diagnosed as either collagen disease or adenovirus-type admission, serum creatinine had decreased to 1.7 mg/dl. 11 infection. and hypocomplementaemia ...
Nephrol Dial Transplant (1999) 14: 2210–2215
Nephrology Dialysis Transplantation
Case Report
Acute interstitial nephritis with immune complex deposition and MHC class II antigen presentation along the tubular basement membrane Masanori Tokumoto1, Kyoichi Fukuda1, Michiya Shinozaki1, Minoru Kashiwagi1, Ritsuko Katafuchi2, Tetsuhiko Yoshida1, Taihei Yanagida1, Hidetoshi Kanai1, Hideki Hirakata1, Kiyoshi Tamaki3, Seiya Okuda3 and Masatoshi Fujishima1 1Second Department of Internal Medicine, Faculty of Medicine, Kyushu University, 2Kidney Center, Division of Internal Medicine, Fukuoka Red Cross Hospital Fukuoka City and 3Third Department of Internal Medicine, Faculty of Medicine, Kurume University, Kurume City, Japan
Key words: acute renal failure; interstitial nephritis; MHC class II antigen; tubular basement membrane immune deposition
Introduction Renal tubulointerstitium has been recognized to be a common site of immune-complexes deposition leading to tissue destruction [1–3]. However, cases of interstitial nephritis in which interstitial immune complex deposition play a major role are not commonly reported [4–14]. Most reported cases have been finally diagnosed as either collagen disease or adenovirus-type 11 infection. Here we present a case of acute interstitial nephritis with tubular immune complex depositions and MHC class II antigen expression defined on the proximal tubular cells.
Case A 66-year-old Japanese man was admitted to our hospital because of renal functional deterioration on September 19, 1995. He was well until June 1995, when he had had flu-like symptoms with low-grade fever and general malaise. He visited his primary physician in August, and trace proteinuria and increased serum creatinine were noted. Laboratory tests are listed in Table 1. Blood pressure was 144/86 mmHg. He had no skin eruption or peripheral oedema. Urinary sediment was not specific. Mild anaemia (erythrocytes of 419×104/ml and haemoglobin of 12.4 g/dl ), and Correspondence and offprint requests to: Masanori Tokumoto MD, The Second Department of Internal Medicine, Faculty of Medicine, Kyushu University, Maidashi 3-1-1, Higashi-Ku, Fukuoka City, 812-8582 Japan.
elevated serum total protein, together with a slight decrease in serum albumin was noted. Serum creatinine was 3.6 mg/dl and blood urea nitrogen was 53 mg/dl. Serum chloride was slightly increased (112 mmol/l ). The endogenous creatinine clearance was 21.6 ml/min/ 1.73 m2. Serological tests showed hypocomplementaemia (C3 of 24 mg/dl, C4 of 3 mg/dl ), a low titre of antinuclear antibody (×40, speckled type), but other autoantibodies such as ds-DNA Ab, SS-A Ab, and SS-B Ab were negative. His serum creatinine rose progressively to 4.7 mg/dl and he was started on corticosteroids (prednisolone 40 mg/day). On 19 September the patient was transferred to our hospital for renal histological examination. Upon admission, serum creatinine had decreased to 1.7 mg/dl and hypocomplementaemia improved (C3 of 42 mg/dl and C4 of 18 mg/dl ). Renal biopsy was performed and 32 glomeruli were obtained. It revealed a marked cellular infiltration with some scattered fibrosis in the interstitium, but the glomeruli did not show any change ( Figure 1A,B). Immunofluorescence examination revealed coarse granular depositions of IgG, C3, and C1q along the tubular and Bowman’s capsular basement membrane ( TBM ) but not in the glomerular area ( Figure 2A–C ). By electronmicroscopy, electron-dense deposits were found within the TBM, but a feature indicating viral particles was not detected ( Figure 3). In order to clarify the immune pathogenesis, MHC class II antigen expression was examined and antiMHC class II monoclonal antibody (Dakopatts A/S, Denmark) was applied. It yielded positive staining of intact proximal tubular cells, some clusters of infiltrating mononuclear cells and interstitial fibroblasts ( Figure 4 A,B). A normal human kidney specimen, obtained from a kidney removed for clear-cell carcinoma, was stained with serially diluted patient serum, followed by FITC-conjugated rabbit anti-human IgG and IgM antibody. It was found to bind to the nuclei of tubular cells, but not TBM and the nuclei of other cells of the kidney (Figure 5 A,B). In contrast, the
© 1999 European Renal Association–European Dialysis and Transplant Association
AIN with TBM immune deposition
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Table 1. Laboratory data at primary physician visit Urinalysis Protein (+): Occult blood (±) Peripheral blood cell count White blood cell Red blood cell Haemoglobin Haematocrit Platelet Blood chemistry Total protein Albumin Urea nitrogen Creatinine Na K Cl Ca Phosphorus
0.9 g/day 8300/ml 419×104/ml 12.4 g/dl 36.7% 24.8×104/ml 8.9 g/dl 3.4 g/dl 53 mg/dl 3.6 mg/dl 137 mEq/l 4.9 mEq/l 112 mEq/l 8.3 mg/dl 5.5 mg/dl
Fig. 1. Light micrograph of the first renal biopsy specimen. Note remarkable diffuse infiltration of mononuclear cells into the interstitium (A, PAS×100, B, PAS,×400).
healthy control serum did not show any positive staining of either the nuclei of renal cells or TBM. Using normal human liver specimen the same tests revealed no positive staining in the nuclei of hepatic cells. Prednisolone was tapered and discontinued on 5 November 1995. Urinary protein excretion decreased to below 0.4 g/day and his serum creatinine was 1.3 mg/dl and he was discharged. One month later,
Serological tests CRP 1.3 mg/dl C3 24 mg/dl C4 3 mg/dl CH50
