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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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