Predicting the risks of kidney failure and death in adults with moderate to severe chronic kidney disease: multinational, longitudinal, population based, cohort study
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SUBMITTER: Liu P
PROVIDER: S-EPMC11017135 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
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Project description:Rationale & objectiveEarly prediction of chronic kidney disease (CKD) progression to end-stage kidney disease (ESKD) currently use Cox models including baseline estimated glomerular filtration rate (eGFR) only. Alternative approaches include a Cox model that includes eGFR slope determined over a baseline period of time, a Cox model with time varying GFR, or a joint modeling approach. We studied if these more complex approaches may further improve ESKD prediction.Study designProspective cohort.Setting & participantsWe re-used data from two CKD cohorts including patients with baseline eGFR >30ml/min per 1.73m2. MASTERPLAN (N = 505; 55 ESKD events) was used as development dataset, and NephroTest (N = 1385; 72 events) for validation.PredictorsAll models included age, sex, eGFR, and albuminuria, known prognostic markers for ESKD.Analytical approachWe trained the models on the MASTERPLAN data and determined discrimination and calibration for each model at 2 years follow-up for a prediction horizon of 2 years in the NephroTest cohort. We benchmarked the predictive performance against the Kidney Failure Risk Equation (KFRE).ResultsThe C-statistics for the KFRE was 0.94 (95%CI 0.86 to 1.01). Performance was similar for the Cox model with time-varying eGFR (0.92 [0.84 to 0.97]), eGFR (0.95 [0.90 to 1.00]), and the joint model 0.91 [0.87 to 0.96]). The Cox model with eGFR slope showed the best calibration.ConclusionIn the present studies, where the outcome was rare and follow-up data was highly complete, the joint models did not offer improvement in predictive performance over more traditional approaches such as a survival model with time-varying eGFR, or a model with eGFR slope.
| S-EPMC6508737 | biostudies-literature
Project description:Identifying patients at risk of chronic kidney disease (CKD) progression may facilitate more optimal nephrology care. Kidney failure risk equations, including such factors as age, sex, estimated glomerular filtration rate, and calcium and phosphate concentrations, were previously developed and validated in 2 Canadian cohorts. Validation in other regions and in CKD populations not under the care of a nephrologist is needed.To evaluate the accuracy of the risk equations across different geographic regions and patient populations through individual participant data meta-analysis.Thirty-one cohorts, including 721,357 participants with CKD stages 3 to 5 in more than 30 countries spanning 4 continents, were studied. These cohorts collected data from 1982 through 2014.Cohorts participating in the CKD Prognosis Consortium with data on end-stage renal disease.Data were obtained and statistical analyses were performed between July 2012 and June 2015. Using the risk factors from the original risk equations, cohort-specific hazard ratios were estimated and combined using random-effects meta-analysis to form new pooled kidney failure risk equations. Original and pooled kidney failure risk equation performance was compared, and the need for regional calibration factors was assessed.Kidney failure (treatment by dialysis or kidney transplant).During a median follow-up of 4 years of 721,357 participants with CKD, 23,829 cases kidney failure were observed. The original risk equations achieved excellent discrimination (ability to differentiate those who developed kidney failure from those who did not) across all cohorts (overall C statistic, 0.90; 95% CI, 0.89-0.92 at 2 years; C statistic at 5 years, 0.88; 95% CI, 0.86-0.90); discrimination in subgroups by age, race, and diabetes status was similar. There was no improvement with the pooled equations. Calibration (the difference between observed and predicted risk) was adequate in North American cohorts, but the original risk equations overestimated risk in some non-North American cohorts. Addition of a calibration factor that lowered the baseline risk by 32.9% at 2 years and 16.5% at 5 years improved the calibration in 12 of 15 and 10 of 13 non-North American cohorts at 2 and 5 years, respectively (P?=?.04 and P?=?.02).Kidney failure risk equations developed in a Canadian population showed high discrimination and adequate calibration when validated in 31 multinational cohorts. However, in some regions the addition of a calibration factor may be necessary.
