Intra-renal and urinary mRNA expression of podocyte-associated molecules for the estimation of glomerular podocyte loss.

BACKGROUND: Podocyte loss plays an important role in the pathogenesis of diabetic nephropathy, but counting the number of glomerular podocyte in renal biopsy specimen is a labor-intensive task. We study whether intra-renal and urinary messenger RNA expression of podocyte-associated molecules could be used to estimate glomerular podocyte number in patients with diabetic nephropathy. METHOD: We studied 21 consecutive patients with biopsy-proven diabetic nephropathy. The intra-renal and urinary mRNA expression of nephrin, podocin, and synaptopodin were measured by real-time quantitative polymerase chain reaction. Podocyte number was determined in micro-dissected glomerulus. The degree of histological scarring was quantified by morphometric analysis. RESULTS: Glomerular podocyte number correlated with intra-renal expression of nephrin (r=0.510, p=0.044), podocin (r=0.605, p=0.013), and synaptopodin (r=0.480, p=0.060). Glomerular podocyte number also significantly correlated with urinary expression of synaptopodin (r=0.595, p=0.019) but not other targets. Baseline renal function correlated with intra-renal expression of nephrin (r=0.617, p=0.005), synaptopodin (r=0.474, p=0.040), and podocin (r=0.443, p=0.057). The degree of tubulointerstitial scarring also inversely correlated with intra-renal expression of nephrin (r=-0.462, p=0.047), podocin (r=-0.458, p=0.049), and synaptopodin (r=-0.500, p=0.029) but not with urinary gene expression. CONCLUSION: Intra-renal expression of podocyte-associated molecules correlated with glomerular podocyte number, renal function, and tubulointerstitial scarring. The results suggest that intra-renal, but not urinary expression of podocyte-associated molecules, might be used to assess the degree of podocyte loss in diabetic nephropathy.

Discrepancy between intrarenal messenger RNA and protein expression of ACE and ACE2 in human diabetic nephropathy.

BACKGROUND: The intrarenal angiotensin-converting enzyme (ACE) and type 2 ACE (ACE2) play important roles in the pathogenesis of diabetic nephropathy, but human data are limited. We studied glomerular and tubulointerstitial mRNA and the protein expression of ACE and ACE2 in patients with diabetic nephropathy. METHODS: We studied renal biopsy specimens of 22 patients with diabetic nephropathy and 11 transplant donors as normal controls. Intrarenal mRNA expression of ACE and ACE2 was measured by laser microdissection and real-time quantitative polymerase chain reaction; expression at the protein level was determined by immunostaining. RESULTS: Glomerular and tubulointerstitial mRNA expression levels of ACE and ACE2 were significantly higher in patients with diabetic nephropathy than in normal controls (p < 0.001 for all comparisons). Glomerular ACE and ACE2 protein levels of patients with diabetic nephropathy were significantly higher than those of kidney donors (4.90 +/- 2.55% vs. 2.64 +/- 0.98%, p = 0.022, and 7.40 +/- 3.36% vs. 4.37 +/- 2.36%, p = 0.017, respectively). The tubulointerstitial ACE at the protein level, however, was similar between diabetic patients and controls (8.76 +/- 4.18% vs. 10.44 +/- 6.61%, p = 0.453), and the tubulointerstitial ACE2 at the protein level was significantly lower in diabetic nephropathy (16.48 +/- 7.68% vs. 23.23 +/- 7.65%, p = 0.025). CONCLUSION: The mRNA expression of ACE and ACE2 increased in both the glomerular and tubulointerstitial area of diabetic nephropathy. However, the tubulointerstitial ACE expression at the protein level remained unchanged, while that of ACE2 actually decreased. Our results suggest a posttranscriptional modulation of tubulointerstitial ACE and ACE2 expression. Experimental data of intrarenal mRNA expression of ACE and ACE2 should be interpreted with caution.

Outline of 2023 updated International Society for Peritoneal Dialysis catheter-related infection recommendations / 中华肾脏病杂志

Peritoneal dialysis (PD) catheter-related infections are important risk factors for catheter loss and peritonitis. 2023 International Society for Peritoneal Dialysis (ISPD) catheter-related infection recommendations have revised and clarified definitions and classifications of exit site infection and tunnel infection, such as cause-specific catheter-related infection, culture-negative catheter-related infection, refractory catheter-related infection, and infection- related catheter removal. A new target for the exit site infection rate should not exceed 0.40 episodes per year at risk. The recommendation about topical antibiotic cream or ointment to catheter exit site has been downgraded. New recommendations for exit site infection include clarified suggestion of exit site dressing cover and revised topical antibacterial agents as well as antibiotics treatment duration. In addition to catheter removal and reinsertion, new salvage options for catheter are suggested. The paper outlines the updated main content of the guide.

Messenger RNA expression of podocyte-associated molecules in the urinary sediment of patients with diabetic nephropathy.

