Chronic Kidney Disease Outcomes Research Articles

An Artificial Intelligence-Based Gout Management System Reduced Chronic Kidney Disease Incident and Improved Target Serum Urate Achievement

Abstract Objectives Stage ≥ 3 chronic kidney disease (CKD) affects ∼25% of people with gout. The effects of urate-lowering therapy (ULT) on CKD incidence and progression have remained inconclusive. Here, we assessed the impact of a gout urate-lowering therapy (ULT) clinic intervention using artificial intelligence (AI) on CKD incidence and achievement of serum urate target. Methods An observational study compared propensity score-matched gout cohorts from an AI-based Gout Intelligent Management System (GIMS) and a standard Electronic Medical Records system (EMRS) clinic database. The GIMS included a mobile application, data fusion interface, and modules for expert consultation and laboratory results management. All patients had gout and a starting eGFR > 60 ml/min. Using a 1:2 propensity score (PS)-matched cohort study design we assessed the impact of the AI-based system on CKD outcomes and ULT effectiveness over 4 years of follow-up. Results Compared with EMRS, GIMS was associated with reduced incidence of CKD stage ≥ 3. Specifically, 169/4117 new onset CKD stage ≥ 3 (incidence 4.1 per 100 person-years) with GIMS compared with 164/2128 with EMRS (incidence 7.7 per 100 person-years) during follow-up. More participants achieved serum urate <6.0 mg/dl with GIMS vs EMRS during follow-up (49.8% vs 25.9%, p < 0.001). Conclusion Application of the AI-based GIMS was associated with lower incidence of CKD stage ≥ 3 and superior target serum urate achievement in people with gout. The AI-based GIMS represents a novel approach to improve real-world renal outcomes and ULT success in gout.

Physical activity and renal outcome in diabetic and non-diabetic patients with chronic kidney disease stage G3b to G5

The association of physical activity with renal outcome and mortality in advanced chronic kidney disease (CKD; i.e., estimated glomerular filtration rate [eGFR] < 45 ml/min/1.73m2) is poorly studied. We examined this association in patients with advanced CKD in Japan. We used the Rapid Assessment of Physical Activity to assess baseline physical activity and classify patients as active or inactive. CKD progression was defined as 40% decline in eGFR, eGFR < 10, or requiring dialysis or transplantation. Among the 1,808 eligible patients, after adjusting for possible confounders, hazard ratios (HRs) for poor renal outcome in the active group were 0.68 (95% CI, 0.44–1.04), 1.09 (0.86–1.38), and 1.01 (0.82–1.25) in CKD stage G3b, G4, and G5, respectively, suggesting a renal benefit of exercise in CKD stage G3b. Adjusted HRs for death were 0.79 (0.40–1.57), 0.55 (0.38–0.80), and 0.75 (0.44–1.26) in stage G3b, G4, and G5, respectively. While the adjusted HRs of death were 0.84 (0.52–1.38) and 0.60 (0.43–0.83) in diabetic and non-diabetic patients, suggesting that exercise may reduce mortality in non-diabetic patients. Our study suggests that exercise is associated with better survival in non-diabetic patients with CKD stage G3b-5, and better renal outcome in diabetic and non-diabetic CKD stage G3b.

Effects of ertugliflozin on uric acid and gout-related outcomes in persons with type 2 diabetes and cardiovascular disease: Post hoc analyses from VERTIS CV.

