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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
Phosphate/calcium homeostasis is crucial for health maintenance. Lithocholic acid, a bile acid produced by intestinal bacteria, is an agonist of vitamin D receptor. However, its effects on phosphate/calcium homeostasis remain unclear. Here, we demonstrated that lithocholic acid increases intestinal phosphate/calcium absorption in an enterocyte vitamin D receptor-dependent manner. Lithocholic acid was found to increase serum phosphate/calcium levels and thus to exacerbate vascular calcification in animals with chronic kidney disease. Lithocholic acid did not affect levels of intestinal sodium-dependent phosphate transport protein 2b, Pi transporter-1, -2, or transient receptor potential vanilloid subfamily member 6. Everted gut sac analyses demonstrated that lithocholic acid increased phosphate/calcium absorption in a transcellular pathway-independent manner. Lithocholic acid suppressed intestinal mucosal claudin 3 and occludin in wild-type mice, but not in vitamin D receptor knockout mice. Everted gut sacs of claudin 3 knockout mice showed an increased permeability for phosphate, but not calcium. In patients with chronic kidney disease, serum 1,25(OH)2 vitamin D levels are decreased, probably as an intrinsic adjustment to reduce phosphate/calcium burden. In contrast, serum and fecal lithocholic acid levels and fecal levels of bile acid 7α-dehydratase, a rate-limiting enzyme involved in lithocholic acid production, were not downregulated. The effects of lithocholic acid were eliminated by bile acid adsorptive resin in mice. Thus, lithocholic acid and claudin 3 may represent novel therapeutic targets for reducing phosphate burden.
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Cálcio , Receptores de Calcitriol , Animais , Cálcio/metabolismo , Humanos , Absorção Intestinal , Ácido Litocólico , Camundongos , Fosfatos , Receptores de Calcitriol/genética , Receptores de Calcitriol/metabolismo , Transcitose , Vitamina DRESUMO
BACKGROUND: Serum chloride (Cl) levels confer better prognostic value than serum sodium (Na) levels among patients with heart failure. Little is known about the relationship between serum Cl levels and clinical outcomes among patients with chronic kidney disease (CKD). METHODS: This was a retrospective cohort study enrolling patients with Stages G3-G5 CKD who visited the nephrology outpatient department of Osaka University Hospital from April 2005 to December 2014. The main exposure was time-varying serum Cl levels categorized as quartiles. The study outcome was a composite of all-cause death and cardiovascular events. RESULTS: A total of 2661 patients with CKD were included in the analysis. During a median follow-up of 4.0 years, 284 deaths and 416 cardiovascular events occurred. Compared with patients in the third Cl quartile, those in the first Cl quartile showed a significantly higher risk of the outcome after adjustment for demographics and clinical factors including time-varying serum Na, serum albumin and bicarbonate levels, and use of diuretics and sodium bicarbonate [hazard ratio (HR) 2.13; 95% confidence interval (CI) 1.20-3.81; P = 0.01] and, additionally, anion gap (HR 2.13; 95% CI 1.26-3.57; P = 0.004). Adding serum Cl levels, but not serum Na levels, to the multivariable model significantly improved net reclassification index (0.335; P < 0.001) and integrated discrimination improvement (0.0113; P = 0.01). CONCLUSIONS: Lower serum Cl levels are an independent predictor of death and cardiovascular events. The incremental prognostic value of Cl was superior to that of Na in patients with CKD.
