Kidney Research and Clinical Practice最新文献

Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease. The glomerulus is the primary site of injury in DKD progression. Pathologically, the integrity of the glomerular filtration barrier is disrupted, characterized by podocyte process fusion and detachment, glomerular basement membrane thickening, and reduction of the endothelial cell glycocalyx. These disruptions result in albuminuria due to impaired function of glomerular selective filtration. Additionally, mesangial expansion driven by mesangial cell proliferation and excessive mesangial matrix accumulation in glomeruli is a hallmark of the disease, leading to nodular sclerosis and glomerulosclerosis eventually. Multiple molecular mechanisms involving abnormal metabolism of nutrients, oxidative stress, inflammation, and hyperactivity of the renin-angiotensin system contribute to glomerular pathophysiological changes and renal function deterioration in diabetes mellitus. This review focuses on disturbances in nutrient metabolism and their roles in the pathophysiology of glomerular impairments. Blood glucose control, cardiovascular risk factors intervention, blood pressure management, and renin-angiotensin system blockade are pivotal in preventing the development and progression of DKD. Future research is urgently needed to identify innovative therapeutic targets based on advances in molecular mechanisms.

Background: This study aimed to investigate the relationship between the creatinine-to-cystatin C ratio (CCR) and handgrip strength in individuals with prediabetes, to identify patients with reduced handgrip strength.

Methods: This study used a nationally representative sample from the Chinese middle-aged and elderly population. The cross-sectional portion utilized data from the first wave of the 2011 China Health and Retirement Longitudinal Study (CHARLS), while the longitudinal portion used data from the fourth wave of the 2015 CHARLS. Data on CCR, handgrip strength, and other relevant variables were collected and analyzed using univariate and multivariate regression.

Results: A total of 2,704 participants were included, with 1,276 males (47.2%) and 1,428 females (52.8%), and the mean age was 60.5 ± 9.5 years. Univariate analysis showed a positive correlation between CCR and handgrip strength (β = 18.3; 95% confidence interval [CI], 16.46-20.14; p < 0.001). After adjusting for confounding variables, the β value was 3.52 (95% CI, 1.95-5.09; p < 0.001). Compared to the lowest CCR group (Q1, 0.27 to 0.67), the adjusted β values for Q2 (0.67 to 0.77), Q3 (0.77 to 0.89), and Q4 (0.89 to 2.39) were 0.37 (95% CI, -0.46 to 1.2; p = 0.38), 1.6 (95% CI, 0.73-2.47; p < 0.001), and 2.16 (95% CI, 1.24-3.09; p < 0.001), respectively. Subgroup and stratified analyses further supported these results.

Conclusion: This study suggests that in individuals with prediabetes, there is a positive correlation between the CCR and handgrip strength.

Background: Living kidney donors with hypertension are potential candidates for solving the donor shortages in renal transplantation. However, the safety of donors with hypertension after nephrectomy has not been sufficiently confirmed.

Methods: A total of 642 hypertensive and 4,848 normotensive living kidney donors who were enrolled in the Korean Organ Transplantation Registry between May 2014 and December 2020 were included in this study. The study endpoints were a decreased estimated glomerular filtration rate (eGFR) and proteinuria.

Results: In the entire cohort, donors with hypertension had a lower eGFR before nephrectomy in comparison to normotensive donors which remained lower after kidney transplantation. The incidence of proteinuria in hypertensive donors increased during follow-up. In propensity score-matched analysis, the risk of eGFR being <60 mL/min/1.73 m2 (hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.50-1.19) or <45 mL/min/1.73 m2 (HR, 0.50; 95% CI, 0.06-4.03) was not significantly increased in donors with hypertension. However, hypertensive donors were found to have a significantly higher risk of proteinuria than normotensive donors (HR, 2.28; 95% CI, 1.05-4.94). Similar findings were also observed in the analysis of the entire cohort, indicating that hypertensive donors had a significantly higher risk of proteinuria (adjusted HR, 1.77; 95% CI, 1.10-2.85), without a substantial increase in the risk of decreased renal function.