To conduct post hoc analyses of the VERTIS CV (NCT01986881) trial to explore the effects of ertugliflozin on serum uric acid (UA) and gout-related outcomes. Participants with type 2 diabetes and atherosclerotic cardiovascular disease were randomised (1:1:1) to placebo, ertugliflozin 5 mg or ertugliflozin 15 mg. Mean UA over time (260 weeks) was evaluated for pooled ertugliflozin versus placebo overall, and by baseline quintile of UA (≤4.3 mg/dL [≤255.8 µmol/L], >4.3-5.1 mg/dL [>255.8-303.4 µmol/L], >5.1-5.8 mg/dL [>303.4-345.0 µmol/L], >5.8-6.9 mg/dL [>345.0-410.4 µmol/L] and >6.9 mg/dL [>410.4 µmol/L]), glycated haemoglobin level, albuminuria status, estimated glomerular filtration rate and KDIGO (Kidney Disease: Improving Global Outcomes in Chronic Kidney Disease) risk category. The effect of ertugliflozin on a composite of gout onset or initiation of anti-gout medication was assessed. The mean UA levels at baseline were 5.67 and 5.62 mg/dL in the placebo and ertugliflozin groups, respectively. Ertugliflozin reduced UA over Weeks 6-260 compared with placebo, with least squares mean (LSM) changes (95% confidence interval [CI]) from baseline at Week 260 of 0.07 mg/dL (-0.02, 0.15) and -0.19 mg/dL (-0.25, -0.13) in the placebo and pooled ertugliflozin groups, respectively. At Week 260, placebo-adjusted LSM change (95% CI) from baseline in UA was -0.26 mg/dL (-0.36, -0.16) with ertugliflozin. Ertugliflozin was associated with reductions in UA across baseline UA quintiles compared with placebo. The incidence of the composite of gout-related outcomes was 84/2539 (3.3%) for placebo and 133/5091 (2.6%) for ertugliflozin (hazard ratio for the composite 0.76 [95% CI 0.580, 1.002]). Ertugliflozin was generally associated with lowering UA overall and across subgroups compared with placebo, and numerically reduced rates of gout-related outcome events.

Dual inhibition of SGLT 1 and 2 alleviates intracellular sodium overload in uraemic cardiomyopathy

Abstract Background Chronic kidney disease (CKD) is a leading cause of mortality with the risk of developing cardiovascular disease higher than progression to kidney failure. The aetiology of uraemic cardiomyopathy is multifactorial and includes metabolic derangement. It was previously shown that elevated intracellular sodium (Nai) is causally linked to cardiac metabolic impairment and that targeting sodium homeostasis can reprogramme cardiac metabolism. Dual inhibition of sodium-glucose co-transporters (SGLT) 1 and 2 is an emerging therapy for CKD, however the impact on intracellular sodium and cardiac metabolism is yet to be elucidated. Purpose This study aimed to assess whether dual SGLT1/2 inhibitor sotagliflozin impacts cardiometabolic phenotype in CKD. Methods CKD was surgically induced by 5/6 nephrectomy in Wistar rats (n=46) for a period of 4 weeks, with chronic sotagliflozin treatment (5mg/kg) given for the last 3 weeks. Upon termination, hearts were Langendorff-perfused and studied using 31P and 23Na NMR spectroscopy (Sham n=7, CKD n=6, CKD+sotagliflozin n=5). To assess the cardiac-specific effect of the drug, acute sotagliflozin treatment (30mM) was delivered in the Langendorff perfusate to an additional group of CKD hearts (n=5). Furthermore, the effect of chronic sotagliflozin treatment on in vivo cardiac function (echocardiography n=23) and metabolic profile (1H NMR spectroscopy n=15) was assessed. Results CKD animals were characterized by significant renal dysfunction (2-fold increase in urea and creatinine vs sham, p&amp;lt;0.05), and HFpEF (EF(%) sham 82±2 vs CKD 80±1 p&amp;gt;0.05; diastolic dysfunction (E/A) sham 1.39±0.03 vs CKD 1.11±0.01, p=0.0018). Myocardial Nai was significantly elevated in CKD animals compared to sham controls (TQF 23Na 3.04±0.18 vs 2.01±0.32 arb units, p=0.03). Chronic sotagliflozin treatment didn’t impact renal or cardiac dysfunction. Neither chronic nor acute drug treatment impacted baseline CKD cardiac energetics (PCr/ATP sham 1.53±0.22, CKD 1.25±0.13, chronic 1.16±0.14, acute 1.18±0.13, p&amp;gt;0.05; ΔGATP (kJ/mol) sham -64±4, CKD -66±8, chronic -56±1, acute -59±3, p&amp;gt;0.05). However, both chronic and acute sotagliflozin treatment normalised the increased myocardial Nai (TQF 23Na chronic 2.17±0.12, acute 2.23±0.14 arb units, p&amp;gt;0.05 vs sham). Chronic drug dosing altered the systemic metabolic profile of CKD animals reducing the levels of circulating triglycerides and FFA (p&amp;lt;0.05) as well as altering metabolomic profile of liver, muscle and kidneys. Conclusion(s) We have shown that uraemic cardiomyopathy is characterised by HFpEF, elevated myocardial Nai and altered systemic metabolic profile. Both chronic and acute treatment with dual SGLT1/2 inhibitor sotagliflozin normalised myocardial Nai. The alleviation of Nai load could lead to improved cardiometabolic outcomes in CKD.

