Baseline kidney function as predictor of mortality and kidney disease progression in HIV-positive patients.
ABSTRACT: Chronic kidney disease (CKD) is associated with increased all-cause mortality and kidney disease progression. Decreased kidney function at baseline may identify human immunodeficiency virus (HIV)-positive patients at increased risk of death and kidney disease progression.Observational cohort study.7 large HIV cohorts in the United Kingdom with kidney function data available for 20,132 patients.Baseline estimated glomerular filtration rate (eGFR).Death and progression to stages 4-5 CKD (eGFR <30 mL/min/1.73 m(2) for >3 months) in Cox proportional hazards and competing-risk regression models.Median age at baseline was 34 (25th-75th percentile, 30-40) years, median CD4 cell count was 350 (25th-75th percentile, 208-520) cells/?L, and median eGFR was 100 (25th-75th percentile, 87-112) mL/min/1.73 m(2). Patients were followed up for a median of 5.3 (25th-75th percentile, 2.0-8.9) years, during which 1,820 died and 56 progressed to stages 4-5 CKD. A U-shaped relationship between baseline eGFR and mortality was observed. After adjustment for potential confounders, eGFRs <45 and >105 mL/min/1.73 m(2) remained associated significantly with increased risk of death. Baseline eGFR <90 mL/min/1.73 m(2) was associated with increased risk of kidney disease progression, with the highest incidence rates of stages 4-5 CKD (>3 events/100 person-years) observed in black patients with eGFR of 30-59 mL/min/1.73 m(2) and those of white/other ethnicity with eGFR of 30-44 mL/min/1.73 m(2).The relatively small numbers of patients with decreased eGFR at baseline and low rates of progression to stages 4-5 CKD and lack of data for diabetes, hypertension, and proteinuria.Although stages 4-5 CKD were uncommon in this cohort, baseline eGFR allowed the identification of patients at increased risk of death and at greatest risk of kidney disease progression.
Project description:Although symptoms of sleepiness and fatigue are common in adults with chronic kidney disease (CKD), little is known about the prevalence of these symptoms in children with CKD.Cross-sectional analysis within a cohort study.We describe the frequency and severity of sleep problems and fatigue and assess the extent of their association with measured glomerular filtration rate (mGFR) and health-related quality of life (HRQOL) in 301 participants of the Chronic Kidney Disease in Children cohort.Sleep and fatigue-related items from the Pediatric Quality of Life Inventory 4.0 Generic Scales and the CKD-related Symptoms List were used.Median mGFR was 42.0 mL/min/1.73 m(2) (25th-75th percentiles, 31.2-53.2), and median age was 13.9 years (25th-75th percentiles, 10.8-16.2). Children with mGFR of 40-<50, 30-<40, or <30 mL/min/1.73 m(2) had 2.07 (95% CI, 1.05-4.09), 2.35 (95% CI, 1.17-4.72), and 2.59 (95% CI, 1.15-5.85) higher odds of having more severe parent reports of low energy than children with mGFR > or = 50 mL/min/1.73 m(2). Compared with participants with mGFR > or = 50 mL/min/1.73 m(2), those with mGFR < 30 mL/min/1.73 m(2) had 3.92 (95% CI, 1.37-11.17) higher odds of reporting more severe weakness, and those with mGFR of 40-<50 mL/min/1.73 m(2) had 2.95 (95% CI, 1.26-6.88) higher odds of falling asleep during the day. Low energy, trouble sleeping, and weakness were associated with lower HRQOL scores.Symptoms of sleep and fatigue represent the child's or parent's perception of symptom severity, whereas individual items can lead to imprecise measurements of sleep and fatigue.Lower mGFR was associated with increased weakness, low energy, and daytime sleepiness. Furthermore, a strong association between trouble sleeping, low energy, and weakness with decreases in overall HRQOL was observed. Detection and treatment of poor sleep and fatigue may improve the development and HRQOL of children and adolescents with CKD.