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Biomarcadores/sangue , Doenças Cardiovasculares/etiologia , Cloretos/sangue , Hiponatremia/sangue , Insuficiência Renal Crônica/diagnóstico , Sódio/sangue , Desequilíbrio Ácido-Base , Idoso , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/mortalidade , Progressão da Doença , Feminino , Taxa de Filtração Glomerular , Humanos , Hiponatremia/complicações , Masculino , Pessoa de Meia-Idade , Prognóstico , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Taxa de SobrevidaRESUMO
BACKGROUND: Developing strategies for managing coronary artery calcification (CAC) in patients with CKD is an important clinical challenge. Experimental studies have demonstrated that magnesium inhibits vascular calcification, whereas the uremic toxin indoxyl sulfate aggravates it. METHODS: To assess the efficacy of magnesium oxide (MgO) and/or the oral carbon adsorbent AST-120 for slowing CAC progression in CKD, we conducted a 2-year, open-label, randomized, controlled trial, enrolling patients with stage 3-4 CKD with risk factors for CAC (diabetes mellitus, history of cardiovascular disease, high LDL cholesterol, or smoking). Using a two-by-two factorial design, we randomly assigned patients to an MgO group or a control group, and to an AST-120 group or a control group. The primary outcome was percentage change in CAC score. RESULTS: We terminated the study prematurely after an interim analysis with the first 125 enrolled patients (of whom 96 completed the study) showed that the median change in CAC score was significantly smaller for MgO versus control (11.3% versus 39.5%). The proportion of patients with an annualized percentage change in CAC score of ≥15% was also significantly lower for MgO compared with control (23.9% versus 62.0%). However, MgO did not suppress the progression of thoracic aorta calcification. The MgO group's dropout rate was higher than that of the control group (27% versus 17%), primarily due to diarrhea. The percentage change in CAC score did not differ significantly between the AST-120 and control groups. CONCLUSIONS: MgO, but not AST-120, appears to be effective in slowing CAC progression. Larger-scale trials are warranted to confirm these findings.
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Carbono/administração & dosagem , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/epidemiologia , Óxido de Magnésio/administração & dosagem , Óxidos/administração & dosagem , Calcificação Vascular/tratamento farmacológico , Calcificação Vascular/epidemiologia , Administração Oral , Idoso , Comorbidade , Doença da Artéria Coronariana/prevenção & controle , Progressão da Doença , Feminino , Hospitais Universitários , Humanos , Masculino , Pessoa de Meia-Idade , Cooperação do Paciente/estatística & dados numéricos , Prevenção Primária , Prognóstico , Valores de Referência , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/terapia , Índice de Gravidade de Doença , Resultado do Tratamento , Calcificação Vascular/prevenção & controleRESUMO
Autoantibodies against thrombospondin type 1 domain-containing 7A (THSD7A) cause membranous nephropathy (MN); however, the mechanisms involved in THSD7A expression and immunization are uncertain. We present 2 cases of THSD7A-associated MN accompanied by angiolymphoid hyperplasia with eosinophilia (ALHE), a benign tumor characterized by proliferation of plump endothelial cells. Prednisolone therapy, but not surgical resection of ALHE tumors, successfully suppressed eosinophilia and proteinuria in both cases. Because ALHE is characterized by the proliferation of plump endothelial cells, we focused on the roles of vascular endothelial growth factor A (VEGF-A) in MN pathogenesis. We found that plump endothelial cells in ALHE modestly expressed THSD7A in both cases. We also found that eosinophils in ALHE expressed VEGF-A, which upregulated THSD7A expression, especially under T-helper type 2-prone conditions in cultured endothelial cells. Furthermore, double-positive cells for THSD7A and CD83 surrounded the proliferated small vessels. Our results suggest that VEGF-A-induced THSD7A expression outside the kidney may be important for MN pathogenesis.
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Hiperplasia Angiolinfoide com Eosinofilia/patologia , Glomerulonefrite Membranosa/imunologia , Prednisolona/uso terapêutico , Trombospondinas/imunologia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Adulto , Hiperplasia Angiolinfoide com Eosinofilia/complicações , Hiperplasia Angiolinfoide com Eosinofilia/tratamento farmacológico , Biomarcadores , Biópsia por Agulha , Feminino , Seguimentos , Testa/patologia , Glomerulonefrite Membranosa/complicações , Glomerulonefrite Membranosa/patologia , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Medição de Risco , Estudos de Amostragem , Fatores de TempoRESUMO
BACKGROUND: Magnesium is known to protect against phosphate-induced tubular cell injuries in vitro. We investigated in vivo effects of magnesium on kidney injuries and phosphate metabolism in mice exposed to a high phosphate diet. METHODS: Heminephrectomized mice were maintained on a high phosphate/normal magnesium diet or a high phosphate/low magnesium diet for 6 weeks. We compared renal histology, phosphaturic hormones and renal α-Klotho expression between the two diet groups. RESULTS: High phosphate diet-induced tubular injuries and interstitial fibrosis were remarkably aggravated by the low-magnesium diet. At 1 week after high phosphate feeding when serum creatinine levels were similar between the two groups, the low magnesium diet suppressed not only fecal phosphate excretion but also urinary phosphate excretion, resulting in increased serum phosphate levels. Parathyroid hormone (PTH) levels were not appropriately elevated in the low magnesium diet group despite lower 1,25-dihydroxyvitamin D and serum calcium levels compared with the normal magnesium diet group. Although fibroblast growth factor 23 (FGF23) levels were lower in the low magnesium diet group, calcitriol-induced upregulation of FGF23 could not restore the impaired urinary phosphate excretion. The low magnesium diet markedly downregulated α-Klotho expression in the kidney. This downregulation of α-Klotho occurred even when mice were fed the low phosphate diet. CONCLUSIONS: A low magnesium diet aggravated high phosphate diet-induced kidney injuries. Impaired PTH secretion and downregulation of renal α-Klotho were likely to be involved in the blunted urinary phosphate excretion by the low magnesium diet. Increasing dietary magnesium may be useful to attenuate phosphate-induced kidney injury.
