+ Etiology
+ + can be primary
+ + + Acute
+ + + Chronic
+ can result from glomerular damage / renovascular disorders
+ acute form caused by
+ + allergic drug reactions
+ + infections
+ chronic form caused by
+ + genetic / metabolic disorders
+ + obstructive uropathy
+ + chronic exposure to environmental toxins / to certain drugs & herbs
+ Diagnosis
+ + suggested by history & urinalysis
+ + confirmed by biopsy
+ Treatment & prognosis vary by the etiology & potential reversibility of the disorder at the time of diagnosis
| Types | Acute tubulointerstitial nephritis (ATIN) | Chronic tubulointerstitial nephritis (CTIN) |
| + involves an inflammatory infiltrate & edema affecting the renal interstitium + often develops over days to months + > 95% caused by infection / an allergic drug reaction + a syndrome of ATIN associated with + + uveitis (renal-ocular syndrome) + ATIN causes acute renal insufficiency / failure + severe cases, delayed therapy, / continuance of an offending drug can lead to permanent injury with chronic renal failure | + arises when chronic tubular insults cause + + gradual interstitial infiltration & fibrosis + + tubular atrophy & dysfunction + + a gradual deterioration of renal function, usually over years. + Glomerular involvement (glomerulosclerosis) is > common in CTIN than in ATIN + Causes + + immunologically mediated disorders + + infections + + reflux / obstructive nephropathy + + drugs + + other disorders + Symmetric & bilateral disease in CTIN caused by + + toxins + + metabolic derangements + + hypertension + + inherited disorders + Renal scarring may be unequal & involve only one kidney are caused by the other causes + Some well-characterized forms of CTIN include + + analgesic + + metabolic + + heavy metal + + reflux nephropathy + + myeloma kidney | |
| Causes | 1 Drugs + + Antibiotics + + + β-Lactam antibiotics + + + Ciprofloxacin + + + Ethambutol + + + Indinavir + + + Isoniazid + + + Macrolides + + + Minocycline + + + Rifampin + + + Tetracycline + + + Trimethoprim/ sulfamethoxazole + + + Vancomycin + + Anticonvulsants + + + Carbamazepine + + + Phenobarbital + + + Phenytoin + + + Valproate + + Diuretics + + + Bumetanide + + + Furosemide + + + Thiazides + + + Triamterene + + NSAIDs + + + Diclofenac + + + Ibuprofen + + + Indomethacin + + + Naproxen + + Other + + + Allopurinol + + + Aristocholic acid + + + Captopril + + + Cimetidine + + + Interferon alfa + + + Lansoprazole + + + Mesalazine + + + Omeprazole + + + Ranitidine 2 Metabolic + + Hyperoxalaturia + + + Ethylene glycol poisoning + + Hyperuricosuria + + + Tumor lysis syndrome 3 Renal parenchymal infection + + Bacterial + + + Brucella sp + + + Corynebacterium diphtheriae + + + Legionella sp + + + Leptospira sp + + + Mycobacterium sp + + + Mycoplasma sp + + + Rickettsia sp + + + Salmonella sp + + + Streptococci + + + Staphylococci + + + Treponema pallidum + + + Yersinia sp + + Fungal + + + Candida sp + + Parasitic + + + Toxoplasma gondii + + Viral + + + Cytomegalovirus + + + Epstein-Barr virus + + + Hantavirus + + + Hepatitis C virus + + + HIV + + + Mumps + + + Polyomavirus 4 Other + + Idiopathic without & with uveitis + + Immunologic + + + Cryoglobulinemia + + + IgA nephropathy + + + Renal transplant rejection + + + Sarcoidosis + + + SLE (rare) + + + Sjögren's syndrome + + + Wegener's granulomatosis + + Neoplastic + + + Lymphoma + + + Myeloma | 1 Balkan nephropathy 2 Cystic diseases + + Acquired cystic disease + + Medullary cystic disease + + Medullary sponge kidney + + Nephronophthisis + + Polycystic kidney disease* 3 Drugs + + Analgesics* + + The antineoplastics cisplatin & nitrosourea + + The immunosuppressants cyclosporine * & tacrolimus + + Lithium * 4 Granulomatous + + Inflammatory bowel disease + + Sarcoidosis + + TB + + Wegener's granulomatosis 5 Hematologic + + Aplastic anemia + + Leukemia + + Lymphoma + + Multiple myeloma* + + Sickle cell anemia 6 Hereditary nephropathy associated with hyperuricemia & gout 7 Idiopathic 8 Immunologic + + Amyloidosis + + Cryoglobulinemia + + Goodpasture's syndrome + + IgA nephropathy + + Renal transplant rejection + + Sarcoidosis + + Sjögren's syndrome + + SLE 9 Infection + + Renal parenchymal: pyelonephritis, Hantavirus—Puumula type infection (nephropathia epidemica) + + Systemic 10Mechanical + + Obstructive uropathy + + Reflux nephropathy* 11Metabolic + + Chronic hypokalemia + + Cystinosis + + Fabry's disease + + Hypercalcemia, hypercalciuria + + Hyperoxaluria + + Hyperuricemia*, hyperuricosuria 12Radiation nephritis 13Toxins + + Aristocholic acid† + + Heavy metals (eg, arsenic, bismuth, cadmium, chromium, copper, gold, iron, lead, mercury, uranium) 14Vascular + + Atheroembolism + + Hypertension + + Renal vein thrombosis |
| Symptoms & Signs | + may be nonspecific + often absent unless symptoms & signs of renal failure develop + polyuria & nocturia (due to a defect in urinary concentration & Na reabsorption) + Symptom onset may be + + 1 day with rifampin + + 3 to 5 days after a 2nd exposure + + several weeks after initial toxic exposure + + 18 mo with an NSAID + drug induced + + Fever & urticarial rash are early manifestations + + classically, triad of + + + fever + + + rash + + + eosinophilia + Abdominal pain, weight loss, & bilateral renal masses (caused by interstitial edema) + fever may mistakenly suggest renal cancer / polycystic kidney disease + Peripheral edema & hypertension are uncommon unless renal insufficiency / renal failure occurs | + generally absent unless renal failure develops + Edema usually is not present + BP is normal / only mildly elevated in the early stages + Polyuria & nocturia may develop |
