Myelodysplastic Syndromes and Risk of Kidney Function Decline: Findings from a Nationwide Japanese Cohort Study

This study assessed the association of dietary patterns with the incidence of chronic kidney disease (CKD) and kidney function decline among Korean adults. Data were collected from the records of 20,147 men and 39,857 women who participated in the Health Examinees study. Principal component analysis was used to identify 3 dietary patterns (prudent, flour-based food and meat, and white rice-based), and CKD risk was defined using the Epidemiology Collaboration equation for estimated glomerular filtration rate: (eGFR) <60 mL/min/1.73 m2. A kidney function decline was defined as a >25% decrease in eGFR from baseline. During the 4.2-year follow-up, 978 participants developed CKD and 971 had a 25% decline in kidney function. After adjusting for potential impact variables, compared with the lowest quartile of the prudent dietary pattern, participants in the highest quartile had a 37% lower risk of kidney function decline among men (hazard ratio [HR], 0.63; 95% confidence interval [CI], 0.47 to 0.85); while higher adherence to the flour-based food and meat dietary pattern was associated with an increased risk of CKD in both men (HR, 1.63; 95% CI, 1.22 to 2.19) and women (HR, 1.47; 95% CI, 1.05 to 2.05) as well as a decline in kidney function in both men (HR, 1.49; 95% CI, 1.07 to 2.07) and women (HR, 1.77; 95% CI, 1.33 to 2.35). Although a higher adherence to the prudent dietary pattern was inversely associated with the risk of kidney function decline in men, there was no association with CKD risk. In addition, a higher adherence to the flour-based food and meat dietary pattern increased the risk of CKD and kidney function decline. Further clinical trials are needed to confirm these associations.

Introduction: There were limited data regarding the association between remnant cholesterol (RC), an emerging novel lipid marker, and chronic kidney disease (CKD). This study aimed to investigate the association of baseline and cumulative exposure of RC (cumRC) with kidney function decline (KFD) risk in the general population of China. Methods: Using data from the physical examination database in the Third Xiangya Hospital of Central South University (Changsha, China), 22,702 participants (age =18 years) without KFD, who underwent 3 consecutive annual health examinations between 2012 and 2015, were included. KFD was recorded during the interval between the third examination and the end of follow-up through 2020. Results: The cumRC was classified into 4 groups according to these cutoff values: 0.92, 1.33, and 1.99 (mmol/L). During a median follow-up of 3.17 years, 1,085 new KFD events were confirmed. Participants in the highest quartile of cumRC had 43% higher risk of KFD (hazard ratio, 1.43 [95% confidence interval, 1.16–1.77]), compared with the lowest quartile. Similarly, restricted cubic spline analysis showed a significant dose-response relationship between cumRC and the risk of KFD (P nonlinearity = 0.0314). However, baseline RC did not show any typical dose-dependent positive relationship with KFD development. In the discordance analysis, high baseline RC/low baseline low-density lipoprotein cholesterol (LDL-C) or high cumRC/low cumLDL-C were all associated with KFD in adjusted models. Conclusion: These data suggest a significant association between cumRC and risk of KFD independent of traditional CVD risk factors as well as the LDL-C level. Therefore, consistent RC monitoring should be given to individuals for early KFD prevention, especially in population with normal LDL-C levels who are often overlooked.

