Transcript Slide 1
Tubulointerstitial nephritis Dr F. MOEINZADEH Case 1 A 34 y/o female is evaluated for Cr rising. She has low back pain from 15days ago and consume Iboprofen tab 4times /day. Nausea +, no vomiting, no oliguria PH.Ex: T=37.1°C RR=18/min PR= 85/min Other finding is unremarkable Case 2 A 74 years old man with low back pain and anemia referred to nephrology clinic due to Cr rising. Lab data: Cr= 3.2 mg/dL Ca= 11.7mg/dL Alb= 3.8 g/dL Hb= 9.3g/dL MCV=85fl PLT=143000/mm3 Kidney sonography: RT kidney= 120mm LT kidney= 115mm and some calcifications in both kidneys. Tubulointerstitial Nephritis A group of clinical disorders that affect principally the renal tubules and interstitium with relative sparing of glomeruli and renal vasculature Classification: 1. AIN: acute IN 2. CIN: chronic IN Acute Interstitial Nephritis AIN is a clinicopathologic syndrome of: ARF Associated with interstitial edema and cellular infiltrate Acute Interstitial Nephritis Etiology Idiopathic Secondary Secondary Causes of ATIN Drugs: Antibiotics: Penicillins, Cephalosporins, Sulfa drugs, Ciprofloxacin, Acyclovir NSAIDS Diuretics: Thiazides, Furosemide, Triamterene Others: Cimetidine, Omeprazole, Phenytoin, Allopurinol Systemic infection: Legionnaires disease, Leptospirosis, Streptococcal infection, CMV infection Primary kidney infections: Acute bacterial pyelonephritis. Autoimmune disorders: Sarcoidosis, Sjogrene syndrome Pathophysiology – drug induced AIN Drug-induced AIN is secondary to immune reaction AIN occurs only in a small percentage of individuals taking the drug AIN is not dose-dependent Association with extrarenal manifestations of hypersensitivity Recurrencence after re-exposure to the drug TYPICAL CLINICAL MANIFESTATION OF ACUTE INTERSTITIAL NEPHRITIS History of drug hypersensitivity or recent infection and taking antibiotics Sudden onset of fever lasting several days to weeks Variable degrees of hypertension Triad: fever, rash, eosinophilia: typical but unusual presentation Flank pain due to capsule distention Most presentation: any of this features Hypertension , edema is uncommon in AIN A particularly severe and rapid-onset AIN may occur upon reintroduction of rifampin after a drug-free period Laboratory Findings in AIN Acute rise in plasma cr Eosinophilia Sterile pyuria Positive Hansel stain (>1% total WBCs are eos): rarely Laboratory Findings in AIN Active urine sediment with WBC, RBC, and WBC casts Normal or mildly increased protein excretion (usually no more than 1g/day) Renal tubular acidosis Rise in creatinine with FENa >1.0; no expected acute tubular necrosis or glomerulonephritis Kidney size normal or increased Eosinophiluria Other conditions associated with Eosinophiluria Prostatitis Upper & lower UTI Bladder Cancer Renal Atheroembolic disease Diagnostic Studies CBC Urinalysis Hansel stain Renal ultrasound Gallium scan Renal biopsy Gold standard is renal biopsy. Indications are: Uncertainty of diagnosis Advanced RF Lack of spontaneous recovery after cessation of offending drug If immunosupressive therapy is considered Renal biopsy is generally not required for diagnosis but reveals extensive interstitial and tubular infiltration of leukocytes, including eosinophils. Algorithm for the treatment of allergic and other immune-mediated AIN Prognosis Most cases of AIN resolve completely after offending factor has been removed. The longer the patient remains in renal failure, the less likely it is that complete recovery of renal function will occur. Chronic interstitial nephritis A clinicopathologic entity defined as slowly progressive renal insufficiency due to tubular cell atrophy and progressive interstitial fibrosis caused by a chronic interstitial mononuclear cell infiltrate. CTIN is responsible for 15-30% of all cases of ESRD. Conditions assiciated with CTIN Hereditary: ADPKD, Alport Metabolic disturbances: hypercalcemia, hyperoxaluria, hyperuricemia, hypokalemia, cystinosis Drugs & toxins: NSAIDS, lead, lithium, cisplatin, cyclosporine, tacrolimus, Chinese herbs. Immune