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1.
Pediatr Nephrol ; 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-32020338

RESUMO

BACKGROUND: Congenital anomalies of the kidney and urinary tract (CAKUT) is associated with a slower progression to end-stage renal disease (ESRD) in pre-dialysis patients. However, little is known about the associated mortality risks after transitioning to dialysis. METHODS: This retrospective cohort study included 0-21 year-old incident dialysis patients from the United States Renal Data System starting dialysis between 1995 and 2016. We examined the association of CAKUT vs. non-CAKUT with all-cause mortality, using Cox regression adjusted for case mix variables. We also examined the mortality risk associated with 14 non-CAKUT vs. CAKUT ESRD etiologies and under stratification by estimated glomerular filtration rate (eGFR). RESULTS: Among 25,761 patients, the median (interquartile range) age was 17 (11-19) years, and 4780 (19%) had CAKUT. CAKUT was associated with lower mortality, with an adjusted hazard ratio (aHR) of 0.72 (95%CI, 0.64-0.81) (reference: non-CAKUT). In age-stratified analyses, CAKUT vs. non-CAKUT aHRs (95%CI) were 0.66 (0.54-0.80), 0.56 (0.39-0.80), 0.66 (0.50-0.86), and 0.97 (0.80-1.18) among patients < 6, 6-< 13, 13-< 18, and ≥ 18 years at dialysis initiation, respectively. Among non-CAKUT ESRD etiologies, the risk of mortality associated with primary glomerulonephritis (aHR, 0.93; 95%CI 0.80-1.09) and focal segmental glomerulosclerosis (aHR, 0.89; 95%CI, 0.75-1.04) were comparable or slightly lower compared to CAKUT, whereas most other primary causes were associated with higher mortality risk. While the CAKUT group had lower mortality risk compared to the non-CAKUT group patients with eGFR ≥5 mL/min/1.73m2, CAKUT was associated with higher mortality in patients with eGFR < 5 mL/min/1.73 m2. CONCLUSIONS: CAKUT is associated with lower mortality among children < 18 years old, but showed comparable mortality with non-CAKUT among patients ≥ 18 years old. ESRD etiology should be considered in risk assessment for children initiating dialysis.

2.
Artigo em Inglês | MEDLINE | ID: mdl-32049326

RESUMO

BACKGROUND: Eosinophils are traditionally known as moderators of allergic reactions; however, they have now emerged as one of the principal immune-regulating cells as well as predictors of vascular disease and mortality in the general population. Although eosinophilia has been demonstrated in hemodialysis (HD) patients, associations of eosinophil count (EOC) and its changes with mortality in HD patients are still unknown. METHODS: In 107 506 incident HD patients treated by a large dialysis organization during 2007-11, we examined the relationships of baseline and time-varying EOC and its changes (ΔEOC) over the first 3 months with all-cause mortality using Cox proportional hazards models with three levels of hierarchical adjustment. RESULTS: Baseline median EOC was 231 (interquartile range 155-339) cells/µL and eosinophilia (>350 cells/µL) was observed in 23.4% of patients. There was a gradual increase in EOC over time after HD initiation with a median ΔEOC of 5.1 (IQR -53-199) cells/µL, which did not parallel the changes in white blood cell count. In fully adjusted models, mortality risk was highest in subjects with lower baseline and time-varying EOC (<100 cells/µL) and was also slightly higher in patients with higher levels (≥550 cells/µL), resulting in a reverse J-shaped relationship. The relationship of ΔEOC with all-cause mortality risk was also a reverse J-shape where both an increase and decrease exhibited a higher mortality risk. CONCLUSIONS: Both lower and higher EOCs and changes in EOC over the first 3 months after HD initiation were associated with higher all-cause mortality in incident HD patients.

