scholarly journals Validation of a Novel Predictive Algorithm for Kidney Failure in Patients Suffering from Chronic Kidney Disease: The Prognostic Reasoning System for Chronic Kidney Disease (PROGRES-CKD)

Author(s):  
Francesco Bellocchio ◽  
Caterina Lonati ◽  
Jasmine Ion Titapiccolo ◽  
Jennifer Nadal ◽  
Heike Meiselbach ◽  
...  

Current equation-based risk stratification algorithms for kidney failure (KF) may have limited applicability in real world settings, where missing information may impede their computation for a large share of patients, hampering one from taking full advantage of the wealth of information collected in electronic health records. To overcome such limitations, we trained and validated the Prognostic Reasoning System for Chronic Kidney Disease (PROGRES-CKD), a novel algorithm predicting end-stage kidney disease (ESKD). PROGRES-CKD is a naïve Bayes classifier predicting ESKD onset within 6 and 24 months in adult, stage 3-to-5 CKD patients. PROGRES-CKD trained on 17,775 CKD patients treated in the Fresenius Medical Care (FMC) NephroCare network. The algorithm was validated in a second independent FMC cohort (n = 6760) and in the German Chronic Kidney Disease (GCKD) study cohort (n = 4058). We contrasted PROGRES-CKD accuracy against the performance of the Kidney Failure Risk Equation (KFRE). Discrimination accuracy in the validation cohorts was excellent for both short-term (stage 4–5 CKD, FMC: AUC = 0.90, 95%CI 0.88–0.91; GCKD: AUC = 0.91, 95% CI 0.86–0.97) and long-term (stage 3–5 CKD, FMC: AUC = 0.85, 95%CI 0.83–0.88; GCKD: AUC = 0.85, 95%CI 0.83–0.88) forecasting horizons. The performance of PROGRES-CKD was non-inferior to KFRE for the 24-month horizon and proved more accurate for the 6-month horizon forecast in both validation cohorts. In the real world setting captured in the FMC validation cohort, PROGRES-CKD was computable for all patients, whereas KFRE could be computed for complete cases only (i.e., 30% and 16% of the cohort in 6- and 24-month horizons). PROGRES-CKD accurately predicts KF onset among CKD patients. Contrary to equation-based scores, PROGRES-CKD extends to patients with incomplete data and allows explicit assessment of prediction robustness in case of missing values. PROGRES-CKD may efficiently assist physicians’ prognostic reasoning in real-life applications.

2018 ◽  
Vol 172 (2) ◽  
pp. 174 ◽  
Author(s):  
Erica Winnicki ◽  
Charles E. McCulloch ◽  
Mark M. Mitsnefes ◽  
Susan L. Furth ◽  
Bradley A. Warady ◽  
...  

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Ibrahim Ali ◽  
Rosemary L. Donne ◽  
Philip A. Kalra

Abstract Background The Kidney Failure Risk Equation (KFRE) predicts the 2- and 5-year risk of end-stage renal disease (ESRD) in patients with chronic kidney disease (CKD) stages 3a-5. Its predictive performance in advanced CKD and in specific disease aetiologies requires further exploration. This study validates the 4- and 8-variable KFREs in an advanced CKD population in the United Kingdom by evaluating discrimination, calibration and clinical utility. Methods Patients enrolled in the Salford Kidney Study who were referred to the Advanced Kidney Care Service (AKCS) clinic at Salford Royal NHS Foundation Trust between 2011 and 2018 were included. The 4- and 8-variable KFREs were calculated on the first AKCS visit and the observed events of ESRD (dialysis or pre-emptive transplantation) within 2- and 5-years were the primary outcome. The area under the receiver operator characteristic curve (AUC) and calibration plots were used to evaluate discrimination and calibration respectively in the whole cohort and in specific disease aetiologies: diabetic nephropathy, hypertensive nephropathy, glomerulonephritis, autosomal dominant polycystic kidney disease (ADPKD) and other diseases. Clinical utility was assessed with decision curve analyses, comparing the net benefit of using the KFREs against estimated glomerular filtration rate (eGFR) cut-offs of < 20 ml/min/1.73m2 and < 15 ml/min/1.73m2 to guide further treatment. Results A total of 743 patients comprised the 2-year analysis and 613 patients were in the 5-year analysis. Discrimination was good in the whole cohort: the 4-variable KFRE had an AUC of 0.796 (95% confidence interval [CI] 0.762–0.831) for predicting ESRD at 2-years and 0.773 (95% CI 0.736–0.810) at 5-years, and there was good-to-excellent discrimination across disease aetiologies. Calibration plots revealed underestimation of risk at 2-years and overestimation of risk at 5-years, especially in high-risk patients. There was, however, underestimation of risk in patients with ADPKD for all KFRE calculations. The predictive accuracy was similar between the 4- and 8-variable KFREs. Finally, compared to eGFR-based thresholds, the KFRE was the optimal tool to guide further care based on decision curve analyses. Conclusions The 4- and 8-variable KFREs demonstrate adequate discrimination and calibration for predicting ESRD in an advanced CKD population and, importantly, can provide better clinical utility than using an eGFR-based strategy to inform decision-making.


