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Background: Human blood metabolites have demonstrated close associations with chronic kidney disease (CKD) in observational studies. Nonetheless, the causal relationship between metabolites and CKD is still unclear. This study aimed to assess the associations between metabolites and CKD risk. Methods: We applied a two-sample Mendelian randomization (MR) analysis to evaluate relationships between 1400 blood metabolites and eight phenotypes (outcomes) (CKD, estimated glomerular filtration rate(eGFR), urine albumin to creatinine ratio, rapid progress to CKD, rapid decline of eGFR, membranous nephropathy, immunoglobulin A nephropathy, and diabetic nephropathy). The inverse variance weighted (IVW), MR-Egger, and weighted median were used to investigate the causal relationship. Sensitivity analyses were performed with Cochran's Q, MR-Egger intercept, MR-PRESSO Global test, and leave-one-out analysis. Bonferroni correction was used to test the strength of the causal relationship. Results: Through the MR analysis of 1400 metabolites and eight clinical phenotypes, a total of 48 metabolites were found to be associated with various outcomes. Among them, N-acetylleucine (OR = 0.923, 95%CI: 0.89–0.957, PIVW = 1.450 × 10–5) has a strong causal relationship with lower risk of CKD after the Bonferroni-corrected test, whereas Glycine to alanine ratio has a strong causal relationship with higher risk of CKD (OR = 1.106, 95%CI: 1.063–1.151, PIVW = 5.850 × 10–7). No horizontal pleiotropy and heterogeneity were detected. Conclusion: Our study offers groundbreaking insights into the integration of metabolomics and genomics to reveal the pathogenesis of and therapeutic strategies for CKD. It underscores 48 metabolites as potential causal candidates, meriting further investigation. [ABSTRACT FROM AUTHOR]

Background and hypothesis Lipoprotein(a) [Lp(a)] and renal dysfunction are both independent risk factors for cardiovascular disease. However, it remains unclear whether renal function mediates the association between Lp(a) and cardiovascular outcomes in patients undergoing percutaneous coronary intervention (PCI). Methods From a large prospective cohort study, 10 435 eligible patients undergoing PCI from January 2013 to December 2013 were included in our analysis. Patients were stratified into three renal function groups according to their baseline estimated glomerular filtration rate (eGFR) (<60; 60–90; ≥90 ml/min/1.73 m2). The primary endpoint was a composite of all-cause death, nonfatal MI, ischemic stroke, and unplanned revascularization [major adverse cardiac and cerebrovascular events (MACCE)]. Results Over a median follow-up of 5.1 years, a total of 2144 MACCE events occurred. After multivariable adjustment, either eGFR <60 ml/min/1.73 m2 or elevated Lp(a) conferred a significantly higher MACCE risk. Higher Lp(a) was significantly associated with an increased risk of MACCE in patients with eGFR <60 ml/min/1.73 m2. However, this association was weakened in subjects with only mild renal impairment and diminished in those with normal renal function. A significant interaction for MACCE between renal categories and Lp(a) was observed (P  = 0.026). Patients with concomitant Lp(a) ≥30 mg/dl and eGFR <60 ml/min/1.73 m2 experienced worse cardiovascular outcomes compared with those without. Conclusion The significant association between Lp(a) and cardiovascular outcomes was mediated by renal function in patients undergoing PCI. Lp(a)-associated risk was more pronounced in patients with worse renal function, suggesting close monitoring and aggressive management are needed in this population. [ABSTRACT FROM AUTHOR]

Background Tenofovir alafenamide fumarate (TAF) was promoted as a safer alternative to tenofovir disoproxil fumarate (TDF) for human immunodeficiency virus oral preexposure prophylaxis (PrEP). It is unknown if switching from TDF to TAF translates to improved renal function. We used electronic health record (EHR) data to assess changes in creatinine-estimated glomerular filtration rate (eGFR) after switching from TDF to TAF. Methods We conducted a retrospective cohort study using EHR data from Kaiser Permanente Southern California. We identified individuals who switched from TDF to TAF between October 2019 and May 2022 and used time-varying propensity score matching to identify controls who were on TDF ("nonswitchers"). We then used Bayesian longitudinal modeling to compare differences in eGFR between switching and nonswitching scenarios. Results Among 5246 eligible individuals, we included 118 TDF to TAF switchers and 114 nonswitchers. Compared to nonswitchers, switchers had older age of starting TDF but similar body weights at index date. A higher proportion of switchers were White, on Medicare or Medicaid, and had dyslipidemia at index date. Switching to TAF was associated with a higher eGFR compared to staying on TDF in 3–15 months post-switch, but the differences were not statistically significant (eg, month 9 difference: 1.27 [95% credible interval, −1.35 to 3.89]). While most of the estimated changes showed eGFR increase associated with switching, most were <2 eGFR units. Sensitivity analyses to address missingness or nonadherence showed similar results. Conclusions Switching from TDF to TAF for PrEP was associated with a nonsignificant increase in eGFR. Findings need to be confirmed using larger cohorts. [ABSTRACT FROM AUTHOR]

