CKD Progression Research Articles

Effect of osteosarcopenia on longitudinal mortality risk and chronic kidney disease progression in older adults

IntroductionChronic kidney disease (CKD) causes a progressive loss of muscle and bone mass, which frequently overlap with and affect clinical outcomes. However, the impact of sarcopenia, low bone mineral density (BMD; osteopenia or osteoporosis), and osteosarcopenia (sarcopenia and low BMD) on CKD progression is yet to be determined. We aimed to address these issues in patients with CKD without kidney replacement therapy (KRT). MethodsThis prospective cohort study included 251 outpatients aged ≥65 years with CKD without KRT enrolled in our hospital between June 2016 and March 2017. Sarcopenia was defined according to the 2014 criteria of the Asian Working Group for Sarcopenia (AWGS), and low BMD was defined as a T-score of ≤−1.0. The patients were divided into four groups: normal (no sarcopenia/normal BMD), only low BMD (no sarcopenia/low BMD), only sarcopenia (sarcopenia/normal BMD), and osteosarcopenia (sarcopenia/low BMD). The primary outcome was a composite of all-cause deaths, initiating KRT, and admissions owing to major adverse cardiovascular and cerebrovascular events (MACEs). The secondary outcome was a kidney composite outcome that included a 30 % reduction in creatinine-based estimated glomerular filtration rate (eGFR) and initiating KRT. The outcome risk was determined using the Cox regression models adjusted for potential confounders. ResultsMedian age (25th–75th percentile) and eGFR of the outpatients (35 % women) were 76 (69–81) years and 32.1 (20.8–41.7) ml/min/1.73 m2, respectively. During a median follow-up period of 5.2 years, there were 22 deaths, 117 30 % eGFR reductions, 48 KRTs, and 18 admissions owing to MACEs. The osteosarcopenia group rather than the only low BMD or only sarcopenia groups exhibited a higher risk of the primary (hazard ratio [HR]: 3.28, 95 % confidence interval [CI]: 1.52–7.08) and kidney composite (HR: 2.07, 95 % CI: 1.10–3.89) outcomes. Among the osteosarcopenia-related body compositions and physical functions, low handgrip strength (HGS) was strongly associated with a high risk of primary and kidney composite outcomes (HR: 2.44, 95 % CI: 1.46–4.08; HR: 1.48, 95 % CI: 0.97–2.24, respectively). The increase in HGS but not the body mass index, skeletal muscle mass index, or BMD was associated with lower risks of primary and kidney composite outcomes (HR: 0.93, 95 % CI: 0.89–0.98; HR: 0.96, 95 % CI: 0.92–0.99 per 1 kg, respectively). ConclusionsOsteosarcopenia was associated with poor survival and kidney outcomes in older patients with CKD. Low HGS, which is common in patients with osteosarcopenia and CKD, was associated with increased mortality risk and kidney function decline. These findings can help the risk prediction and pathogenesis of the kidney–bone–muscle axis and improving muscle strength can help mitigate CKD progression.

Plasma Metabolomics of Dietary Intake of Protein-Rich Foods and Kidney Disease Progression in Children

Evidence regarding the efficacy of a low-protein diet for patients with CKD is inconsistent and recommending a low-protein diet for pediatric patients is controversial. There is also a lack of objective biomarkers of dietary intake. The purpose of this study was to identify plasma metabolites associated with dietary intake of protein and to assess whether protein-related metabolites are associated with CKD progression. Nontargeted metabolomics was conducted in plasma samples from 484 Chronic Kidney Disease in Children (CKiD) participants. Multivariable linear regression estimated the cross-sectional association between 949 known, nondrug metabolites and dietary intake of total protein, animal protein, plant protein, chicken, dairy, nuts and beans, red and processed meat, fish, and eggs, adjusting for demographic, clinical, and dietary covariates. Cox proportional hazards models assessed the prospective association between protein-related metabolites and CKD progression defined as the initiation of kidney replacement therapy or 50% eGFR reduction, adjusting for demographic and clinical covariates. One hundred and twenty-seven (26%) children experienced CKD progression during 5years of follow-up. Sixty metabolites were significantly associated with dietary protein intake. Among the 60 metabolites, 10 metabolites were significantly associated with CKD progression (animal protein: n=1, dairy: n=7, red and processed meat: n=2, nuts and beans: n=1), including one amino acid, one cofactor and vitamin, 4 lipids, 2 nucleotides, one peptide, and one xenobiotic. 1-(1-enyl-palmitoyl)-2-oleoyl-glycerophosphoethanolamine (GPE, P-16:0/18:1) was positively associated with dietary intake of red and processed meat, and a doubling of its abundance was associated with 88% higher risk of CKD progression. 3-ureidopropionate was inversely associated with dietary intake of red and processed meat, and a doubling of its abundance was associated with 48% lower risk of CKD progression. Untargeted plasma metabolomic profiling revealed metabolites associated with dietary intake of protein and CKD progression in a pediatric population.