3.
Stat Med ; 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31997372

RESUMO

Profiling analysis aims to evaluate health care providers, such as hospitals, nursing homes, or dialysis facilities, with respect to a patient outcome. Previous profiling methods have considered binary outcomes, such as 30-day hospital readmission or mortality. For the unique population of dialysis patients, regular blood works are required to evaluate effectiveness of treatment and avoid adverse events, including dialysis inadequacy, imbalance mineral levels, and anemia among others. For example, anemic events (when hemoglobin levels exceed normative range) are recurrent and common for patients on dialysis. Thus, we propose high-dimensional Poisson and negative binomial regression models for rate/count outcomes and introduce a standardized event ratio measure to compare the event rate at a specific facility relative to a chosen normative standard, typically defined as an "average" national rate across all facilities. Our proposed estimation and inference procedures overcome the challenge of high-dimensional parameters for thousands of dialysis facilities. Also, we investigate how overdispersion affects inference in the context of profiling analysis. The proposed methods are illustrated with profiling dialysis facilities for recurrent anemia events.

4.
Cardiorenal Med ; 10(2): 97-107, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31935740

RESUMO

OBJECTIVE: Incremental hemodialysis (HD) is a strategy utilized to gradually intensify dialysis among patients with incident end-stage renal disease. However, there are scarce data about which patients' clinic status changes by increasing treatment frequency. METHODS: We retrospectively examined statistically de-identified data from 569 patients who successfully transitioned from twice- to thrice-weekly HD (2007-2011) and compared the differences in monthly-averaged values of hemodynamic and laboratory indices during the 3 months before and after the transition with the values at 1 month prior to transition serving as the reference. RESULTS: At 3 months after transitioning from twice- to thrice-weekly HD, ultrafiltration volume decreased by 0.5 (95% CI 0.3-0.6) L/session among 189 patients (33%) with weekly interdialytic weight gain (IDWG) ≥5.4 kg/week, and increased by 0.4 (95% CI 0.3-0.5) L/session among 186 patients (33%) with weekly IDWG <3.3 kg/week. Weekly IDWG consistently increased after the transition irrespective of baseline values (1.7 [95% CI 1.5-1.9] kg/week). Pre-HD systolic blood pressure (SBP) decreased by 12 (95% CI 9-14) mm Hg among 177 patients (31%) with baseline pre-HD SBP ≥160 mm Hg, which coincided with a decreasing trend in post-HD body weight (1.3 [95% CI 0.8-1.7] kg). DISCUSSION: In conclusion, patients who increased HD frequency from twice to thrice weekly treatment experienced increased weekly IDWG and better pre-HD SBP control with lower post-HD body weight.

5.
Am J Nephrol ; 51(2): 86-95, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31935741

RESUMO

BACKGROUND: Mortality in patients with end-stage renal disease (ESRD) on maintenance hemodialysis (MHD) remains exceptionally high. While traditional risk factors such as obesity are paradoxically associated with better survival, nontraditional risk factors including cachexia increase the likelihood of poor outcomes. There is accumulating evidence that the endocannabinoid (ECB) system plays a major role in energy preservation and storage, factors which can prevent the deleterious effects of cachexia. Hence, in this study, we evaluated the association of circulating ECB levels with mortality in MHD patients. METHODS: Serum concentrations of anandamide (AEA) and 2-arachidonoyl-sn-glycerol (2-AG), major ECB ligands, were measured in MHD patients. Their correlation with various clinical/laboratory indices and association with 12-month all-cause mortality were examined. RESULTS: Serum 2-AG levels positively correlated with body mass index, serum triglycerides and body anthropometric measures. Meanwhile, serum AEA levels correlated positively with serum interleukin-6, and negatively with serum very low-density lipoprotein levels. While increased serum 2-AG levels were associated with reduced risk of all-cause mortality (hazard ratio [HR] 0.52, 95% CI 0.28-0.98), there was no clear association between serum AEA levels and mortality (HR 0.91, 95% CI 0.48-1.72). CONCLUSIONS: In MHD patients, the circulating levels of ECB ligand, 2-AG, may play an important role in determining body mass and risk of mortality. These observations were unique to 2-AG as similar findings were not obtained with serum AEA. Future studies need to investigate the mechanisms responsible for these associations and examine the modulation of the ECB system as a potential target for therapy in ESRD.

