)

General Considerations

  • Obstructive uropathy may result from prolonged or recurrent obstruction; causes of obstructive uropathy include

    • Prostate disease in men

    • Ureteral calculus in a single functioning kidney

    • Bilateral ureteral calculi

    • Carcinoma of the cervix, colon, or bladder

    • Retroperitoneal tumors or fibrosis

  • Reflux nephropathy from vesicoureteral reflux

    • Second most common cause of chronic tubulointerstitial disease

    • Occurs when urine passes retrograde from the bladder to the kidneys during voiding

    • Urine can extravasate into the interstitium, triggering an inflammatory response that leads to fibrosis over time

    • The inflammatory response is due to either bacteria or normal urinary components

  • Analgesic nephropathy

    • Most commonly seen in patients who ingest large quantities of pain medications

    • Medications of concern are phenacetin, paracetamol, aspirin, and other nonsteroidal anti-inflammatory drugs (NSAIDs); acetaminophen is a possible but less certain culprit

  • Heavy metals

    • Environmental exposure to lead, cadmium, mercury, and bismuth can cause tubulointerstitial disease but is seen infrequently in the United States

    • Individuals at risk for lead-induced tubulointerstitial disease are those with occupational exposure (eg, welders who work with lead-based paint) and drinkers of alcohol distilled in automobile radiators ("moonshine" whiskey users)

  • Mesoamerican nephropathy

    • A form of chronic tubulointerstitial disease disproportionately affecting male agricultural workers in Central America is increasingly recognized as an important cause of end-stage kidney disease (ESKD)

    • Exact pathophysiology is still unknown

    • Affected individuals tend to be age 30–50 years without diabetes mellitus, hypertension or other causes of kidney disease who work under hot conditions, particularly in sugar cane or cotton fields, and thus are susceptible to dehydration

  • Balkan nephropathy

    • Found in the Danube region

    • Affected individuals are usually in their 50s–60s and have been exposed to aristolochic acid, typically in contaminated wheat products

Clinical Findings

Symptoms and Signs

  • Polyuria is common because tubular damage leads to nephrogenic diabetes insipidus, possibly from vasopressin insensitivity

  • Volume depletion can occur as a result of a salt-wasting nephropathy in some individuals

  • Obstructive uropathy

    • In partial obstruction, patients can exhibit

      • Polyuria (possibly due to vasopressin insensitivity and poor ability to concentrate the urine) or

      • Oliguria (due to decreased GFR)

    • Azotemia and hypertension (due to increased renin-angiotensin production) are usually present

  • Vesicoureteral reflux

    • Hypertension

    • Substantial proteinuria

  • Analgesics

    • Hematuria

    • Mild proteinuria

    • Polyuria (from tubular damage)

    • Anemia (from gastrointestinal bleeding or erythropoietin deficiency)

    • Sterile pyuria

  • Heavy metals

    • Decreased secretion of uric acid, resulting in hyperuricemia and saturnine gout

    • Hypertension

  • Balkan nephropathy: urothelial carcinomas are present in approximately 50% of affected individuals at time of diagnosis


General Findings

  • Patients can become hyperkalemic because the GFR is lower and the distal tubules ...

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