CKD Stage 4A and 4B… On the Horizon???

As clinical nephrologists, we are faced with the dilemma of which of our CKD patients will actually progress to ESRD. Oftentimes, our patients ask, “When am I going to need dialysis?”

When I see CKD stage 4 patients in my office, I usually start counseling them about the various dialysis modalities and transplantation options. For those wishing to pursue hemodialysis, I usually refer them to vascular surgery to discuss the AVF placement procedure along with risks and complications.

So, when should I refer a patient for elective AVF creation? I always invoke the adage that treatment should be individualized, especially for those with complex medical issues and multiple co-morbid illnesses. At present, there is no magic number of creatinine or eGFR supported by evidence-based data, but should there be?

The decision is never straightforward, simply because of the competing risk of death prior to ESRD. Early preparation for dialysis may expose patients to the unnecessary risk and cost without actually gaining any purported benefit. The latest NKF-KDOQI Guidelines recommend that when patients eGFR drops to ≤30 mL/min/1.73 m2, we should initiate preparation for RRT (education about dialysis and transplantation, venous mapping studies, etc).
Sud et al, however, address this question by attempting to estimate the risks of both ESRD and death prior to ESRD based on known CKD progression predictors such as stage at the time of referral, demographics (age, sex), and laboratory values (Ca, P, CO2, eGFR, SUN, albumin, Hgb, albuminuria) and clinical characteristics (BP). They also looked at comorbid conditions such as DM, hypertension, and CVD.

In their limited retrospective study, they enrolled 3273 CKD patients at stages 3 to 5 (mean eGFR, 36 mL/min/1.73 m2) with a mean age of 70 years. 459 (14%) participants progressed to ESRD, whereas 540 (16%) died prior to ESRD. Interestingly, when they adjusted for age, sex, physical findings, co-morbid conditions, and laboratory predictors of progression, they demonstrated that the risk of death prior to ESRD was highest in CKD stage 3, and lowest in CKD stage 5. This data supports the current practice of focusing on reducing morbidity and mortality rather than preparing for dialysis and transplantation in those with CKD stage 3. Similarly, in those with CKD stage 5, because there is a greater risk of ESRD vs dying prior to ESRD, preparation for RRT is appropriate. However, the authors demonstrated that in CKD stage 4, the risk of death prior to ESRD relative to ESRD was the same. This adds to the dilemma of when is the optimal time to prepare for RRT.

Sud et al OI AJKD fig 1

Rate and Risk of ESRD and Death prior to ESRD by CKD Stage. Fig 1 Sud et al AJKD, © National Kidney Foundation.

Evaluating the laboratory features and clinical characteristics (in order of model entry), higher albuminuria, younger age, lower eGFR, lower CO2, DM, higher DBP, lower albumin, higher SUN, heart failure, hypertension, higher PO4, and male sex were associated with higher risk of ESRD. In addition, older age, heart failure, lower Hgb, lower PO4, active or past malignancy, DM, and male sex were associated with higher risk of death prior to ESRD. The authors suggest that when making decisions regarding RRT initiation and preparations, the above clinical parameters for ESRD and death prior to ESRD may be useful in evaluating CKD stage 4 patients.

The subdivision of CKD stage 3 into 3a (eGFR, 45-59 mL/min/1.73 m2) and 3b (eGFR, 30-44 mL/min/1.73 m2) was initially recommended by the NICE 2008 Guidance on CKD, having recognized the higher risk of CVD and ESRD with the latter. This was also adapted by the latest KDIGO 2012 Clinical Practice Guideline for the Evaluation and Management of CKD.

So, should CKD stage 4 be further sub-classified into stage 4a and 4b, and if so, how? Until then, treatment should be individualized especially in those with complex medical issues and multiple co-morbid illnesses.

Edgar V. Lerma, MD
Clinical Professor of Medicine, Section of Nephrology, University of Illinois at Chicago College of Medicine; Associates in Nephrology, SC, Chicago, IL

eAJKD Contributor

To view the article abstract or full-text (subscription required), please visit

Leave a Reply

%d bloggers like this: