Nephrology R4 이홍주 / prof. 임천규

J Clin Pathol 2009;62:505–515

Ann Acad Med Singapore 2009:38:240~50

ATIN ??? AIN ??? ATN ???

ATIN Acute Tubulointerstitial nephritis AIN Acute interstitial nephritis ATN Acute tubular necrosis =

Acute interstitial nephritis(AIN) –inflammatory infiltrates in interstitium –Interstitial edema –usually associated with an acute deterioration in renal function.

1-3% 15-27% Clin Nephrol 1984; 22: 217–222 Q J Med 1998; 66: 97–115 Am J Kidney Dis 2000; 35: 433–447 Q J Med 1989;70: 221–233

Kidney International (2010) 77, 956–961

immunological basis Kidney International (2001)

LM Interstitium Inflammatory cell infiltration - diffuse or patchy - lymphocytes(CD4+ T cells), macrophages, eosinophils, plasma cells edema - typical finding granulomas Glomeruli & vessels distinctly normal

IF negative in most of patients EM nonspecific lesions... NSAIDs-induced AIN : diffuse effacement of podocyte’s foot processes Fibrotic changes advanced interstitial fibrosis accompanied by tubular atrophy within 7-10 days of initiation of the inflammatory process unless rapid withdrawal of offending drug or onset of steroid treatment

Features Acute renal failure100% Acute renal failure requiring dialysis40% Arthralgias45% Fever36% Skin rash22% Eosinophilia (4500 eosinophils per mm3)35% Microhematuria67% Gross hematuria5% Leukocyturia82% Non-nephrotic proteinuria93% Nephrotic-range proteinuria2.5% Complete nephrotic syndrome0.8% Kidney Int 2008; 73: 940–946

Drug-induced AIN acute worsening of renal function : all the patients starting of the offending drug ~ appearance of renal manifestations =10 days (1 day ~ several months) specific clinical findings in drug-induced AIN : allergic-type reaction low-grade fever maculopapular skin rash Eosinophilia urinary eosinophils - ‘No’ diagnostic usefulness.

AIN secondary to infectious diseases / idiopathic AIN extrarenal manifestations maculopapular rash, arthralgias, eosinophilia – uncommon TINU syndrome = AIN + bilateral anterior uveitis  follow renal dysfunction AIN coincidental with autoimmune pancreatitis : a dense infiltration of IgG4-positive mononuclear cells in renal interstitium

rapid improvement of renal function after the removal of the inducing agent longer follow-up ‘Not’ fully recovered their baseline renal function in significant proportion (30-70%) duration of treatment –offending drug or duration and severity of renal failure –not a correlation with the levels of SCr at the end of follow-up predictive role of diffuse interstitial infiltrates ? extent of interstitial fibrosis - ↑ risk of chronic renal impairment <1.2mg/dL (49%) <1.7mg/dL (68%)

role of steroids in the treatment of drug-induced AIN : controversial retrospective study 60 patients with biopsy-proven AIN  F/U data in 42 patients. 60% - steroid vs 40% - supportive care. ‘no’ difference in sCr levels after 1, 6, and 12 months following AIN chronic renal impairments in significant proportion  considerable delay between the onset of AIN Sx and renal biopsy (3 weeks)  considerable delay to start steroids after renal biopsy Nephrol Dial Transplant 2004; 19: 2778–2783

whether the timing of treatment initiation ? early vs late retrospective multicenter study 61 patients with biopsy-proven, drug induced AIN. 85% - steroids vs 15% of - conservative need of chronic dialysis : 3.8 vs 44%  steroid treatment is indicated in drug-induced AIN  start soon or immediately after the diagnosis to diminish the risk of chronic renal impairment. Kidney Int 2008; 73: 940–946

steroids mainstay of treatment in idiopathic AIN TINU AIN associated with systemic diseases AIN with autoimmune pancreatitis. plasmapheresis and cytotoxics (cyclophosphamide, cyclosporine / MMF) in idiopathic AIN resistant to steroids

retrospectively cases of biopsy-proven IgA nephropathy from July 2000 to June 2009 at a medical center in Taiwan