Meat Your Veggies:: Could Plant-Based Meat Alternatives Help Improve Outcomes in Chronic Kidney Disease and Urinary Stone Disease?

Meat Your Veggies:: Could Plant-Based Meat Alternatives Help Improve Outcomes in Chronic Kidney Disease and Urinary Stone Disease?

Prevalence and Outcomes of Chronic Kidney Disease Associated Pruritus: International Results from PDOPPS.

Pruritus is common in hemodialysis (HD) patients. Less is known about the prevalence and outcomes of pruritus among patients receiving peritoneal dialysis (PD). Herein, we describe the prevalence of pruritus and its associations with patient-reported outcomes (PROs) and mortality/transfer to HD. We analyzed a multicenter, international cohort of PD patients enrolled in the Peritoneal Dialysis Outcomes and Practice Patterns Study (PDOPPS) from 2014-2022. Pruritus was assessed at entry into PDOPPS with a single-question Likert Scale capturing the extent to which patients were bothered by itch ranging from 1: Not at all, to 5: Extremely. The KDQOL-36 and the Centre for Epidemiological Studies Depression Scale assessed various PROs. Moderate to extreme pruritus was defined as a Likert scale score ≥3. The associations of pruritus with PROs were assessed using linear/logistic regression where appropriate. Death or HD transfer was assessed using multivariable Cox regression models. Overall, 5535 patients from seven countries were included; 43% had moderate to extreme pruritus which was highest in Thailand (50%) and lowest in the United States (33%). The adjusted odds ratios (aOR) of moderate to extreme pruritus were higher for diabetes, low albumin, and elevated phosphorus but lower for residual urine volume (aOR= 0.98 per 200 ml increase in 24-hour urine volume, 95% confidence interval [CI]; 0.96-1.00, P=0.05). Patients with extreme pruritus had the lowest mental and physical health component scores and a higher burden of other PROs including restless legs and disturbed sleep. Overall, 899 patients died and 1221 transferred to HD. Patients with moderate to extreme pruritus were at higher adjusted risk for death or HD transfer (adjusted hazard ratio [aHR] 1.12, 95% CI 1.02-1.23, P=0.02) with similar point estimates for each subcomponent of the composite outcome. Pruritus is highly prevalent in PD and associated with poor health outcomes. Efforts to better identify and manage pruritus should be considered in this population.

Exploring Adiposity and Chronic Kidney Disease: Clinical Implications, Management Strategies, Prognostic Considerations.

Obesity poses a significant and growing risk factor for chronic kidney disease (CKD), requiring comprehensive evaluation and management strategies. This review explores the intricate relationship between obesity and CKD, emphasizing the diverse phenotypes of obesity, including sarcopenic obesity and metabolically healthy versus unhealthy obesity, and their differential impact on kidney function. We discuss the epidemiological evidence linking elevated body mass index (BMI) with CKD risk while also addressing the paradoxical survival benefits observed in obese CKD patients. Various measures of obesity, such as BMI, waist circumference, and visceral fat assessment, are evaluated in the context of CKD progression and outcomes. Mechanistic insights into how obesity promotes renal dysfunction through lipid metabolism, inflammation, and altered renal hemodynamics are elucidated, underscoring the role of adipokines and the renin-angiotensin-aldosterone system. Furthermore, the review examines current strategies for assessing kidney function in obese individuals, including the strengths and limitations of filtration markers and predictive equations. The management of obesity and associated comorbidities like arterial hypertension, type 2 diabetes mellitus, and non-alcoholic fatty liver disease in CKD patients is discussed. Finally, gaps in the current literature and future research directions aimed at optimizing the management of obesity-related CKD are highlighted, emphasizing the need for personalized therapeutic approaches to mitigate the growing burden of this intertwined epidemic.

Causality of visceral adipose tissue on chronic kidney disease and renal function measure indicators, and mediation role of hypertension: Mendelian randomization study.