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Dieta/efeitos adversos , Nefropatias/patologia , Magnésio/administração & dosagem , Fosfatos/toxicidade , Animais , Fator de Crescimento de Fibroblastos 23 , Fatores de Crescimento de Fibroblastos/sangue , Glucuronidase/metabolismo , Nefropatias/sangue , Nefropatias/etiologia , Magnésio/sangue , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Hormônio Paratireóideo/sangue , Fosfatos/sangueRESUMO
BACKGROUND: Hypomagnesemia (Hypo-Mg) predicts mortality and chronic kidney disease (CKD) progression. However, in CKD, its prevalence, kidney-intrinsic risk factors, and the effectiveness of oral magnesium (Mg) therapy on serum Mg levels is uncertain. METHODS: In a cross-sectional study enrolling pre-dialysis outpatients with CKD, the prevalence of electrolyte abnormalities (Mg, sodium, potassium, calcium and phosphorus) was compared. In an open-label randomized controlled trial (RCT), we randomly assigned CKD patients to either the magnesium oxide (MgO) or control arm. The outcome was serum Mg levels at 1 year. RESULTS: In 5126 patients, Hypo-Mg was the most common electrolyte abnormality (14.7%) with similar prevalence across stages of CKD. Positive proteinuria was a risk factor of Hypo-Mg (odds ratio 2.2; 95% confidence interval 1.2-4.0). However, stratifying the analyses by diabetes mellitus (DM), it was not significant in DM (Pinteraction = 0.04). We enrolled 114 patients in the RCT. Baseline analyses showed that higher proteinuria was associated with higher fractional excretion of Mg. This relationship between proteinuria and renal Mg wasting was mediated by urinary tubular markers in mediation analyses. In the MgO arm, higher proteinuria or tubular markers predicted a significantly lower 1-year increase in serum Mg. In patients with a urinary protein-to-creatinine ratio (uPCR) <0.3 g/gCre, serum Mg at 1 year was 2.4 and 2.0 mg/dL in the MgO and control arms, respectively (P < 0.001), with no significant between-group difference in patients whose uPCR was ≥0.3 g/gCre (Pinteraction=0.001). CONCLUSIONS: Proteinuria leads to renal Mg wasting through tubular injuries, which explains the high prevalence of Hypo-Mg in CKD.