Background/Aims: The relationship between carotid artery plaque burden, phenotype and serum cystatin C at normal and impaired renal function is still unclear. Methods: Demographic characteristics, carotid ultrasonography and other relevant information of 1,477 patients were collected. The association of carotid artery plaque burden, plaque phenotype with serum cystatin C was evaluated by strategy analysis based on renal function. Results: Serum cystatin C (OR=2.05, 95% CI: 1.83-2.29, P<.01) was a risk factor of stable plaque among patients with normal glomerular filtration rate. However, in the patients with mild impaired renal function, serum cystatin C was not only a risk factor for stable plaque (OR=1.60, 95%CI: 1.43-1.78, P<.001) but also was a risk factor for unstable plaque (OR=1.21, 95%CI: 1.10-1.32, P<.001). The smoothing function curve and a three-piecewise linear regression revealed that a nonlinear relationship was observed between serum cystatin C and plaque burden. When serum cystatin C was in the range of 0.75-1.30 (mg/L), the plaque burden tended to increase. Conclusion: In normal renal function, serum cystatin C may confer stability of plaques. In mildly impaired renal function, serum cystatin C is a risk predictor of plaques. In normal renal function circumstances, serum cystatin C may benefit to the stability of plaques. In mild impaired renal function circumstances, serum cystatin C are a risk predictors of plaques. [ABSTRACT FROM AUTHOR]

Introduction: This systematic review aimed to summarize the existing evidence from published randomized controlled trials (RCTs) on the impact of sodium–glucose cotransporter (SGLT) inhibitors on albuminuria levels and renal function in patients with type 1 diabetes mellitus (T1D). Methods: The literature search was performed through Medline (via PubMed), Cochrane Library, and Scopus until November 11, 2023. Double-independent study selection, data extraction, and quality assessment were performed. Evidence was pooled with three-level mixed-effects meta-analysis. Results: In total, 5221 participants with T1D among 11 RCTs were analyzed. All RCTs had low risk of bias according to the Cochrane Collaboration tool (RoB 2). SGLT inhibitors were associated with a significantly greater reduction in urine albumin-to-creatinine ratio (UACR) compared to controls (MD = − 23.13%; 95% CI = [− 33.69, − 12.57]; P < 0.001; level of evidence high). On the basis of subgroup analysis, this effect was consistent across all available SGLT inhibitors, irrespective of the dosage. Finally, a neutral class effect was observed on the estimated glomerular filtration rate (eGFR, MD = − 1.03 mL/min/1.73 m2; 95% CI = [− 2.26, 0.19]; P = 0.1; level of evidence moderate). Only empagliflozin was associated with a significant reduction in eGFR compared to placebo (MD = − 2.23 mL/min/1.73 m2; 95% CI = [− 3.62, − 0.84]; P = 0.002). Conclusion: Our findings suggest that adjunctive therapy with SGLT inhibitors results in a significant reduction in albuminuria, while their use is associated with a neutral effect on creatinine clearance, as a measure of renal function. Future renal outcome trials are needed to assess SGLT inhibitors' role in the pharmacological armamentarium against diabetic nephropathy in T1D. [ABSTRACT FROM AUTHOR]

Background: Chronic kidney disease (CKD) refers to permanent damage to the kidneys that occurs gradually over time. Further progression may be preventable depending on its stage. Purpose: This study was developed to evaluate the effect of a health literacy education program (HLEP) on mental health and renal functioning in patients with CKD. Methods: A single-blind, randomized controlled trial study was conducted. Data were collected from March 25 to December 18, 2021. Participants were randomly assigned to either the experimental group (n = 42), which received multidisciplinary care and HLEP, or the control group (n = 42), which received multidisciplinary care only. Data were collected at baseline (T1), Month 3 (T2), and Month 6 (T3), and the data included patient characteristics, estimated glomerular filtration rate, and responses to the Mandarin Multidimensional Health Literacy Questionnaire and Beck Depression Inventory. Results: After 6 months of the HLEP intervention, the results of generalized estimating equations analysis showed that, compared with the control group, the experimental group had significantly higher health literacy at Month 3 (β = −3.37, 95% CI [−5.68, −1.06]), significantly improved depression at Month 3 (β = −2.24, 95% CI [−4.11, −0.37]) and Month 6 (β = −4.36, 95% CI [−6.60, −2.12]), and a significantly higher estimated glomerular filtration rate at Month 6 (β = 5.87, 95% CI [1.35, 10.38]). Conclusions/Implications for Practice: The findings of this study may provide a reference for healthcare providers to educate patients with Stage 3–4 CKD using the HLEP. Positive effects on health literacy, depression, and renal function in patients with Stage 3–4 CKD were observed in the short term. Findings from this study may facilitate the implementation of multidisciplinary and nurse-led strategies in primary care to reinforce patients' health literacy, self-care ability, and adjustment to CKD as well as delay disease progression. [ABSTRACT FROM AUTHOR]