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RATIONALE & OBJECTIVE: Both hypervolemia and hypovolemia are associated with chronic kidney disease (CKD) progression. Although longitudinal monitoring of B-type natriuretic peptide (BNP) may aid physicians' decision making about the optimization of volume status, its clinical benefit remains uncertain in CKD. This study assessed the association between BNP monitoring and the risk of incident kidney replacement therapy (KRT). STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: A total of 2,998 outpatients with stages 3-5 of nondialyzed CKD referred to the department of nephrology at an academic hospital. EXPOSURE: BNP monitoring. OUTCOME: KRT, acute kidney injury (AKI), and heart failure hospitalization. ANALYTICAL APPROACH: Marginal structural models, which create a balanced pseudo population at each time point, were applied to account for potential time-dependent confounders. Inverse probability weighted pooled logistic regression models were employed to estimate hazard ratios. RESULTS: At baseline, the median age and estimated glomerular filtration rate were 66 years and 38.1mL/min/1.73m2, respectively. During the follow-up period (median, 5.9 [IQR, 2.8-9.9] years), 449 patients required KRT, 765 had AKI, and 236 were hospitalized for heart failure. After adjustment for time-updated clinical characteristics and physician-specific practice styles, BNP monitoring was associated with lower risks of KRT (HR, 0.44 [95% CI, 0.21-0.92]), AKI (HR, 0.36 [95% CI, 0.18-0.72]), and heart failure hospitalization (HR, 0.37 [95% CI, 0.14-0.95]). The association between BNP monitoring and KRT was attenuated after additional adjustment for AKI or heart failure hospitalization as a time-varying covariate. LIMITATIONS: Residual confounding by measured and unmeasured variables or indications for BNP measurements. CONCLUSIONS: BNP monitoring was associated with a lower risk of KRT among patients with CKD that did not require dialysis. This association is potentially mediated through a reduced risk of AKI or heart failure hospitalization. PLAIN-LANGUAGE SUMMARY: Both volume overload and volume depletion are deleterious to kidney function. B-type natriuretic peptide (BNP) is a biomarker that reflects volume status not only in heart failure but also in nondialysis chronic kidney disease (CKD). Although longitudinal BNP monitoring may aid physicians' decision making about the optimization of volume status, its clinical benefit remains uncertain in CKD. In this cohort study analyzing 2,998 patients with nondialyzed CKD, BNP monitoring was associated with a lower risk of kidney replacement therapy, acute kidney injury, and heart failure hospitalization over the follow-up period. The association with kidney replacement therapy may be mediated through a reduced risk of acute kidney injury or heart failure hospitalization. BNP monitoring may aid physicians in optimal fluid management, potentially conferring better kidney outcomes.
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RATIONALE & OBJECTIVE: High anion gap acidosis frequently develops in patients with advanced chronic kidney disease (CKD) and might be involved in kidney injury. Its impact on kidney outcomes, however, has not been well studied. We sought to examine the association between time-updated anion gap and the risk of kidney failure with replacement therapy (KFRT) among patients with advanced CKD. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: 1,168 patients with CKD glomerular filtration rate categories 3b-5 (G3b-G5) who had available data on anion gap. EXPOSURE: High time-updated anion gap defined as values ≥ 9.2 (top 25th percentile). OUTCOME: KFRT and death. ANALYTICAL APPROACH: Marginal structural models were fit to characterize the association between anion gap and study outcomes while accounting for potential time-dependent confounding. RESULTS: The mean baseline estimated glomerular filtration rate (eGFR) of the study participants was 28 mL/min/1.73 m2. Over a median follow-up period of 3.1 years, 317 patients progressed to KFRT (7.5 per 100 patient-years), and 146 died (3.5 per 100 patient-years). In the marginal structural models, a high anion gap was associated with a higher rate of KFRT (HR, 3.04 [95% CI, 1.94-4.75]; P < 0.001). This association was stronger in patients with a baseline eGFR of <30 mL/min/1.73 m2 (P for interaction = 0.05). High anion gap was also associated with a higher mortality rate (HR, 5.56 [95% CI, 2.95-10.5]; P < 0.001). Sensitivity analyses with different definitions of high anion gap showed similar results. LIMITATIONS: Observational study design and selection bias due clinical indications for measuring anion gap. CONCLUSIONS: Among patients with advanced CKD, high anion gap was associated with an increased risk of progression to KFRT and death.
