Background: Chronic kidney disease (CKD) is a global health threat affecting approximately 10% of the adult population worldwide. Multimorbidity is common in CKD, but its impacts on disease outcomes are seldom investigated. Methods: This prospective cohort analysis followed patients, who were part of a multidisciplinary CKD care program, for 10 years. We aimed to determine the impact of multimorbidity on renal outcomes. Results: Overall, 1463 patients with stage 3–5 CKD were enrolled and stratified by the number of comorbidities. Mean follow-up time was 6.39 ± 1.19 years. We found that stage 3–5 CKD patients with at least three comorbidities at enrollment initiated dialysis earlier (hazard ratio (HR): 2.971) than patients without comorbidities. Risk factors for multimorbidity included old age, smoking, and proteinuria. Conclusions: By analyzing the number of comorbidities, a simple and readily applicable method, we demonstrated an association between multimorbidity and poor renal outcomes in stage 3–5 CKD patients. In addition to current guideline-based approaches, our results suggest an urgent need for tailored CKD care strategies for high-risk groups.

Diabetic kidney disease (DKD) is the leading cause of chronic kidney disease (CKD). Elucidating the mechanisms underlying proteinuria in DKD is crucial because it is a common problem in DKD-related mortality and morbidity. MicroRNAs (miRs) associated with DKD have been detected in experimental diabetes models and in patients with both diabetes and CKD. Here, we aimed to investigate pathologic miRs in diabetic nephropathy (DN) by prospectively following six nephrotic, biopsy-proven isolated DN patients (enrolled between August 2015 and July 2017) for one year. The urinary exosomes were isolated at the time of the biopsy and the contained miRs were analyzed by next-generation sequencing. The results were compared to the control group, composed of age-, gender-, and CKD stage-matched patients with proteinuric CKD who did not present diabetes. Among the 72 identified miRs, we investigated eight (miR-188-5p, miR-150-3p, miR-760, miR-3677-3p, miR-548ah-3p, miR-548p, miR-320e, and miR-23c) exhibiting the strongest upregulation (13–15 fold) and two (miR-133a-3p and miR-153-3p) with the strongest downregulation (7–9 fold). The functional analysis of these miRs showed that they were involved in known and novel pathways of DN, supporting their pathologic roles. The bioinformatics-based prediction of the target genes of these miRs will inspire future research on the mechanisms underlying DN pathogenesis.

Hemodialysis (HD) patients are vulnerable to coronavirus disease 2019 (COVID-19) and have a high mortality rate. We evaluated the anti-SARS-CoV-2 spike protein antibody (ACOV2S) levels in 385 HD patients before and 4 and 8 weeks after the second dose of vector-based ChAdOx1 nCoV-19 vaccine. For study control, week 4 ACOV2S levels after the second vaccination dose were measured in 66 healthcare workers (HCWs). The seroconversion rate of HD patients was 98.96% 4 weeks after the second vaccination. Despite low antibody levels before the second dose (week 0), week 4 ACOV2S levels after the second vaccine dose in HD patients increased prominently and were compatible with those in HCWs (p = 0.814 for HCWs vs. HD patients). The ACOV2S levels in HD patients waned significantly 8 weeks after the second vaccination dose (p < 0.001 at week 8 vs. 4). Older age and immunosuppressant use were negative predictors, while higher C-reactive protein (CRP) levels were positive predictors of ACOV2S waxing after the second vaccine dose in HD patients. Higher CRP levels and platelet counts were independently associated with decreased ACOV2S waning. The ChAdOx1 nCoV-19 vaccine is effective and safe for primary vaccination in HD patients and a booster dose is necessary.

Current strategies targeting serum cholesterol bring limited benefits to mortality and macrovascular events prevention among hemodialysis patients. Direct measurements and analysis on circulating markers of cholesterol homeostasis could be promising solutions to this bottleneck. We prospectively enrolled 90 maintenance hemodialysis patients and 9 healthy controls in 2019 for 1 year. We measured circulating desmosterol and lathosterol as markers for cholesterol synthesis and campesterol and sitosterol for cholesterol absorption. At baseline, hemodialysis patients showed higher levels of campesterol (p = 0.023) compared to healthy controls. During follow-up, we identified 14 (15.4%) patients who experienced macrovascular events. Comparisons of cholesterol homeostasis markers between cohorts with and without macrovascular events showed no significant differences in markers of cholesterol synthesis or absorption. Using logistic regression analysis, the odds ratio was not statistically significant for the prediction of macrovascular events after full-adjusting for age, sex, diabetes, serum albumin, cholesterol, and triglyceride. We concluded that hemodialysis patients demonstrated higher level of cholesterols absorption, indicated by circulating campesterol compared to healthy subjects. Markers for cholesterol homeostasis were not significantly associated with macrovascular events during a 1-year follow-up. Our results shed light on the novel therapeutic target of modulating cholesterol absorption in HD patients.

Background: Peritoneal dialysis (PD) is an established kidney replacement therapy, but long-term exposure to bioincompatible dialysate, uremic toxins, recurrent peritonitis, glucose degradation products, oxidative stress, and sterile inflammation progressively remodels the peritoneal membrane and contributes to peritoneal fibrosis (PF). This review summarizes the molecular basis of PF in PD and evaluates the therapeutic rationale for incretin-based interventions beyond weight loss and glycemic control. Methods: This narrative review synthesizes mechanistic, translational, and clinically relevant literature on PD-associated PF, with emphasis on DPP-4 biology, GLP-1 receptor agonism, inflammatory and oxidative signaling, angiogenesis, mesothelial-to-mesenchymal transition, glycemic management in PD, and selected author-conducted translational studies interpreted alongside independent evidence. Results: Available evidence supports a model in which DPP-4 activation, altered GLP-1/GLP-1R signaling, TGF-β/Smad3-driven mesothelial transition, NF-κB/MyD88 inflammation, ROS-mediated oxidative stress, angiogenesis, apoptosis, and cytoskeletal remodeling converge to impair peritoneal membrane integrity. DPP-4 inhibition, exendin-4, and dulaglutide attenuated these pathways in experimental models, while GLP-1 receptor agonists have established metabolic benefits in appropriate diabetic and obese populations. Conclusions: Direct clinical evidence that incretin-based therapies prevent or treat peritoneal fibrosis in humans undergoing PD is currently lacking. Therefore, peritoneal membrane protection, reduced ultrafiltration failure, and improved technique survival should be regarded as investigational, hypothesis-generating possibilities that require prospective clinical validation.