Dataset Information

Progressive Decline in Estimated GFR in Patients With Sickle Cell Disease: An Observational Cohort Study.

ABSTRACT:

Rationale & objective

Progression of chronic kidney disease (CKD) in sickle cell disease (SCD) and its risk factors remain poorly defined. We identified characteristics associated with CKD as well as decline in estimated glomerular filtration rate (eGFR) and presence of proteinuria over time in adults with SCD.

Study design

Retrospective observational study.

Setting & participants

Patients with SCD 18 years or older in a single center from 2004 to 2013.

Predictors

Baseline clinical and laboratory measures, comorbid conditions, SCD-related complications, relevant treatments, and severity of genotypes defined as severe (homozygous SCD [HbSS]/sickle-β⁰-thalassemia [HbSβ⁰]) or mild (hemoglobin SC disease [HbSC]/sickle-β⁺-thalassemia [HbSβ⁺]-thalassemia).

Outcomes

Presence at baseline of CKD, defined here as eGFR<90mL/min/1.73m² or proteinuria (≥1+) on urinalysis or current kidney transplant or dialysis therapy; change in eGFR; and presence of proteinuria over time.

Analytical approach

Logistic regression for baseline CKD. Linear mixed-effects model for eGFR decline and generalized linear mixed-effects model for proteinuria during the study period evaluating for interaction with time. Stratified by genotype severity.

Results

Among 427 patients, 331 had 2 or more measurements of creatinine. During a median follow-up of 4.01 (interquartile range, 1.66-7.19) years, annual eGFR decline was 2.05mL/min/1.73m² for severe genotypes (P<0.001) and 1.16mL/min/1.73m² (P=0.02) for mild genotypes. At baseline, 21.4% of patients with severe genotypes had CKD versus 17.2% of those with mild genotypes. For severe genotypes, angiotensin-converting enzyme-inhibitor/angiotensin receptor blocker use (OR, 6.10; 95% CI, 2.03-18.29; P=0.001) and avascular necrosis (OR, 0.40; 95% CI, 0.16-0.97; P=0.04) were associated with baseline CKD. Among those with mild genotypes, higher hemoglobin level was associated with lower probability of CKD (OR per 1-g/dL greater hemoglobin level, 0.63; 95% CI, 0.43-0.93; P=0.02). Rate of eGFR decline was inversely related to hemoglobin level (β = 0.46 [SE, 0.23]; P=0.04) within the severe genotype subgroup. No factors were identified to be associated with proteinuria over time.

Limitations

Retrospective observational study, limited direct measures of albuminuria.

Conclusions

Patients with SCD exhibit rapid decline in eGFR over time. Decline in eGFR is associated with markers of disease severity and associated comorbid conditions.

SUBMITTER: Derebail VK

PROVIDER: S-EPMC9449709 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Publications

Progressive Decline in Estimated GFR in Patients With Sickle Cell Disease: An Observational Cohort Study.

Derebail Vimal K VK Ciccone Emily J EJ Zhou Qingning Q Kilgore R Rosina RR Cai Jianwen J Ataga Kenneth I KI

American journal of kidney diseases : the official journal of the National Kidney Foundation 20190221 1

<h4>Rationale & objective</h4>Progression of chronic kidney disease (CKD) in sickle cell disease (SCD) and its risk factors remain poorly defined. We identified characteristics associated with CKD as well as decline in estimated glomerular filtration rate (eGFR) and presence of proteinuria over time in adults with SCD.<h4>Study design</h4>Retrospective observational study.<h4>Setting & participants</h4>Patients with SCD 18 years or older in a single center from 2004 to 2013.<h4>Predictors</h4>Ba ...[more]