Background and Aims Dietary acid load is associated with low grade metabolic acidosis and might accelerate kidney function decline in patients with chronic kidney disease (CKD). We investigated whether dietary acid load, estimated as net endogenous acid production (NEAP), is associated with kidney function decline in kidney transplant recipients (KTR) and to what extent this association is mediated by variation in venous bicarbonate (HCO3-). Method We used data from 642 KTR with a functioning graft ≥1 year after transplantation who were enrolled in the Transplantlines Food &amp; Nutrition Cohort Study between 2008-2011. We applied the Frassetto equation (NEAP = (54.5 X protein (g/d) / potassium (mEq/d) - 10.2)) to calculate NEAPFFQ using intake reported in food frequency questionnaires and NEAPUrine from assessments of 24 hours urinary urea and potassium excretion. Patients were divided into tertiles of NEAP and differences across tertiles were analyzed by ANOVA, Kruskall-Wallis and Chi-Square tests, as appropriate. Cox regression models were used to study the associations between NEAPFFQ and NEAPUrine (both continuous variables and categories) with the composite endpoint kidney function decline, defined as doubling of serum creatinine or graft failure. Mediation analyses were performed to evaluate whether these associations were explained by venous bicarbonate. Results Mean age was 53±13 years, 56.1% were men, and mean eGFR was 52±20 ml/min/1.73m2. Patients within the highest tertile of NEAPFFQ were younger (P=0.04), more recently transplanted (P=0.002), consumed less fruit and vegetables (P&amp;lt;0.001), more fish (P=0.001), less alcohol (P=0.01), more meat (P&amp;lt;0.001) and had lower serum HCO3- concentration (P=0.02). During a median follow-up time of 5.3 (4.1-6.0) years, 121 (18.8%) patients developed kidney function decline. In multivariable Cox regression analysis, higher NEAPFFQ (per SD increase) was associated with increased risk of kidney function decline, independent of potential confounders, including age, sex, BMI, time after transplantation, primary kidney disease, eGFR and proteinuria (adjusted HR 1.30; 95%CI 1.10-1.53, P=0.002). Compared to patients in the lowest NEAPFFQ tertile, those in the highest tertile had a &amp;gt;1.5 higher risk of kidney function decline (adjusted HR 1.67; 95%CI 1.07-2.62, P=0.03). We observed similar results using NEAPUrine as the study exposure (adjusted HR 1.46 per SD increase; 95%CI 1.24-1.73, P&amp;lt;0.001; adjusted HR 1.99; 95%CI 1.24-3.18, P=0.004 for patients in the highest versus lowest tertile of NEAPUrine). These associations between NEAPFFQ (Figure A) and NEAPUrine (Figure B) with kidney function decline were visualized by fitting multivariable Cox regression models based on restricted cubic splines. Mediation analyses estimated that venous HCO3- at baseline mediated 19.3% (P=0.008) of the association between NEAPFFQ and kidney function decline and 26.5% (P=0.002) of the association between NEAPUrine with kidney function decline. Conclusion Higher NEAP is associated with a higher risk for kidney function decline in KTR, and this association was in part mediated by venous HCO3-. We speculate that reducing dietary acid load might mitigate the risk of kidney function decline in KTR.

Background the role of uric acid (UA) in chronic kidney disease (CKD) remains controversial. In this study, the effects of UA levels on risk of kidney function (KF) decline in patients with normal or mildly decreased KF at baseline were investigated. Methods Data were extracted from the community-based Tongzhou Cohort Study. The cohort of 4246 patients was divided into the normal KF group (estimated glomerular filtration rate [eGFR] ≥ 90 mL/min/1.73 m2) or mildly decreased KF group (60 ≤ eGFR &amp;lt; 90 mL/min/1.73 m2). The primary endpoint was the risk of kidney function decline, which defined as a composite of a ≥ 30% decrease in eGFR from baseline or new onset of CKD diagnosed during the annual checkups. Results A total of 284 participants reached the primary endpoint during the 5-year follow-up period. There was a significant interaction between UA levels and baseline eGFR (p &amp;lt; 0.001). Restricted cubic spline analysis revealed a U-shaped association between baseline UA levels and the risk of decreased KF for participants with normal KF (cut-off value = 5.0 mg/dL; pnonlinear = 0.025) and a linear association for participants with mildly decreased KF (pnonlinear = 0.384). The odds ratio of an increase in UA levels by 1 mg/dL was 1.15 [95% confidence interval (CI) 1.02–1.31, p = 0.028] for the primary endpoint and 1.15 (95% CI = 1.01–1.31, p = 0.037) for new onset of CKD for participants with mildly decreased KF. Conclusion The association between uric acid and risk of KF decline was U-shaped in participants with normal KF while linear in participants with mildly decreased KF.

