Independent External Validation and Comparison of Death and Kidney Replacement Therapy Prediction Models in Advanced CKD.

The Kidney Failure Risk Equation (KFRE) is widely used to predict the risk of kidney replacement therapy (KRT) initiation in chronic kidney disease (CKD) stages G3-G5. The new Grams calculator developed for advanced CKD (stage G4+) predicts KRT initiation, cardiovascular events, and death by uniquely incorporating the competing risk of death. We aimed to validate this tool in a stage G4+ cohort for death and KRT. Retrospective cohort study. 442 patients with CKD stage G4+ (mean ± SD age, 73 ± 12 years; mean ± SD estimated glomerular filtration rate, 20 ± 6.2 mL/min/1.73 m2) who visited the multidisciplinary CKD clinic at Kingston Health Sciences Center in Ontario, Canada. Discrimination and calibration were examined for the outcome of death using the 2- and 4-year Grams scores. The 2- and 5-year KFRE and 2- and 4-year Grams scores were compared in terms of discrimination and calibration for KRT. There were 91, 161, and 206 death events and 90, 145, and 159 KRT events in our cohort at 2, 4, and 5 years, respectively. The Grams model demonstrated modest discrimination for death at 4 years (area under the curve [AUC] 0.70; 95% CI, 0.65-0.75) and performed worse at 2 years (AUC, 0.63; 95% CI, 0.57-0.70). It only overpredicted death by approximately 10% across most of the predicted range. Both models had similar discrimination for KRT at 2 years (KFRE AUC, 0.83; 95% CI, 0.78-0.88 and Grams AUC, 0.8; 95% CI, 0.76-0.87), 4 years (Grams AUC, 0.82; 95% CI, 0.77-0.86), and 5 years (KFRE AUC, 0.81; 95% CI, 0.76-0.85). There was excellent calibration for KRT using the 2-year KFRE and Grams values for predicted risk thresholds of ≤15% and using the 5-year KFRE and 4-year Grams values for predicted risk thresholds of ≤20%. At higher risk ranges, KFRE overpredicts and Grams underpredicts the KRT risk. This is a single-center study with a primarily White cohort limited by smaller sample sizes at the higher ranges of the predicted risks, particularly for the Grams calculator. The Grams model provides moderately accurate death predictions, and consideration should be given to its incorporation into patient education and advanced care planning. Both the Grams and KFRE models remain clinically useful for determining KRT risks in advanced CKD.

Thanabalasingam SJ ，Iliescu EA ，Norman PA ，Day AG ，Akbari A ，Hundemer GL ，White CA ... -  《-》

External validation of the KFRE and Grams prediction models for kidney failure and death in a Spanish cohort of patients with advanced chronic kidney disease.

Gallego-Valcarce E ，Shabaka A ，Tato-Ribera AM ，Landaluce-Triska E ，León-Poo M ，Roldan D ，Gruss E ... -  《-》

Using the kidney failure risk equation to predict end-stage kidney disease in CKD patients of South Asian ethnicity: an external validation study.

The kidney failure risk equation (KFRE) predicts the 2- and 5-year risk of needing kidney replacement therapy (KRT) using four risk factors - age, sex, urine albumin-to-creatinine ratio (ACR) and creatinine-based estimated glomerular filtration rate (eGFR). Although the KFRE has been recalibrated in a UK cohort, this did not consider minority ethnic groups. Further validation of the KFRE in different ethnicities is a research priority. The KFRE also does not consider the competing risk of death, which may lead to overestimation of KRT risk. This study externally validates the KFRE for patients of South Asian ethnicity and compares methods for accounting for ethnicity and the competing event of death. Data were gathered from an established UK cohort containing 35,539 individuals diagnosed with chronic kidney disease. The KFRE was externally validated and updated in several ways taking into account ethnicity, using recognised methods for time-to-event data, including the competing risk of death. A clinical impact assessment compared the updated models through consideration of referrals made to secondary care. The external validation showed the risk of KRT differed by ethnicity. Model validation performance improved when incorporating ethnicity and its interactions with ACR and eGFR as additional risk factors. Furthermore, accounting for the competing risk of death improved prediction. Using criteria of 5 years ≥ 5% predicted KRT risk, the competing risks model resulted in an extra 3 unnecessary referrals (0.59% increase) but identified an extra 1 KRT case (1.92% decrease) compared to the previous best model. Hybrid criteria of predicted risk using the competing risks model and ACR ≥ 70 mg/mmol should be used in referrals to secondary care. The accuracy of KFRE prediction improves when updated to consider South Asian ethnicity and to account for the competing risk of death. This may reduce unnecessary referrals whilst identifying risks of KRT and could further individualise the KFRE and improve its clinical utility. Further research should consider other ethnicities.