Although chronic kidney disease (CKD) is associated with obesity, few studies have used visceral adipose tissue (VAT) as an indicator to investigate its causal effect on CKD. Therefore, Mendelian randomization (MR) was employed to study the causal effects of VAT on CKD and its potential mediation by hypertension. Genome-wide association study (GWAS) statistics on VAT exposure were obtained from the UK Biobank, while GWAS datasets of CKD outcomes were obtained from CKDGen and FinnGen (validation study). Furthermore, VAT was considered the exposure, with the estimated glomerular filtration rate based on creatinine (eGFR (crea)), estimated glomerular filtration rate based on cystatin C (eGFR(cys)), and blood urea nitrogen (BUN) employed to assess the causal effect of VAT on kidney test indicators. Lastly, a two-step MR method was used to study the mediating role of hypertension in the pathogenesis of VAT among patients with CKD. VAT exhibited a positive causal association with CKD, irrespective of whether the GWAS datasets from CKDGen (odds ratio [OR] = 1.18, 95% CI: 1.08 to 1.29, P = 1.433140e-04) or FinnGen (1.47, 1.30 to 1.67, p = 2.500000e-09). VAT was not causally associated with eGFR (crea) (1.00, 0.99 to 1.00, p = 0.53), was negatively associated with eGFR (cys) (0.95, 0.93 to 0.97, P = 5.070000e-10), and was positively associated with BUN (1.02,1.01 to 1.02, P = 7.824860e-04). The mediating effect of VAT on CKD via hypertension was 45.8% (95% CI: 26.4 65.1). VAT has a positive causal effect on CKD, with hypertension playing a significant role. However, the effects of VAT on renal function indicators require further investigation.

Patient and Caregiver Perspectives on Gender Disparity in CKD: An Interview Study.

Chronic kidney disease (CKD) affects more women than men worldwide, however, men comprise the majority of patients who receive kidney replacement therapy. We aimed to describe the perspectives of patients and their caregivers regarding gender disparities in CKD. Semi-structured interviews were conducted with 45 patients with CKD (20 women) and 14 caregivers (12 women) from seven clinics in Austria. The interviews were analyzed thematically. Five themes were identified in this study. Participants perceived that women were "disadvantaged and vulnerable" (silent and intimidated, single mother predicament, impeded access to care and support due to socioeconomic disadvantage, had to fend for themselves); "fulfilling gender roles and norms" (primarily responsible for childcare, pressure to perform well as homemakers, put others' needs before their own, encouraging husband's treatment adherence), and "protecting their own health" (self-disciplined, vigilant, confronted health challenges, advocated for their needs). Men were seen to "place the onus of care on others" (expected help from family, relied on others for decisions). Both men and women experienced a "disease-related identity crisis and distress" (women: impaired body image, mental distress; men: denial and self-destruction, emasculated by sickness). Women with CKD felt vulnerable and were inclined to fulfill gender norms and responsibilities as caregivers but were also vigilant about protecting their own health. Men tended to be reluctant to accept CKD and appeared to depend on others for disease management. Better awareness and addressing these concerns can inform strategies to minimize gender disparities in access to care and outcomes in CKD.

Physical Activity Elements and Adverse Outcomes in Patients with Chronic Kidney Disease in Guangdong (PEAKING) project: protocol for a prospective cohort study

IntroductionPhysical inactivity is prevalent and associated with adverse outcomes among patients with chronic kidney disease (CKD). Most previous studies have relied on subjective questionnaires to assess levels of physical activity...

Low-dose spironolactone and cardiovascular outcomes in moderate stage chronic kidney disease: a randomized controlled trial.

Chronic kidney disease (CKD) is associated with a substantial risk of progression to end-stage renal disease and vascular events. The nonsteroidal mineralocorticoid receptor antagonist (MRA), finerenone, offers cardiorenal protection for people with CKD and diabetes, but there is uncertainty if the steroidal MRA, spironolactone, provides the same protection. In this prospective, randomized, open, blinded endpoint trial, we assessed the effectiveness of 25 mg spironolactone in addition to usual care or usual care alone for reducing cardiovascular outcomes in stage 3b CKD among an older community cohort (mean age = 74.8 years and s.d. = 8.1). We recruited 1,434 adults from English primary care, of whom 1,372 (96%) were included in the primary analysis. The primary outcome was time from randomization until the first occurrence of death, hospitalization for heart disease, stroke, heart failure, transient ischemic attack or peripheral arterial disease, or first onset of any condition listed not present at baseline. Across 3 years of follow-up, the primary endpoint occurred in 113 of 677 participants randomized to spironolactone (16.7%) and 111 of 695 participants randomized to usual care (16.0%) with no significant difference between groups (hazard ratio = 1.05, 95% confidence interval: 0.81-1.37). Two-thirds of participants randomized to spironolactone stopped treatment within 6 months, predominantly because they met prespecified safety stop criteria. The most common reason for stopping spironolactone was a decrease in the estimated glomerular filtration rate that met prespecified stop criteria (n = 239, 35.4%), followed by participants being withdrawn due to treatment side effects (n = 128, 18.9%) and hyperkalemia (n = 54, 8.0%). In conclusion, we found that spironolactone was frequently discontinued due to safety concerns, with no evidence that it reduced cardiovascular outcomes in people with stage 3b CKD. Spironolactone should not be used for people with stage 3b CKD without another explicit treatment indication. ClinicalTrials.gov registration: ISRCTN44522369 .