Abstract 12470: Sacubitril/Valsartan in Patients With Heart Failure and Deterioration of Kidney Function to Estimated Glomerular Filtration Rate Less Than 30ml/min/1.73m 2 : Insights From PARAGON-HF and PARADIGM-HF

Background: Sacubitril/valsartan is a foundational therapy for patients with heart failure (HF). Although current US FDA labeling does not identify threshold kidney function below which initiation or continuation of sacubitril/valsartan is precluded, guidelines generally identify eGFR<30mL/min/1.73m 2 as a contraindication to therapy. Methods: The RCTs PARAGON-HF and PARADIGM-HF assessed sacubitril/valsartan versus valsartan or enalapril in patients with HF. Patients with eGFR <30 (PARADIGM) or <25 mL/min/1.73 m 2 (PARAGON) at randomization were excluded. Discontinuation below this eGFR during follow-up was not mandated. We examined the effects of sacubitril/valsartan on efficacy and safety in patients experiencing progression of CKD to eGFR<30mL/min/1.73m 2 in follow-up. Results: Among 4,746 patients in PARAGON-HF and 8,346 patients in PARADIGM-HF (with eGFR>30ml/min/1.73m 2 at randomization), 613 (12.9%) and 691 (8.3%), respectively, had an eGFR<30mL/min/1.73m 2 at least once in follow-up. Patients with CKD progression had higher rates of study drug discontinuation and hyperkalemia (>5.5 mmol/L); however, rates remained similar between treatment groups. Patients with deterioration in kidney function to eGFR<30ml/min/1.73m 2 were at a higher risk of the primary composite outcome in both PARAGON-HF (RR 2.08; 95% CI: 1.72-2.52) and PARADIGM-HF (HR 2.32; 95% CI: 1.94-2.76). The incidence of the primary composite outcome was lower in patients treated with sacubitril/valsartan irrespective of deterioration in kidney function to eGFR<30mL/min/1.73m 2 in both PARAGON-HF (P int =0.74) and PARADIGM-HF (P int =0.50); Figure 1 . Conclusion: HF patients with progression of CKD to eGFR<30ml/min/1.73m 2 experience high risk of CV outcomes and continuation of sacubitril/valsartan was associated with persistent benefit. These data support potential continuation of sacubitril/valsartan, even among patients experiencing progression to advanced CKD.

Comparative Safety of Antidepressants in Adults with CKD.

Depression is prevalent in patients with CKD and is related to poor prognosis. Despite the widespread use of antidepressants in the CKD population, their safety remains unclear. We identified adults with CKD stages G3-5 (eGFR <60 ml/min per 1.73 m 2 not treated with dialysis) and incident depression diagnosis during 2007-2019 from the Stockholm Creatinine Measurements project. Using the target trial emulation framework, we compared the following treatment strategies: ( 1 ) initiating versus not initiating antidepressants, ( 2 ) initiating mirtazapine versus selective serotonin reuptake inhibitors (SSRIs), and ( 3 ) initiating SSRIs with a lower dose versus a standard dose. Of 7798 eligible individuals, 5743 (74%) initiated antidepressant treatment. Compared with noninitiation, initiation of antidepressants was associated with higher hazards of short-term outcomes, including hip fracture (hazard ratio [HR], 1.23; 95% confidence interval [CI], 0.88 to 1.74) and upper gastrointestinal bleeding (HR, 1.38; 95% CI, 0.82 to 2.31), although not statistically significant. Initiation of antidepressants was not associated with long-term outcomes, including all-cause mortality, major adverse cardiovascular event, CKD progression, and suicidal behavior. Compared with SSRIs, initiation of mirtazapine was associated with a lower hazard of upper gastrointestinal bleeding (HR, 0.52; 95% CI, 0.29 to 0.96), but a higher hazard of mortality (HR, 1.11; 95% CI, 1.00 to 1.22). Compared with the standard dose, initiation of SSRIs with a lower dose was associated with nonstatistically significantly lower hazards of upper gastrointestinal bleeding (HR, 0.68; 95% CI, 0.35 to 1.34) and CKD progression (HR, 0.80; 95% CI, 0.63 to 1.02), but a higher hazard of cardiac arrest (HR, 2.34; 95% CI, 1.02 to 5.40). Antidepressant treatment was associated with short-term adverse outcomes but not long-term outcomes in people with CKD and depression.

