Section 4 -

Granulomatous Tubulointerstitial Nephritis Donna J. Lager, M.D. Matthew Lewin, M.D.

Case 3: Granulomatous Tubulointerstitial Nephritis A 56 year old man with a history of type II diabetes mellitus and recent pacemaker placement, presented with acute renal failure. Eight months prior his creatinine was 1.7 mg/dl, but at presentation was 6 mg/dl. His serum calcium was 11 mg/dl. Granulomatous TIN has been described in cases of drug-induced allergic acute tubulointerstitial nephritis, however granulomatous TIN may also be seen in infection, sarcoidosis, Wegener's granulomatosis and in the acute tubulointerstitial nephritis and uveitis syndrome. Granulomatous TIN has rarely been reported to occur in association with malignancy (CLL) and in renal allografts infected with polyoma (BK) virus. Sarcoidosis: Sarcoidosis is a systemic disease of unknown etiology characterized by the presence of non-caseating granulomata in affected organs and is usually dominated by involvement of lungs, skin and eyes. Renal involvement is due to infiltration of the renal interstitium by granulomata and/or by granuloma-induced disturbances of calcium homeostasis. The glomeruli in sarcoidosis are usually normal, however granulomata occasionally involve renal vessels. Other findings include interstitial fibrosis and tubular atrophy as well as interstitial calcification in patients with hypercalcemia and/or hypercalciuria. The incidence of renal involvement in sarcoidosis is unknown with a reported prevalence of 7 and 37% in two autopsy series. Renal involvement is often clinically silent and patients may have mild proteinuria or an abnormal urinary sediment, renal calculi and tubular defects including diabetes insipidus, renal tubular acidosis and glycosuria. Thirty to 40% of patients with sarcoidosis have granulomatous TIN on renal biopsy. The incidence of hypercalciuria ranges from 10-60%, hypercalcemia in 10% and nephrocalcinosis in 5% of patients with sarcoidosis. Tubulointerstitial Nephritis and Uveitis Syndrome (TINU): This syndrome was intitially described by Dobrin in 1975 in a report of two patients with the unique triad of acute eosinophilic tubulointerstitial nephritis with renal failure, bone marrow and lymph node granulomata and bilateral anterior uveitis. Following this intitial description, a number of cases have been reported. The patients are more commonly young women who present with symptoms of uveitis and renal insufficiency, but without significant hypertension or urinary protein excretion. Renal biopsy demonstrates tubulointerstitial nephritis with infiltration of the interstitium by lyphocytes, plasma cells and less commonly neutrophils. Eosinophils are variably present and granulomas may also be seen. Tubular epithelial cells often show degenerative changes. The infiltrating lymphocytes are predominantly memory T-lymphocytes with few B-lymphocytes. References: Dobrin RS, Vernier RL, Fish AJ. Acute eosinophilic interstitial nephritis and renal failure with bone marrow-lymph node granulomas and anterior uveitis: A new syndrome. Am J Med 59:325-333, 1975. Magil AB. Drug-induced acute interstitial nephritis with granulomas. Hum Pathol 13:36-41, 1983. Vanhille PH, Kleinknecht D, Morel-Maroger L, et al. Drug-induced granulomatous interstitial nephritis. Proc EDTA 20:646-649, 1983. Rodriguez-Perez JC, Cruz-Alamo M, Perez-Aciego P, et al. Clinical and immune aspects of idiopathic acute tubulointerstitial nephritis and uveitis syndrome. Am J Nephro 15:386-391, 1995. Bergner R, Hoffman M, Waldherr R, Uppenkamp M. Frequency of kidney disease in chronic sarcoidosis. Sarcoidosis Vasculitis and Diffuse Lung Disease 20:126-132, 2003.