The Relationship between Vascular Biomarkers (Serum Endocan and Endothelin-1), NT-proBNP, and Renal Function in Chronic Kidney Disease, IgA Nephropathy: A Cross-Sectional Study

IgA nephropathy (IgAN) is the most common primary glomerular disease. Endothelin-1 (ET-1) is one of the strongest vasoconstrictor materials in the blood. The N-terminal prohormone of brain natriuretic peptide (NT-proBNP) is associated with renal function and poor outcomes in chronic kidney disease (CKD). Serum endocan is a biomarker associated with proinflammatory cytokines, and the increase in the serum level plays a critical role in inflammatory, proliferative, and neovascularization processes and is associated with poor cardiovascular outcomes in patients with CKD too. Identifying high-risk patients using biomarkers could help to optimize their treatment. Ninety patients with biopsy-confirmed IgAN were included in the study (50 males/40 females, mean age: 54.9 ± 14.4 years). Serum endocan, ET-1, and NT-proBNP were measured by enzyme-linked immunosorbent assay kits. Echocardiography was performed, and carotid-femoral pulse wave velocity (cfPWV) was measured by SphygmoCor in this cross-sectional study. Patients were divided into two groups based on serum endocan median level (cut-off: 44 ug/L). There was significantly higher aorta systolic blood pressure (SBPao) (p = 0.013), NT-proBNP (p = 0.028), albumin/creatinine ratio (p = 0.036), and uric acid (p = 0.045) in the case of the higher endocan group compared to the lower. There was also significantly higher SBPao (p = 0.037) and NT-proBNP (p = 0.038) in the case of higher endothelin-1 (ET-1) levels compared to the lower (cut-off: 231 pg/mL) group by the two-sample t-test. Then, we divided the patients into two groups based on the eGFR (CKD 1–2 vs. CKD 3–5). The levels of serum endocan, NT-proBNP, cfPWV, SBPao, left ventricular mass index (LVMI), uric acid, and albuminuria were significantly higher in the CKD 3–5 group compared to the CKD 1–2 group. The serum endocan and NT-proBNP levels were significantly higher in the diastolic dysfunction group (p = 0.047, p = 0.015). There was a significant increase in serum endocan levels (CKD 1 vs. CKD 5; p = 0.008) with decreasing renal function. In IgAN, vascular biomarkers (endocan, ET-1) may play a role in endothelial dysfunction through vascular damage and elevation of SBPao. Serum endocan, ET-1, and NT-proBNP biomarkers may help to identify IgAN patients at high risk.

Influence of Kidney Diseases on Lipid Profile in Patients Undergoing Conservative Managements and Hemodialysis

Kidney function gradually declines as a result of chronic kidney disease (CKD). The current study was conducted at Princess Iman Hospital in Muadi, Jordan from December to March 2024. It aimed to investigate the association between lipids and chronic renal failure (CRF), which refers to the advanced stages of CKD where kidney function has declined significantly, and to understand how dyslipidemia affects the development of CKD and general health outcomes. The study involved three groups of participants: patients with CRF who were on hemodialysis, those receiving conservative management for CRF, and healthy individuals as controls. According to the findings, CRF patients (hemodialysis and conservative management) had significantly higher lipid levels than the control group besides showing low indicators for kidney function (p&lt;0.001). In addition, triglyceride, cholesterol, low-density lipoprotein (LDL) levels, Cholesterol/high-density lipoprotein (HDL) ratio, and LDL/HDL ratio were also found to be significantly high in the hemodialysis group when compared to the conservative group (p&lt;0.001). In this population with CRFs, it was observed that lipid levels correlated positively with markers for kidney disease progression. Therefore, monitoring of lipids should be done regularly across all stages of CKDs to reduce cardiovascular complications associated with atherosclerosis. Hence, incorporating lipid evaluations into standard CKD care regimens, even during the initial phases, is vital for enhancing patient outcomes and lowering mortality risks. In essence, the results highlight the importance of proactive management of lipid levels in CKD individuals to tackle cardiovascular complications effectively. By understanding dyslipidemia's impact on CKD advancement, healthcare practitioners can customize interventions to enhance patient care and diminish related risks, ultimately improving prognosis and decreasing mortality rates among CKD cohorts.