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Insuficiência Renal Crônica , Insuficiência Renal , Equilíbrio Ácido-Base , Estudos de Coortes , Progressão da Doença , Taxa de Filtração Glomerular , Humanos , Insuficiência Renal/terapia , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/terapia , Estudos RetrospectivosRESUMO
Inhibiting tubular urate reabsorption may protect the kidney from urate-induced tubular injury. However, this approach may promote intratubular uric acid crystallization, especially in acidified urine, which could be toxic to the kidney. To assess how tubular urate handling affects kidney outcomes, we conducted a retrospective cohort study including 1042 patients with estimated glomerular filtration rates (eGFR) of 15-60 mL/min/1.73 m2. The exposures were fractional excretion of uric acid (FEUA) and urinary uric acid-to-creatinine ratio (UUCR). The kidney outcome was defined as a halving of eGFR from baseline or initiating kidney replacement therapy. The median FEUA and UUCR were 7.2% and 0.33 g/gCre, respectively. During a median follow-up of 1.9 years, 314 kidney outcomes occurred. In a multivariate Cox model, the lowest FEUA quartile exhibited a 1.68-fold higher rate of kidney outcome than the highest FEUA quartile (95% confidence interval, 1.13-2.50; P = 0.01). Similarly, lower UUCR was associated with a higher rate of kidney outcome. Notably, patients in the highest quartile of FEUA and UUCR were at the lowest risk of kidney outcome even among those with aciduria. In conclusion, lower FEUA and UUCR were associated with a higher risk of kidney failure, suggesting that increased urate reabsorption is harmful to the kidney.
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Insuficiência Renal Crônica , Ácido Úrico , Humanos , Ácido Úrico/urina , Estudos Retrospectivos , Rim , Taxa de Filtração Glomerular , Insuficiência Renal Crônica/urinaRESUMO
BACKGROUND: Gait abnormality is a serious problem among hemodialysis patients. Whole-body vibration is a simple exercise that induces sustained muscular contractions through mechanical vibrations. This training improved gait ability in older adults. We aimed to investigate the effect of whole-body vibration on balance and gait ability in older hemodialysis patients. METHODS: We conducted a 12-week, open-label, multicenter, randomized controlled trial of 98 hemodialysis patients, who were aged ≥65 years, from three dialysis centers in Japan. Those who had difficulty walking alone or dementia were excluded. Patients were randomly allocated to the whole-body vibration group or control group. The training was performed for 3 minutes thrice a week on dialysis days. The primary outcome was the Timed Up and Go test. The secondary outcomes were the single-leg stand test and 30-second chair stand test. RESULTS: The mean (SD) age of the participants was 76 (7) years. The mean (SD) Timed Up and Go test was 12.0 (6.6) and 11.8 (7.0) seconds in the whole-body vibration and control groups, respectively. During the 12-week study period, 6 (12%) of 49 patients in the whole-body vibration group and 3 (6%) of 49 patients in the control group dropped out. In the whole-body vibration group, 42 (86% of the randomly allocated patients) completed the training according to the protocol. The mean (SD) changes in the Timed Up and Go test were -1.1 (4.0) and -1.4 (4.4) seconds in the whole-body vibration and control groups, respectively (change, 0.3 seconds in the whole-body vibration group; 95% confidence interval, -1.4 to 2.0; P=0.71). The changes in the single-leg stand test and 30-second chair stand test did not differ significantly between groups. There were no musculoskeletal adverse events directly related to this training. CONCLUSIONS: Whole-body vibration did not improve balance and gait ability. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Effect of Whole Body Vibration on Walking Performance in Elderly Hemodialysis Patients NCT04774731.
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Terapia por Exercício , Vibração , Idoso , Humanos , Terapia por Exercício/métodos , Vibração/uso terapêutico , Equilíbrio Postural , Estudos de Tempo e Movimento , MarchaRESUMO
BACKGROUND: Interstitial eosinophilic aggregates are observed in various kidney diseases, but their clinical implications remain unknown. We assessed the association between interstitial eosinophilic aggregates and kidney outcomes and further analyzed the association between blood eosinophil count, as a surrogate for interstitial eosinophilic aggregates, and the risk of kidney failure in patients with advanced CKD. METHODS: We analyzed datasets from two retrospective cohort studies: ( 1 ) the kidney biopsy cohort including 563 patients who underwent native kidney biopsy at Osaka University Hospital between 2009 and 2021 and ( 2 ) the retrospective CKD cohort including 2877 patients with an eGFR of 10-60 ml/min per 1.73 m 2 referred to the nephrology outpatient center at Osaka University Hospital between 2005 and 2018. Interstitial eosinophilic aggregates were defined as ≥5 interstitial eosinophils in the high-power field on hematoxylin and eosin staining. This study outcome was initiation of KRT or ≥40% decline in eGFR. RESULTS: In the kidney biopsy cohort, interstitial eosinophilic aggregates were found in 17% of patients, most frequently in those with diabetic nephropathy (50%). Interstitial eosinophilic aggregates were associated with a higher rate of the composite kidney outcome after adjustment for clinical and histological variables (hazard ratio, 3.61; 95% confidence interval, 2.47 to 5.29; P < 0.001). LASSO revealed that blood eosinophil count was the strongest predictor of interstitial eosinophilic aggregates. In the retrospective CKD cohort, higher baseline and time-updated blood eosinophil counts were significantly associated with a higher rate of KRT initiation in Cox proportional hazards models and marginal structural models. CONCLUSIONS: Interstitial eosinophilic aggregates were associated with a higher risk of a composite of KRT initiation or ≥40% decline in eGFR. PODCAST: This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/CJASN/2023_12_08_CJN0000000000000277.mp3.
