Development and validation of resource-driven risk prediction models for incident chronic kidney disease in type 2 diabetes.
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ABSTRACT:
SUBMITTER: Gurudas S
PROVIDER: S-EPMC8249456 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundVarious prognostic models have been derived to predict chronic kidney disease (CKD) development in type 2 diabetes (T2D). However, their generalisability and predictive performance in different populations remain largely unvalidated. This study aimed to externally validate several prognostic models of CKD in a T2D Thai cohort.MethodsA nationwide survey was linked with hospital databases to create a prospective cohort of patients with diabetes (n = 3416). We undertook a systematic review to identify prognostic models and traditional metrics (i.e., discrimination and calibration) to compare model performance for CKD prediction. We updated prognostic models by including additional clinical parameters to optimise model performance in the Thai setting.ResultsSix relevant previously published models were identified. At baseline, C-statistics ranged from 0.585 (0.565-0.605) to 0.786 (0.765-0.806) for CKD and 0.657 (0.610-0.703) to 0.760 (0.705-0.816) for end-stage renal disease (ESRD). All original CKD models showed fair calibration with Observed/Expected (O/E) ratios ranging from 0.999 (0.975-1.024) to 1.009 (0.929-1.090). Hosmer-Lemeshow tests indicated a good fit for all models. The addition of routine clinical factors (i.e., glucose level and oral diabetes medications) enhanced model prediction by improved C-statistics of Low's of 0.114 for CKD and Elley's of 0.025 for ESRD.ConclusionsAll models showed moderate discrimination and fair calibration. Updating models to include routine clinical factors substantially enhanced their accuracy. Low's (developed in Singapore) and Elley's model (developed in New Zealand), outperformed the other models evaluated. These models can assist clinicians to improve the risk-stratification of diabetic patients for CKD and/or ESRD in the regions settings are similar to Thailand.
| S-EPMC9300508 | biostudies-literature
Project description:Many studies had established the chronic kidney disease (CKD) prediction models, but most of them were conducted on the general population and not on patients with type 2 diabetes, especially in Asian populations. This study aimed to develop a risk prediction model for CKD in patients with type 2 diabetes from the Diabetes Care Management Program (DCMP) in Taiwan. This research was a retrospective cohort study. We used the DCMP database to set up a cohort of 4,601 patients with type 2 diabetes without CKD aged 40-92 years enrolled in the DCMP program of a Taichung medical center in 2002-2016. All patients were followed up until incidences of CKD, death, and loss to follow-up or 2016. The dataset for participants of national DCMP in 2002-2004 was used as external validation. The incident CKD cases were defined as having one of the following three conditions: ACR data greater than or equal to 300 (mg/g); both eGFR data less than 60 (ml/min/1.73 m2) and ACR data greater than or equal to 30 (mg/g); and eGFR data less than 45 (ml/min/1.73 m2). The study subjects were randomly allocated to derivation and validation sets at a 2:1 ratio. Cox proportional hazards regression model was used to identify the risk factors of CKD in the derivation set. Time-varying area under receiver operating characteristics curve (AUC) was used to evaluate the performance of the risk model. After an average of 3.8 years of follow-up period, 3,067 study subjects were included in the derivation set, and 786 (25.63%) were newly diagnosed CKD cases. A total of 1,534 participants were designated to the validation set, and 378 (24.64%) were newly diagnosed CKD cases. The final CKD risk factors consisted of age, duration of diabetes, insulin use, estimated glomerular filtration rate, albumin-to-creatinine ratio, high-density lipoprotein cholesterol, triglyceride, diabetes retinopathy, variation in HbA1c, variation in FPG, and hypertension drug use. The AUC values of 1-, 3-, and 5-year CKD risks were 0.74, 0.76, and 0.77 in the validation set, respectively, and were 0.76, 0.77, and 0.76 in the sample for external validation, respectively. The value of Harrell's c-statistics was 0.76 (0.74, 0.78). The proposed model is the first CKD risk prediction model for type 2 diabetes patients in Taiwan. The 1-, 3-, and 5-year CKD risk prediction models showed good prediction accuracy. The model can be used as a guide for clinicians to develop medical plans for future CKD preventive intervention in Chinese patients with type 2 diabetes.