Instantaneous and Persistent Elevation of Serum Potassium and Progression of CKD

Instantaneous and Persistent Elevation of Serum Potassium and Progression of CKD

Nocturnal Systolic Blood Pressure Dipping and Progression of CKD

Nocturnal Systolic Blood Pressure Dipping and Progression of CKD

The 2021 KDIGO Blood Pressure Target and the Progression of CKD: Findings from KNOW-CKD

The 2021 KDIGO Blood Pressure Target and the Progression of CKD: Findings from KNOW-CKD

Correlation Between Neutrophil-to-Lymphocyte and Platelet-to-Lymphocyte Ratios and Progression of CKD in Elderly Patients

Correlation Between Neutrophil-to-Lymphocyte and Platelet-to-Lymphocyte Ratios and Progression of CKD in Elderly Patients

Association of N-Terminal Pro-Brain Natriuretic Peptide (NT-proBNP) with the Progression of CKD in Indian CKD Cohort

Association of N-Terminal Pro-Brain Natriuretic Peptide (NT-proBNP) with the Progression of CKD in Indian CKD Cohort

Association Between Systolic Blood Pressure Time in Target Range and Progression of CKD: Findings from KNOW-CKD Study

Association Between Systolic Blood Pressure Time in Target Range and Progression of CKD: Findings from KNOW-CKD Study

Ideal Cardiovascular Health and CKD Progression in Hispanic Adults

Ideal Cardiovascular Health and CKD Progression in Hispanic Adults

The Transcriptomic Landscape of microRNAs Encapsulated in Circulating Extracellular Vesicles and CKD Progression in Japanese Adults

The Transcriptomic Landscape of microRNAs Encapsulated in Circulating Extracellular Vesicles and CKD Progression in Japanese Adults

Greater Variability in eGFR Is Associated with CKD Progression: A Retrospective Japanese Nationwide Database Study

Greater Variability in eGFR Is Associated with CKD Progression: A Retrospective Japanese Nationwide Database Study

Cardiovascular Health and CKD Progression Among US Hispanic/Latino Adults of the Hispanic Community Health Study/Study of Latinos, 2008-2017

Cardiovascular Health and CKD Progression Among US Hispanic/Latino Adults of the Hispanic Community Health Study/Study of Latinos, 2008-2017

Urine Proteomic Profiling and Insights into CKD Progression in Children

Urine Proteomic Profiling and Insights into CKD Progression in Children

Estimated Potassium Intake in Patients with CKD Is Associated with CKD Progression: The Fukuoka Kidney Disease Registry (FKR) Study

Estimated Potassium Intake in Patients with CKD Is Associated with CKD Progression: The Fukuoka Kidney Disease Registry (FKR) Study

CKD Progression in Patients with Complement 3 Glomerulopathy (C3G) in a US Multi-Center Assessment

CKD Progression in Patients with Complement 3 Glomerulopathy (C3G) in a US Multi-Center Assessment

ESKD and CKD Progression Among a Diverse Immunoglobulin A Nephropathy (IgAN) Population

ESKD and CKD Progression Among a Diverse Immunoglobulin A Nephropathy (IgAN) Population

Construction of a Prediction Equation for the Progression and Worsening of CKD Using Artificial Intelligence

Construction of a Prediction Equation for the Progression and Worsening of CKD Using Artificial Intelligence

Therapeutic Potential of Oxalobacter formigenes in CKD Development and Progression

Therapeutic Potential of Oxalobacter formigenes in CKD Development and Progression