6.
J Bone Miner Res ; 35(2): 317-325, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31610040

RESUMO

Abnormalities of mineral bone disorder (MBD) parameters have been suggested to be associated with poor renal outcome in predialysis patients. However, the impact of those parameters on decline in residual kidney function (RKF) is uncertain among incident hemodialysis (HD) patients. We performed a retrospective cohort study in 13,772 patients who initiated conventional HD during 2007 to 2011 and survived 6 months of dialysis. We examined the association of baseline serum phosphorus, calcium, intact parathyroid hormone (PTH), and alkaline phosphatase (ALP) with a decline in RKF. Decline in RKF was assessed by estimated slope of renal urea clearance (KRU) over 6 months from HD initiation. Our cohort had a mean ± SD age of 62 ± 15 years; 64% were men, 57% were white, 65% had diabetes, and 51% had hypertension. The median (interquartile range [IQR]) baseline KRU level was 3.4 (2.0, 5.2) mL/min/1.73 m2 . The median (IQR) estimated 6-month KRU slope was -1.47 (-2.24, -0.63) mL/min/1.73 m2 per 6 months. In linear regression models, higher phosphorus categories were associated with a steeper 6-month KRU slope compared with the reference category (phosphorus 4.0 to <4.5 mg/dL). Lower calcium and higher intact PTH and ALP categories were also associated with a steeper 6-month KRU slope compared with their respective reference groups (calcium 9.2 to <9.5 mg/dL; intact PTH 150 to <250 pg/mL; ALP <60 U/L). The increased number of parameter abnormalities had an additive effect on decline in RKF. Abnormalities of MBD parameters including higher phosphorus, intact PTH, ALP and lower calcium levels were independently associated with decline in RKF in incident HD patients. © 2019 American Society for Bone and Mineral Research. © 2019 American Society for Bone and Mineral Research.

7.
Am J Kidney Dis ; 75(3): 342-350, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31813665

RESUMO

RATIONALE & OBJECTIVE: Patients receiving twice-weekly or less-frequent hemodialysis (HD) may need to undergo higher ultrafiltration rates (UFRs) to maintain acceptable fluid balance. We hypothesized that higher UFRs are associated with faster decline in residual kidney function (RKF) and a higher rate of mortality. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: 1,524 patients with kidney failure who initiated maintenance HD at a frequency of twice or less per week for at least 6 consecutive weeks at some time between 2007 and 2011 and for whom baseline data for UFR and renal urea clearance were available. PREDICTOR: Average UFR during the first patient-quarter during less-frequent HD (<6, 6-<10, 10-<13, and≥13mL/h/kg). OUTCOME: Time to all-cause and cardiovascular death, slope of decline in RKF during the first year after initiation of less-frequent HD (with slopes above the median categorized as rapid decline). ANALYTICAL APPROACH: Cox proportional hazards regression for time to death and logistic regression for the analysis of rapid decline in RKF. RESULTS: Among 1,524 patients, higher UFR was associated with higher all-cause mortality; HRs were 1.43 (95% CI, 1.09-1.88), 1.51 (95% CI, 1.08-2.10), and 1.76 (95% CI, 1.23-2.53) for UFR of 6 to<10, 10 to<13, and≥13mL/h/kg, respectively (reference: UFR < 6mL/h/kg). Higher UFR was also associated with higher cardiovascular mortality. Baseline RKF modified the association between UFR and mortality; the association was attenuated among patients with renal urea clearance≥5mL/min/1.73m2. Higher UFR had a graded association with rapid decline in RKF; ORs were 1.73 (95% CI, 1.18-2.55), 1.89 (95% CI, 1.12-3.17), and 2.75 (95% CI, 1.46-5.18) at UFRs of 6 to<10, 10 to<13, and≥13mL/h/kg, respectively (reference: UFR < 6mL/h/kg). LIMITATIONS: Residual confounding from unobserved differences across exposure categories. CONCLUSIONS: Higher UFR was associated with worse outcomes, including shorter survival and more rapid loss of RKF, among patients receiving regular HD treatments at a frequency of twice or less per week.