| S-EPMC4752167 | biostudies-literature
Project description:IntroductionPredicting the timing and occurrence of kidney replacement therapy (KRT), cardiovascular events, and death among patients with advanced chronic kidney disease (CKD) is clinically useful and relevant. We aimed to externally validate a recently developed CKD G4+ risk calculator for these outcomes and to assess its potential clinical impact in guiding vascular access placement.MethodsWe included 1517 patients from the European Quality (EQUAL) study, a European multicentre prospective cohort study of nephrology-referred advanced CKD patients aged ≥65 years. Model performance was assessed based on discrimination and calibration. Potential clinical utility for timing of referral for vascular access placement was studied with diagnostic measures and decision curve analysis (DCA).ResultsThe model showed a good discrimination for KRT and "death after KRT," with 2-year concordance (C) statistics of 0.74 and 0.76, respectively. Discrimination for cardiovascular events (2-year C-statistic: 0.70) and overall death (2-year C-statistic: 0.61) was poorer. Calibration was fairly accurate. Decision curves illustrated that using the model to guide vascular access referral would generally lead to less unused arteriovenous fistulas (AVFs) than following estimated glomerular filtration rate (eGFR) thresholds.ConclusionThis study shows moderate to good predictive performance of the model in an older cohort of nephrology-referred patients with advanced CKD. Using the model to guide referral for vascular access placement has potential in combating unnecessary vascular surgeries.
| S-EPMC9546766 | biostudies-literature
Project description:BACKGROUND:Serum uric acid concentrations increase in chronic kidney disease (CKD) and may lead to tubular injury, endothelial dysfunction, oxidative stress, and intrarenal inflammation. Whether uric acid concentrations are associated with kidney failure and death in CKD is unknown. STUDY DESIGN:Prospective observational cohort study. SETTINGS & PARTICIPANTS:3,885 individuals with CKD stages 2 to 4 enrolled in the Chronic Renal Insufficiency Cohort (CRIC) between June 2003 and September 2008 and followed up through March 2013. PREDICTOR:Baseline uric acid concentrations. OUTCOMES:Kidney failure (initiation of dialysis therapy or transplantation) and all-cause mortality. RESULTS:During a median follow-up of 7.9 years, 885 participants progressed to kidney failure and 789 participants died. After adjustment for demographic, cardiovascular, and kidney-specific covariates, higher uric acid concentrations were independently associated with risk for kidney failure in participants with estimated glomerular filtration rates (eGFRs) ? 45mL/min/1.73m2 (adjusted HR per 1-standard deviation greater baseline uric acid, 1.40; 95% CI, 1.12-1.75), but not in those with eGFRs<30mL/min/1.73m2. There was a nominally higher HR in participants with eGFRs of 30 to 44mL/min/1.73m2 (adjusted HR, 1.13; 95% CI, 0.99-1.29), but this did not reach statistical significance. The relationship between uric acid concentration and all-cause mortality was J-shaped (P=0.007). LIMITATIONS:Potential residual confounding through unavailable confounders; lack of follow-up measurements to adjust for changes in uric acid concentrations over time. CONCLUSIONS:Uric acid concentration is an independent risk factor for kidney failure in earlier stages of CKD and has a J-shaped relationship with all-cause mortality in CKD. Adequately powered randomized placebo-controlled trials in CKD are needed to test whether urate lowering may prove to be an effective approach to prevent complications and progression of CKD.