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Eletrólitos/metabolismo , Óxido de Magnésio/uso terapêutico , Magnésio/metabolismo , Pacientes Ambulatoriais , Proteinúria/complicações , Insuficiência Renal Crônica/complicações , Erros Inatos do Transporte Tubular Renal/etiologia , Adulto , Biomarcadores/sangue , Biomarcadores/urina , Estudos Transversais , Progressão da Doença , Feminino , Seguimentos , Humanos , Japão/epidemiologia , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Prevalência , Proteinúria/tratamento farmacológico , Proteinúria/metabolismo , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/metabolismo , Erros Inatos do Transporte Tubular Renal/epidemiologia , Erros Inatos do Transporte Tubular Renal/prevenção & controle , Estudos RetrospectivosRESUMO
Protein carbamylation is a posttranslational modification that can occur non-enzymatically in the presence of high concentrations of urea. Although carbamylation is recognized as a prognostic biomarker, the contribution of protein carbamylation to organ dysfunction remains uncertain. Because vascular calcification is common under carbamylation-prone situations, we investigated the effects of carbamylation on this pathologic condition. Protein carbamylation exacerbated the calcification of human vascular smooth muscle cells (hVSMCs) by suppressing the expression of ectonucleotide pyrophosphate/phosphodiesterase 1 (ENPP1), a key enzyme in the generation of pyrophosphate, which is a potent inhibitor of ectopic calcification. Several mitochondrial proteins were carbamylated, although ENPP1 itself was not identified as a carbamylated protein. Rather, protein carbamylation reduced mitochondrial membrane potential and exaggerated mitochondria-derived oxidative stress, which down-regulated ENPP1. The effects of carbamylation on ectopic calcification were abolished in hVSMCs by ENPP1 knockdown, in mitochondrial-DNA-depleted hVSMCs, and in hVSMCs treated with a mitochondria-targeted superoxide scavenger. We also evaluated the carbamylation effects using ex vivo and in vivo models. The tunica media of a patient with end-stage renal disease was carbamylated. Thus, our findings have uncovered a previously unrecognized aspect of uremia-related vascular pathology.
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Falência Renal Crônica/complicações , Diester Fosfórico Hidrolases/metabolismo , Carbamilação de Proteínas , Pirofosfatases/metabolismo , Uremia/complicações , Calcificação Vascular/patologia , Animais , Linhagem Celular , Modelos Animais de Doenças , Progressão da Doença , Técnicas de Silenciamento de Genes , Humanos , Falência Renal Crônica/sangue , Masculino , Potencial da Membrana Mitocondrial/fisiologia , Músculo Liso Vascular , Estresse Oxidativo , Diester Fosfórico Hidrolases/genética , Pirofosfatases/genética , Ratos , Ratos Sprague-Dawley , Uremia/sangue , Calcificação Vascular/etiologiaRESUMO
Several experimental studies have shown that fibroblast growth factor 23 (FGF23) induces left ventricular hypertrophy (LVH). However, the opposite directional relationship, namely a potential effect of LVH on FGF23, remains uncertain. Here we evaluated the effects of LVH on FGF23 using cardiomyocyte-specific calcineurin A transgenic mice. At six weeks, these mice showed severe LVH, with elevated levels of serum intact FGF23. FGF23 levels were elevated in cardiomyocytes, but not osteocytes, of the transgenic animals. Moreover, transverse aortic constriction also upregulated myocardial FGF23 expression in wild type mice. The promoter region of the FGF23 gene contains two putative nuclear factors of activated T cells (NFAT)-binding sites, with NFAT1 activating the promoter in a proximal NFAT-binding site dependent manner. Neither serum, urinary, or fractional excretion values of calcium and phosphate nor serum levels of 1,25(OH)2 vitamin D were different between wild type and transgenic mice. Moreover, the renal expression of FGF receptors and α-Klotho was comparable. However, plasma levels of antidiuretic hormone were significantly increased in the transgenic mice, and aquaporin-2 immunohistochemical staining was mainly positive in the apical membrane of the collecting duct, compared to a primarily cytoplasmic staining in wild type mice. Real-time PCR analyses of kidney CYP27B1 and CYP24A1 expression in wild type mice showed that exogenous antidiuretic hormone blocked FGF23's actions on these vitamin D activating or inactivating enzymes. Finally, the renal resistance of transgenic mice to FGF23 was partly overcome by tolvaptan. Thus, LVH in transgenic mice is associated with an increase in myocardial and serum intact FGF23, with the kidneys being protected against FGF23 excess by elevated antidiuretic hormone levels.