8.
Am J Nephrol ; 50(6): 481-488, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31661683

RESUMO

BACKGROUND: High ultrafiltration rate (UFR) has been associated with increased mortality in hemodialysis (HD) patients. However, the impact of UFR on decline of residual kidney function (RKF) has not been elucidated among patients receiving conventional HD. METHODS: We performed a retrospective cohort study of 7,753 patients who initiated conventional HD from 2007 to 2011 and survived the first year of dialysis with baseline UFR and renal urea clearance (KRU) data at baseline and 1 year (5th patient-quarter). The primary exposure was average UFR at the 1st patient-quarter from dialysis initiation (<4, 4 to <6, 6 to <9, 9 to <13, and ≥13 mL/h/kg). Decline in RKF was defined as the percent change in KRU and decline in urine output during the first year after initiation of dialysis. We used a logistic regression model for rapid decline in RKF and a linear regression model for change in urine volume. RESULTS: In our HD cohort, mean baseline UFR was 7.0 ± 3.1 mL/h/kg, and median (interquartile range) baseline KRU was 3.5 (2.1-5.3) mL/min/1.73 m2. There was a graded association between UFR and a rapid decline in RKF; the expanded case mix-adjusted ORs and 95% CIs were 1.21 (1.04-1.40), 1.34 (1.16-1.55), 1.73 (1.46-2.04), and 1.93 (1.48-2.52) for baseline UFR 4 to <6, 6 to <9, 9 to <13, and ≥13  mL/h/kg, respectively (reference: <4 mL/h/kg). KRU trajectories showed a greater KRU decline over time in higher UFR categories. Higher UFR was also associated with a greater decline in urine output after 1 year. CONCLUSION: Higher UFR was associated with a rapid decline in RKF among conventional HD patients. Further clinical trials are needed to elucidate a causal effect of UFR on RKF among HD patients.

9.
J Endocr Soc ; 3(10): 1869-1880, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31583368

RESUMO

Context: Previous studies have shown that the endocannabinoid system plays a major role in energy metabolism through the actions of its main mediators, 2-arachidonoyl-sn-glycerol (2-AG) and anandamide (AEA). Objective: We examined serum levels of major endocannabinoid mediators and their association with clinical parameters in patients with end-stage renal disease (ESRD). Design and Setting: Serum concentrations of 2-AG and AEA were measured in patients on maintenance hemodialysis (MHD) and controls, and correlations with various clinical and laboratory indices were examined. 2-AG was also measured in age and sex-matched healthy subjects for comparison of levels in patients undergoing MHD. Main Outcome Measure: Serum 2-AG. Results: Serum 2-AG levels were significantly elevated in patients with ESRD compared with healthy controls. Higher levels of 2-AG were found in patients on MHD compared to healthy subjects, and similar findings were seen in a second set of subjects in independent analyses. Among 96 patients on MHD, 2-AG levels correlated significantly and positively with serum triglycerides (ρ = 0.43; P < 0.0001), body mass index (ρ = 0.40; P < 0.0001), and body anthropometric measures and negatively with serum high-density lipoprotein cholesterol (ρ = -0.33; P = 0.001) following adjustment for demographic and clinical variables. Conclusions: In patients on MHD, levels of serum 2-AG, a major endocannabinoid mediator, were increased. In addition, increasing serum 2-AG levels correlated with increased serum triglycerides and markers of body mass. Future studies will need to evaluate the potential mechanisms responsible for these findings.

10.
Kidney Int Rep ; 4(9): 1205-1218, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31517140

RESUMO

Persons with acquired solitary kidney, including those who have had a unilateral nephrectomy for living kidney donation, renal malignancies, or trauma, have decreased renal mass that leads to increased intraglomerular pressure and glomerular hyperfiltration. These physiologic adaptations of solitary kidney may exacerbate other preexisting and genetic conditions that could create a predisposition to or worsen glomerular pathologies, leading to unfavorable renal outcomes. Hence, these persons may benefit from special care and lifestyle modifications, including nutritional interventions. There is a lack of consensus and evidence for proper surveillance and management after nephrectomy, and misconceptions in both directions of having a "normal" versus "abnormal" kidney status may cause confusion among patients and healthcare providers pertaining to long-term kidney health monitoring and management. We have reviewed available data on the impact of lifestyle modifications, particularly nutritional measures, and pharmacologic interventions, on short- and long-term outcomes after nephrectomy. We recommend avoidance of excessively high dietary protein intake (>1 g/kg per day) and high dietary sodium intake (>4 grams/d), adequate dietary fiber intake from plant-based foods, a target body mass index of <30 kg/m2 (in non-athletes and non-bodybuilders), and judicious management of risk factors of progressive chronic kidney disease (CKD), and future studies should help to better determine optimal care practices for these persons.

