There are racial differences in primary renal diseases for end-stage renal disease (ESRD) and the incidence and prevalence of cardiovascular disease (CVD). To reduce the number of patients with both ESRD and CVD, an effective screening method for CKD should be established. In Japan, screening with the urine dip-stick test for proteinuria has been used since 1972 targeting every child and worker and since 1983 for every resident over 40 years old. There are several reasons for continuing this screening program. First, the positive rate of proteinuria is high in the Japanese general population, especially subjects with neither hypertension nor diabetes. Most of these subjects have no symptoms, and the only sign of renal disease is asymptomatic urinary abnormalities. Second, the prevalence and incidence of glomerulonephritis, especially IgA nephropathy, are high in the Japanese and Asian races, and urinalysis is the only method for early detection of chronic glomerulonephritis. Third, 10-year survival of the ESRD patients due to glomerulonephritis was approximately twice that of ESRD patients due to diabetes and nephrosclerosis. Consequently, reducing the incidence of ESRD due to glomerulonephritis is one of the best ways to reduce the prevalence of ESRD. Furthermore, higher incidence of ESRD in Asian races than in Caucasians was reported. Proteinuria is known to be the best predictor for reducing renal function, and the urine dip-stick test for proteinuria is less expensive and is cost-effective. For an effective screening strategy to reduce the ESRD population in Japanese and Asians, universal screening with the urine dip-stick test for proteinuria could be one solution.

Toll-like receptors (TLRs) play a pivotal role in pathogen recognition and subsequent cytokine synthesis by immune cells. Uremic patients have a high infectious morbidity, but it remains unclear if this arises from the defective innate immune responses related to TLRs. We studied TLR4 expression in monocytes and their intracellular cytokine synthesis in response to lipopolysaccharide (LPS) stimulation in 35 predialysis patients with chronic kidney disease (CKD) with or without predisposition to bacterial infections and 16 age-matched controls. Expression of TLR4 in unstimulated peripheral monocytes was determined by staining with anti-TLR4 antibody and analysis with flow cytometry. Monocytes were then stimulated by LPS, labeled with anti-CD14 antibody, and subjected to intracellular cytokine staining and flow cytometry. Tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, and IL-8 synthesis was examined in CD14(+) monocytes. TLR4 expression was constitutively diminished in CKD patients with reduced expression being more severe in those CKD patients who were predisposed to infections. Monocytes from these infection prone CKD patients exhibited significantly reduced synthesis of TNF-alpha, IL-1beta, IL-6, and IL-8 in response to LPS challenge compared with those from control subjects. The intensity of synthesis of each cytokine significantly correlated with TLR4 expression levels in monocytes (P<0.01). The capacity of monocytes to synthesize proinflammatory cytokines was significantly reduced in infection prone CKD patients, and this may possibly be due to the reduced monocyte expression of TLR4. Abnormal TLR4 expression by monocytes may play a role in the susceptibility of such patients to bacterial infections.

Circulating immune cells in CAPD patients may be hyporeactive against infections, indicating an unfavourable innate host defence.

Objective The activity of systemic lupus erythematosus (SLE) has been reported to decrease in patients who have developed end-stage renal disease (ESRD). However, extrarenal symptomsattributable to the disease activity are noted, especially during the first year of dialysis. Westudied the clinical course and evaluate the disease activity of SLEin patients with ESRDon hemodialysis for more than 6 months. Subject and Methods Fourteen patients with SLEwho had been initiated on maintenance dialysis at our center between 1982 and 1999 were examined retrospectively.Their clinical details, organ system manifestations, serologic profiles and immunosuppressive treatment regimens were reviewed. Patients with and without postdialysis flaras of SLEwere compared statistically. Results Five patients exhibited 6 SLE flares under treatment with corticosteroids. Twoflares occurred within the first year of the initiation of dialysis, and in 1 patient, aggravation of the disease activity was noted 98 months after the initiation of dialysis. Polyarthritis was noted in 5 cases and fever in 4 cases. The serum complement levels decreased in all 6 cases with relapse of SLEactivity. Comparedwith the other 9 patients who did not exhibit SLE relapse, no significant differences were found in 5 patients who did with respect to the demographic and serologic features at the initiation of dialysis.Conclusion Weconclude that the disease activity does not always burn out in patients of SLEwhoshow progression to ESRD. SLEflares can sometimesoccur even after one year of the initiation of dialysis. SLEpatients on dialysis should be carefully followed up by clinical and serological monitoring, and treated by appropriate immunosuppressive therapy. (Internal Medicine 40: 598-602, 2001)

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