Project description:OBJECTIVE:To examine whether lifestyle factors, including sedentary time and physical activity, could independently contribute to risk of end-stage renal disease (ESRD). STUDY DESIGN:Case-cohort study. SETTING:South-eastern USA. PARTICIPANTS:The Southern Community Cohort Study recruited ~86?000 black and white participants from 2002 to 2009. We assembled a case cohort of 692 incident ESRD cases and a probability sample of 4113 participants. PREDICTORS:Sedentary time was calculated as hours/day from daily sitting activities. Physical activity was calculated as metabolic equivalent (MET)-hours/day from engagement in light, moderate and vigorous activities. OUTCOMES:Incident ESRD. RESULTS:At baseline, among the subcohort, mean (SD) age was 52 (8.6) years, and median (25th, 75th centile) estimated glomerular filtration rate (eGFR) was 102.8 (85.9-117.9) mL/min/1.73?m2. Medians (25th-75th centile) for sedentary time and physical activity were 8.0 (5.5-12.0) hours/day and 17.2 (8.7-31.9) MET-hours/day, respectively. Median follow-up was 9.4 years. We observed significant interactions between eGFR and both physical activity and sedentary behaviour (p<0.001). The partial effect plot of the association between physical activity and log relative hazard of ESRD suggests that ESRD risk decreases as physical activity increases when eGFR is 90?mL/min/1.73?m2. The inverse association is most pronounced at physical activity levels >27 MET-hours/day. High levels of sitting time were associated with increased ESRD risk only among those with reduced kidney function (eGFR ?30?mL/min/1.73?m2); this association was attenuated after excluding the first 2?years of follow-up. CONCLUSIONS:In a population with a high prevalence of chronic kidney disease risk factors such as hypertension and diabetes, physical activity appears to be associated with reduced risk of ESRD among those with preserved kidney function. A positive association between sitting time and ESRD observed among those with advanced kidney disease is likely due to reverse causation.
Project description:BACKGROUND:In populations with prevalent chronic kidney disease (CKD), lower serum bicarbonate levels are associated with more rapid CKD progression, but whether lower bicarbonate levels also are associated with risk of incident estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m(2) and CKD progression among community-living persons with predominantly preserved kidney function is unknown. STUDY DESIGN:Longitudinal observational cohort study. SETTING & PARTICIPANTS:Well-functioning community-living elders aged 70-79 years at inception. PREDICTOR:Serum bicarbonate level measured at the time of collection by arterialized venous blood sample using an arterial blood gas analyzer. OUTCOMES:Change in eGFR over 7 years, and new eGFR < 60 mL/min/1.73 m(2) with a rate of loss of at least 1 mL/min/1.73 m(2) per year. MEASUREMENTS:Linear and logistic regressions were used to evaluate associations of baseline serum bicarbonate level with change in eGFR and incident eGFR < 60 mL/min/1.73 m(2). RESULTS:At baseline, mean eGFR was 84 ± 16 (SD)mL/min/1.73 m(2), and serum bicarbonate level was 25.2 ± 1.9 mmol/L. Compared with participants with higher bicarbonate concentrations (23.0-28.0 mmol/L), those with bicarbonate concentrations < 23 mmol/L (n = 85 [8%]) lost eGFR0.55 (95% CI, 0.13-0.97) mL/min/1.73 m(2) per year faster in models adjusted for demographics, CKD risk factors, baseline eGFR, and urine albumin-creatinine ratio. Among the 989 (92%) participants with baseline eGFRs > 60 mL/min/1.73 m(2), 252 (25%) developed incident eGFRs < 60 mL/min/1.73 m(2) at follow-up. Adjusting for the same covariates, participants with bicarbonate concentrations < 23 mmol/L had nearly 2-fold greater odds of incident eGFRs < 60 mL/min/1.73 m(2) (OR, 1.72; 95% CI, 0.97-3.07) compared with those with higher bicarbonate concentrations. LIMITATIONS:Only 2 measurements of kidney function separated by 7 years and loss to follow-up due to intervening mortality in this elderly population. CONCLUSIONS:Lower serum bicarbonate concentrations are associated independently with decline in eGFR and incident eGFR < 60 mL/min/1.73 m(2) in community-living older persons. If confirmed, serum bicarbonate levels may give insight into kidney tubule health in persons with preserved eGFRs and suggest a possible new target for intervention to prevent CKD development.