Conclusion: The risk of proteinuria after donation was substantially increased in donors with hypertension. These findings underscore the need for careful monitoring of proteinuria in hypertensive donors following donation.

Background: Cardiovascular disease is an important risk factor for mortality among kidney transplant recipients. In this study, we aimed to investigate the association between cardiovascular risk score at kidney transplantation and long-term outcomes of patients.

Methods: In this prospective, observational cohort study, we enrolled kidney transplant recipients who participated in the Korean Organ Transplantation Registry and underwent transplantation between April 2014 and December 2019. The cardiovascular risk status of kidney transplant recipients was assessed using the Framingham risk score. All-cause mortality, major adverse cardiovascular events, allograft failure, estimated glomerular filtration rates (eGFRs), and composite outcomes were evaluated after kidney transplantation.

Results: Of the 4,682 kidney transplant recipients, 96 died during 30.7 ± 19.1 months of follow-up. The Kaplan-Meier survival analysis results showed that high Framingham risk scores were associated with all-cause mortality, major adverse cardiovascular events, and composite outcomes. According to the multivariable Cox analysis, high Framingham risk scores were associated with an increased risk of mortality (hazard ratio [HR], 3.20; 95% confidence interval [CI], 1.30-7.91), major adverse cardiovascular events (HR, 8.43; 95% CI, 2.41-29.52), and composite outcomes (HR, 2.05; 95% CI, 1.19-3.46). The eGFRs after transplantation were significantly higher among patients in the low Framingham risk score group (p < 0.001). However, Framingham risk scores were not associated with graft loss or rapid decline in eGFRs.

Conclusion: The Framingham risk score is a useful indicator of cardiovascular events, mortality, and kidney function after kidney transplantation.

Alport syndrome, characterized by renal failure, hearing loss, and ocular abnormalities due to collagen type IV gene mutations, exhibits distinctive ocular manifestations in the various ocular tissues including the cornea, lens, and retina. Ophthalmological examinations, providing noninvasive visibility of basement membrane anomalies caused by collagen type IV mutations, can have a role in Alport syndrome diagnostics. Lenticonus, macular fleck, and other abnormalities also can serve as indicators of inheritance patterns and predictors of severe mutations or early-onset renal failure. Recognizing these manifestations in advance enables timely surgical intervention, potentially improving long-term visual outcomes. This review highlights the ocular features in Alport syndrome and contributes to the understanding of the relationships among ocular abnormalities as well as the genotype-phenotype correlations in Alport syndrome. In these ways, hopefully, it will guide further research and help to inform the development of clinical strategies.

Background: The COVID-19 pandemic accelerated the use of digital health technologies to improve care access and quality of life. The Korean Ministry of Health and Welfare introduced a home care program for end-stage renal disease patients on peritoneal dialysis (PD), incorporating educational consultations and remote monitoring. This study evaluates the long-term economic effectiveness of this digital health-based home care program.

Methods: A Markov model was developed to assess the lifetime cost-effectiveness of the PD home care program. Simulations involved 1,000 patients aged 50 in a PD health state, transitioning annually. Effectiveness was measured in quality-adjusted life years (QALYs), and a cost-utility analysis was performed from a limited societal perspective. The willingness-to-pay (WTP) threshold was US$ 32,255 (gross domestic product per capita) per QALY, with a 4.5% discount rate for both QALYs and costs. Outcomes included the incremental cost-effectiveness ratio (ICER) and incremental net monetary benefit, with scenario, sensitivity, and expected value of perfect information (EVPI) analyses addressing uncertainty.

Results: The base case analysis yielded an ICER of $4,895 per QALY, well within the WTP threshold. Sensitivity analysis highlighted PD-associated costs as the most critical parameters. Monte Carlo simulations (10,000 iterations) indicated a 79.0% probability of the home care program being optimal. EVPI analysis suggested an additional $2,963 per patient with perfect parameter information.