Geniposidic Acid Attenuates Chronic Tubulointerstitial Nephropathy Through Regulation of the NF-ƙB/Nrf2 Pathway Via Aryl Hydrocarbon Receptor Signaling.

Renal fibrosis is an outcome of chronic kidney disease, independent of the underlying etiology. Renal fibrosis is caused primarily by oxidative stress and inflammation. We identified the components of Plantaginis semen and elucidated their anti-fibrotic and anti-inflammatory mechanisms. The renoprotective components and underlying molecular mechanisms of P. semen were investigated in rats with adenine-induced chronic tubulointerstitial nephropathy (TIN) and in idole-3-acetic acid (IAA)-stimulated NRK-52E cells. Acetate and n-butanol extracts were found to be the bioactive fractions of P. semen. A total of 65 compounds including geniposidic acid (GPA), apigenin (APG), and acteoside (ATS) were isolated and identified. Among the seven main extract components, treatment with GPA, APG, and ATS reduced the serum levels of creatinine and urea in TIN rats. Mechanistically, GPA ameliorated renal fibrosis through repressing aryl hydrocarbon receptor (AHR) signaling and regulating redox signaling including inhibiting proinflammatory nuclear factor kappa B (NF-ƙB) and its target gene products as well as activated antioxidative nuclear factor-erythroid-2-related factor 2 (Nrf2) and its downstream target gene products in both TIN rats and IAA-stimulated NRK-52E cells. The inhibitory effect of GPA on AHR, NF-Ƙb, and Nrf2 signaling were partially abolished in IAA-stimulated NRK-52E cells treated with CH223191 compared with untreated IAA-stimulated NRK-52E cells. These data demonstrated that GPA alleviates oxidative stress and inflammation partly by suppressing AHR signaling.

Associations between obstructive sleep apnea and sleep characteristics with chronic kidney disease in rural Pennsylvania

Study objectivesTo examine the association between moderate-severe obstructive sleep apnea (msOSA) and sleep characteristics with chronic kidney disease (CKD) in a population of rural and urban adults in Pennsylvania. MethodsA cross-sectional study of 23,643 adults who underwent polysomnography (PSG) at a rural healthcare system in Pennsylvania between 2009 and 2019. Serum creatinine was abstracted from electronic health records to calculate estimated glomerular filtration rate (eGFR). CKD was defined as an eGFR <60 mL/min/1.73 m2. msOSA was defined as an apnea-hypoxia index (AHI) ≥15 events/hour. Poisson regression was performed to estimate the prevalence ratio (PR) of CKD for various sleep measures while adjusting for age, sex, race, smoking (never, former, current), body mass index, diabetes, and hypertension at time of PSG. ResultsIn this clinically-referred sample comprised of over one-third (35 %) rural individuals, the prevalence of CKD and msOSA was 9.4 % and 32.1 %, respectively. Patients with CKD had more severe OSA based on AHI and intermittent hypoxia profile and presented worse sleep quality across all studied measures. Having OSA was associated with a 13 % higher prevalence of CKD (95%CI: 1.04, 1.22). In addition, for every 5 % increment in sleep efficiency, the prevalence of CKD was 3 % lower (PR = 0.97, 95%CI: 0.96, 0.98). Significant associations that were in the expected direction were observed across most sleep characteristics in adjusted models. ConclusionsModerate-severe OSA, nocturnal hypoxemia, and disruptions to normal sleep duration, continuity, and architecture are associated with increased CKD prevalence in Pennsylvania adults. Management of OSA and/or sleep disturbances may be an opportunity to improve CKD outcomes. The unique health disparities among vulnerable rural populations are deserving of future study.

