Tubulointristitial Nephritis

A disorder of the interstitium and tubules

Acute Interstitial Nephritis

70% Drug hypersensitivity• 30% Antibiotics: PCNs (Methicillin), Cephalosporins, Cipro• Sulfa drugs• NSAIDs• Allopurinol...

15% Infection• Strep, Legionella, CMV, other bact/viruses8% Idiopathic6% Autoimmune Dz (Sarcoidosis, Tubulointerstitial

nephritis/Uveitis)

Drug Causes of AIN

Antibiotics Cephalosporins, Ciprofloxacin, Ethambutol, Isoniazid, Macrolides, Penicillins, Rifampin, Sulfonamides, Tetracycline, Vancomycin

NSAIDs Almost all agents, including selective COX-2 inhibitors

Diuretics Furosemide, Thiazides, Triamterene

Miscellaneous Acyclovir, Allopurinol, Amlodipine, Azathioprine, Captopril, Carbamazepine, Clofibrate, Cocaine, Diltiazem, Famotidine, Indinavir, Mesalazine, Omeprazole, Phenteramine, Phenytoin, Pranlukast, Propylthioruacil, Quinine, Ranitidine

AIN from DrugsRenal damage is NOT dose-dependentMay take weeks after initial exposure to drug• More common is seen several months to a year after useBut as early as 1 week after medication is begun• Fever (27%)• Serum Eosinophilia (23%)• Maculopapular rash (15%)

• Bland sediment or WBCs, RBCs, non-nephrotic proteinuria• WBC Casts are pathognomonic!• Urine eosinophils on Wright’s or Hansel’s Stain

• Also see urine eos in RPGN, renal atheroemboli• Leukocytoclastic vasculitis

Interstitial nephritis

• Acute allergic IN- presents with fever, maculopapular rash, arthralgia, eosinophilia with use of certain drugs or systemic infection

• UA_ microscopic hematuria, pyuria, non nephrotic proteinuria, eosinophiluria

• Usually resolves after d/c of offending drug and steroids

Clinical Presentation

•Nausea•Vomiting•Malaise

•Rash 15%•Fever 27%•Eosinophilia 23%•Triad 10%

AIN of any AIN of any causecause

Drug-Induced AINDrug-Induced AIN

Laboratory Manifestions

• Acute rise in plasma creatinine concentration

• Eosinophilia and eosinophiluria

• Urine sediment: wbcs, rbcs, white cell casts

• Proteinuria (< 1 g/day)

• Signs of tubulointerstitial damage

Infectious Causes of AIN

Bacterial Corynebacterium diphtheriae, legionella, staphylococci, streptococci, yersinia

Viral CMV, EBV, HIV, HCV, HSV, hantaviruses, mumps, polyoma virus

Other Leptospira, mycobacterium, mycoplasma, rickettsia, syphilis, toxoplasmosis

• Acute bilateral pyelonephritis• Flank pain, toxic, febrile• U/A : pyoria, hematuria, proteinuria,

bacteriuria• B/C & U/C help to diagnosis

Infiltrative/Autoimmune Causes of AIN

•Sarcoidosis•Sjogren’s Syndrome•TINU•Leukemia•Lymphoma•Systemic lupus erythematosus

Acute Renal Failure

Prerenal HypovolemiaDecreased cardiac outputRenal vasoconstriction

Intrinsic Acute Tubular NecrosisGlomerulonephritisVascular disorders

Postrenal Bladder NeckUreteral Tubular

Renal biopsy

•Uncertainty of diagnosis

•Advanced renal failure

•Lack of spontaneous recovery following removal of offending drug

IndicationsIndications

Treatment

•Discontinuation of offending agent

•Corticosteroids Prednisone 1 mg/kg to a max of 40-60 Prednisone 1 mg/kg to a max of 40-60 mg x 1-2 weeksmg x 1-2 weeksIV Methylprednisolone 0.5 – 1 g/day x 3 IV Methylprednisolone 0.5 – 1 g/day x 3 daysdays

AIN Management

• Remove offending agent• Most patients recover full kidney function

in 1 year• Poor prognostic factors

• ARF > 3 weeks• Advanced age at onset

Causes of chronic interstitial nephritis

• Toxins( analgesic nephropathy, lead nephropathy)

• Infection (chronic pyelonephritis)• Autoimmune( Sjogren syndrome, SLE, renal

rejection)• Metabolic( hyperuricemia, hypercalcemia)• Radiation• Neoplastic infiltration( leukemia, lymphoma,

multiple myeloma)• Hereditary renal diseases(ADPKD,MCD,MSK)

Analgesic abuse nephropathy

• chronic interstitial nephritis• Result from excessive consumption

(Phenacetin & Aspirin)• Dose dependent (at least 1 kg)• Being responsible for 1% to 3% of ESRD

cases

• The earliest lesion is thickening of GBM of vasa recta and capillary medulla then at later stage, focal area of necrosis in medulla and fibrosis and atrophy of tubules that leads to papillary necrosis and calcification.