PLoS ONE ◽  
2018 ◽  
Vol 13 (6) ◽  
pp. e0198456 ◽  
Author(s):  
Christopher McCudden ◽  
Ayub Akbari ◽  
Christine A. White ◽  
Mohan Biyani ◽  
Swapnil Hiremath ◽  
...  

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
T Vaitsiakhovich ◽  
C I Coleman ◽  
F Kleinjung ◽  
S Kloss ◽  
B Vardar ◽  
...  

Abstract Background Anticoagulation therapy with vitamin K antagonists (e.g. warfarin) has recently been shown to contribute to the accelerated vascular calcification and worsening of renal function. Therefore, it is compelling to investigate the impact of different oral anticoagulants (OACs) on kidney function in non-valvular atrial fibrillation (NVAF) patients. Common co-morbidities in these patients are chronic kidney disease (CKD) and type 2 diabetes mellitus (T2DM), which might be presented at the OAC therapy initiation. Purpose The overall objective of the CALLIPER study was to evaluate the effectiveness and safety of the reduced dose rivaroxaban (15 mg once daily) as compared to warfarin in NVAF patients with renal dysfunction in real-world setting. In particular, we evaluated the risk of worsening of renal function in NVAF patients with CKD stage 3 and 4 at baseline (1 year prior to the cohort entry). Additionally, a sub-group analysis of patients with T2DM was performed. We defined worsening of renal function as progression to CKD stage 5, kidney failure or need for dialysis. Methods Individual level data of warfarin- and rivaroxaban-naïve NVAF patients from the MarketScan database for the years 2012 through 2017 were used. Patients with moderate-to-severe CKD (stage 3 and 4) were included in the study cohort and were followed until progression to CKD 5, kidney failure or dialysis, OAC discontinuation/switch, insurance disenrollment or end of data availability. A comparative analysis evaluating the hazard ratios (HRs) with the corresponding 95% confidence intervals (CIs) under warfarin or rivaroxaban treatment was performed using Cox regression. A stabilized inverse probability of treatment weighting was used to adjust for imbalances in baseline patient characteristics. Results We identified 5,906 warfarin- and 1,466 rivaroxaban-naïve patients with NVAF and CKD stage 3 and 4, of which 60% were male, median (25–75% range) age=79 (71- 84) years, CHADS2 score=2.67 (2.00- 3.50), CHA2DS2-VASc score=4.43 (3.40–5.62), modified HAS-BLED score=3.00 (2.40 - 3.65). T2DM was present in more than 50% of patients (Table), namely, in 3,160 warfarin- and 746 rivaroxaban-users. Hazard ratios and 95% CI for worsening of renal function were evaluated at 0.53 (0.35; 0.78) in the main cohort and 0.50 (0.30; 0.83) in the T2DM sub-group, meaning that rivaroxaban was associated with a significant 47% and 50% risk reduction of this outcome in NVAF patients with CKD stage 3 and 4 with and without T2DM, respectively. Conclusion The reduced dose of rivaroxaban has appeared to lower significantly the risk of worsening of renal function versus warfarin in NVAF patients with CKD stage 3 and 4 present at the OAC therapy initiation. The conclusion holds true for the patients with the co-morbid T2DM. This evidence was generated by the CALLIPER study using one of the largest US administrative claims database. Acknowledgement/Funding CI Coleman has received research grants from Bayer AG


Author(s):  
Alberto Ortiz ◽  
Charles J Ferro ◽  
Olga Balafa ◽  
Michel Burnier ◽  
Robert Ekart ◽  
...  

