The ratio of epidermal growth factor to monocyte chemotactic peptide-1 in the urine predicts renal prognosis in IgA nephropathy.

The production of cytokines by resident and non-resident renal cells during immunoglobulin A nephropathy (IgAN) plays a key role in the progression of renal damage. The aim of this study was to determine if measurements of urinary epidermal growth factor (EGF) and monocyte chemotactic peptide-1 (MCP-1), at the time of renal biopsy, were a predictor of end-stage renal disease (ESRD) in a cohort of 132 patients with biopsy-proven IgAN. Outcome measures were a doubling of the baseline serum creatinine (sCr) and/or ESRD. Patients with ratios of EGF/MCP-1 in the lowest tertile had a significant decline in renal survival, while patients in the highest tertile maintained 100% renal survival at 48 and 84 months of follow-up. Multivariate Cox's regression analysis showed that the urine EGF/MCP-1 ratio was an independent prognostic factor and indirectly correlated with the combined outcome. The predictive value was also measured by the area under the receiver operating characteristic curve (ROC). The area of the EGF/MCP-1 ratio was significantly higher than that of EGF or MCP-1 alone, histologic grade, creatinine clearance, or proteinuria. Our study suggests that the urinary EGF/MCP-1 ratio may be used as a prognostic marker of ESRD for patients with IgAN.

Searching for IgA nephropathy candidate genes: genetic studies combined with high throughput innovative investigations.

Idiopathic IgA Nephropathy (IgAN) is the most common biopsy-proven glomerulonephritis worldwide. All races with the exception of Blacks and Indians are involved. Families with two or more relatives affected by IgAN may be observed in 15-20% of pedigrees of IgAN patients. Genome wide linkage study has been considered the most promising approach to identify IgAN susceptibility genes. Therefore, some European investigators constituted the European IgAN Consortium which was initially funded by the European Union. Data from linkage analysis studies, family association studies and case-control association studies are reported. To date, the Consortium has identified two loci (located on chromosomes 4q26-31 and 17q12-22), in addition to the previous study which described the first IgAN locus on chromosome 6q22-23. The functional mapping of genes involved in the disease proceeds from the identification of susceptibility loci identified by linkage analysis (step 1) to the isolation of candidate genes within gene disease-susceptibility loci, after obtaining information by microarray analysis carried out on peripheral leukocytes and renal tissue samples (step 2). Then, the process will proceed from the design of RNA interferenceagents against selected genes (step 3) to the application of systematically tested effect of RNA agents on functional cellular assay (step 4). The above combined high-throughput technologies will give information on the pathogenic mechanisms of IgAN. In addition, these data may indicate potential targets for screening, prevention and early diagnosis of the disease and more appropriate and effective treatment.

Antimicrobial agents and catheter-related interventions to prevent peritonitis in peritoneal dialysis: Using evidence in the context of clinical practice.

BACKGROUND: Peritonitis still represents a common and major complication of peritoneal dialysis. The broader adoption of several strategies, including antimicrobial and catheter related interventions, has been advocated to prevent or reduce the risk of peritonitis in peritoneal dialysis. METHODS: In this article we start with the presentation of a clinical case where concern exists about the strategies for preventing peritoneal dialysis peritonitis. We then look at the available evidence in the form of systematic reviews of randomized trials and individual randomized trials of interventions to prevent peritonitis in peritoneal dialysis. A summary of the evidence is provided and then put in context with the clinical case scenario. RESULTS: Nineteen eligible trials (1949 patients) of antimicrobial agents and 37 (2822 patients) of catheter related interventions to prevent peritonitis in peritoneal dialysis were identified. Nasal mupirocin compared with placebo significantly reduced the exit-site and tunnel infection rate (1 trial, 2716 patient months, RR 0.58, 95% CI 0.40 to 0.85) but not peritonitis rate (1 trial, 2716 patient months, RR 0.84, 95% CI 0.44 to 1.60). As for antimicrobial strategies, perioperative intravenous antibiotics compared with no treatment significantly reduced the risk of early peritonitis (4 trials, 335 patients, RR 0.35, 95% CI 0.15 to 0.80) but not exit site and tunnel infection (3 trials, 114 patients, RR 0.32, 95% CI 0.02 to 4.81). As for catheter related strategies, Y-set and twin-bag systems were superior to conventional spike systems (7 trials, 485 patients, RR 0.64, 95% CI 0.53 to 0.77) and no other catheter-related intervention was demonstrated to prevent peritonitis in PD. CONCLUSIONS: Evidence exists to support the use of perioperative intravenous antibiotic prophylaxis at the time of catheter placement, the twin-bag and Y-set system, as well as prophylaxis with mupirocin in Staphylococcus aureus nasal carriers. Despite lack of evidence, several other agents are used and recommended in major international guidelines, which is reasonable but requires further investigation.