Project description:INTRODUCTION:The Southern Community Cohort Study is a prospective study of low socioeconomic status (SES) blacks and whites from the southeastern US, where the burden of end-stage renal disease (ESRD) and its risk factors are high. We tested whether the 2.4-fold elevated risk of ESRD we previously observed in blacks compared to whites was explained by differences in baseline kidney function. METHODS:We conducted a case-cohort study of incident ESRD cases (n = 737) with stored blood and a probability sampled subcohort (n = 4238) and calculated estimated glomerular filtration rate (eGFR) from serum creatinine. 86% of participants were enrolled from community health centers in medically underserved areas and 14% from the general population in 12 states in the southeastern United States. Incident ESRD after entry into the cohort was ascertained by linkage of the cohort with the US Renal Data System (USRDS). RESULTS:Median (25th, 75th percentile) eGFR at baseline was 63.3 (36.0, 98.2) ml/min/1.73m2 for ESRD cases and 103.2 (86.0, 117.9) for subcohort. Black ESRD cases had higher median (25th, 75th) eGFR [63.3 (35.9, 95.9)] compared to whites [59.1 (39.4, 99.2)]. In multivariable Cox models accounting for sampling weights, baseline eGFR was a strong predictor of ESRD risk, and an interaction with race was detected (P = 0.029). The higher ESRD risk among blacks relative to whites persisted (hazard ratio: 2.58; 95% confidence interval: 1.65, 4.03) after adjustment for eGFR. CONCLUSION:In this predominantly lower SES cohort, the racial disparity in ESRD risk is not explained by differences in baseline kidney function.
Project description:The Brain in Kidney Disease (BRINK) Study aims to identify mechanisms that contribute to increased risk for cognitive impairment in patients with chronic kidney disease (CKD). We describe the rationale, design, and methods of the study and report baseline recruitment and cognitive function results.Longitudinal observational cohort study of the epidemiology of cognitive impairment in CKD. The primary aim is to characterize the association between (1) baseline and incident stroke, white matter disease, estimated glomerular filtration rate (eGFR), inflammation, microalbuminuria, and dialysis initiation and (2) cognitive decline over 3 years in a CKD cohort with a mean eGFR<45 mL/min/1.73 m(2).Community-dwelling participants 45 years or older recruited from 4 health systems into 2 groups: reduced eGFR, defined as eGFR<60 mL/min/1.73 m(2) (non-dialysis dependent), and control, defined as eGFR?60 mL/min/1.73 m(2).eGFR group.Performance on cognitive function tests and structural brain magnetic resonance imaging.Sequential cognitive and physical function testing, serum and urine biomarker measurement, and brain magnetic resonance images over 3 years.Of 554 participants, mean age was 69.3 years; 333, 88, and 133 had eGFRs<45 (non-dialysis dependent, nontransplantation), 45 to <60, and ?60 (controls) mL/min/1.73 m(2), respectively. Mean eGFR in reduced-eGFR participants was 34.3 mL/min/1.73 m(2). Baseline cognitive performance was significantly associated with eGFR in all domains except language. Participants with eGFRs<30 mL/min/1.73 m(2) performed significantly worse than those with eGFRs?30 mL/min/1.73 m(2) on tests of memory, processing speed, and executive function. Participants with reduced eGFRs overall scored worst on the Immediate Brief Visual-Spatial Memory Test-Revised.Healthy cohort bias, competing risk for death versus cognitive decline.Cognitive function was significantly worse in participants with eGFRs<30 mL/min/1.73 m(2). Future BRINK analyses will measure risk factors for cognitive decline using the longitudinal data.
Project description:Background:Exposure to vitamin K antagonists (VKA) has been suggested to accelerate progression of chronic kidney disease (CKD) but robust clinical data are currently lacking. Methods:We retrospectively evaluated the impact of VKA exposure on kidney function in patients with atrial fibrillation (AF) and CKD stage 3/4. Patients were prospectively followed within a primary care electronic database (median follow-up of 1.45 years). The kidney function trajectory over time, defined as the annualized change in estimated glomerular filtration rate (eGFR), was analyzed with linear mixed-effects regression including propensity score adjustment. Results:14 432 patients (median age 78 years, median CHA 2 DS 2-VASc score 4 points) contributed 97 792 eGFR measurements (mean 6.8 measurements/patient; range: 1-197). Mean baseline eGFR was 50.3 mL/min/1.73 m2; and declined by 1.10 mL/min/1.73 m2/year (95% CI: 0.91-1.28, P < 0.0001). In 7409 patients with VKA exposure, CKD progression was significantly faster compared to patients without VKA exposure (5-year absolute eGFR loss from baseline: 6.0 mL/min/1.73 m2 vs 4.5 mL/min/1.73 m2, for an absolute 5-year excess eGFR decline with VKA exposure of 1.5 mL/min/1.73 m2 (95% CI: 0.4-2.7, P = 0.002). These results prevailed upon adjusting for CHA 2 DS 2-VASc score and other potential imbalances in prognostic variables, and in several sensitivity analyses. In the group without documented VKA exposure, 1775 VKA patients (24%) and 1012 patients (14%) developed a 30% decline in eGFR during follow-up (P < 0.0001). Conclusions:In patients with AF and CKD, VKA use is associated with accelerated eGFR decline. Within the limitations of a retrospective analysis, this finding supports the "VKA-renal-calcification hypothesis." However, although statistically significant, the excess loss in eGFR over 5 years with VKA was modest.
