Improving the prognosis of patients with severely decreased glomerular filtration rate (CKD G4+): conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference

Abstract

Patients with severely decreased glomerular filtration rate (GFR) (i.e., chronic kidney disease [CKD] G4+) are at increased risk for kidney failure, cardiovascular disease (CVD) events (including heart failure), and death. However, little is known about the variability of outcomes and optimal therapeutic strategies, including initiation of kidney replacement therapy (KRT). Kidney Disease: Improving Global Outcomes (KDIGO) organized a Controversies Conference with an international expert group in December 2016 to address this gap in knowledge. In collaboration with the CKD Prognosis Consortium (CKD-PC) a global meta-analysis of cohort studies (n = 264,515 individuals with CKD G4+) was conducted to better understand the timing of clinical outcomes in patients with CKD G4+ and risk factors for different outcomes. The results confirmed the prognostic value of traditional CVD risk factors in individuals with severely decreased GFR, although the risk estimates vary for kidney and CVD outcomes. A 2- and 4-year model of the probability and timing of kidney failure requiring KRT was also developed. The implications of these findings for patient management were discussed in the context of published evidence under 4 key themes: management of CKD G4+, diagnostic and therapeutic challenges of heart failure, shared decision-making, and optimization of clinical trials in CKD G4+ patients. Participants concluded that variable prognosis of patients with advanced CKD mandates individualized, risk-based management, factoring in competing risks and patient preferences.

Keywords: chronic kidney disease; kidney failure; prediction; prognosis; progression; supportive care.

Figure 1. Schematic presentation of chronic kidney disease (CKD) categories and conference focus

Per definition, CKD G5 includes patients with kidney failure with and without kidney replacement therapy (KRT). The conference focus (dashed line) was on patients within glomerular filtration rate (GFR) categories G4 and G5, excluding individuals already on KRT, but including KRT as an important end point. D = patients on dialysis therapy, T = patients with a kidney transplant. Colors reflect different risk categories for adverse outcomes as compared with individuals without CKD: green = no increase in risk; yellow = slightly elevated risk; orange = moderately elevated risk; and red = severely elevated risk. Adapted with permission from Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney Int Suppl. 2013;3:1–150.

Figure 2. Hazard ratios for KRT, CVD events, and death associated with different variables

Colors indicate the strength of association, from protective in green to strongly positive in red. Based on 19 cohorts with KRT, CVD, and death outcomes. Bold denotes statistically significant values. ACR, albumin-to-creatinine ratio; CI, confidence interval; CVD, cardiovascular disease; eGFR, estimated glomerular filtration rate; KRT, kidney replacement therapy; SBP, systolic blood pressure. Adapted with permission from Evans M, Grams ME, Sang, Y, et al. Risk factors for prognosis in patients with severely decreased GFR. Kidney Int Rep. https://doi.org/10.1016/j.ekir.2018.01.002.

Figure 3. Example from the chronic kidney disease (CKD) G4+ risk calculator

The probability and timing of adverse events at (upper panel) 2 years and (lower panel) 4 years with increasing level of albuminuria. In these models, the scenario was set at age 60 years, male, white, with a history of cardiovascular disease, not a current smoker, systolic blood pressure of 140 mm Hg, with diabetes, and an estimated glomerular filtration rate of 25 ml/min per 1.73 m². ACR, albumin-to-creatinine ratio; CVD, cardiovascular disease; KRT, kidney replacement therapy. For comparison, risk predictions for individuals with the same patient characteristics but no diabetes are presented in Grams ME, Sang Y, Ballew SH, et al. Predicting timing of clinical outcomes in patients with chronic kidney disease and severely decreased glomerular filtration rate. Kidney Int. https://doi.org/10.1016/j.kint.2018.01.009.

Figure 4. Unadjusted survival in patients with heart failure, by chronic kidney disease (CKD) status, 2010 to 2011

Reproduced from United States Renal Data System. 2015 USRDS annual data report: Epidemiology of Kidney Disease in the United States. National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, 2015.Available at: www.usrds.org/2013/pdf/v1_ch4_13.pdf. Accessed February 28, 2017.