| S-EPMC5828916 | biostudies-literature
Project description:OBJECTIVES:To examine whether chronic kidney disease (CKD) at any stage is associated with fracture risk after adjusting for competing mortality and to determine whether age or race modify the relationship between CKD and fracture risk. DESIGN:Prospective cohort study. SETTING:Department of Veterans Affairs (VA) national healthcare system. PARTICIPANTS:Men receiving VA primary care aged 65 and older with no history of fracture or osteoporosis therapy (N = 712, 918). MEASUREMENTS:We determined CKD stage from baseline estimated glomerular filtration rate (eGFR). Participants were followed for up to 10 years for occurrence of any fracture or death. We ascertained fractures and covariates from VA medical records and Medicare claims. RESULTS:Of the 356,459 older veterans with CKD (defined as eGFR <60 mL/min per 1.73 m2 ), 15.7% (n = 56,032) experienced a fracture, and 43.0% (n = 153,438) died over a median time at risk of 5.2 years. Veterans with CKD Stages 3 to 5 had a greater risk of death than those without CKD, which biased estimates from traditional survival models. Competing risk models showed that Stage 3 CKD was associated with greater hazard (adjusted subdistribution hazard ratio (sdHR) = 1.07, 95% confidence interval (CI) = 1.02-1.11) of fracture (than those without CKD) and a trend toward greater hazard for Stage 4 (sdHR = 1.07, 95% CI = 0.94-1.22) and Stage 5 (sdHR = 1.31, 95% CI = 0.97-1.77) CKD. Age, race, and bone mineral density did not modify the relationship between CKD and fracture risk. CONCLUSIONS:In older male veterans, CKD, including Stage 3, is associated with a moderately greater fracture risk irrespective of age, race, or bone mineral density.
| S-EPMC5849495 | biostudies-literature
Project description:Background: There is a high incidence of acute respiratory failure (ARF) in moderate or severe traumatic brain injury (M-STBI), worsening outcomes. This study aimed to design a predictive model for ARF. Methods: Adult patients with M-STBI [3 ≤ Glasgow Coma Scale (GCS) ≤ 12] with a definite history of brain trauma and abnormal head on CT images, obtained from September 2015 to May 2017, were included. Patients with age >80 years or <18 years, multiple injuries with TBI upon admission, or pregnancy (in women) were excluded. Two models based on machine learning extreme gradient boosting (XGBoost) or logistic regression, respectively, were developed for predicting ARF within 48 h upon admission. These models were evaluated by out-of-sample validation. The samples were assigned to the training and test sets at a ratio of 3:1. Results: In total, 312 patients were analyzed including 132 (42.3%) patients who had ARF. The GCS and the Marshall CT score, procalcitonin (PCT), and C-reactive protein (CRP) on admission significantly predicted ARF. The novel machine learning XGBoost model was superior to logistic regression model in predicting ARF [area under the receiver operating characteristic (AUROC) = 0.903, 95% CI, 0.834-0.966 vs. AUROC = 0.798, 95% CI, 0.697-0.899; p < 0.05]. Conclusion: The XGBoost model could better predict ARF in comparison with logistic regression-based model. Therefore, machine learning methods could help to develop and validate novel predictive models.
| S-EPMC8739486 | biostudies-literature
Project description:We conducted a randomized, double-blind, placebo-controlled trial in adults with moderate-to-severe AD unresponsive to conventional topical or systemic treatment. Fezakinumab (ILV-094; anti IL-22 monoclonal antibody) monotherapy was administered for 12 weeks (primary endpoint), and clinical responses were followed until week 20. AD transcriptome significantly improved at week 12 in fezakinumab vs. placebo (p<1E-18).
2018-09-17 | GSE99802 | GEO
Project description:ImportancePeople with chronic kidney disease (CKD) are risk-stratified for adverse events based on estimated glomerular filtration rate (eGFR) and albuminuria level. CKD has often a favorable course (CKD regression) regardless of eGFR. Determining whether lower albuminuria is associated with CKD regression may have implications on CKD management.ObjectiveTo assess the 5-year probability of CKD regression across albuminuria categories accounting for the competing risks of CKD progression and death in people with newly diagnosed CKD and the association between albuminuria level and CKD regression.Design, setting, and participantsThis population-based cohort study used administrative and laboratory data from Alberta, Canada, for adults with incident moderate to severe CKD (defined as sustained eGFR of 15-44 mL/min/1.73 m2 for >90 days), between April 1, 2008, and March 31, 2017, and