Abstract Diabetic kidney disease develops in about 40% of patients with diabetes and is the commonest cause of chronic kidney disease worldwide. Patients with chronic kidney disease, especially those with diabetes mellitus, are at high risk of both developing kidney failure and cardiovascular death. The use of renin-angiotensin system blockers to reduce the incidence of kidney failure in patients with diabetic kidney disease dates back to studies that are now 20 or more years old. During the last few years sodium-glucose co-transporter-2 inhibitors have shown beneficial renal effects in randomized trials. However, even in response to combined treatment with renin-angiotensin system blockers and sodium-glucose co-transporter-2 inhibitors, the renal residual risk remains high with kidney failure only deferred, but not avoided. The risk of cardiovascular death also remains high even with optimal current treatment. Steroidal mineralocorticoid receptor antagonists reduce albuminuria and surrogate markers of cardiovascular disease in patients already on optimal therapy. However, their use has been curtailed by the significant risk of hyperkalaemia. In The FInerenone in reducing kiDnEy faiLure and dIsease prOgression in Diabetic Kidney Disease (FIDELIO-DKD) study comparing the actions of the non-steroidal mineralocorticoid receptor antagonist finerenone with placebo, finerenone reduced the progression of diabetic kidney disease and the incidence of cardiovascular events with a relatively safe adverse event profile. This document presents in detail the available evidence on the cardioprotective and nephroprotective effects of mineralocorticoid receptor antagonists, analyses the potential mechanisms involved and discusses their potential future place in the treatment of patients with diabetic chronic kidney disease.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Deniz Can Güven ◽  
Deniz Aral Ozbek ◽  
Taha Koray Sahin ◽  
Melek Seren Aksun ◽  
Gozde Kavgaci ◽  
...  

Abstract Background and Aims The immune checkpoint inhibitors (ICIs) became a vital part of cancer treatment. The ICIs seem to be safer than chemotherapy for kidneys in clinical trials. However, recent observational studies from high-resource settings pointed out the possible underreporting of renal adverse events like acute kidney injury (AKI) in the clinical trials due to focusing only to the renal immune-related adverse events. Additionally, clinical trials generally enroll a fitter population with lesser comorbidities and include mostly treatment-naive patients making studies in real-life cohorts imperative for evaluating the AKI rates during ICI treatment. From these points, we aimed to evaluate the AKI rates and predisposing factors in ICI-treated patients. Method This retrospective study has evaluated the data of adult metastatic cancer patients treated with ICIs in Hacettepe University Cancer Center from 01.2014 to 12.2019. All patients other than the ones treated within the context of clinical trials or followed in other institutions after the first dose of ICIs were included. Baseline demographics, cancer types, patient weight and heights, ICI type and the number of cycles, serum creatinine and the estimated GFR values under treatment, regular medications, and comorbidities were recorded. AKI was defined by Kidney Disease Improving Global Outcomes criteria. The predisposing factors to AKI development were evaluated with the univariate and multivariate analyses. Results A total of 147 patients were included in the analyses. Median age was 61 [interquartile range (IQR) 51-67], and 69.4% of the patients were male. Patients were given a median of 8 (IQR 5-17) ICI cycles. Patients with melanoma (24.5%), non-small cell lung cancer (15%), and renal cell carcinoma (25.9%) comprised almost 2/3 of the cohort and 72.8% of the patients were treated with nivolumab. Hypertension was the most common comorbidity (38.1%), followed by chronic kidney disease (21.2%) and type 2 diabetes (19.7%). Median Charlson Comorbidity Index (CCI) was 8 (7-9). Median follow-up was 10.3 (IQR 6.3-19.4) months, and patients had median 9 (IQR 5-18) serum creatinine measurements. During the follow-up, 28 patients (19%) had at least one AKI episode with multiple AKI episodes in 3 patients (10.7%). The median time to AKI development was 2.53 (IQR 1.39-6.19) months. Almost all AKI events were mild (grade 1 or 2 in 27/28) and reversible (25/28). In univariate analyses, coronary artery disease (CAD) (p=&lt;0.001), chronic kidney disease (CKD) (p=0.002), previous nephrectomy (p=0.015), iodinated contrast exposure in the week before immunotherapy (p=0.035), the use of renin-angiotensin-aldosterone system inhibitors (p=0.046) or proton pump inhibitors (PPI) (p=0.041) was associated with an increased AKI risk. The association between diabetes (p=0.067), higher CCI (9 vs. ≥9, p=0.107), baseline lactate dehydrogenase levels (p=0.177), and performance status (ECOG 0 vs. ≥1, p=0.235) and AKI risk did not reach statistical significance. In multivariate analyses, patients with CKD (OR: 3.719, 95% CI: 1.375- 10.057, p=0.010) or CAD (OR: 4.774, 95% CI: 1.803- 12.641, p=0.002) had increased AKI risk. Additionally, regular PPI use (OR: 2.734, 95% CI: .991- 7.542, p=0.052) had borderline statistical significance for AKI development. The development of AKI was not associated with decreased survival (HR: 0.726, 95% CI: 0.409-1.291, p=0.276). Conclusion In this study, we observed AKI development under ICIs in almost one in five cancer patients. The increased AKI rates in patients with CAD, CKD, or regular PPI use pointed out the need for better onco-nephrology collaboration in all ICI-treated patients, with a particular emphasis in these high-risk patients.


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