11.
Kidney Int Rep ; 4(9): 1219-1229, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31517141

RESUMO

Introduction: Given the high mortality rate within the first year of dialysis initiation, an accurate estimation of postdialysis mortality could help patients and clinicians in decision making about initiation of dialysis. We aimed to use machine learning (ML) by incorporating complex information from electronic health records to predict patients at risk for postdialysis short-term mortality. Methods: This study was carried out on a contemporary cohort of 27,615 US veterans with incident end-stage renal disease (ESRD). We implemented a random forest method on 49 variables obtained before dialysis transition to predict outcomes of 30-, 90-, 180-, and 365-day all-cause mortality after dialysis initiation. Results: The mean (±SD) age of our cohort was 68.7 ± 11.2 years, 98.1% of patients were men, 29.4% were African American, and 71.4% were diabetic. The final random forest model provided C-statistics (95% confidence intervals) of 0.7185 (0.6994-0.7377), 0.7446 (0.7346-0.7546), 0.7504 (0.7425-0.7583), and 0.7488 (0.7421-0.7554) for predicting risk of death within the 4 different time windows. The models showed good internal validity and replicated well in patients with various demographic and clinical characteristics and provided similar or better performance compared with other ML algorithms. Results may not be generalizable to non-veterans. Use of predictors available in electronic medical records has limited the assessment of number of predictors. Conclusion: We implemented and ML-based method to accurately predict short-term postdialysis mortality in patients with incident ESRD. Our models could aid patients and clinicians in better decision making about the best course of action in patients approaching ESRD.

12.
J Clin Lipidol ; 13(5): 744-753.e15, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31562050

RESUMO

BACKGROUND: In the general population, elevated triglyceride (TG) levels are an important risk factor for cardiovascular disease and mortality. However, in chronic kidney disease, the association of serum TGs with mortality is less clear. OBJECTIVE: We sought to examine the association of TGs with mortality across chronic kidney disease (CKD) stages in a large cohort of U.S. veterans. METHODS: We examined 2,086,904 U.S. veterans with a TG measurement obtained between a baseline period of October 2004 and September 2006, with follow-up until December 2014 (median [interquartile range {IQR}]: 9.2 [6.5, 9.9] years). Associations of TGs with all-cause and cardiovascular mortality across CKD stages were evaluated using Cox proportional hazard models. RESULTS: Patients were 64 ± 14 years old with a median (IQR) baseline TG of 129 [88, 193] mg/dL and estimated glomerular filtration rate of 76 [61, 91] mL/min/1.73 m2. More advanced CKD was associated with higher odds of TGs ≥ 240 mg/dL. Low levels of TGs < 80 mg/dL were associated with a higher risk of mortality across all stages, whereas TG levels ≥ 240 mg/dL were only associated with a higher risk of all-cause mortality in non-CKD and CKD stages 3A, 3B, and 4 (reference: TG 120 to <160 mg/dL). The relationship of higher TGs with mortality incrementally attenuated across worsening stages of CKD and attenuated to the null among patients with CKD stage 5/end-stage renal disease. Similar results were observed for cardiovascular mortality, in strata by age and diabetes, and further adjustment for high-density lipoprotein and low-density lipoprotein. CONCLUSION: Associations of elevated TGs with all-cause and cardiovascular mortality were incrementally attenuated across more advanced stages of CKD.