PMID: 30797615

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Project description:ImportanceIndividuals with sickle cell disease (SCD) have reduced life expectancy; however, there are limited data available on lifetime income in patients with SCD.ObjectiveTo estimate life expectancy, quality-adjusted life expectancy, and income differences between a US cohort of patients with SCD and an age-, sex-, and race/ethnicity-matched cohort without SCD.Design, setting, and participantsCohort simulation modeling was used to (1) build a prevalent SCD cohort and a matched non-SCD cohort, (2) identify utility weights for quality-adjusted life expectancy, (3) calculate average expected annual personal income, and (4) model life expectancy, quality-adjusted life expectancy, and lifetime incomes for SCD and matched non-SCD cohorts. Data sources included the Centers for Disease Control and Prevention, National Newborn Screening Information System, and published literature. The target population was individuals with SCD, the time horizon was lifetime, and the perspective was societal. Model data were collected from November 29, 2017, to March 21, 2018, and the analysis was performed from April 28 to December 3, 2018.Main outcomes and measuresLife expectancy, quality-adjusted life expectancy, and projected lifetime income.ResultsThe estimated prevalent population for the SCD cohort was 87 328 (95% uncertainty interval, 79 344-101 398); 998 were male and 952 were female. Projected life expectancy for the SCD cohort was 54 years vs 76 years for the matched non-SCD cohort; quality-adjusted life expectancy was 33 years vs 67 years, respectively. Projected lifetime income was $1 227 000 for an individual with SCD and $1 922 000 for a matched individual without SCD, reflecting a lost income of $695 000 owing to the 22-year difference in life expectancy. One study limitation is that the higher estimates of life expectancy yielded conservative estimates of lost life-years and income. The analysis only considered the value of lost personal income owing to premature mortality and did not consider direct medical costs or other societal costs associated with excess morbidity (eg, lost workdays for disability, time spent in the hospital). The model was most sensitive to changes in income levels and mortality rates.Conclusions and relevanceIn this simulated cohort modeling study, SCD had societal consequences beyond medical costs in terms of reduced life expectancy, quality-adjusted life expectancy, and lifetime earnings. These results underscore the need for disease-modifying therapies to improve the underlying morbidity and mortality associated with SCD.

Project description:Rationale & objectiveChronic kidney disease (CKD) is associated with impaired physical performance. However, the association between albuminuria, a marker of vascular endothelial dysfunction, and physical performance has not been fully characterized. We hypothesized that estimated glomerular filtration rate (eGFR) and albuminuria would be independently associated with physical performance.Study designCross-sectional analysis.Setting & participantsA total of 571 adults with and without CKD.PredictorsCreatinine-based eGFR (eGFRCr) and cystatin C-based eGFR (eGFRCysC) and urine albumin to creatinine ratio (UACR).OutcomeShort Physical Performance Battery (SPPB).Analytical approachUnivariate and multivariable logistic regression models were used to examine associations of eGFR and UACR with impaired physical performance.ResultsOf the 571 participants (mean age, 69.3 years), 157 (27.5%) had eGFRCr (mL/min/1.73m2) <30, 276 (48.3%) had eGFRCr 30-<60, and 138 (24.2%) had eGFRCr ≥60; 303 (55.3%) participants had eGFRcysC <30, 141 (25.7%) had eGFRcysC 30-<60, and 104 (19.0%) had eGFRcysC ≥60. Impaired physical performance was observed in 222 (38.9%) participants. Separate univariate analyses showed that lower eGFRCr, lower eGFRCysC, and higher UACR were associated with higher odds of impaired physical performance. In the adjusted model with eGFRCr or eGFRCysC, UACR, and covariates, UACR retained a statistically significant association with impaired physical performance (adjusted odds ratio [OR], 2.04; 95% confidence interval [CI], 1.21-3.47 for UACR from 30-300 mg/g vs <30 mg/g and adjusted OR, 1.93; 95% CI, 1.01-3.69 for UACR >300 mg/g vs <30 mg/g), but eGFRCr and eGFRCysC did not.LimitationsCross-sectional analysis, estimated rather than measured GFR.ConclusionsOnly UACR was associated with worse physical performance in the fully adjusted model, suggesting that vascular endothelial function and inflammation may be important mechanisms of decreased physical function. Similar results were found using eGFRCr or eGFRCysC, suggesting that confounding based on muscle mass does not explain the lack of an association between eGFRCr and physical performance.