| S-EPMC8938464 | biostudies-literature
Project description:ImportanceSome patients will develop chronic kidney disease after a hospitalization with acute kidney injury; however, no risk-prediction tools have been developed to identify high-risk patients requiring follow-up.ObjectiveTo derive and validate predictive models for progression of acute kidney injury to advanced chronic kidney disease.Design, setting, and participantsData from 2 population-based cohorts of patients with a prehospitalization estimated glomerular filtration rate (eGFR) of more than 45 mL/min/1.73 m2 and who had survived hospitalization with acute kidney injury (defined by a serum creatinine increase during hospitalization > 0.3 mg/dL or > 50% of their prehospitalization baseline), were used to derive and validate multivariable prediction models. The risk models were derived from 9973 patients hospitalized in Alberta, Canada (April 2004-March 2014, with follow-up to March 2015). The risk models were externally validated with data from a cohort of 2761 patients hospitalized in Ontario, Canada (June 2004-March 2012, with follow-up to March 2013).ExposuresDemographic, laboratory, and comorbidity variables measured prior to discharge.Main outcomes and measuresAdvanced chronic kidney disease was defined by a sustained reduction in eGFR less than 30 mL/min/1.73 m2 for at least 3 months during the year after discharge. All participants were followed up for up to 1 year.ResultsThe participants (mean [SD] age, 66 [15] years in the derivation and internal validation cohorts and 69 [11] years in the external validation cohort; 40%-43% women per cohort) had a mean (SD) baseline serum creatinine level of 1.0 (0.2) mg/dL and more than 20% had stage 2 or 3 acute kidney injury. Advanced chronic kidney disease developed in 408 (2.7%) of 9973 patients in the derivation cohort and 62 (2.2%) of 2761 patients in the external validation cohort. In the derivation cohort, 6 variables were independently associated with the outcome: older age, female sex, higher baseline serum creatinine value, albuminuria, greater severity of acute kidney injury, and higher serum creatinine value at discharge. In the external validation cohort, a multivariable model including these 6 variables had a C statistic of 0.81 (95% CI, 0.75-0.86) and improved discrimination and reclassification compared with reduced models that included age, sex, and discharge serum creatinine value alone (integrated discrimination improvement, 2.6%; 95% CI, 1.1%-4.0%; categorical net reclassification index, 13.5%; 95% CI, 1.9%-25.1%) or included age, sex, and acute kidney injury stage alone (integrated discrimination improvement, 8.0%; 95% CI, 5.1%-11.0%; categorical net reclassification index, 79.9%; 95% CI, 60.9%-98.9%).Conclusions and relevanceA multivariable model using routine laboratory data was able to predict advanced chronic kidney disease following hospitalization with acute kidney injury. The utility of this model in clinical care requires further research.
| S-EPMC5820711 | biostudies-literature
Project description:BackgroundPeople with intermediate hyperglycemia (IH), including impaired fasting glucose and/or impaired glucose tolerance, are at higher risk of developing type 2 diabetes (T2D) than those with normoglycemia. We aimed to evaluate the performance of published T2D risk prediction models in Chinese people with IH to inform them about the choice of primary diabetes prevention measures.MethodsA systematic literature search was conducted to identify Asian-derived T2D risk prediction models, which were eligible if they were built on a prospective cohort of Asian adults without diabetes at baseline and utilized routinely-available variables to predict future risk of T2D. These Asian-derived and five prespecified non-Asian derived T2D risk prediction models were divided into BASIC (clinical variables only) and EXTENDED (plus laboratory variables) versions, with validation performed on them in three prospective Chinese IH cohorts: ACE (n = 3241), Luzhou (n = 1333), and TCLSIH (n = 1702). Model performance was assessed in terms of discrimination (C-statistic) and calibration (Hosmer-Lemeshow test).ResultsForty-four Asian and five non-Asian studies comprising 21 BASIC and 46 EXTENDED T2D risk prediction models for validation were identified. The majority were at high (n = 43, 87.8%) or unclear (n = 3, 6.1%) risk of bias, while only three studies (6.1%) were scored at low risk of bias. BASIC models showed poor-to-moderate discrimination with C-statistics 0.52-0.60, 0.50-0.59, and 0.50-0.64 in the ACE, Luzhou, and TCLSIH cohorts respectively. EXTENDED models showed poor-to-acceptable discrimination with C-statistics 0.54-0.73, 0.52-0.67, and 0.59-0.78 respectively. Fifteen BASIC and 40 EXTENDED models showed poor calibration (P < 0.05), overpredicting or underestimating the observed diabetes risk. Most recalibrated models showed improved calibration but modestly-to-severely overestimated diabetes risk in the three cohorts. The NAVIGATOR model showed the best discrimination in the three cohorts but had poor calibration (P < 0.05).ConclusionsIn Chinese people with IH, previously published BASIC models to predict T2D did not exhibit good discrimination or calibration. Several EXTENDED models performed better, but a robust Chinese T2D risk prediction tool in people with IH remains a major unmet need.