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Insuficiência Renal Crônica , Insuficiência Renal , Humanos , Estudos Retrospectivos , Rim , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/diagnósticoRESUMO
BACKGROUND: Intradialytic hypotension is related to patient-reported outcomes such as post-dialysis fatigue, but its impact on physical activity has not been fully studied. We aimed to examine the relationship between intradialytic blood pressure (BP) and objectively measured physical activity. METHODS: In this cross-sectional study, 192 hemodialysis patients underwent 4 weeks of physical activity measurement using triaxial accelerometers to measure step counts and moderate-to-vigorous physical activity (MVPA). Intradialytic BP parameters (pre-dialysis BP, post-dialysis BP, nadir BP, and fall in BP) were measured during all dialysis sessions. Mixed-effects linear regression models were used to analyze associations between intradialytic BP parameters and physical activity (1) after dialysis sessions on dialysis days and (2) on the following non-dialysis days. RESULTS: The mean age of the patients was 71 years, and 47% had diabetes mellitus. Valid physical activity data were obtained in a total of 1938 dialysis days and 2629 non dialysis days. Lower nadir diastolic BP was significantly associated with lower step counts and shorter moderate-to-vigorous physical activity not only on dialysis days but also on the following non-dialysis days. Nadir diastolic BP showed a higher discrimination capacity for physical inactivity, defined as a step count < 4000 on non-dialysis days, than the other BP parameters. The optimal cutoff point of nadir diastolic BP for discriminating physical inactivity was 68 mmHg; its sensitivity and specificity were 66% and 67%, respectively. CONCLUSIONS: Lower nadir diastolic BP was strongly associated with lower physical activity on both dialysis and non-dialysis days. Nadir diastolic BP may be a predictor for physical inactivity.
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Hipotensão , Falência Renal Crônica , Idoso , Pressão Sanguínea/fisiologia , Estudos Transversais , Exercício Físico , Humanos , Hipotensão/diagnóstico , Hipotensão/etiologia , Falência Renal Crônica/complicações , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/terapia , Diálise Renal/efeitos adversosRESUMO
BACKGROUND: Real-world evidence about mineralocorticoid receptor antagonist (MRA) use has been limited in chronic kidney disease, particularly regarding its association with hard renal outcomes. METHODS: In this retrospective cohort study, adult chronic kidney disease outpatients referred to the department of nephrology at an academic hospital between January 2005 and December 2018 were analyzed. The main inclusion criteria were estimated glomerular filtration rate ≥10 and <60 mL/min per 1.73 m2 and follow-up ≥90 days. The exposure of interest was MRA use, defined as the administration of spironolactone, eplerenone, or potassium canrenoate. The primary outcome was renal replacement therapy initiation, defined as the initiation of chronic hemodialysis, peritoneal dialysis, or kidney transplantation. A marginal structural model using inverse probability of weighting was applied to account for potential time-varying confounders. RESULTS: Among a total of 3195 patients, the median age and estimated glomerular filtration rate at baseline were 66 years and 38.4 mL/min per 1.73 m2, respectively. During follow-up (median, 5.9 years), 770 patients received MRAs, 211 died, and 478 started renal replacement therapy. In an inverse probability of weighting-weighted pooled logistic regression model, MRA use was significantly associated with a 28%-lower rate of renal replacement therapy initiation (hazard ratio, 0.72 [95% CI, 0.53-0.98]). The association between MRA use and renal replacement therapy initiation was dose-dependent (P for trend <0.01) and consistent across patient subgroups. The incidence of hyperkalemia (>5.5 mEq/L) was somewhat higher in MRA users but not significant (hazard ratio, 1.14 [95% CI, 0.88-1.48]). CONCLUSIONS: MRA users showed a better renal prognosis across various chronic kidney disease subgroups in a real-world chronic kidney disease population.