13.
Am J Nephrol ; 50(5): 361-369, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31522173

RESUMO

BACKGROUND: Abnormalities in serum potassium are risk factors for sudden cardiac death and arrhythmias among dialysis patients. Although a previous study in hemodialysis patients has shown that race/ethnicity may impact the relationship between serum potassium and mortality, the relationship remains unclear among peritoneal dialysis (PD) patients where the dynamics of serum potassium is more stable. METHODS: Among 17,664 patients who started PD between January 1, 2007 and December 31, 2011 in a large US dialysis organization, we evaluated the association of serum potassium levels with all-cause and arrhythmia-related deaths across race/ethnicity using time-dependent Cox models with adjustments for demographics. We also used restricted cubic spline functions for serum potassium levels to explore non-linear associations. RESULTS: Baseline serum potassium levels were the highest among Hispanics (4.2 ± 0.7 mEq/L) and lowest among non-Hispanic blacks (4.0 ± 0.7 mEq/L). Among 2,949 deaths during the follow-up of median 2.2 (interquartile ranges 1.3-3.2) years, 683 (23%) were arrhythmia-related deaths. Overall, both hyperkalemia and hypokalemia (i.e., serum potassium levels >5.0 and <3.5 mEq/L, respectively) were associated with higher all-cause and arrhythmia-related mortality. In a stratified analysis according to race/ethnicity, the association of hypokalemia with all-cause and arrhythmia-related mortality was consistent with an attenuation for arrhythmia-related mortality in non-Hispanic blacks. Hyperkalemia was associated with all-cause and arrhythmia-related mortality in non-Hispanic whites and non-Hispanic blacks, but no association was observed in Hispanics. CONCLUSION: Among incident PD patients, hypokalemia was consistently associated with all-cause and arrhythmia-related deaths irrespective of race/ethnicity. However, while hyperkalemia was associated with both death outcomes in non-Hispanic blacks and whites, it was not associated with either death outcome in Hispanic patients. Further studies are needed to demonstrate whether different strategies should be followed for the management of serum potassium levels according to race/ethnicity.

15.
Pediatr Nephrol ; 34(10): 1799-1809, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31218394

RESUMO

BACKGROUND: Hypoalbuminemia is a strong predictor of hospitalization and mortality among adult dialysis patients. However, data are scant on the association between serum albumin and hospitalization among children new to dialysis. METHODS: In a retrospective cohort study of children 1-17 years old with end-stage renal disease receiving dialysis therapy in a large US dialysis organization 2007-2011, we examined the association of serum albumin with hospitalization frequency and total hospitalization days using a negative binomial regression model. RESULTS: Among 416 eligible patients, median (interquartile range) age was 14 (10-16) years and mean ± SD baseline serum albumin level was 3.7 ± 0.8 g/dL. Two hundred sixty-six patients (64%) were hospitalized during follow-up with an incidence rate of 2.2 (95%CI, 1.9-2.4) admissions per patient-year. There was a U-shaped association between serum albumin and hospitalization frequency; hospitalization rates (95%CI) were 2.7 (2.2-3.2), 1.9 (1.5-2.4), 1.6 (1.3-1.9), and 2.7 (1.7-3.6) per patient-year among patients with serum albumin levels < 3.5, 3.5- < 4.0, 4.0- < 4.5, and ≥ 4.5 g/dL, respectively. Case mix-adjusted hospitalization incidence rate ratios (IRRs) (95%CI) were 1.63 (1.24-2.13), 1.32 (1.10-1.58), and 1.25 (1.06-1.49) at serum albumin levels 3.0, 3.5, and 4.5 g/dL, respectively (reference: 4.0 g/dL). Similar trends were observed in hospitalization days. These associations remained robust against further adjustment for laboratory variables associated with malnutrition and inflammation. CONCLUSIONS: Both high and low serum albumin were associated with higher hospitalization in children starting dialysis. Because the observed association is novel and not fully explainable especially for high serum albumin levels, interpreting the results requires caution and further studies are needed to confirm and elucidate this association before clinical recommendations are made.

