Interstitial Renal Disease

S. Kadiri

Introduction

DefinitionClassification Causes Clinical featuresInvestigations Treatment

Definition

InterstitiumUnilateral or bilateralWorldwide Age, gender, race issuesAbout 15% CKD, maybe higherIssue of hypertensive nephrosclerosis

Acute interstitial nephritisImmunologic

Hypersensitivity

Infections

Transplant rejection

Acute tubular necrosis

Immunologic Perhaps commonest

SLE

Goodpastures syndrome

Wegeners granulomatosis

Drugs Antibiotics-penicillin, sulfa, quinolones, rifampin, cephalsNSAIDSDiuretics-thiazides, frusemideAllopurinolPhenytoin

Infections Bacterial with obstruction, reflux

Viral CMV, HIV, Hep-B

Fungal

Parasitic

Clinical features - AIN Usually within daysRashFeverUsually mild proteinuriaAcute renal failureEosinophiliaEosinophiluriaElevated IgE

Chronic interstitial nephritis

CIN - CausesImmunologic diseasesDrugsObstructive uropathy, reflux diseaseHeavy metalsAtherosclerotic renal diseaseNeoplasiaMetabolic diseasesBalkan nephropathyAristolochic acid nephropathyGenetic causes

Immunologic diseasesSLE, Prim glomerulopathies, Sjogrens, sarcoidosis

Vasculitis, ANCA + vasculitis, Wegeners

Chronic transplant nephropathy

Drugs Analgesics

Lithium

Cyclosporine

tacrolimus

Heavy metalsLead

Cadmium

mercury

NeoplasiaMyeloma

Lymphomas

Leukaemias

Metabolic DisordersGouty nephropathyHypercalcaemiaHypokalaemiaHyperoxaluriaCystinosisFabrys disease

Hereditary disordersAutosomal dominant interstitial kidney disease (medullary cystic kidney disease, uromodulin-associated kidney disease, renin-associated hereditary interstitial kidney disease)Medullary sponge kidneyADPKDHereditary nephritis (Alports syndrome)

Pathogenesis Injury to renal cellsNew local antigensInflammatory cells infiltrationActivation of proinflammatory and chemoattractant cytokines

Renal tubular dysfunctionRole of basement membrane

Fibrogenesis TGF-beta -Stimulates production of collagen and non- collagen basement membrane components-Inhibits collagenases and metalloproteinases

Activation of nuclear transcription factors such as nuclear factor kappa B- release of proinflammatory cytokines

Clinical features - CIN

Insidious Hypertension Renal tubular acidosisFanconi syndrome Mild proteinuria

Investigations

Urinalysis Proteinuria albuminuria. beta-2 microglobulin, RBP, N-acetylglucosaminidaseHaematuriaLeucocyturiaEosinophiluria White cell casts

Blood countEosinophilia

Eosinophiluria

Eosinophilia absent in NSAID induced AIN

Elevated ESR

Blood chemistry Acidosis

Low phosphate, potassium in PT disorders

Elevated K and acidosis in type-4 RTACreatinine and urea

Imaging Plain film, Ultrasound, CT scan

Renal size, echogenicityCalyceal dilatationStonesCalcifications

Other tests EDTA Lead mobilization testsX-ray fluorescence

Renal biopsy

Treatment

ACUTECessation of offending agentAntimicrobial therapySteroid therapy1mg/Kg for 4-6 weeks

CHRONICSupportive measures

Specific forms

NSAID induced AINCommoner in elderly

Allergic

Eosinophilia uncommon

Nephrotic syndrome common

Minimal change disease + interstitial nephritis

Antibiotic induced AINWithin days to weeksRashEosinophilia, eosinophiluria (not with rifampin)Sterile pyuriaHaematuriaProteinuria usually < 1g

Analgesic nephropathyMost common cause of CIN worldwideLong term ingestionPhenacetin, NSAIDs, Phenacetin + NSAID2-3 Kg over yearsCommoner F>M, 6th-7th decadesHaematuria, flank pain, infectionMild proteinuria, sterile pyuria, reduced GFRPapillary tip microcalcificationsTreatment supportiveIncreased incidence of uroepithelial tumours

Lead nephropathyLong biologic half lifeCIN in 3rd-4th decadePaints, batteries, leaded fuel welding, smeltingHypertension almost always presentHyperuricaemiaConfusion with hypertensive nephrosclerosis and gouty nephropathyRemoval from leadChelation more useful in acute poisoning

Ischaemic nephropathyElderly, smoking, dyslipidaemiaHypertension, proteinuria 1-2 g, Elevated se-creatinine Duplex scanning, DSA, MRITubular atrophy, fibrosis, arteriolar sclerosisLittle cellular infiltrationTreatment supportive

Aristolochic acid NephropathyAristolochic acid in Chinese slimming herbsBanned productDose-response relationshipProgressive interstitial fibrosisLikely cause of Balkan nephropathy(wheat flour contamination by seeds of Aristolochia clematitis)Uro-epithelial cancer

Cholesterol microembolic diseaseDestabilisation of plaquesLodging of needle shaped cholesterol crystalsKidneys, also skin, brain, retina, extremitiesMay be fever, leucocytosis, eosinophilia, raised ESR, hypocomplementaemiaARF with residual impairmentNeedle shaped clefts in small and medium arteriesMononuclear cellular infiltrationNo effective treatment

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