BackgroundChronic kidney disease (CKD) has become a major issue worldwide and hyperglycemia is known as an important risk factor responsible for CKD progression. Few studies have investigated whether fasting plasma glucose (FPG) could predict kidney function decline (KFD) risk better than postprandial plasma glucose, and vice versa. In this study, we investigated the roles of FPG and 2-hour plasma glucose (2 h-PG) in predicting KFD risk in a Chinese community-based population without baseline deterioration of kidney functions.MethodsSubjects with normal kidney function from an atherosclerosis cohort in Beijing, China were followed up for 2.3 years. The outcome was KFD (a drop in glomerular filtration rate category accompanied by 25% or greater decline of estimated glomerular filtration rate from the baseline or a sustained decline of more than 5 mL/min/1.73 m2/year rate).ResultsA total of 3,738 subjects were included of which, 7.7% of the subjects suffered from KFD. After covariates adjustments, both FPG (OR =1.23, P<0.001) and 2 h-PG (OR =1.07, P<0.001) were associated with KFD. Furthermore, FPG was independent of 2 h-PG to predict KFD (OR =1.26, P<0.001). Subgroup analyses and interaction tests including diabetes mellitus, after adjusting all covariates, revealed no significant heterogeneity among analyzed subgroups. We also found subjects with FPG level of 6.1–7.0 mmol/L and >7.0 mmol/L had 1.83 times and 2.51 times KFD risk respectively, compared to subjects with FPG level <5.6 mmol/L.ConclusionFPG was superior to 2 h-PG in predicting KFD in a Chinese community-based population without CKD. FPG screening may be an important measure for CKD primary prevention even in subjects with impaired fasting glucose.

Serum Calcitriol Concentrations and Kidney Function Decline, Heart Failure, and Mortality in Elderly Community-Living Adults: The Health, Aging, and Body Composition Study

Blood Pressure Goals: How Low Is Safe in CKD?

Primary Versus Secondary Prevention of Chronic Kidney Disease: The Case of Dietary Protein

Background and Aims Hypokalemia is associated with progression of chronic kidney disease (CKD), although the possible underlying mechanisms are not well established. Several observational studies showed that low or even low to normal serum potassium levels predict the decline of kidney function in the general population. However, this hypothesis has not been yet investigated in patients with reduced nephron number as are congenital single kidney (cSK) patients. Our aim was to prospectively examine the association of plasma potassium with risk of rapid kidney function decline in a cSK patients’ cohort. Method A cohort of 67 consecutive patients with cSK (mean age = 44.4+/-15.7 years; males 29p (43.28%)), with a mean estimated glomerular filtration rate (eGFR) = 65.2+/-28 ml/min/1.73m2, were enrolled in this longitudinal observational study. We evaluated the associations of plasma potassium levels with longitudinal kidney function decline by estimated glomerular filtration rate (eGFR). The eGFR was assessed with CKD-EPI formula. The rapid kidney function decline was defined as a fall in eGFR of more than 5 ml/min/1.73 m2/year, according to the KDIGO guidelines. Results During a mean follow-up time of 20.16+/-9.3 months, 31.34% (21p) of patients presented decline of eGFR, with a fall of mean – 11.6+/-5.43 ml/min/1.73m2/year. In univariable regression analysis, the decline of eGFR was associated with baseline eGFR (R2=0.09, p=0.013), age (R2=0.31, p&amp;lt;0.001), male gender (R2=0.14, p=0.001), arterial hypertension (R2=0.17, p=0.001), diabetes mellitus (R2=0.13, p=0.003), coronary artery disease (R2=0.12, p=0.005), uric acid (R2=0.23, p&amp;lt;0.001), C-reactive protein (R2=0.09, p=0.011), proteinuria/24h (R2=0.14, p=0.002) and serum potassium (R2=0.29, p&amp;lt;0.001). The serum potassium levels were significantly lower in the group with rapid decline of eGFR, with a mean of 3.62+/-0.41 mmol/L vs. 4.51+/-0.74 mmol/L, p&amp;lt;0.001. In multivariable regression analysis, the association between lower serum potassium levels and risk of rapid eGFR decline remained significant (HR=1.65; 95%CI, 1.105-2.49; p=0.015). Conclusion These results suggest that lower serum potassium levels may play a role in rapid kidney function decline in the cSK population. Further research is required to assess whether the higher risk of kidney function decline in cSK individuals could be diminished when optimised serum potassium levels strictly.