16.
Cardiorenal Med ; 9(4): 212-221, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30995638

RESUMO

BACKGROUND: Observational studies show that African American (AA) dialysis patients have longer survival than European Americans. We hypothesized that apolipoprotein L1 (APOL1) genetic variation, associated with nephropathy in AAs, contributes to the survival advantage in AA dialysis patients. METHODS: We examined the association between race and mortality among 37,097 adult dialysis patients, including 54% AAs and 46% European Americans from a large dialysis organization (entry period from July 2001 to June 2006, follow-up through June 2007), within each cause of end-stage renal disease (ESRD) category associated with APOL1 renal risk variants using Cox proportional hazard models. RESULTS: AA dialysis patients had numerically lower mortality than their European American counterparts for all causes of ESRD. The mortality reduction among AAs compared to European Americans was statistically significant in patients with ESRD attributed to diabetes mellitus, hypertension, and APOL1-enriched glomerulonephritis (GN) (HR [95% CI]: 0.69 [0.66-0.72], 0.73 [0.68-0.79], and 0.89 [0.79-0.99], respectively); these are conditions in which APOL1 variants promote kidney disease. By contrast, the significant survival advantage of AA dialysis patients was not observed in patients with ESRD attributed to other kidney disease (including polycystic kidney disease, interstitial nephritis, and pyelonephritis) and other GN, which are not associated with APOL1 variants. CONCLUSIONS: These data suggest the hypothesis that the relative survival advantage of AA dialysis patients may be related to APOL1 variation. Further large population-based genetic studies are required to test this hypothesis.

17.
J Am Heart Assoc ; 8(6): e011869, 2019 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-30885048

RESUMO

Background Although studies have shown that statin therapy in patients with non-dialysis-dependent chronic kidney disease was associated with a lower risk of death, this was not observed in dialysis patients newly initiated on statins. It is unclear if statin therapy benefits administered during the predialysis period persist after transitioning to end-stage renal disease. Methods and Results In 47 720 veterans who transitioned to end-stage renal disease during 2007 to 2014, we examined the association of statin therapy use 1 year before transition with posttransition all-cause and cardiovascular mortality and hospitalization incidence rates over the first 12 months of follow-up. Associations were examined using multivariable adjusted Cox proportional hazard models and negative binomial regressions. Sensitivity analyses included propensity score and subgroup analyses. The cohort's mean± SD age was 71±11 years, and the cohort included 4% women, 23% blacks, and 66% diabetics. Over 12 months of follow-up, there were 13 411 deaths, with an incidence rate of 35.3 (95% CI , 34.7-35.8) deaths per 100 person-years. In adjusted models, statin therapy compared with no statin therapy was associated with lower risks of 12-month all-cause (hazard ratio [95% CI], 0.79 [0.76-0.82]) and cardiovascular (hazard ratio [95% CI ], 0.83 [0.78-0.88]) mortality, as well as with a lower rate of hospitalizations (incidence rate ratio [95% CI ], 0.89 [0.87-0.92]) after initiating dialysis. These lower outcome risks persisted across strata of clinical characteristics, and in propensity score analyses. Conclusions Among veterans with non-dialysis-dependent chronic kidney disease, treatment with statin therapy within the 1 year before transitioning to end-stage renal disease is associated with favorable early end-stage renal disease outcomes.

18.
J Clin Endocrinol Metab ; 104(10): 4848-4856, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-30920627

RESUMO

CONTEXT: In end-stage renal disease (ESRD), serum high-density lipoprotein cholesterol (HDL-C) level is not an accurate predictor of mortality, partly because it does not necessarily correlate with indices of HDL function. Paraoxonase (PON) is a major enzyme constituent of HDL and a key component of HDL antioxidant activity. Apolipoprotein A-I (Apo A-1) is the core HDL structural protein that plays a major role in various aspects of HDL function. OBJECTIVE: We sought to examine PON activity and Apo A-I levels in patients with ESRD vs healthy controls. DESIGN AND SETTING: PON/arylesterase activity was measured in 499 patients with maintenance hemodialysis (MHD) and 24 healthy controls with similar distributions of age, sex, and race/ethnicity. Serum acrolein-modified Apo A-I was measured in 30 patients with MHD and 10 healthy controls. MAIN OUTCOME MEASURES: Multilevel Cox models were used to assess associations among PON activity, Apo A-I, and HDL-C levels with 12-month all-cause mortality. RESULTS: PON activity was significantly lower in patients with MHD vs controls. Furthermore, acrolein-modified Apo A-I levels were higher in patients with MHD vs controls. In fully adjusted models, high PON activity was associated with lower 12-month mortality, whereas no difference of mortality risk was observed across HDL-C levels. The combination of high PON and low Apo A-I compared with low PON and low Apo A-I was associated with lower mortality risk. CONCLUSIONS: In patients with MHD, PON activity had a stronger association with 12-month mortality than HDL-C. Future studies are needed to examine the role of these markers as potential diagnostic and therapeutic tools in ESRD.

