High mortality in dialysis patients is linked to malnutrition and inflammation. Prognostic nutritional index (PNI), calculated from serum albumin level and total lymphocyte count, has been developed as a prognostic marker for cancer patients. We investigated the clinical utility of PNI in predicting mortality in patients undergoing hemodialysis. Thus, 101,616 patients who initiated hemodialysis in United States dialysis centers between 2007 and 2011 were included in this retrospective cohort study. Using the Cox regression model, we assessed the relationship between PNI and mortality. Further, the predictive value of PNI for one-year mortality was compared with that of its constituent using area under the receiver operating characteristic curve, net reclassification improvement, and integrated discrimination improvement. Higher PNI quartiles were incrementally associated with lower mortality; in patients with PNI values of 39.5–<43.1, 43.1–<46.6, and ≥46.6 (reference: PNI < 39.5), case-mix adjusted hazard ratios (95% confidence intervals) were 0.66 (0.64, 0.68), 0.49 (0.48, 0.51), and 0.36 (0.34, 0.37), respectively. PNI predicted mortality better than serum albumin level or total lymphocyte count alone. In the subgroup analysis, PNI performed well in predicting mortality in patients aged < 65 years. Our results indicate that PNI is a simple and practical prognostic marker in patients undergoing hemodialysis.

In proteinuric renal diseases, the serine protease (SP) plasmin activates the epithelial sodium channel (ENaC) by cleaving its γ subunit. We previously demonstrated that a high-salt (HS) diet provoked hypertension and proteinuria in Dahl salt-sensitive (DS) rats, accompanied by γENaC activation, which were attenuated by camostat mesilate (CM), an SP inhibitor. However, the effects of CM on plasmin activity in DS rats remain unclear. In this study, we investigated the effects of CM on plasmin activity, ENaC activation, and podocyte injury in DS rats. The DS rats were divided into the control diet, HS diet (8.0% NaCl), and HS+CM diet (0.1% CM) groups. After weekly blood pressure measurement and 24-h urine collection, the rats were sacrificed at 5 weeks. The HS group exhibited hypertension, massive proteinuria, increased urinary plasmin, and γENaC activation; CM treatment suppressed these changes. CM prevented plasmin(ogen) attachment to podocytes and mitigated podocyte injury by reducing the number of apoptotic glomerular cells, inhibiting protease-activated receptor-1 activation, and suppressing inflammatory and fibrotic cytokine expression. Our findings highlight the detrimental role of urinary plasmin in the pathogenesis of salt-sensitive hypertension and glomerular injury. Targeting plasmin with SP inhibitors, such as CM, may be a promising therapeutic approach for these conditions.

Background: Malnutrition is associated with discontinuing peritoneal dialysis (PD). The prognostic nutritional index (PNI), composed of serum albumin level and total lymphocyte count, has been suggested as a prognostic marker for mortality in patients undergoing PD. However, the relationship between PNI and PD discontinuation has not yet been well addressed. We evaluated the relationship between PNI and PD discontinuation in patients with end-stage kidney disease who initiated PD treatment. Methods: This retrospective cohort study included patients who underwent PD at a single academic hospital between 2007 and 2022. We examined the association between PNI (< 40 vs. ≥ 40) and PD discontinuation using Cox proportional hazards regression models. We used restricted cubic spline analysis to examine the continuous associations between the PNI and outcomes. Results: The mean age (and standard deviation) of the 91 patients was 57.1 ± 13.4 years; 72 (79.1%) discontinued PD during the median follow-up period of 25.0 months. Lower PNI was associated with an increased risk of PD discontinuation. The hazard ratios (95% confidence intervals) with three levels of adjustments were 1.74 (1.08, 2.79), 2.21 (1.32, 3.66), and 1.81 (1.01, 3.24) (reference: PNI ≥ 40). Restricted cubic spline analysis showed that a PNI < 40 was continuously associated with a higher risk of PD discontinuation. Conclusion: A lower PNI (< 40) was associated with a higher risk of PD discontinuation. Our findings suggest that evaluating the PNI may help identify patients at high risk of PD discontinuation and lead to appropriate nutritional management for dialysis maintenance.