Background and Aims Kidney stone disease (KSD) is a common urological condition that can progress to chronic kidney disease (CKD). However, not all individuals with KSD develop CKD, despite the presence of established risk factors. The sodium dicarboxylate cotransporter-1 (NaDC1), encoded by the SLC13A2 gene, is essential for regulating urinary citrate levels, intestinal oxalate absorption, and stone formation. We hypothesize that specific SLC13A2 genotypes are associated with a greater risk of kidney function decline in patients with KSD and may serve as genetic markers for identifying high-risk individuals. Therefore, the present study aimed to investigate the association between the rs11567842 variant of the SLC13A2 gene and kidney function in patients with calcium-oxalate KSD. Method This cross-sectional study included 80 patients with KSD admitted to the urology department in Kyiv, Ukraine. The determination of the rs11567842 variant of the SLC13A2 gene was performed using the PCR-RFLP method. Clinical and laboratory data were collected, and the estimated glomerular filtration rate (eGFR) was calculated using the CKD-EPI formula. Statistical analyses, including chi-square tests, Kruskal-Wallis tests, and logistic regression (univariate and multivariate), were performed to evaluate the association between SLC13A2 genotypes (AA, AG, GG) and kidney function decline (eGFR &amp;lt;60 mL/min/1.73 m²). Results The cohort comprised 50 males (62.5%) and 30 females (37.5%) with a mean age of 54.2 ± 16.2 years and a median disease duration of 12 (1–120) months. Among the patients, 39 (48.7%) had a history of recurrent KSD, 9 (11.3%) had diabetes, and 47 (58.7%) had arterial hypertension. The median eGFR level was 61 (49–72.5) mL/min/1.73 m², with 35 patients (43.7%) having an eGFR &amp;lt;60 mL/min/1.73 m². Genotype frequencies for the rs11567842 variant of the SLC13A2 gene were as follows: AA 45% (n = 36), AG 43.7% (n = 35), and GG 11.3% (n = 9). There were no significant differences in KSD duration (P = 0.15) and eGFR levels (P = 0.52) between genotypes. However, the G allele was associated with an increased risk of kidney function decline, with the GG genotype exhibiting the highest frequency of eGFR &amp;lt;60 mL/min/1.73 m² compared to the AA and AG genotypes (χ² = 10.2, P = 0.006). Univariate logistic regression showed that the GG genotype of the SLC13A2 gene was significantly associated with kidney function decline (OR = 12.2, 95% CI: 2.2–27.8, P = 0.002). This association was further confirmed by multivariate logistic regression adjusted for key confounders, including sex, age, diabetes, hypertension, KSD duration, and recurrence (OR = 8.7, 95% CI: 1.2–16.9, P = 0.02) (Fig. 1). Conclusion This study suggests that genetic variations in SLC13A2 may significantly impact the risk of kidney function decline in Ukrainian patients with KSD. The GG genotype of the rs11567842 variant of the SLC13A2 gene is strongly associated with a higher risk of kidney function decline, even after adjusting for clinical factors, while the AA genotype seems to offer a protective effect. However, larger-scale prospective studies are needed to confirm these preliminary findings.

Does Inflammation Fuel the Fire in CKD?