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Fatores de Crescimento de Fibroblastos/sangue , Hipertrofia Ventricular Esquerda/sangue , Animais , Calcineurina/genética , Calcineurina/metabolismo , Modelos Animais de Doenças , Fator de Crescimento de Fibroblastos 23 , Fatores de Crescimento de Fibroblastos/metabolismo , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Miócitos Cardíacos/metabolismo , Osteócitos/metabolismo , Vasopressinas/sangueRESUMO
BACKGROUND: In Japan, "Guidelines for iodinated contrast in a patient with chronic kidney disease (CKD) 2012" was published, but preventive protocols for specific contrast-induced nephropathy (CIN) have not been specified. Therefore, we developed a CIN preventive protocol, and validated its operation and renal protective effect. METHODS: In a retrospective cohort study, we determined eGFR within 3 months before contrast-enhanced computed tomography (CECT). We evaluated CKD stage 3b - 4 adult patients (eGFR 15 - 45 mL/min/1.73m2) who underwent CECT. We observed changes in renal function over 9 months and compared the changes between the pre-protocol group, which received CIN preventive measures from clinicians, and the post-protocol group, which received 500 mL 0.9% saline intravenously over 4 hours or drank 2,000 mL water over 36 hours. RESULTS: The numbers of CT and CECT patients after validation of the protocol were 5,450 and 2,037, respectively. Among the CECT patients, 310 (15.2%) and 77(3.8%)had eGFRs < 60 and 45 mL/min/1.73 m2, respectively. Among the CECT patients whose eGFRs were < 60 mL/min/1.73 m2, 74.5% were 70 years or older. Tumor scanning accounted for 77% of all CECT cases. The number of CECT patients after 3 months did not significantly differ between the groups (2,189 vs 2,037). The percentage of patients with CKD stage G3b - 4 showed no significant differences (3.3% vs 3.7%, p = 0.89). The proportion of patients whose eGFR did not deteriorate at 3, 6 and 9 months was significantly higher in the post-protocol group than in the pre-protocol group (p < 0.001), and the protocol was the only independently-significant predictor. CONCLUSIONS: Our protocol prevented CIN and provided a renal protective effect without reducing the number of CECT patients.
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Protocolos Clínicos , Meios de Contraste/efeitos adversos , Nefropatias/prevenção & controle , Idoso , Estudos de Coortes , Feminino , Taxa de Filtração Glomerular , Humanos , Nefropatias/induzido quimicamente , Nefropatias/fisiopatologia , Masculino , 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
Diabetic kidney disease (DKD) is heterogeneous in terms of proteinuria. Patients with DKD who present with low-grade proteinuria are more likely to have nephrosclerosis rather than traditional diabetic nephropathy. The amount of proteinuria might reflect the underlying pathology of renal failure and influence the prognosis after dialysis initiation. Clinical implications of proteinuria at the start of dialysis have not been confirmed, while greater proteinuria is associated with higher risk of cardiovascular disease (CVD) in the predialysis stages of chronic kidney disease. We performed a retrospective multicenter cohort study enrolling incident hemodialysis patients with diabetes. Patients were stratified using proteinuria quartiles. We examined the association of proteinuria quartiles with types of subsequent CVD. Among the enrolled 361 patients, the estimated mean glomerular filtration rate and proteinuria was 5.4 mL/min/1.73 m2 and 6.3 g/gCr, respectively. Lower quartile of proteinuria (cut-offs: 3.0, 5.4, and 8.8 g/gCr) was significantly associated with male, older age, and history of atherosclerotic CVD including coronary artery disease, peripheral arterial disease, and cerebral infarction (Ptrend<0.05). Kidney size was smaller in patients with lower levels of proteinuria. Patients with higher levels of proteinuria were more likely to have proliferative diabetic retinopathy (Ptrend<0.05). Multivariate competing risk analysis revealed that the first quartile of proteinuria was associated with a greater risk of atherosclerotic CVD than the third quartile (subhazard ratio [95% confidence interval]: 2.04 [1.00-4.14]). This association was attenuated after additional adjustments for history of atherosclerotic CVD. Furthermore, patients with lower quartiles of proteinuria were more likely to die of atherosclerotic CVD than those with non-atherosclerotic CVD (Ptrend = 0.01). Diabetic patients with lower proteinuria at dialysis initiation were characterized by severer macroangiopathy, as shown by a more atrophic kidney and higher prevalence of past atherosclerotic CVD. Hence, they are at a high risk of developing atherosclerotic CVD.
Assuntos
Doenças Cardiovasculares/patologia , Nefropatias Diabéticas/patologia , Proteinúria/patologia , Idoso , Doenças Cardiovasculares/complicações , Estudos de Coortes , Creatina/urina , Nefropatias Diabéticas/complicações , Feminino , Taxa de Filtração Glomerular , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Proteínas/análise , Proteinúria/complicações , Diálise Renal , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de DoençaRESUMO
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.
Assuntos
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.
Assuntos
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.