To elucidate the clinical characterization of drug-induced allergic nephritis (DIAN), we analyzed the cases attending our department. We now report on the 14 cases of DIAN due to administration of penicillin in 2 cases, cephem antibiotics in 6 cases, nonsteroidal anti-inflammatory drugs in 4 cases and new quinolone anticidal drugs in 2 cases. With 1 exception, all these cases reached the stage of acute renal failure after taking these drugs for 2–13 days, followed by characteristic allergic symptoms such as fever, skin eruptions and serum IgE elevation in 5 of the 14 cases. A lymphocyte stimulation test (LST) with the suspected drugs proved to be positive in 10 of the 12 cases examined, and the uptake of ⁶⁷Ga in the kidneys was extremely positive in all 6 cases examined, reflecting the natural course of this disease. Furthermore, there were some cases where ⁶⁷Ga accumulated in the kidneys in spite of the negative result of LST examination. In all of these cases, a needle or open renal biospy was performed, and acute tubulointerstitial nephritis (AIN) was diagnosed. Almost all cases were treated with glucocorticoid for AIN or dialysis for acute uremic symptoms several times. However, 4 of the 14 cases could not return to normal condition in spite of these forms of treatment. We would therefore like to suggest that LST and ⁶⁷Ga scintigram are useful diagnostic tools for DIAN as an alternative to renal biopsy.

The effect of Sairei-to, an oriental traditional medicine, against gentamicin nephrotoxicity was examined in gentamicin nephrotoxicity rat models. Gentamicin nephrotoxicity was induced by s.c. injection of gentamicin (100 mg/kg/day, for 3 days) in male Sprague-Dawley rats. Renal functions of two rat groups were compared, one eating rat chow containing 2.5% Sairei-to, the other eating normal rat chow. Sairei-to administration reduced the increase of urinary N-acetyl-beta-D-glucosaminidase (NAG) and protein excretion, and decreased creatinine clearance induced by gentamicin. Gentamicin increased renal cortical malondialdehyde (MDA) concentration in normal diet group but not in the Sairei-to diet group. The renal cortical gentamicin concentration was not different between the two groups. In conclusion, Sairei-to shows reno-protective action against gentamicin nephrotoxicity, possibly through its anti-oxidant action.

Mizoribine (MZR), a purine nucleoside antibiotic, is an effective immunosuppressive agent that prevents rejection reactions after kidney transplantation in humans. The present study was performed to examine the effect of MZR on nephrosis produced in rats given puromycin aminonucleoside (PAN). Urinary protein excretion in rats injected with PAN and MZR (PAN + MZR rats) was shown to be reduced significantly in comparison with rats given only PAN (PAN rats). Although mild hypoproteinemia persisted during the experimental period in PAN + MZR rats, no loss of body weight or state of malnutrition was observed. The reduction of serum IgG and C3 was reversed by administration of MZR. Polyethyleinamine (PEI) staining of renal sections showed increased numbers of anionic sites in PAN + MZR rats in comparison with PAN rats, suggesting that MZR improved the permselectivity of the glomerular basement membrane (GBM). Moreover, the production of thromboxane B₂ (TxB₂) was significantly inhibited in PAN + MZR rats compared with PAN rats. No serious adverse effects of MZR were observed after a large dose of the agent. It is possible that restoration of the charge barrier of the GBM damaged by PAN, or reduction of TxB₂ production by the glomeruli may underlie the reduction of protein excretion induced by administration of MZR.

Serum levels of lipase (Lp) during the end of the dialysis showed a significant increase after the administration of heparin in hemodialysis patients. However, serum Lp levels were not increased after the administration of the anticoagulant nafamostat mesylate in hemodialysis patients. Serum levels of Lp were significantly correlated with serum levels of lipoprotein lipase (LPL), hepatic triglyceride lipase (H-TGL) and nonesterified fatty acid (NEFA) 20 min after the administration of heparin during maintenance hemodialysis. Lp activity did not appear with the NEFA ligand for determining the NEFA activity. Inhibitors of LPL and H-TGL reduced the measured Lp activity in vitro. The main mechanism of elevated measured serum Lp activity in hemodialysis patients was determined to be cross-reactivity with LPL or H-TGL. Furthermore, measurement of Lp may be a method for determining optimal coagulation time in patients with hemodialysis.

We report a case of a 35-year-old man with secondary amyloidosis chiefly involving the kidney and heart. The patient showed severe proteinuria and ischemic heart damage and had hepatic adenoma at the age of 33. Biopsy specimens from the kidney, heart, stomach and rectum showed extensive deposition of amyloid. After the surgical resection of a 300-gram hepatic adenoma, highly elevated c-reactive protein (CRP) levels decreased and the serum amyloid A (SAA) level was completely normalized. Normal liver cells were immunostained with rabbit anti-SAA antibody, but the cells in adenoma tissue and kidney were not. Electron microscopic examination revealed extracellular deposition of amyloid fibrils in the hepatic adenoma and kidney tissue. The concentration of tumor necrosis factor-α (TNF-α) (312 pg/ mg tissue protein) was 7-fold higher in adenoma tissue than in normal liver tissue. Moreover, SAA (2.8 ng/mg tissue protein) was 2-fold higher in normal liver tissue than in adenoma tissue. Since TNF-α has been known to induce SAA production in target cells, the present results suggest that the hepatic adenoma produced TNF-α, which then caused mainly secondary amyloidosis in the kidney and heart. Currently, 2 years after surgical resection, urinary excretion of protein has been markedly reduced (from 3.5 to 0.8 g/day) and renal and cardiac functions are normal without specific medical treatment.