Project description:BackgroundCardiac structural abnormalities, common in African Americans, are associated with adverse clinical outcomes. Associations between echocardiography-measured subclinical heart failure and kidney function decline are unknown and may identify novel risk factors for kidney disease in this population.Study designProspective cohort study.Setting & participants2,418 Jackson Heart Study participants with baseline echocardiograms and longitudinal measures of estimated glomerular filtration rate (eGFR) calculated from the CKD-EPI creatinine equation. 2,219 participants had baseline eGFRs≥60mL/min/1.73m2.PredictorsLeft ventricular mass (LVM) and ejection fraction (LVEF) and pulmonary artery systolic pressure (PASP) quantified from baseline echocardiograms.OutcomesPrimary outcome was >30% eGFR decline or progression to end-stage renal disease (ESRD; need for dialysis therapy) over a mean of 8 years. Secondary outcome, eGFR<60mL/min/1.73m2 or progression to ESRD and eGFR decline >1mL/min/1.73m2 per year among those with baseline eGFRs≥60mL/min/1.73m2.MeasurementsLogistic regression models, adjusted for demographics, physical characteristics, comorbid conditions, and medication use.ResultsMean age was 52.2±11.9 (SD) years, 37% of participants were men; mean baseline eGFR was 87.3±17.3mL/min/1.73m2. The primary and secondary outcomes occurred in 148 (6.1%) and 162 (7.1%) participants, respectively. In unadjusted models, every 25-g greater LVM was significantly associated with greater odds of eGFR decline > 30% or ESRD (OR, 1.38; 95% CI, 1.26-1.51) and incident eGFR<60mL/min/1.73m2 or ESRD (OR, 1.30; 95% CI, 1.20-1.42); only the former remained statistically significant after adjustment. There was no association of LVEF or PASP with either eGFR decline > 30% or ESRD (LVEF: adjusted OR, 0.95 [95% CI, 0.84-1.07]; PASP: adjusted OR, 0.98 [95% CI, 0.87-1.11]) or incident eGFR<60mL/min/1.73m2 or ESRD (LVEF: adjusted OR, 0.98 [95% CI, 0.86-1.11]; PASP: adjusted OR, 1.05 [95% CI, 0.94-1.18]) in multivariable models.LimitationsNo midstudy creatinine measurement at examination 2.ConclusionsGreater LVM was significantly associated with eGFR decline > 30% or ESRD among African Americans in a community-based cohort. Treating and reversing elevated LVM may reduce the burden and progression of kidney disease in this high-risk population.

Project description:BACKGROUND:Low ankle-brachial index (ABI) is associated with increases in serum creatinine level. Whether low ABI is associated with the development of rapid estimated glomerular filtration rate (eGFR) decline, stage 3 chronic kidney disease (CKD), or microalbuminuria is uncertain. STUDY DESIGN:Prospective cohort study. SETTING & PARTICIPANTS:Framingham Offspring cohort participants who attended the sixth (1995-1998) and eighth (2005-2008) examinations. PREDICTOR:ABI, categorized as normal (>1.1 to <1.4), low-normal (>0.9 to 1.1), and low (?0.9). OUTCOMES:Rapid eGFR decline (eGFR decline ?3 mL/min/1.73 m(2) per year), incident stage 3 CKD (eGFR <60 mL/min/1.73 m(2)), incident microalbuminuria. MEASUREMENTS:GFR was estimated using the serum creatinine-based CKD-EPI (CKD Epidemiology Collaboration) equation. Urinary albumin-creatinine ratio (UACR) was determined based on spot urine samples. RESULTS:During 9.5 years, 9.0% (232 of 2,592) experienced rapid eGFR decline and 11.1% (270 of 2,426) developed stage 3 CKD. Compared to normal ABI, low ABI was associated with 5.73-fold increased odds of rapid eGFR decline (95% CI, 2.77-11.85; P<0.001) after age, sex, and baseline eGFR adjustment; this persisted after multivariable adjustment for standard CKD risk factors (OR, 3.60; 95% CI, 1.65-7.87; P = 0.001). After adjustment for age, sex, and baseline eGFR, low ABI was associated with a 2.51-fold increased odds of stage 3 CKD (OR, 2.51; 95% CI, 1.16-5.44; P = 0.02), although this was attenuated after multivariable adjustment (OR, 1.68; 95% CI, 0.75-3.76; P = 0.2). In 1,902 free of baseline microalbuminuria, low ABI was associated with increased odds of microalbuminuria after adjustment for age, sex, and baseline UACR (OR, 2.81; 95% CI, 1.07-7.37; P = 0.04), with attenuation upon further adjustment (OR, 1.88; P = 0.1). LIMITATIONS:Limited number of events with low ABI. Outcomes based on single serum creatinine and UACR measurements at each examination. CONCLUSIONS:Low ABI is associated with an increased risk of rapid eGFR decline, suggesting that systemic atherosclerosis predicts a decrease in kidney function.

Dataset Information

Progressive Decline in Estimated GFR in Patients With Sickle Cell Disease: An Observational Cohort Study.

Rationale & objective

Study design

Setting & participants

Predictors

Outcomes

Analytical approach

Results

Limitations

Conclusions

Publications

Progressive Decline in Estimated GFR in Patients With Sickle Cell Disease: An Observational Cohort Study.

Similar Datasets

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