Project description:BACKGROUND:Estimation of GFR (eGFR) using formulae based on serum creatinine concentrations are commonly used to assess kidney function. Physical exercise can increase creatinine turnover and lean mass; therefore, this method may not be suitable for use in exercising individuals. Cystatin-C based eGFR formulae may be a more accurate measure of kidney function when examining the impact of exercise on kidney function. The aim of this study was to assess the agreement of four creatinine and cystatin-C based estimates of GFR before and after a 12-month exercise intervention. METHODS:One hundred forty-two participants with stage 3-4 chronic kidney disease (CKD) (eGFR 25-60 mL/min/1.73 m2) were included. Subjects were randomised to either a Control group (standard nephrological care [n = 68]) or a Lifestyle Intervention group (12 months of primarily aerobic based exercise training [n = 74]). Four eGFR formulae were compared at baseline and after 12 months: 1) MDRDcr, 2) CKD-EPIcr, 3) CKD-EPIcys and 4) CKD-EPIcr-cys. RESULTS:Control participants were aged 63.5[9.4] years, 60.3% were male, 42.2% had diabetes, and had an eGFR of 40.5 ± 8.9 ml/min/1.73m2. Lifestyle Intervention participants were aged 60.5[14.2] years, 59.5% were male, 43.8% had diabetes, and had an eGFR of 38.9 ± 8.5 ml/min/1.73m2. There were no significant baseline differences between the two groups. Lean mass (r = 0.319, p < 0.01) and grip strength (r = 0.391, p < 0.001) were associated with serum creatinine at baseline. However, there were no significant correlations between cystatin-C and the same measures. The Lifestyle Intervention resulted in significant improvements in exercise capacity (+ 1.9 ± 1.8 METs, p < 0.001). There were no changes in lean mass in both Control and Lifestyle Intervention groups during the 12 months. CKD-EPIcys was considerably lower in both groups at both baseline and 12 months than CKD-EPIcr (Control = - 10.5 ± 9.1 and - 13.1 ± 11.8, and Lifestyle Intervention = - 7.9 ± 8.6 and - 8.4 ± 12.3 ml/min/1.73 m2), CKD-EPIcr-cys (Control = - 3.6 ± 3.7 and - 4.5 ± 4.5, and Lifestyle Intervention = - 3.6 ± 3.7 and - 2.5 ± 5.5 ml/min/1.73 m2) and MDRDcr (Control = - 9.3 ± 8.4 and - 12.0 ± 10.7, Lifestyle Intervention = - 6.4 ± 8.4 and - 6.9 ± 11.2 ml/min/1.73 m2). CONCLUSIONS:In CKD patients participating in a primarily aerobic based exercise training, without improvements in lean mass, cystatin-C and creatinine based eGFR provided similar estimates of kidney function at both baseline and after 12 months of exercise training. TRIAL REGISTRATION:The trial was registered at www.anzctr.org.au (Registration Number ANZCTR12608000337370) on the 17/07/2008 (retrospectively registered).
Project description:BACKGROUND:Chronic kidney disease (CKD) progression among German patients in a representative setting has not been described previously. The Verband Deutsche Nierenzentren and Chronic Kidney Disease Outcomes and Practice Patterns Study established a longitudinal observational cohort among German CKD patients to research variations in patient care and outcomes in real-world nephrology practices. METHODS:A cohort of CKD Stages 3 (25%) and 4 (75%) patients was established from German nephrologist-run CKD clinics in 2013-16. Linear models were used to determine the estimated glomerular filtration rate (eGFR) slope during follow-up and Cox models were used to assess outcomes of end-stage kidney disease (ESKD) and death. RESULTS:A total of 1834 patients (median age 75?years, 58% male, 42% diabetics, median baseline eGFR 25?mL/min/1.73?m2) were followed for a median of 29?months. More than 50% had slow or no decline and 17% declined ?5?mL/min/1.73?m2/year. After 4.5?years, the incidence of ESKD was 8% and of deaths without ESKD 16% among patients with eGFR??30?mL/min/1.73?m2 and 37% and 19% for eGFR?<30?mL/min/1.73?m2. Adjusted models showed higher risks of ESKD or death for patients with worse kidney function at baseline, male sex, diabetes and higher blood pressure; a higher risk of ESKD with higher albuminuria; and a higher risk of death with older age or cardiovascular comorbidity. CONCLUSIONS:Routine nephrology care of patients in Germany comprises mostly elderly patients, many with slow CKD progression. Identification of risk factors for CKD progression and mortality may help guide resources by closer follow-up of high-risk patients.