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Taxa de Filtração Glomerular/efeitos dos fármacos , Rim/efeitos dos fármacos , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Insuficiência Renal Crônica/tratamento farmacológico , Idoso , Feminino , Humanos , Rim/fisiopatologia , Masculino , Pessoa de Meia-Idade , Antagonistas de Receptores de Mineralocorticoides/farmacologia , Prognóstico , Insuficiência Renal Crônica/mortalidade , Insuficiência Renal Crônica/fisiopatologia , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do TratamentoRESUMO
Background: Studies examining associations between metabolic acidosis and cardiovascular events in chronic kidney disease (CKD) have shown conflicting results and have not differentiated between normal anion gap (hyperchloremic) acidosis and high anion gap acidosis. We aimed to examine the impact of normal and high anion gap acidosis, separately, on the risk of cardiovascular events among patients with CKD. Methods: This retrospective cohort study included 1168 patients with an estimated glomerular filtration rate (eGFR) of 10-60 mL/min/1.73 m2 and available data on anion gap. We analyzed the association of time-updated high anion gap (anion gap ≥9.2) with the rate of cardiovascular events using marginal structural models (MSMs) to account for time-dependent confounding. We also analyzed the association between time-updated normal anion gap acidosis (anion-gap-adjusted bicarbonate level ≤22.8 mEq/L) and cardiovascular events. Results: The mean baseline eGFR of the cohort was 28 mL/min/1.73 m2. The prevalence rates of high anion gap in CKD stages G3a, G3b, G4 and G5 were 20%, 16%, 27% and 46%, respectively. During a median follow-up period of 2.9 years, 132 patients developed cardiovascular events (3.3/100 patient-years). In MSMs, high anion gap was associated with a higher rate of cardiovascular events [hazard ratio (HR) 1.87; 95% confidence interval (95% CI) 1.13â3.09; P = 0.02] and the composite of cardiovascular events or all-cause death (HR 3.28; 95% CI 2.19â4.91; P < 0.001). Normal anion gap acidosis was not associated with cardiovascular events (HR 0.74; 95% CI, 0.47â1.17; P = 0.2). Conclusions: Among patients with advanced CKD, high anion gap was associated with an increased risk of cardiovascular events.
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Metabolic acidosis is one of the most common complications of chronic kidney disease (CKD). It is associated with the progression of CKD, and many other functional impairments. Until recently, only serum bicarbonate levels have been used to evaluate acid-base changes in patients with reduced kidney function. However, recent emerging evidence suggests that nephrologists should reevaluate the clinical approach for diagnosing metabolic acidosis in patients with CKD based on two perspectives; pH and anion gap. Biochemistry and physiology textbooks clearly indicate that blood pH is the most important acid-base parameter for cellular function. Therefore, it is important to determine if the prognostic impact of hypobicarbonatemia varies according to pH level. A recent cohort study of CKD patients showed that venous pH modified the association between a low bicarbonate level and the progression of CKD. Furthermore, acidosis with a high anion gap has recently been recognized as an important prognostic factor, because veverimer, a nonabsorbable hydrochloride-binding polymer, has been shown to improve kidney function and decrease the anion gap. Acidosis with high anion gap frequently develops in later stages of CKD. Therefore, the anion gap is a time-varying factor and renal function (estimated glomerular filtration rate) is a time-dependent confounder for the anion gap and renal outcomes. Recent analyses using marginal structural models showed that acidosis with a high anion gap was associated with a high risk of CKD. Based on these observations, reconsideration of the clinical approach to diagnosing and treating metabolic acidosis in CKD may be warranted.
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The LAMA5 gene encodes laminin α5, an indispensable component of glomerular basement membrane and other types of basement membrane. A homozygous pathological variant in LAMA5 is known to cause a systemic developmental syndrome including glomerulopathy. However, the roles of heterozygous LAMA5 gene variants in human renal and systemic diseases have remained unclear. We performed whole-exome sequencing analyses of a family with slowly progressive nephropathy associated with hereditary focal segmental glomerulosclerosis, and we identified what we believe to be a novel probable pathogenic variant of LAMA5, NP_005551.3:p.Val3687Met. In vitro analyses revealed cell type-dependent changes in secretion of variant laminin α5 laminin globular 4-5 (LG4-5) domain. Heterozygous and homozygous knockin mice with a corresponding variant of human LAMA5, p.Val3687Met, developed focal segmental glomerulosclerosis-like pathology with reduced laminin α5 and increased glomerular vinculin levels, which suggested that impaired cell adhesion may underlie this glomerulopathy. We also identified pulmonary defects such as bronchial deformity and alveolar dilation. Reexaminations of the family revealed phenotypes compatible with reduced laminin α5 and increased vinculin levels in affected tissues. Thus, the heterozygous p.Val3687Met variant may cause a new syndromic nephropathy with focal segmental glomerulosclerosis through possibly defective secretion of laminin α5. Enhanced vinculin may be a useful disease marker.