Kidney function and the risk of heart failure in patients with new-onset atrial fibrillation

The Association of Intravitreal Anti-VEGF Injections With Kidney Function in Diabetic Retinopathy

BackgroundPrevious studies have been limited by their inability to differentiate between the effects of insulin sensitivity and β-cell function on the risk of kidney function decline, cardiovascular disease (CVD), and all-cause mortality. To address this knowledge gap, we aimed to investigate whether the physiological subtypes based on homeostasis model assessment-2 (HOMA2) indices of β-cell function (HOMA2-B) and insulin sensitivity (HOMA2-S) could be used to identify individuals with subsequently high or low of clinical outcome risk.MethodsThis retrospective cohort study included 7,317 participants with a follow-up of up to 5 years. Based on HOMA2 indices, participants were categorized into four physiologic subtypes: the normal phenotype (high insulin sensitivity and high β-cell function), the insulinopenic phenotype (high insulin sensitivity and low β-cell function), the hyperinsulinaemic phenotype (low insulin sensitivity and high β-cell function), and the classical phenotype (low insulin sensitivity and low β-cell function). The outcomes included kidney function decline, CVD events (fatal and nonfatal), and all-cause mortality. Cox regression models were used to calculate hazard ratios (HRs) for outcomes, and spline models were used to examine the dose-dependent associations of HOMA2-B and HOMA2-S with outcomes.ResultsA total of 1,488 (20.3%) were classified as normal, 2,179 (29.8%) as insulinopenic, 2,173 (29.7%) as hyperinsulinemic, and 1,477 (20.2%) as classical subtypes. Compared with other physiological subtypes, the classical subtype presented the highest risk of kidney function decline (classical vs. normal HR 11.50, 95% CI 4.31–30.67). The hyperinsulinemic subtype had the highest risk of CVD and all-cause mortality (hyperinsulinemic vs. normal: fatal CVD, HR 6.56, 95% CI 3.09–13.92; all-cause mortality, HR 4.56, 95% CI 2.97–7.00). Spline analyses indicated the dose-dependent associations of HOMA2-B and HOMA2-S with outcomes.ConclusionsThe classical subtype had the strongest correlation with the risk of kidney function decline, and the hyperinsulinemic subtype had the highest risk of CVD and all-cause mortality, which should be considered for interventions with precision medicine.Graphical abstract

Canagliflozin reduced kidney disease progression in participants with type 2 diabetes in the CANagliflozin cardioVascular Assessment Study (CANVAS) Program. This analysis explored potential mediators of the effects of canagliflozin on kidney outcomes. The percent mediating effect of 18 biomarkers indicative of disease was determined by comparing the hazard ratios for the effect of randomized treatment from an unadjusted model and from a model adjusting for the average post-randomization level of each biomarker. Multivariable analyses assessed the joint effects of biomarkers that mediated most strongly in univariable analyses. The kidney outcome was defined as a composite of 40% estimated glomerular filtration rate decline, end-stage kidney disease, or death due to kidney disease. Nine biomarkers (systolic blood pressure [8.9% of effect explained], urinary albumin:creatinine ratio [UACR; 23.9%], gamma glutamyltransferase [4.1%], hematocrit [51.1%], hemoglobin [41.3%], serum albumin [19.5%], erythrocytes [56.7%], serum urate [35.4%], and urine pH [7.5%]) individually mediated the effect of canagliflozin on the kidney outcome. In a parsimonious multivariable model, erythrocyte concentration, serum urate, and systolic blood pressure maximized cumulative mediation (115%). Mediating effects of UACR, but not other mediators, were highly dependent upon the baseline level of UACR: UACR mediated 42% and 7% of the effect in those with baseline UACR 30 mg/g or more and under 30 mg/g, respectively. The identified mediators support existing hypothesized mechanisms for the prevention of kidney outcomes with sodium glucose co-transporter 2 inhibitors. Thus, the disparity in mediating effects across baseline UACR subgroups suggests that the mechanism for kidney protection with canagliflozin may vary across patient subgroups.