Project description:Introduction:Cardiac biomarkers soluble ST2 (sST2) and galectin-3 may reflect cardiac inflammation and fibrosis. It is plausible that these mechanisms may also contribute to the progression of kidney disease. We examined associations of sST2 and galectin-3 with kidney function decline in participants with chronic kidney disease (CKD). Methods:This was a pooled analysis of 2 longitudinal cohorts of participants with CKD: the Clinical Phenotyping and Resource Biobank (C-PROBE) study and the Seattle Kidney Study (SKS). We measured circulating concentrations of sST2 and galectin-3 at baseline. Our primary outcome was progression to estimated glomerular filtration rate (eGFR) <15 ml/min per 1.73 m2 or end-stage renal disease (ESRD). We used competing risk Cox regression models to study the association of sST2 and galectin-3 with CKD progression, adjusting for demographics, kidney function, and comorbidity. Results:Among the 841 participants in the pooled cohort, baseline eGFR was 51 ± 27 ml/min per 1.73 m2 and median urine albumin-to-creatinine ratio (UACR) was 141 (interquartile range = 15-736) mg/g. Participants with higher sST2 and galectin-3 were more likely to be older, to have heart failure and diabetes, and to have lower eGFR. Adjusting for demographics, kidney function, and comorbidity, every doubling of sST2 was not associated with progression to eGFR <15 ml/min per 1.73 m2 or ESRD (adjusted hazard ratio 1.02, 95% confidence interval = 0.76-1.38). Every doubling of galectin-3 was significantly associated with a 38% (adjusted hazard ratio = 1.35, 95% confidence interval = 1.01-1.80) increased risk of progression to eGFR <15 ml/min per 1.73 m2 or ESRD. Conclusion:Higher concentrations of the cardiac biomarker galectin-3 may be associated with progression of CKD, highlighting potential novel mechanisms that may contribute to the progression of kidney disease.
Project description:The prognostic significance of histopathologic (sub)classes in the current classification of lupus nephritis (LN) is controversial. We analyzed clinical and histopathologic predictors of renal outcome in LN outside the framework of the classification.Variables (50 histopathologic and ten clinical) were tested in mixed, linear, and Cox regression models for their association with renal flare, ESRD, and eGFR during follow-up (1, 5, and 10 years) in 105 patients with LN who underwent biopsy from 1987 to 2011. The Cockcroft-Gault (normalized to a body surface area of 1.73 m2) and Schwartz formulas were used to calculate eGFR for adults and children, respectively.During median follow-up of 9.9 years (25th-75th percentile, 5.9-13.8), 47 patients experienced a renal flare and 21 progressed to ESRD. Renal flare was predicted by fibrinoid necrosis (hazard ratio [HR], 1.04 per %; 95% confidence interval [95% CI], 1.00 to 1.07) and nonwhite race (HR, 2.23; 95% CI, 1.23 to 4.04). ESRD was predicted by fibrinoid necrosis (HR, 1.08 per %; 95% CI, 1.02 to 1.13), fibrous crescents (HR, 1.09 per %; 95% CI, 1.02 to 1.17), interstitial fibrosis/tubular atrophy (IF/TA) ?25% (HR, 3.89; 95% CI, 1.25 to 12.14), eGFR at baseline (HR, 0.98 per ml/min per 1.73 m2; 95% CI, 0.97 to 1.00), and nonwhite race (HR, 7.16; 95% CI, 2.34 to 21.91). A higher mean eGFR during follow-up was associated with normal glomeruli (+0.2 ml/min per 1.73 m2 per %; 95% CI, 0.1 to 0.4). Like ESRD, a lower eGFR during follow-up was associated with fibrous crescents, IF/TA?25%, and nonwhite race, as well as with cellular/fibrocellular crescents (-0.4 ml/min per 1.73 m2 per %; 95% CI, -0.6 to -0.2) and age (-0.8 ml/min per 1.73 m2 per year; 95% CI, -1.2 to -0.4).The LN classification should include an index of evidence-based prognosticators. Awaiting validation of a formal index, we suggest that at least fibrinoid necrosis, fibrous crescents, and IF/TA warrant explicit independent scoring to assess the risk of progressive renal dysfunction in conjunction with clinical findings.