| Diagnosis | + Risk factors + Active urinary sediment, particularly with sterile pyuria (including eosinophils) + Sometimes biopsy + Specific findings. High suspicion when: + + Typical symptoms / signs + + Risk factors + + + particularly a temporal relationship between onset & use of a potentially causative drug + + Urinalysis + + + sterile pyuria (including eosinophils) + + Modest proteinuria + + + usually < 1 g/day (except with use of NSAIDs, which may cause nephrotic-range proteinuria) + + Evidence of tubular dysfunction eg + + + renal tubular acidosis + + + Fanconi syndrome + Other tests (eg, imaging) may be necessary to differentiate ATIN / CTIN from other disorders. + Renal biopsy is sometimes done. | |
| + Signs of active kidney inflammation (active urinary sediment), including + + RBCs + + WBCs + + WBC casts + + absence of bacteria on culture (sterile pyuria) + + marked hematuria + + dysmorphic RBCs are uncommon + + Eosinophiluria + + + positive predictive value of 50% (specificity 85 to 93%) + + + negative predictive value of up to 90% for ATIN (sensitivity 63 to 91%) + + + the presence of urinary eosinophils is not diagnostic + + + their absence significantly decreases the likelihood of the diagnosis + + Proteinuria + + + is usually minimal + + + may reach nephrotic range with combined ATIN-glomerular disease induced by NSAIDs, ampicillin, rifampin, interferon alfa, ranitidine. + Blood test findings of tubular dysfunction include + + hypokalemia + + + caused by a defect in K reabsorption + + a nonanion gap metabolic acidosis + + + caused by a defect in HCO3 reabsorption / acid excretion + Ultrasonography, radionuclide scanning, / both + + may be needed to differentiate ATIN from other causes of acute renal failure, such as acute tubular necrosis + + In ATIN ultrasonography shows kidneys that are greatly enlarged & echogenic + + + because of interstitial inflammatory cells & edema + Radionuclide scans + + show kidneys avidly taking up radioactive gallium-67 / radionuclide-labeled WBCs + + positive scans strongly suggest ATIN + + + indicate that acute tubular necrosis is less likely + + negative scan does not exclude ATIN. + Renal biopsy is usually reserved for patients with the following + + An uncertain diagnosis + + Progressive renal injury + + No improvement after potential causative drugs are stopped + + glomeruli are usually normal + + The earliest finding is interstitial edema + + followed by interstitial infiltration with + + + lymphocytes + + + plasma cells + + + eosinophils + + + a few PMNs + + In severe cases + + + inflammatory cells seen invading the space between the cells lining the tubular basement membrane (tubulitis) + + + granulomatous reactions seen from exposure to methicillin, sulfonamides, mycobacteria, / fungi + + presence of noncaseating granulomas suggests sarcoidosis + + Immunofluorescence / electron microscopy reveals pathognomonic changes | + Findings generally similar to ATIN + urinary RBCs & WBCs are uncommon + CTIN is insidious in onset + interstitial fibrosis is common + imaging tests may show small kidneys with evidence of scarring & asymmetry + renal biopsy + + is not often done for diagnostic purposes + + has helped characterize the nature & progression of tubulointerstitial disease + + Glomeruli vary from normal to completely destroyed + + Tubules may be absent / atrophied + + Tubular lumina vary in diameter but may show marked dilation, with homogeneous casts + + The interstitium contains varying degrees of inflammatory cells & fibrosis + + Nonscarred areas appear almost normal + + Grossly, the kidneys are small & atrophic. | |
| Prognosis | + + renal function recovers within 6 to 8 wk when the offending drug is withdrawn + + some residual scarring is common + + Recovery may be incomplete, with persistent azotemia above baseline | + + prognosis depends on the cause & on the ability to recognize & stop the process before irreversible fibrosis occurs + + Many genetic (eg, cystic kidney disease), metabolic (eg, cystinosis), & toxic (eg, heavy metal) causes may not be modifiable, in which case CTIN usually evolves to end-stage renal disease. |
| + other causes of ATIN + + histologic changes usually are reversible if the cause is recognized & removed + + some severe cases progress to fibrosis & renal failure + Regardless of cause, irreversible injury is suggested by the following: + + Diffuse rather than patchy interstitial infiltrate + + Significant interstitial fibrosis + + Delayed response to prednisone + + Acute kidney injury > 3 wk | ||
| Treatment | + Treat cause (acute and chronic) + + Corticosteroids for + + + immune-mediated + + + drug-induced tubulointerstitial nephritis + + corticosteroids (eg, prednisone 1 mg/kg po once/day with gradual tapering of the dose over 4 to 6 wk) may accelerate recovery | |
| + Treatment of CTIN often requires supportive measures + + controlling BP + + treating anemia associated with kidney disease + In patients with CTIN & progressive renal injury + + ACE inhibitors / angiotensin II receptor blockers may slow disease progression. | ||
see also
- Analgesic Nephropathy
- Metabolic Nephropathies
- Heavy Metal Nephropathy
- Reflux Nephropathy
- Myeloma-Related Kidney Disease
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