Conclusion: The PD home care program in Korea appears to be a cost-effective strategy, potentially reducing peritonitis incidence and enhancing healthcare efficiency.

Background: Few studies have evaluated the global burden of chronic kidney disease (CKD) in adolescents and young adults (AYAs).

Methods: Age-standardized rates of incidence (ASIR), mortality (ASMR), and disability-adjusted life-years (ASDR) were used to describe the CKD burden in AYAs. The estimated annual percentage changes (EAPCs) were calculated to evaluate the temporal trends from 1990 to 2019. Risk factors were calculated by population attributable fractions.

Results: In 2019, the ASIR, ASMR, and ASDR of CKD in AYAs were 32.21 (95% uncertainty interval [UI], 23.73-40.81) per 100,000, 2.86 (2.61-3.11) per 100,000 and 236.85 (209.03-268.91) per 100,000, respectively. The ASIR was higher among females than males, whereas the ASMR was higher among males than females in 2019. From 1990 to 2019, significant increases in ASIR were found for CKD (EAPC, 0.98%; 95% confidence interval [CI], 0.95%-1.01%), although the ASMR had decreased (EAPC, -0.40%; 95% CI, -0.56% to -0.24%). The largest increase in ASIR was observed in countries with a middle sociodemographic index (SDI) (EAPC, 1.30%; 95% CI, 1.28%-1.33%), while the largest increase in ASMR was observed in high SDI. Globally, the proportional contribution of risk factors for CKD mortality varied across regions, with the highest proportions of high fasting plasma glucose being 14.04% in low SDI, compared with 24.01% in high SDI.

Conclusion: CKD is a growing global health problem in AYAs, especially in countries with a middle SDI. Targeted measures are needed to address the rising burden of CKD in AYAs, focusing on prevention, early diagnosis, and reducing disparities.

Background: EW-7197, a potent oral ALK5 inhibitor, was assessed for its impact on transforming growth factor beta 1 (TGF-β1)-induced fibrosis in a three-dimensional (3D) renal fibrosis-on-a-chip and a mouse model. The evaluation included tubular epithelial- mesenchymal transition, angiogenesis, and inflammatory cytokine expression.

Methods: In a 3D renal fibrosis-on-a-chip model, three cell types(kidney fibroblasts, human proximal tubular cells, and human umbilical vein endothelial cells) were cultured and treated with TGF-β1 and EW-7197. Alpha smooth muscle actin (α-SMA) and keratin 8 (KRT-8) was assessed, angiogenesis observed via confocal microscopy, and cytokine levels measured by polymerase chain reaction, immunoassay, and enzyme-linked immunosorbent assay. In a cisplatin-induced renal fibrosis mouse model, blood urea nitrogen levels, TGF-β, and Smad 2/3 were determined, and fibrosis was assessed with Masson's trichrome stain.

Results: The α-SMA expression was significantly lower in the EW-7197 group than in the TGF-β fibrosis group. TGF-β decreased the expression of the epithelial marker KRT-8, an effect that was reversed by EW-7197 and SB431542. In the TGF-β-induced fibrosis model, the length of the thick vessels was reduced, and the diameter of both thick and thin vessels was decreased, but EW-7197 reversed these effects. EW-7197 significantly reduced the messenger RNA expression of TGF-β and increased the levels of vascular endothelial growth factor receptor 2, interleukin (IL)-10, and IL-6. EW-7197 reduced the levels of secretory cytokines TGF-β1, TGF-β3, IL- 1β. In the cisplatin-induced renal fibrosis mouse model, EW-7197 reduced renal fibrosis by down-regulating TGF-β signaling.

Conclusion: EW-7197 attenuated the TGF-β1-induced fibrotic cellular response in the 3D chip model and animal model. These findings indicate the potential effect of EW-7197 in attenuating renal fibrosis.