albuminuria measures before cohort entry. Data analysis occurred in January to June 2022.ExposureAlbuminuria categories were defined by albumin to creatinine ratios (ACRs): A1 (ACR, <3 mg/mmol), A2 (ACR, 3-29 mg/mmol), A3<60 (ACR, 30-59 mg/mmol), and A3≥60 (ACR, ≥60 mg/mmol).Main outcomes and measuresThe main outcome was time to the earliest of CKD regression or progression (sustained change in CKD stage for >3 months and ≥25% increase or decrease in eGFR from baseline or kidney failure, respectively), death, or censoring (outmigration or study end date: March 31, 2019). Cumulative incidence functions were used to estimate absolute risks, and cause-specific Cox models were used to assess the association between albuminuria and CKD regression, accounting for age, sex, eGFR, comorbidities, and health services use indicators.ResultsOf 58 004 people with moderate to severe CKD (mean [SD] age, 77 [12] years; 31 725 [55%] women), 35 360 had A1 albuminuria (61%), 15 597 had A2 albuminuria (27%), 1527 had A3<60 albuminuria (3%), and 5520 had A3≥60 albuminuria (10%). Five-year probability of regression was highest with A1 (22.6%), followed by A2 (16.5%), and A3<60 (11.6%) and lowest with A3≥60 (5.3%). Using A1 albuminuria as the reference group, the hazard of regression was highest for A2 (hazard ratio [HR], 0.75; 95% CI, 0.72-0.79), then A3<60 (HR, 0.47; 95% CI, 0.40-0.54), and lowest for A3≥60 (HR, 0.27; 95% CI, 0.24-0.30).Conclusions and relevanceIn this cohort study of people with moderate to severe CKD, albuminuria levels were inversely associated with CKD regression. These findings extend the key prognostic role of albuminuria, offering novel opportunities to discuss both favorable and adverse outcomes in people with CKD and inform CKD management.
| S-EPMC9364131 | biostudies-literature
Project description:Rationale & objectiveThere have been no longitudinal studies examining the evolution of psychosocial health of young adults with kidney failure as they age. We aimed to address this in the Surveying Patients Experiencing Young Adult Kidney Failure-2 (SPEAK-2) study.Study design5-year follow-up longitudinal survey of the original SPEAK cohort.Setting & participants16- to 30-year-olds in the UK receiving kidney replacement therapy (KRT) between 2015 and 2017 who participated in the SPEAK study.ExposureKidney failure and KRT modality.OutcomesPsychosocial health and lifestyle behaviors.Analytical approachWithin-cohort changes in psychosocial health were analyzed using the paired t test, Wilcoxon signed-rank test and McNemar's test. We compared responses to the age-matched population and examined the impact of changes in KRT modality on psychological health using linear regression for continuous outcome variables as well as logistic, ordered logistic and multinomial logistic regression for binary, ordered categorical and unordered categorical variables, respectively.ResultsWe obtained 158 survey responses; 129 had previously responded to SPEAK. Of these, 90% had a kidney transplant. Compared to the general population, respondents were less likely to be married or have children and were more likely to be living with their parents. Respondents had nearly 15 times greater odds of being unable to work due to health (odds ratio [OR] = 14.41; 95% confidence interval [CI], 8.0-26.01; P < 0.001). Respondents had poorer quality of life and mental wellbeing and were more likely to report psychological problems (OR = 5.37; 95% CI, 3.45-8.35; P < 0.001). A negative association between remaining on or moving to dialysis and psychosocial health was observed, although this was attenuated when controlling for the psychosocial state in SPEAK.LimitationsLow response rate resulting in imprecise and potentially biased estimates and impact of COVID-19 pandemic while survey was active on psychosocial health.ConclusionsYoung adults with kidney failure have persistent poorer psychosocial health compared to their healthy peers as they age. Our findings also suggest a potential causal relationship between KRT modality and psychosocial health.
| S-EPMC10840100 | biostudies-literature
Project description:This was a phase II, randomized, placebo-controlled, double-blinded single center study (clinicaltrials.gov: NCT01806662) to investigate safety and efficacy of ustekinumab treatment in moderate-to-severe AD patients. Patients underwent 1:1 randomization using a computer generated subject randomization table by an unblinded pharmacist. to Subjects received subcutaneous ustekinumab or placebo at weeks 0, 4, and 16 with a crossover to the other agent (either ustekinumab or placebo) at weeks 16, 20, and 32 (Figure 1A) to ensure patient retention.
2019-11-20 | GSE140684 | GEO