19.
Am J Kidney Dis ; 73(6): 797-805, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30833086

RESUMO

RATIONALE & OBJECTIVE: The association of estimated glomerular filtration rate (eGFR) at dialysis therapy initiation with mortality among adult dialysis patients has been greatly debated, with some studies showing no benefit from early dialysis therapy initiation. However, this association has not been well investigated in pediatric dialysis patients. The objective of this study was to evaluate the mortality risk associated with eGFR at dialysis therapy initiation in children and adolescents with kidney failure. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: 9,963 incident dialysis patients aged 1 to 17 years in the US Renal Data System registry (1995-2016). PREDICTOR: eGFRs at dialysis therapy initiation calculated using the pediatric-specific bedside Schwartz equation (<5, 5-<7, 7-<9, 9-<12, and ≥12mL/min/1.73m2). OUTCOME: Time to all-cause death. ANALYTICAL APPROACH: Cox proportional hazards regression adjusted for case-mix variables, height, body mass index, hemoglobin level, and serum albumin level. RESULTS: Median eGFR was 7.8 (IQR, 5.6-10.5) mL/min/1.73m2 and median age was 13 (IQR, 9-16) years. 696 deaths were observed during the median follow-up of 1.4 (IQR, 0.7-2.7) years, and overall crude mortality rate was 31 per 1,000 patient-years. There appeared to be a trend toward higher mortality risk across higher eGFRs at dialysis therapy initiation. Compared with eGFRs of 7 to <9mL/min/1.73m2, eGFRs <5 and ≥12mL/min/1.73m2 were associated with lower and higher mortality, with adjusted HRs of 0.57 (95% CI, 0.43-0.74) and 1.31 (95% CI, 1.05-1.65), respectively. In age-stratified analysis, there were consistent relationships among patients 6 years and older while the eGFR-mortality association was attenuated among patients younger than 6 years (Pinteraction = 0.002). LIMITATIONS: Possible errors in eGFRs due to methods for serum creatinine measurement. Unmeasured confounders related to eGFR at dialysis therapy initiation. CONCLUSIONS: Higher eGFR at dialysis therapy initiation was associated with higher mortality risk. Further studies of eGFR at initiation are needed in pediatric dialysis patients, especially among those younger than 6 years.

20.
Bone ; 124: 158-165, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30858148

RESUMO

BACKGROUND: Vitamin D deficiency is common among dialysis patients and may impact blood concentrations of calcium, phosphorus, intact parathyroid hormone (iPTH), and alkaline phosphatase (ALP). Seasonal variation of serum 25-hydroxyvitamin D [25(OH)D] concentrations has been well established for the general population; however, less is known about circannual variation in 25(OH)D as well as other parameters of mineral and bone disorder among dialysis patients. METHOD: Based on 57,500 serum 25(OH)D measurements collected over two years from January 2009 to December 2010 among 25,025 dialysis patients, we evaluated the circannual variations in serum concentrations of 25(OH)D, calcium, phosphorus, iPTH, and ALP by a linear regression model with a cosinor function for the time period (month). We adjusted for potential confounders including case-mix variables, and ultraviolet index. RESULTS: Serum 25(OH)D concentrations showed significant circannual variation and mean serum 25(OH)D was 3.2 ng/mL higher in summer than in winter. Furthermore, 25(OH)D concentration increased steadily by 1.3 ng/mL per year. While serum calcium concentrations showed statistically significant but clinically negligible seasonal variation (0.02 mg/dL in peak-trough difference), serum phosphorus did not follow such a pattern. Serum iPTH concentrations also showed a modest seasonal variation with 9% higher values in winter than in summer. Concordantly, ALP concentrations in the winter were 2% higher than in the summer time. Seasonal variation of 25(OH)D was greater in male (vs. female), African-American (vs. non-African-American), and younger (vs. older) dialysis patients. CONCLUSION: Serum 25(OH)D and iPTH concentrations show seasonal variation among dialysis patients while the variation in other parameters of mineral and bone disorder was clinically irrelevant, if any. Serum 25(OH)D also showed a gradual increase over time. Clinicians and researchers should be aware of these changes when interpreting laboratory results in dialysis patients.

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