| S-EPMC9472437 | biostudies-literature
Project description:Aims/hypothesisThe identification of people who are at high risk of developing type 2 diabetes is a key part of population-level prevention strategies. Previous studies have evaluated the predictive utility of omics measurements, such as metabolites, proteins or polygenic scores, but have considered these separately. The improvement that combined omics biomarkers can provide over and above current clinical standard models is unclear. The aim of this study was to test the predictive performance of genome, proteome, metabolome and clinical biomarkers when added to established clinical prediction models for type 2 diabetes.MethodsWe developed sparse interpretable prediction models in a prospective, nested type 2 diabetes case-cohort study (N=1105, incident type 2 diabetes cases=375) with 10,792 person-years of follow-up, selecting from 5759 features across the genome, proteome, metabolome and clinical biomarkers using least absolute shrinkage and selection operator (LASSO) regression. We compared the predictive performance of omics-derived predictors with a clinical model including the variables from the Cambridge Diabetes Risk Score and HbA1c.ResultsAmong single omics prediction models that did not include clinical risk factors, the top ten proteins alone achieved the highest performance (concordance index [C index]=0.82 [95% CI 0.75, 0.88]), suggesting the proteome as the most informative single omic layer in the absence of clinical information. However, the largest improvement in prediction of type 2 diabetes incidence over and above the clinical model was achieved by the top ten features across several omic layers (C index=0.87 [95% CI 0.82, 0.92], Δ C index=0.05, p=0.045). This improvement by the top ten omic features was also evident in individuals with HbA1c <42 mmol/mol (6.0%), the threshold for prediabetes (C index=0.84 [95% CI 0.77, 0.90], Δ C index=0.07, p=0.03), the group in whom prediction would be most useful since they are not targeted for preventative interventions by current clinical guidelines. In this subgroup, the type 2 diabetes polygenic risk score was the major contributor to the improvement in prediction, and achieved a comparable improvement in performance when added onto the clinical model alone (C index=0.83 [95% CI 0.75, 0.90], Δ C index=0.06, p=0.002). However, compared with those with prediabetes, individuals at high polygenic risk in this group had only around half the absolute risk for type 2 diabetes over a 20 year period.Conclusions/interpretationOmic approaches provided marginal improvements in prediction of incident type 2 diabetes. However, while a polygenic risk score does improve prediction in people with an HbA1c in the normoglycaemic range, the group in whom prediction would be most useful, even individuals with a high polygenic burden in that subgroup had a low absolute type 2 diabetes risk. This suggests a limited feasibility of implementing targeted population-based genetic screening for preventative interventions.
| S-EPMC10709231 | biostudies-literature
Project description:ImportanceEarly identification of individuals at elevated risk of developing chronic kidney disease (CKD) could improve clinical care through enhanced surveillance and better management of underlying health conditions.ObjectiveTo develop assessment tools to identify individuals at increased risk of CKD, defined by reduced estimated glomerular filtration rate (eGFR).Design, setting, and participantsIndividual-level data analysis of 34 multinational cohorts from the CKD Prognosis Consortium including 5 222 711 individuals from 28 countries. Data were collected from April 1970 through January 2017. A 2-stage analysis was performed, with each study first analyzed individually and summarized overall using a weighted average. Because clinical variables were often differentially available by diabetes status, models were developed separately for participants with diabetes and without diabetes. Discrimination and calibration were also tested in 9 external cohorts (n = 2 253 540).ExposuresDemographic and clinical factors.Main outcomes and measuresIncident eGFR of less than 60 mL/min/1.73 m2.ResultsAmong 4 441 084 participants without diabetes (mean age, 54 years, 38% women), 660 856 incident cases (14.9%) of reduced eGFR occurred during a mean follow-up of 4.2 years. Of 781 627 participants with diabetes (mean age, 62 years, 13% women), 313 646 incident cases (40%) occurred during a mean follow-up of 3.9 years. Equations for the 5-year risk of reduced eGFR included age, sex, race/ethnicity, eGFR, history of cardiovascular disease, ever smoker, hypertension, body mass index, and albuminuria concentration. For participants with diabetes, the models also included diabetes medications, hemoglobin A1c, and the interaction between the 2. The risk equations had a median C statistic for the 5-year predicted probability of 0.845 (interquartile range [IQR], 0.789-0.890) in the cohorts without diabetes and 0.801 (IQR, 0.750-0.819) in the cohorts with diabetes. Calibration analysis showed that 9 of 13 study populations (69%) had a slope of observed to predicted risk between 0.80 and 1.25. Discrimination was similar in 18 study populations in 9 external validation cohorts; calibration showed that 16 of 18 (89%) had a slope of observed to predicted risk between 0.80 and 1.25.Conclusions and relevanceEquations for predicting risk of incident chronic kidney disease developed from more than 5 million individuals from 34 multinational cohorts demonstrated high discrimination and variable calibration in diverse populations. Further study is needed to determine whether use of these equations to identify individuals at risk of developing chronic kidney disease will improve clinical care and patient outcomes.