BACKGROUND: Podocyte loss plays an important role in the pathogenesis of diabetic nephropathy. We hypothesize that messenger RNA expression of podocyte-associated molecules in urinary sediment may provide important clinical information in patients with diabetic nephropathy. METHOD: We studied 21 patients with biopsy-proven diabetic nephropathy and 9 healthy controls. The mRNA expression of nephrin, podocin, synaptopodin, Wilms' tumor-1 (WT-1) and alpha-actinin-4 in urinary sediment were measured by real-time quantitative polymerase chain reaction. The degree of histological damage was quantified by morphometric analysis. Patients were then followed for an average of 25.63 +/- 10.76 months. The rate of glomerular filtration rate (GFR) decline was calculated by the least-square regression. RESULTS: There were significant differences in nephrin, podocin, synaptopodin, alpha-actinin-4 (p < 0.01 for all comparisons) and WT-1 (p = 0.028) expression between patients and normal controls. Urinary nephrin expression was significantly correlated with proteinuria (r = 0.502, p = 0.020); urinary synaptopodin was significantly correlated with proteinuria (r = 0.585, p = 0.005), serum creatinine (r = 0.516, p = 0.017) and estimated GFR (r = -0.560, p = 0.008), and urinary WT-1 expression was significantly correlated with the degree of tubulointerstitial fibrosis (r = 0.558, p = 0.009). There was no significant correlation between GFR decline and urinary expression of target genes. CONCLUSION: Urinary mRNA expressions of nephrin, podocin, synaptopodin, WT-1 and alpha-actinin-4 are higher in patients with diabetic nephropathy than in normal controls. Urinary nephrin and synaptopodin expressions are correlated with baseline clinical parameters such as proteinuria or renal function, while WT-1 expression is related to the degree of histological damage. Our results suggest that urinary mRNA expression of podocyte-associated molecules may be used for risk stratification of diabetic nephropathy.

Relation between microRNA expression in peritoneal dialysis effluent and peritoneal transport characteristics.

BACKGROUND: The role of microRNAs (miRNAs) in peritoneal transport is uncertain. METHODS: We studied 82 new peritoneal dialysis (PD) patients, 22 prevalent patients without ultrafiltration problem, and 6 patients with documented ultrafiltration problem. Peritoneal transport was determined by standard peritoneal equilibration test (PET). RNA was extracted from the PD effluent after PET, and intra-peritoneal expression of miRNA targets were quantified. RESULTS: There were significant difference in the PDE expressions of miR-15a and miR-21. There were modest inverse correlations between ultrafiltration volume and PDE expression of miR-17 (r= -0.198, p =0.041) and miR-377 (r=-0.201, p=0.041). There was an inverse correlations between dialysate-to-plasma creatinine concentration at 4 hours and PDE expression of miR-192 (r=-0.199, p=0.040); while mass transfer area coefficient of creatinine correlated with PDE expression of miR-192 (r=-0.191, p=0.049) and miR-377 (r=0.201, p=0.041). Amongst 7 randomly selected patients who had repeat PET after one year, there was a significant correlation between baseline PDE expression of miR-377 and change in ultrafiltration volume (r=-0.852, p=0.015). CONCLUSION: The miRNA expression in PDE, including miR-15a, miR-17, miR-21, miR-30, miR-192, and miR-377, correlated with peritoneal transport characteristics. Our result suggests that miRNA may play a role in the regulation of peritoneal membrane function.

KDIGO clinical practice guideline on the evaluation and care of living kidney donors

The 2017 Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline on the Evaluation and Care of Living Kidney Donors is intended to assist medical professionals who evaluate living kidney donor candidates and provide care before, during and after donation. The guideline development process followed the Grades of Recommendation Assessment, Development, and Evaluation (GRADE) approach and guideline recommendations are based on systematic reviews of relevant studies that included critical appraisal of the quality of the evidence and the strength of recommendations. However, many recommendations, for which there was no evidence or no systematic search for evidence was undertaken by the Evidence Review Team, were issued as ungraded expert opinion recommendations. The guideline work group concluded that a comprehensive approach to risk assessment should replace decisions based on assessments of single risk factors in isolation. Original data analyses were undertaken to produce a "proof-in-concept" risk-prediction model for kidney failure to support a framework for quantitative risk assessment in the donor candidate evaluation and defensible shared decision making. This framework is grounded in the simultaneous consideration of each candidate's profile of demographic and health characteristics. The processes and framework for the donor candidate evaluation are presented, along with recommendations for optimal care before, during, and after donation. Limitations of the evidence are discussed, especially regarding the lack of definitive prospective studies and clinical outcome trials. Suggestions for future research, including the need for continued refinement of long-term risk prediction and novel approaches to estimating donation-attributable risks, are also provided.

Messenger RNA expression of podocyte-associated molecules in urinary sediment of patients with lupus nephritis.

OBJECTIVE: To examine urinary expression of podocyte-associated molecules in patients with lupus nephritis (LN). METHODS: We studied 32 patients with active LN (Active group) and 17 patients with inactive lupus (Silent group). Messenger RNA expression of nephrin, podocin, and synaptopodin in urinary sediment was quantified by real-time polymerase chain reaction and compared to other clinical measures. RESULTS: The urinary concentrations of nephrin, podocin, and synaptopodin were significantly higher in the Active than the Silent group (p < 0.05 for all comparisons). There was no relation between urinary gene expression and the histological class of LN, but urinary nephrin expression correlated with proteinuria (r = 0.480, p < 0.01) and the score of the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI; r = 0.578, p < 0.01). Urinary podocin expression also correlated with SLEDAI score (r = 0.389, p = 0.006). After initiation of immunosuppressive treatment, all patients were followed for an average of 13.7 +/- 2.4 months. The decline of the glomerular filtration rate (GFR) correlated with urinary expression of podocin (r = 0.406, p = 0.005) and synaptopodin (r = 0.337, p = 0.021). In a multiple linear regression model, urinary podocin expression and baseline GFR were independent predictors of GFR decline. CONCLUSION: The concentration of podocyte-associated molecules in urinary sediment correlated with lupus activity and GFR decline. The clinical utility of quantifying urinary expression of podocyte-associated molecules for risk stratification of patients with LN deserves further study.