mediated: Wegener granulomatosis, sjogrene, SLE, sarcoidosis, vasculitis Hematologic & malignancies: MM, Sickle cell anemia, lymphoma Infections: chronic pyelonephritis, xanthogranulomatous pyelonephritis Obstruction: tumors, stones, bladder outlet obstruction, vesicoureteral reflux. Others: radiation nephritis, hypertensive atherosclerosis, renal ischemic disease Clinical manifestations Usually asymptomatic until develop CKD eg: malaise, nausea, nocturia, sleep disturbances Is sometimes found incidentally on routine Lab work: decreased GFR (Cr rise), U/A: PU. Microscopic hematuria, pyuria. Clinical findings that suggest chronic TIN Hyperchloremic metabolic acidosis Hyperkalemia (out of proportion of RF) Reduced maximal urinary concentrating ability (polyuria, nocturia) Partial or complete fanconi syndrome( phosphaturia, bicarbonaturia, Aauria, uricosuria, glycosuria) Modest proteinuria (<2 gr/day) RTA II( proximal RTA) : lead poising MM RTA I( Distal): chronic urinary obstruction Polyuria: analgesic nephropathy, sickle cell disease, PKD. Etiologies Metabolic disturbances Analgesic nephropathy Lead nephropathy Chinese herb nephropathy Sarcoidosis MM Metabolic disturbances Hyperclcemia: can lead to nephrocalcinosis ( deposition around tubules and collecting ducts) Acute hyperphosphatemia, sodium phosphate solution lead to nephrocacinosis ( incompletely reversible after hypercalcemia resolve) Prolong hyperuricemia Hyperoxaluria (in jojenoileal bypass) Analgesic nephropathy Medication contain: aspirin, acetaminophen, phenacetin, caffeine, codeine. Acetaminophen: 1. is concentrate in the papillary tips 2. its reactive metabolites can injure cells in the renal papilla, papillary necrosis. This effect can exagerate with concomitant NSAIDs use. Analgesic nephropathy Usually occur in young women who had comorbidities of emotional stress, neuropsychiatric problem, GI disturbances. Plain CT: papillary calcification, abnormal renal cortex contour. Tx: cessation of drug BUT: progression of renal function loss is usually slowed or even arrested with drug discontinuation. Lead nephropathy Lead taken up by PCT that cause aminoaciduria, glycosuria, CIN. Triad: HTN, gout (saturnine gout) and chronic renal insufficiency. Dx: elevated 24h urinary excretion of lead after administration of 2 , 1g doses of EDTA. Tx: chelation therapy with EDTA that arrest or even reverse the CKD. Chinese herb nephropathy Silent renal insufficiency Fanconi syndrome or fatigue from anemia Rapidly progressive CIN with accelerated interstitial fibrosis, lead to ESRD. Tx: cessation of herbs Note: urothelia malignancy monitoring Sarcoidosis The most common cause of renal dysfunction: hypercalcemia. Cause noncaseating granolomatous interstitial nephritis. RTA II CIN respond to corticosteroid therapy: loss of granolomatous & lymphocytic infiltrate. Multiple myeloma Induce acute & chronic renal dysfunction. Tubulointerstitial pathology: light chain cast nephropathy: most common complication. hypercalcemia with nephrocalcinosis hyperuricemia amyloid deposition MM light chain cast nephropathy: cast clogging the tubule initiate a multinucleated giant cell inflammatory reaction. Tx: chemotherapy to reduce excess production, volume repletion and alkalization of the urine. Urinary tract obstruction Acute & chronic urinary tract obstruction are associated with a mononuclear cell infiltrate. Obstruction cause: CIN Impaired excretion of H+& K vasopressin- resistant concentrating defect. Tx: relief of the obstruction Radiation nephritis In radiation more than: 2300cGy Acute and severe injury within 1 year of radiation: HTN, anemia, edema Insidious chronic form: mild renal insufficiency, HTN, mild proteinuria. Pathogenesis: injury to the vascular endothelium, vascular occlusion, tubular atrophy, interstitial fibrosis. Hypertensive arterionephrosclerosis Arteriopathy in the afferent arterioles leading to interstitial & glomerular changes related to ischemia. Prominent cause of the loss of renal function: Tubular atrophy & interstitial fibrosis.