| S-EPMC6865298 | biostudies-literature
Project description:Accurate risk assessment of an individuals' propensity to develop cardiovascular diseases (CVDs) is crucial for the prevention of these conditions. Numerous published risk prediction models used for CVD risk assessment are based on conventional risk factors and include only a limited number of biomarkers. The addition of novel biomarkers can boost the discriminative ability of risk prediction models for CVDs with different pathogenesis. The present study reports the development of risk prediction models for a range of heterogeneous CVDs, including coronary artery disease (CAD), stroke, deep vein thrombosis (DVT), and abdominal aortic aneurysm (AAA), as well as for Type 2 diabetes mellitus (DM2), a major CVD risk factor. In addition to conventional risk factors, the models incorporate various blood biomarkers and comorbidities to improve both individual and population stratification. An automatic variable selection approach was developed to generate the best set of explanatory variables for each model from the initial panel of risk factors. In total, up to 254,220 UK Biobank participants (ranging from 215,269 to 254,220 for different CVDs and DM2) were included in the analyses. The derived prediction models utilizing Cox proportional hazards regression achieved consistent discrimination performance (C-index) for all diseases: CAD, 0.794 (95% CI, 0.787-0.801); DM2, 0.909 (95% CI, 0.903-0.916); stroke, 0.778 (95% CI, 0.756-0.801); DVT, 0.743 (95% CI, 0.737-0.749); and AAA, 0.893 (95% CI, 0.874-0.912). When validated on various subpopulations, they demonstrated higher discrimination in healthier and middle-age individuals. In general, calibration of a five-year risk of developing the CVDs and DM2 demonstrated incremental overestimation of disease-related conditions amongst the highest decile of risk probabilities. In summary, the risk prediction models described were validated with high discrimination and good calibration for several CVDs and DM2. These models incorporate multiple shared predictor variables and may be integrated into a single platform to enhance clinical stratification to impact health outcomes.
| S-EPMC7390268 | biostudies-literature
Project description:While chronic kidney disease (CKD) is regularly evaluated among patients with diabetes, kidney function may be significantly impaired before diabetes is diagnosed. Moreover, disparities in the severity of CKD in such a population are likely. This study evaluated the extent of CKD in a national cohort of 36,764 US veterans first diagnosed with diabetes between 2003 and 2013 and prior to initiating oral antidiabetic therapy. Evidence of CKD (any stage) at the time of diabetes diagnosis was determined using eGFR and urine-albumin-creatinine ratios, the odds of which were assessed using logistic regression controlling for patient characteristics. CKD was evident in 31.6% of veterans prior to being diagnosed with diabetes (age and gender standardized rates: 241.8 per 1,000 adults [overall] and 247.7 per 1,000 adult males), over half of whom had at least moderate kidney disease (stage 3 or higher). The odds of CKD tended to increase with age (OR: 1.88; 95% CI: 1.82-1.93), hemoglobin A1C (OR: 1.05; 95% CI: 1.04-1.06), systolic blood pressure (OR: 1.04; 95% CI: 1.027-1.043), and BMI (OR: 1.016; 95% CI: 1.011-1.020). Both Asian Americans (OR: 1.53; 95% CI: 1.15-2.04) and African Americans (OR: 1.11; 95% CI: 1.03-1.20) had higher adjusted odds of CKD compared to whites, and prevalence was highest in the Upper Midwest and parts of the Mid-South. Results suggest that evidence of CKD is common among veterans before a diabetes diagnosis, and certain populations throughout the country, such as minorities, may be afflicted at higher rates.
