The present study was designed to elucidate whether glomerular epithelial cell (GEC) injury is associated with the mechanism of proteinuria in biopsy-proven IgA nephropathy (IgAN) . Twenty-four IgAN patients were divided into 4 groups based on their grade of proteinuria . Light microscopic examination revealed that GEC injury appeared prior to glomerular lesions such as sclerosis, crescent and adhesion. Reduced glomerular expression of C3b receptor (CR 1), an indicator of GEC injury, was detected initially at the portion of damaged GEC and around the lesions of sclerosis, crescent and adhesion. CR1 expression eventually disappeared in the group IV patients who had nephrotic range proteinuria. Moreover, the grade of proteinuria in IgAN patients was associated with GEC injury and reduced glomerular expression of CR1. Taken together, GEC injury might be an important pathological finding which appears initially in the glomeruli, suggesting that GEC injury is a predictor of proteinuria in IgAN patients.

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The present study was conducted to examine the clinicopathological features of recurrent IgA nephropathy (IgAN) following renal transplantation. Serial renal biopsies were performed regularly at O hour, 1-hour and 2-hours, and 39 episode biopsies were carried out when patients had increased serum creatinine levels and proteinuria. In 49 renal allograft recipients with IgAN, 12 patients were proved to be recurrent IgAN (24.5%) . There was a significantly increased five- and ten-year risk of graft loss in the renal allograft recipients with biopsy-proved recurrent IgAN. Graft survival in 49 renal allograft recipients with IgAN was worse (68.8% at 5 years and 40.4% at 10 years) than that in 997 whole transplants (80.7% at 5 years, and 67.7% at 10 years). We found significant differences in the prevalence of HLA-DR4 (66.7%) and BW35 (25%) in the renal allograft recipients with recurrent IgAN when compared with normal healthy subjects. The renal allograft recipients with recurrent IgAN had a high incidence of proteinuria (8/l2), hypertension (9/12) and renal dysfunction of less than 50ml/min (7/12). Mean hemodialysis duration before renal transplantation in recurrent IgAN transplants was 12.5 months, which was shorter than in those without recurrent IgAN. Histopathological studies revealed that renal lesions due to IgAN frequently appeared in the renal allograft recipients with recurrent IgAN. Taken together, these findings suggest that donor-recipient matching may be carefully reconsidered, and recurrent IgAN after renal transplantation must be treated with effective immunosuppressive therapy.

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In our laboratory, a semi-quantitative pattern classification (PC) for the distribution pattern of glomerular sclerotic lesions in biopsied renal specimens with IgA nephropathy has been utilized, and found to be quite beneficial for predicting the patient's prognosis. In the present study conducted to re evaluate this classification, 503 patients with IgA nephropathy (male/female, 256/247 ; mean age : 32.1±13.5 yrs ; follow-up : 9.3±4.5 yrs) were used. The patients had been divided originally into 5 groups based on a previous PC : minimal, mild, moderate, severe and advanced groups. Their glomerular lesions were classified as mild, moderate, severe and global sclerosis, and were given scores of 1-4 points. The mean glomerular score was then calculated for each patient, as a value of the calculated classification (CC), and all patients were then re- divided into 5 groups based on their scores. The renal survival curves in the CC were similar to those in PC, and no significant differences in the renal survival rates were found between the classifications in each group, thus suggesting that the CC has a similar predictive power for renal survival. Although 7 of 39 cases (18%) with global sclerosis in PC groups 4 and 5 shifted down to CC group 3, of 61 patients with global sclerosis in PC group 1 who had a good prognosis, 26 cases (43%) shifted up to the CC group 2 and 6 cases (8%) changed to the CC group 3. As a result, the predictive power in patients in the lower CC groups was lost for the renal survival rate. In conclusion, statistical comparison between the PC and CC groups revealed that global sclerosis presents in non/minimally affected glomeruli as a nonspecific alteration. Severely advanced cases also possess a high incidence of globally sclerotic glomeruli (87%), and therefore the occurrence of global sclerosis may involve two different pathogenic mechanisms.

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Hyaline glomeruli are observed frequently in biopsied samples with mild to severe glomerular damage. We thus investigated whether or not all hyaline glomeruli have the same semiquantitative values in order to predict accurately the renal prognosis. We histopathologically studied 503 patients with IgA nephropathy (256 males and 247 females ; mean age : 32.1±13.5 yrs), whose prognoses were followed for more than 3 yrs (mean follow-up period : 9.3±4.5 yrs). Cases with severely damaged prolifero-sclerotic glomeruli showed poor prognoses (severely damaged glomeruli : ( - ) vs ( + ) ; renal death rate : 6% vs 52%, p < 0.0001 ; the 15 year-survival rate : 89% vs 52%, p<0.0001) and hyaline glomeruli were seen in 68% of the cases. Hyaline glomeruli were observed in 29% of the cases with mild glomerular damage. However, the renal prognosis was not affected by the presence of hyaline glomeruli based on the analysis of the generalized Wilcoxon test. These results indicated that hyaline glomeruli express two different characteristics for renal prognosis. Therefore, the appearance of hyaline glomeruli alone is less important for the prediction of renal prognosis, but the appearance of both glomeruli with hyalinosis and those with severe damage was found useful in accurately predicting the renal prognosis.