Vitamin D status and intermediate vascular and bone outcomes in chronic kidney disease: a secondary post hoc analysis of IMPROVE-CKD.

Cardiovascular disease is the leading cause of death in patients with chronic kidney disease (CKD) and has been associated with abnormalities of mineral metabolism and vascular calcification. Vitamin D influences parathyroid hormone values and calcium and phosphate metabolism, and may play a role in vascular function and bone health. We aimed to test our hypothesis that vitamin D deficiency is associated with arterial stiffness, aortic calcification and lower bone mineral density (BMD) in patients with CKD. A cross-sectional analysis was performed using baseline data from the IMpact of Phosphate Reduction On Vascular Endpoints in CKD (IMPROVE-CKD) study cohort. Clinical and laboratory parameters were compared between those with and without vitamin D deficiency, defined as 25-hydroxyvitamin D (25(OH)D) <50 nmol/L. Univariable and multivariable linear regression analyses were performed to assess associations between serum 25(OH)D levels and pulse wave velocity (PWV), augmentation index (AIx), abdominal aortic calcification (measured by the Agatston score) and lumbar spine BMD. Baseline 25(OHD) values were available in 208 out of 278 IMPROVE-CKD study participants, with a mean value of 70.1 ± 30.7 nmol/L. Of these, 57 (27%) patients had vitamin D deficiency. Those with 25(OH)D deficiency were more likely to have diabetes (56% vs 38%), cardiovascular disease (54% vs 36%) and lower serum calcium (2.29 ± 0.13 vs 2.34 ± 0.13 mmol/L). On univariable and multivariable regression analyses, baseline 25(OH)D values were not associated with PWV, the AIx, Agatston score or BMD. Baseline 25(OH)D levels were not associated with intermediate markers of vascular function and BMD in patients with CKD stages 3b and 4.

Appropriateness of Ketoanalogues of Amino Acids, Calcium Citrate, and Inulin Supplementation for CKD Management: A RAND/UCLA Consensus.

Current treatment for chronic kidney disease (CKD) focuses on improving manifestations and delaying progression. Nutritional approaches play a crucial role in CKD management, and various supplements have become available. Ketoanalogues of amino acids (KAs), calcium citrate, and inulin have been proposed as suitable supplements, yet their widespread use has been limited due to insufficient evidence. This study aimed to generate general guidance statements on the appropriateness of these supplements through a RAND/UCLA consensus process. A RAND/UCLA consensus panel was convened to evaluate the appropriateness of these supplements in different clinical scenarios. In this study, we present a subgroup analysis focusing on a panel of eleven clinical nephrologists from among the experts. Supplementation of low-protein diets (LPDs) and very low-protein diets (VLPDs) with KA was considered appropriate to reduce manifestations and delay CKD outcomes, supplementation with calcium citrate is considered appropriate to reduce CKD manifestations, and supplementation with inulin is considered appropriate to delay CKD outcomes and manage comorbidities. Based on a combination of clinical experience and scientific evidence, the panel reached a consensus that KA supplementation of LPD and VLPD, calcium citrate, and inulin are appropriate in patients with CKD across various scenarios.

Obesity is associated with incident chronic kidney disease in individuals with normal renal function.

Obesity has known to be a modifiable risk factor associated with worse outcomes in chronic kidney disease (CKD), but few studies have examined the impact of obesity on CKD incidence in the general population. The purpose of this study was to investigate the role of body mass index (BMI) and waist-to-hip ratio (WHR) as predictors of incident CKD and to evaluate the impact of weight reduction on CKD prevention. A total of 2,711 participants from a community-based cohort with normal renal function were prospectively analyzed. Among participants with obesity, we analyzed the change in WHR to evaluate the association of obesity reduction with CKD development. During a mean follow-up of 11.03 ± 4.22 years, incident CKD occurred in 190 (7.0%) participants. In the fully adjusted multivariable Cox proportional hazard models, the risk of incident CKD increased with higher BMI (hazard ratio, 1.06; 95% confidence interval, 1.00-1.11; p = 0.033) and higher WHR (hazard ratio, 1.33; 95% confidence interval, 1.07-1.66; p = 0.009). In the Kaplan-Meier analysis, cumulative adverse renal events were significantly more common in the maintained obesity group than in the reduced obesity group (p = 0.001). Both higher BMI and WHR were associated with development of CKD, but the magnitude of the effect of WHR was higher than that of BMI. Moreover, reducing obesity would be beneficial for renal prognosis.