• Pathogenesis: phenacetin and its metabolites concentrate in the medulla where induce the generation of reactive metabolites

• Aspirin potentiate the toxicity of phenacetin

Bacterial infection

• bacterial infection of the renal parenchyma causes interstitial nephritis

• infection without anatomical abnormality seldom produces permanent damage

• obstruction (stones, prostate etc) in combination with infection can cause progressive disease

• tuberculosis causes extensive destruction from granulomata, fibrosis and caseation

• The upper and lower poles with compound papilla in ascending infection

• At first, interstitial edema and PMN infiltration, then formation of irregular abscesses and eventually scars

• Risk factors: diabetes mellitus obstruction delayed antimicrobial therapy severe infection with ATN reflux nephropathy papillary necrosis

Consequences of urinary tract obstruction• Reduced glomerular filtration rate• Reduced renal blood flow (after initial rise)• Impaired renal concentrating ability• Impaired distal tubular function

• Nephrogenic diabetes insipidus• Renal salt wasting• Renal tubular acidosis• Impaired potassium concentration

• Reduced RBF leads to renal ischemia tubular atrophy

Intraluminal pressure

RBF GFR

Phase A —... due to obstruction Peristalsis

—... due toVasodilation-Prostacyclin-Prostraglandin E2

˜... due to Intratubular pressure

Phase B ˜... due toDisorganised peristalsis dilation of tubules and ureter

˜... due toVasoconstriction-Angiotensin II-Thromboxane A2

˜... due to-Continuing obstruction-vasoconstriction

Acute urinary tract obstruction

Functional consequences

0 6 12 18

Ureteric and tubular pressure

Renal blood flow (RBF)

GFR

Hours

baseline

• myeloma• Bence-Jones protein (light chains from

malignant plasma cell clone) causes interstitial nephritis, tubular obstruction(cast nephropathy) and amyloid deposition

• Myeloma kidney :the classic pathologic include THP+LC casts in dilated, atrophic distal tubuls with infiltration monocyte & macrophage & plasma cells that produce giant cells

• LCs are nephrotoxic through direct injury of tubular epithelial cells & intrarenal obstruction from cast formation

• Predisposing factors: LC concentration LC isoelectric point intraluminal PH tubular flow rate presence of Tamm-Horsfall Pr

Hypercalcemic Nephropathy

• Chronic hypercalcemia is seen in Hyperparathyroidism Sarcoidosis Multiple myeloma Vitamin D toxicity Metastasis bone disease

• Hypercalcemia decrease GFR through renal vasoconstriction

• Calcium deposition in distal nephron and interstitial that leads to mononeuclear cell infiltration and tubular necrosis

• Defective concentration ability, poliuria, nocturia

• Nephrocalcinosis & nephrolitiasis

WBC Casts

Cells in the cast have nuclei(unlike RBC casts)

Pathognomonic for Acute Interstitial Nephritis

Match:

• 1. hyaline casts• 2. muddy brown casts• 3. RBCs• 4. RBC casts• 5. Oval fat bodies• 6. eosinophils

• A. ATN• B. prerenal azotemia• C. glomerulonephritis• D. nephrolithiasis• E. interstitial disease• F. nephrotic syndrome

Question

• 1. 65 year old with H/o HTN, ventricular arrythmias controlled on Amiodarone, OA on NSAIds presents with puffiness on face on waking up. Has bilateral pitting dema. UA 3+ prot, 3 RBC., 15-20 WBC

• 24 h prot – 4 g/day• BUN/creat 80/5• Serum albumin 2.8, TSH normal. The most likely diagnosis?• A) amiodarone induced hypothyroidism• B) RPGN• C) NSAIDs induced nephrotic sdr and interstitial nephritis