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In order to investigate the influence of aldehyde dehydrogenase 2 (ALDH2) genotype in the path ogenesis of nephropathy due to noninsulin dependent diabetes mellitus (NIDDM), genotyping of ALDH2 was measured using the PCR-RFLP method in patients with NIDDM on chronic hemodialysis (HD). The results were as follows ; 1) The frequency of active ALDH2 was 63% and that of inactive ALDH2 was 37%. 2) The percentage of active ALDH2 was significantly higher in patients with alcohol tolerance than that in those without it (38%). 3) The estimated amount of alcohol consumption in the past was 506±720 g/week in the active ALDH2 group, and 156±288g/week in the inactive ALDH2 group, showing a significant difference between the two groups. 4) Interdialytic body weight gain was larger in patients with active ALDH2 than in those with inactive ALDH2. Since the frequency of active ALDH2 was similar to that in patients without nephropathy, these results do not support the hypothesis that ALDH2 gene polymorphism is involved in the development and persistence of chronic renal failure due to NIDDM. However, salt and water craving in dialysis patients may be influenced partially by an active ALDH2 gene.

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A 12-year-old boy was referred to our hospital because of persistent hematuria with proteinuria. He was found to have urine abnormalities by a school mass-screening and visited a hospital, where a routine examination revealed proteinuria of 190 mg/dl, hematuria of 2+ and anti-nuclear antibody (ANA) of 1 : 320 with a speckled pattern. The other laboratory findings, including anti-DNA antibody were unremarka ble. Hypocomplementemia was not seen. Although he had no disabilities and manifestations suggesting systemic lupus erythematosus, urine abnormalities persisted. Percutaneous renal biopsy findings demon strated stage II diffuse membranous glomerulonephritis (MGN). Neither anti-hepatitis B virus antigens and antibodies nor hepatitis C virus antibody were detected in his sera. Thus, the diagnosis of idiopathic MGN was made. Initiation of a 6-month course of alternate-day prednisolone (an initial dosage at 30 mg) combined with an anti-thrombocyte agent resulted in gradual subsidence of the urine abnormalities and ANA titer. Although pathogenesis of his MGN remains speculative, possible activation of autoimmunities, which led to ANA positivity, might be responsible.

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Infection is one of the common causes of death in patients with systemic lupus erythematosus (SLE). It is associated with the use of immunosuppressive agents, renal failure, and increased disease activity. Fournier's gangrene is a necrotizing fasciitis occurring in the genital region. It is rare, but can be crucial if surgical drainage is delayed. We report a female case of Fournier's gangrene occurring in a patient with lupus nephritis and chronic renal failure. The patient was a 21-year-old female with chronic renal failure due to lupus nephritis. She had suffered from watery diarrhea one month before admission. It improved after increasing the dose of prednisolone, but, she was complicated with Bartholin abscess. The vaginal pain rapidly spread to the left lower quadrant abdomen despite treatment with oral cephalosporin. Focal incision was performed and black fluid emerged with a foul smell. Pelvic computed tomography (CT) revealed many bubbles in that region. She was found to have septic shock on transfer to our hospital. Thereafter, emergency debridement was performed, followed by antibiotic therapy and hyperbaric oxygen therapy. Organisms were found to be 5 anaerobes, such as Bacteroides species, and 3 aerobics, such as Morganella morganii. Fournier's gangrene was improved via these treatments, but she needed maintenance hemodialysis. Fournier's gangrene complication should be considered in SLE with urogenital infection.

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A 61-year-old male was referred to our hospital for rapidly progressive azotemia. He was also found to have huge vegetation at the aortic valve causing regurgitation. Biochemical examinations revealed the presence of an immunocomplex associated with decreased circulating complements. In biopsy samples from the kidney, we found the presence of fibrillar crescents, proliferation of mesangial cells, increase in extracellular matrix proteins, atrophy of tubules, infiltration of mononuclear cells in the interstitial regions, high density deposits in the mesangial area and mesangial interposition. Since the patient strongly rejected operative treatment by valvular replacement, we continued non-invasive treatment such as hemodialysis and treatment with penicillin G. This transiently improved the condition of the patient, including biochemical data and cardiac function, but there was no reduction in the size of vegetation at the aortic valve and the bacteria responsible for infective endocarditis were not identified. About three months after admission, overt signs of congestive heart failure emerged and the patients was subjected to intensive care with a respirator and hemodynamic monitoring. Although the cardiac function was improved, concomitant severe pneumonia occurred and the patient died of septic shock. Thus, we report a rare case in whom immune complex-mediated glomerulonephritis was associated with infective endocarditis with aortic valve vegetation

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