Aim: To elucidate prognosis and prevalence of chronic renal diseases among proteinuric and/or hematuric subjects found in mass screening, a long-term follow-up study (6.35 years, range 1.03–14.6 years) was conducted on Japanese working men. Methods: A total of 772 subjects selected from 50,501 Japanese men aged 15–62 years were found to have asymptomatic hematuria (n = 404), concomitant hematuria and proteinuria (n = 155), and proteinuria (n = 213) during their annual urine examination and five consecutive urinalyses. Results: Hematuria patients showed significant improvements in urinary abnormalities as compared with both hematuria/proteinuria and proteinuria patients. Both hematuria/proteinuria patients with normotension and hematuria/proteinuria patients aged under 40 years showed significant improvements. During the follow-up period, 9.5% of the hematuria patients became hematuric/proteinuric. Hematuria/proteinuria patients had the highest risk of developing renal insufficiency. The presence of hypertension at detection of urinary abnormalities did not affect the renal function; however, if proteinuria appeared after the age of 40 years, these patients had a higher risk of developing renal insufficiency. The incidence of IgA nephropathy in the present subjects was as high as 143 cases per 1 million per year. Conclusion: Detailed follow-up and definitive diagnosis of asymptomatic urinary abnormalities may raise the prevalence of IgA nephropathy worldwide.

ABSTRACT. Glomerular epithelial cells are primary pathogenic sites in focal segmental glomerulosclerosis (FGS) lesions. Glomerular epithelial cells are regarded as terminally differentiated cells that do not proliferate. These characteristics are also noted for neurons and muscular cells, which are major sites of mitochondrial DNA (mtDNA) mutation accumulation. Screening for mtDNA mutations was performed with renal biopsy specimens from patients with primary FGS and patients with IgA nephropathy (as subjects with secondary FGS and as control subjects). mtDNA extracted from kidney biopsy specimens was amplified with appropriate primer pairs for study of the mtDNA point mutations 3243A→G, 3271T→C, 8344A→G, and 8993T→G/C, as well as the common deletion (a 4977-bp deletion spanning mtDNA nucleotide pairs 8469 to 13447). In situ amplification of both total mtDNA and the common deletion was also performed. Two patients with FGS demonstrated the 3243A→G point mutation; 12 patients with FGS and seven patients with IgA nephropathy accompanied by glomerulosclerotic lesions exhibited the common deletion in their kidney tissue. No patient demonstrated the mtDNA mutations 3271T→C, 8344A→G, or 8993T→G/C. The degree of heteroplasmy for the 3243A→G point mutation was >85%; however, the heteroplasmy for the common deletion was <1%. As determined with in situ PCR, normal mtDNA was mainly distributed in the tubular epithelium and mtDNA with the common deletion was mainly distributed among glomerular epithelial cells. In conclusion, it is suggested that mtDNA mutations are distributed in glomerular epithelial cells among some patients with primary FGS or secondary FGS with IgA nephropathy. These mutations may be related to glomerular epithelial cell damage.

Objective Several cytokines and proteins are excreted intraperitoneally during the course of peritonitis and stable states in continuous ambulatory peritoneal dialysis (CAPD) patients. Dialysate hyaluronan (HYA) is also regarded as a marker of peritoneal healing during bacterial peritonitis. We examined here, intraperitoneal HYA production in stable CAPD patients and compared the results to those of the peritoneal equilibration test (PET), the length of time on dialysis, and other marker proteins. Design We determined the concentration of HYA and other marker proteins in the 4-hour-dwell dialysate at 1-year intervals. Setting CAPD unit in Hitachi General Hospital. Patients The subjects were 46 stable CAPD patients who underwent 104 PETs. Results A correlation was found between the length of time on dialysis and the amount of HYA excretion in the 4-hr-dwell dialysate ( r = 0.403, p < 0.001). A positive but weak correlation was found between the dialysate-to-plasma ratio of the creatinine concentration and dialysate HYA excretion ( r = 0.229, p < 0.05). Seven patients were over the 90th percentile in both the concentration of HYA (>349.2 ng/mL) and the amount of HYA (>743.6 μg/4-hr dwell). Five patients exceeded 1000 μg of HYA excretion in the 4-hr-dwell dialysate, 4 of whom showed an abrupt increase of HYA excretion to more than 1000 μg/4-hr dwell, and discontinued CAPD within 6 months due to ultrafiltration failure. Two of these 4 patients were diagnosed with sclerosing encapsulating peritonitis at autopsy. Conclusion Intraperitoneal HYA production increased with both higher permeable membrane and the length of time on CAPD. Monitoring of HYA in the peritoneal dialysate may be useful as a marker to assess functional and morphological changes in the peritoneum in long-term CAPD patients.

Hemodialysis (HD) patients are exposed to high oxidative stress, however, the nature of this stress is still unclear. In this study, we employed a specific lipid peroxidative product, phosphatidylcholine hydroperoxide (PCOOH), and evaluated the peroxidative effect of end stage renal disease by measuring thiobarbituric acid reactive substances (TBARS) and PCOOH in both plasma and erythrocyte membrane. We also surveyed plasma TBARS and PCOOH before and after HD sessions thereby assessing oxidative stress by a single HD procedure. The plasma TBARS level of healthy controls was 2.9 ± 0.4 nmol/ml. Those of HD patients before and after HD session were 5.1 ± 1.4 and 3.1 ± 0.5 nmol/ml, respectively, and the pre-HD plasma TBARS levels were significantly higher than those of controls and after HD. The Plasma PCOOH concentration of patients before HD was 119.7 ± 58.4 pmol/ml and was significantly higher than that of controls which was 88.6 ± 14.3 pmol/ml. After HD, the plasma PCOOH level decreased to 103.2 ± 36.0 pmol/ml, which was still significantly higher than that of controls. In erythrocytes, the PCOOH level of patients was 259.3 ± 105.4 nmol/g RBC and was significantly higher than that of controls with 88.6 ± 32.0 nmol/g RBC. Analyzed with respect to the cause of renal disease, the polycystic kidney disease patients showed significantly lower plasma PCOOH levels than the others. These results suggest that there is an increase of lipid peroxidation in both plasma and erythrocytes of HD patients, though this oxidative stress was not brought about by HD.

Objective The present study was undertaken to clarify the clinical course and prognosis of adult patients with primary IgA nephropathy (IgAN), especially with mild pro-teinuria or mild histological alternations. Patients and Methods A population of 735 IgAN patients whomwe were able to observe for morethan two years was examined. Results A total of 115 patients (15.6%) was on dialysis during the observation period. The overall 5-year renal survival rate was 92.0%. On the other hand, 166 patients (22.6%) were in clinical remission. A group with mild pro-teinuria included 197 patients (26.8 %). Forty-seven patients of this group showedminor glomerular abnormalities, whereas 12 patients with mild proteinuria showed severe mesangial involvement. Three patients with mild pro-teinuria were on dialysis during the observation period, whose proteinuria was increased during the clinical course. A group with minor glomerular abnormalities included 82 patients (1 1.2 %). Forty-seven patients of this group showed mild proteinuria, of whom12 patients showed moderate proteinuria. However, three patients with minor glomeru-lar abnormalities who were not on dialysis showed loss of renal function. Conclusion These results indicated the heterogeneity of the course and prognosis in IgAN. Even if a patient's initial clinical or histological findings are comparatively mild, strict follow-up management is needed. (Internal Medicine 40: 697-702, 2001)