Effects of Semaglutide on Heart Failure Outcomes in Diabetes and Chronic Kidney Disease in the FLOW Trial

BackgroundPeople with type 2 diabetes (T2D) and chronic kidney disease (CKD) are at high risk for heart failure (HF) and premature death from cardiovascular (CV) causes. The FLOW (Research Study To See How Semaglutide Works Compared to Placebo in People With Type 2 Diabetes and Chronic Kidney Disease), which enrolled participants with T2D and CKD, demonstrated that semaglutide, a glucagon-like peptide-1 receptor agonist, reduced the incidence of the primary composite outcome (persistent ≥50% decline in estimated glomerular filtration rate, persistent estimated glomerular filtration rate <15 mL/min/1.73 m2, kidney replacement therapy, and kidney or CV death) by 24%. ObjectivesThis prespecified analysis examined the effects of semaglutide on HF outcomes in this high-risk population. MethodsParticipants were randomized (1:1) to once-weekly subcutaneous semaglutide 1 mg or placebo. The prespecified main outcome was a composite of HF events (new onset or worsening of HF leading to an unscheduled hospital admission or an urgent visit, with initiation of or intensified diuretic/vasoactive therapy) or CV death. HF data were collected by the investigator. CV death was adjudicated by an independent committee. ResultsA total of 3,533 randomized participants were followed for a median of 3.4 years. HF was present at baseline in 342 participants (19.4%) in the semaglutide group and 336 (19.0%) in the placebo group. In the overall trial population, semaglutide increased time to first HF events or CV death (HR: 0.73; 95% CI: 0.62-0.87; P = 0.0005), HF events alone (HR: 0.73; 95% CI: 0.58-0.92; P = 0.0068), and CV death alone (HR: 0.71; 95% CI: 0.56-0.89; P = 0.0036). The risk reduction for the composite HF outcome was similar in those with (HR: 0.73; 95% CI: 0.54-0.98; P = 0.0338) and without (HR: 0.72; 95% CI: 0.58-0.89; P = 0.0028) HF at baseline. The risk of HF outcomes (HF events or CV death) was generally higher in participants categorized as NYHA functional class III and those with the HF reduced ejection fraction subtype, regardless of treatment. ConclusionsSemaglutide substantially reduced the risk of time to first composite outcome of HF events or CV death, as well as HF events and CV death alone, in a high-risk population with T2D and CKD. These effects were consistent regardless of history of HF. (A Research Study To See How Semaglutide Works Compared to Placebo in People With Type 2 Diabetes and Chronic Kidney Disease [FLOW]; NCT03819153)

Risk Factors and Outcomes Associated With the Development of Persistent Acute Kidney Injury in Non-Renal Solid Organ Transplant Recipients: Systematic Review and Meta-Analysis.

Persistent acute kidney injury (pAKI), compared with acute kidney injury (AKI) that resolves in <72h, is associated with worse prognosis in critically ill patients. Definitions and prognosis of pAKI are not well characterized in solid organ transplant patients. Our aims were to investigate (a) definitions and incidence of pAKI; (b) association with clinical outcomes; and (c) risk factors for pAKI among heart, lung, and liver transplant recipients. We systematically reviewed the literature including PubMed, Embase, Web of Science, and Cochrane from inception to 8/1/2023 for human prospective and retrospective studies reporting on the development of pAKI in heart, lung, or liver transplant recipients. We assessed heterogeneity using Cochran's Q and I2. We identified 25 studies including 6330 patients. AKI (8%-71.6%) and pAKI (2.7%-55.1%) varied widely. Definitions of pAKI included 48-72h (six studies), 7days (three studies), 14days (four studies), or more (12 studies). Risk factors included age, body mass index (BMI), diabetes, preoperative chronic kidney disease (CKD), intraoperative vasopressor use, and intraoperative circulatory support. pAKI was associated with new onset of CKD (odds ratio [OR] 1.41-11.2), graft dysfunction (OR 1.81-8.51), and long-term mortality (OR 3.01-13.96), although significant heterogeneity limited certainty of CKD and graft dysfunction outcome analyses. pAKI is common and is associated with worse mortality among liver and lung transplant recipients. Standardization of the nomenclature of AKI will be important in future studies (PROSPERO CRD42022371952).