| S-EPMC5806889 | biostudies-literature
Project description:ObjectiveIn 2010, the American Diabetes Association (ADA) added hemoglobin A1c (A1C) to the guidelines for diagnosing type 2 diabetes. However, existing models for predicting diabetes risk were developed prior to the widespread adoption of A1C. Thus, it remains unknown how well existing diabetes risk prediction models predict incident diabetes defined according to the ADA 2010 guidelines. Accordingly, we examined the performance of an existing diabetes prediction model applied to a cohort of African American (AA) and white adults from the Coronary Artery Risk Development Study in Young Adults (CARDIA).Research design and methodsWe evaluated the performance of the Atherosclerosis Risk in Communities (ARIC) diabetes risk prediction model among 2,456 participants in CARDIA free of diabetes at the 2005-2006 exam and followed for 5 years. We evaluated model discrimination, calibration, and integrated discrimination improvement with incident diabetes defined by ADA 2010 guidelines before and after adding baseline A1C to the prediction model.ResultsIn the overall cohort, re-estimating the ARIC model in the CARDIA cohort resulted in good discrimination for the prediction of 5-year diabetes risk (area under the curve [AUC] 0.841). Adding baseline A1C as a predictor improved discrimination (AUC 0.841 vs. 0.863, P = 0.03). In race-stratified analyses, model discrimination was significantly higher in whites than AA (AUC AA 0.816 vs. whites 0.902; P = 0.008).ConclusionsAddition of A1C to the ARIC diabetes risk prediction model improved performance overall and in racial subgroups. However, for all models examined, discrimination was better in whites than AA. Additional studies are needed to further improve diabetes risk prediction among AA.
| S-EPMC4722943 | biostudies-literature
Project description:ImportanceType 2 diabetes increases the risk of progressive diabetic kidney disease, but reliable prediction tools that can be used in clinical practice and aid in patients' understanding of disease progression are currently lacking.ObjectiveTo develop and externally validate a model to predict future trajectories in estimated glomerular filtration rate (eGFR) in adults with type 2 diabetes and chronic kidney disease using data from 3 European multinational cohorts.Design, setting, and participantsThis prognostic study used baseline and follow-up information collected between February 2010 and December 2019 from 3 prospective multinational cohort studies: PROVALID (Prospective Cohort Study in Patients with Type 2 Diabetes Mellitus for Validation of Biomarkers), GCKD (German Chronic Kidney Disease), and DIACORE (Diabetes Cohorte). A total of 4637 adult participants (aged 18-75 years) with type 2 diabetes and mildly to moderately impaired kidney function (baseline eGFR of ≥30 mL/min/1.73 m2) were included. Data were analyzed between June 30, 2021, and January 31, 2023.Main outcomes and measuresThirteen variables readily available from routine clinical care visits (age, sex, body mass index; smoking status; hemoglobin A1c [mmol/mol and percentage]; hemoglobin, and serum cholesterol levels; mean arterial pressure, urinary albumin-creatinine ratio, and intake of glucose-lowering, blood-pressure lowering, or lipid-lowering medication) were selected as predictors. Repeated eGFR measurements at baseline and follow-up visits were used as the outcome. A linear mixed-effects model for repeated eGFR measurements at study entry up to the last recorded follow-up visit (up to 5 years after baseline) was fit and externally validated.ResultsAmong 4637 adults with type 2 diabetes and chronic kidney disease (mean [SD] age at baseline, 63.5 [9.1] years; 2680 men [57.8%]; all of White race), 3323 participants from the PROVALID and GCKD studies (mean [SD] age at baseline, 63.2 [9.3] years; 1864 men [56.1%]) were included in the model development cohort, and 1314 participants from the DIACORE study (mean [SD] age at baseline, 64.5 [8.3] years; 816 men [62.1%]) were included in the external validation cohort, with a mean (SD) follow-up of 5.0 (0.6) years. Updating the random coefficient estimates with baseline eGFR values yielded improved predictive performance, which was particularly evident in the visual inspection of the calibration curve (calibration slope at 5 years: 1.09; 95% CI, 1.04-1.15). The prediction model had good discrimination in the validation cohort, with the lowest C statistic at 5 years after baseline (0.79; 95% CI, 0.77-0.80). The model also had predictive accuracy, with an R2 ranging from 0.70 (95% CI, 0.63-0.76) at year 1 to 0.58 (95% CI, 0.53-0.63) at year 5.Conclusions and relevanceIn this prognostic study, a reliable prediction model was developed and externally validated; the robust model was well calibrated and capable of predicting kidney function decline up to 5 years after baseline. The results and prediction model are publicly available in an accompanying web-based application, which may open the way for improved prediction of individual eGFR trajectories and disease progression.
| S-EPMC10077108 | biostudies-literature