Maher F ，Teece L ，Major RW ，Bradbury N ，Medcalf JF ，Brunskill NJ ，Booth S ，Gray LJ ... -  《-》

Death and Dialysis Following Discharge From Chronic Kidney Disease Clinic: A Retrospective Cohort Study.

Multidisciplinary care is recommended for patients with advanced chronic kidney disease (CKD). A formalized, risk-based approach to CKD management is being adopted in some jurisdictions. In Ontario, Canada, the eligibility criteria for multidisciplinary CKD care funding were revised between 2016 and 2018 to a 2 year risk of kidney replacement therapy (KRT) greater than 10% calculated by the 4-variable Kidney Failure Risk Equation (KFRE). Implementation of the risk-based approach has led to the discharge of prevalent CKD patients. The primary objective of this study was to determine the frequency of occurrence of death and KRT initiation in patients discharged from CKD clinic. Retrospective cohort study. Single center multidisciplinary CKD clinic in Ontario, Canada. Four hundred and twenty five patients seen at least once in 2013 at the multidisciplinary CKD clinic. Outcomes included discharge status, death, re-referral and KRT initiation. Reasons for discharge were recorded. Outcomes were extracted from available electronic medical records and the provincial death registry between the patient's initial clinic visit in 2013 and January 1, 2020. KFRE-2 scores were calculated using the 4-variable KFRE equation. The hazard rates of death and KRT after discharge due to stable eGFR/low KFRE were compared to patients who remained in the clinic. Of the 425 CKD patients, 69 (16%) and 19 (4%) were discharged to primary care and general nephrology, respectively. Of those discharged, 7 (8%) were re-referred to nephrology or CKD clinic, while only 2 (2%) discharged patients required subsequent KRT. The hazard of mortality was reduced after discharge from the clinic due to stable eGFR/low KFRE (adjusted HR = 0.45 [95% CI, 0.25-0.78, P = .005]). Single center, observational retrospective study design and unknown kidney function over time post discharge for most patients. Discharge of low risk patients from multidisciplinary CKD clinic appears feasible and safe, with fewer than 1 in 40 discharged patients subsequently initiated on KRT over the following 7 years.

Che M ，Iliescu E ，Thanabalasingam S ，Day AG ，White CA ... -  《-》

Validation of the kidney failure risk equation in a Portuguese cohort.

In chronic kidney disease (CKD) patients, the risk of kidney replacement therapy (KRT) is highly variable. In 2011, Tangri et al. developed the kidney failure risk equations (KFRE) to predict the 2 and 5-year probability of requiring kidney replacement therapy (KRT). The KFRE is an easily calculated 4-variable equation which has been extensively validated in multiple cohorts. The aim of this study was to validate this risk score in a Portuguese cohort. We conducted a retrospective analysis of CKD patients stage 3-5 referred for nephrology consult at Centro Hospitalar Universitário Lisboa Norte during the first 6 months of 2018. Age, gender, estimated glomerular filtration rate (eGFR) and albuminuria were assessed. The 4-variable kidney failure risk equation (KFRE) calibrated to a non-North American population was calculated. Requirement of KRT was assessed in a 2-year follow-up. We assessed the Cox logistic regression method of the KFRE to predict KRT requirement and the discriminatory ability was determined using the receiver operating characteristic (ROC) curve. A cut-off value was defined as that with the highest validity. 360 patients were included and 54.4% were male. Mean age was 74.9±12.2 years, serum creatinine was 1.97±0.84mg/dL, eGFR was 33.4±12.13ml/min/1.73m2 and albuminuria was 571.1±848.3mg/g. Mean calculated risk score was 6.2±11.2%. Twenty-three patients required KRT (6.4%) in the two-year follow-up. The hazard ratio was 1.1 [95% CI (1.06-1.12), p<0.001] for the 2-year risk of KRT. The KFRE predicted progression to KRT requirement with an auROC of 0.903, [95% CI (0.86-0.95), p<0.001], with a sensitivity 91.3% and specificity of 71.8%. The optimal KFRE cut-off was >4.5% for 2-year nephrologist referral, with an hazard ratio of HR 26.7 [95% CI (6.15-116.3), p<0.001] for 2-year risk of KRT requirement. We have independently externally validated the 2-year KFRE and shown that it has excellent discrimination. The KFRE should be incorporated in clinical care of patients with CKD to improve patient-clinician dialogue and provide guidance on timing of referral for nephrology evaluation and planning for dialysis access.

da Silva BM ，Charreu J ，Duarte I ，Outerelo C ，Gameiro J ... -  《-》