NDT Advance Access originally published online on June 13, 2007
Nephrology Dialysis Transplantation 2007 22(9):2728-2729; doi:10.1093/ndt/gfm349
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Why we should sub-divide CKD stage 3 into early (3a) and late (3b) components
Email: abutaleb_k{at}hotmail.comSir,
According to the DOQI estimate of chronic kidney disease (CKD) populations in the US, CKD stage 3 patients outnumbered those in the following stage (stage 4) almost 20-fold. The reported absolute numbers were 7.6 and 0.4 million for patients in stages 3 and 4, respectively. I feel that this unexpected difference between the two successive CKD stages did not raise sufficient questions, research and analysis. Such a huge difference can either be due to a high mortality rate during the late periods of stage 3, so that only a minority of patients reach stage 4, or it is due to a very high mortality rate during stage 4. It should be indicated that stage 3 extends over a glomerular filtration rate (GFR) range (59–30) that is twice the GFR range of stage 4 (29–15). At the same rate of GFR loss, this latter range difference would result in halving the residence time of CKD patients on stage 4 compared to stage 3. This alone can account for only half (i.e. for a factor of 2x out of 20x) of the overall patient count difference between the two stages. However, current available evidence suggests that the combination of high mortality in these two stages is the main explanation for the sudden drop in patient numbers between the two stages. It could be indicated here that the CKD stage 5 patient count would also have been negligible compared to that of stage 4, as it is the case in fact in many developing countries, except for the availability of the renal replacement therapy (RRT). Such therapy has allowed for longer residence time within (dialysis) or after (transplantation) this stage.
Robert N. Foley et al. [1] reported a renal replacement rate of 1.6% and 3.4% among CKD patients with no DM, or with DM. However, they reported much higher mortality rates of 8.1, 17.7, respectively, among the same patients, during only a 2 year follow-up period. Keith et al. [2] reported 5 year mortality of 24.3% and 45.7% in CKD stages 3 and 4, respectively. Only 1.3% of the patients in stage 3 reached the end stage renal disease (ESRD) stage during this 5 year follow-up period. As is now appreciated, mortality is a much more likely fate for CKD stage 3 patients than reaching ESRD. ‘Recent data have shown that CKD patients are 5–10 times more likely to die than to reach ESRD.’[3]. Similar findings have been also reported by several other studies.
We can safely hypothesize that most of this high mortality within stage 3 is toward the end of stage 3 itself and is the result of the developing uraemic milieu after the progressive reduction of GFR below 60 ml/min. Few uraemia-related pathological changes are expected to have developed prior to reaching GFR range value of 60 ml/min. How to equate GFR of 59 ml/min with 30 ml/min? Such patients are truly heterogeneous, regarding the degree of the developing ‘uraemia’ associated pathological changes.
I believe that stage 3 should be subdivided into two 15 m/min ranged components: 3a (GFR 59–45 ml/min) and 3b (GFR 44–30 ml/min). This would help to define more precisely the edge within stage 3 at which mortality becomes the main worry. Higher efforts to reverse or even abort the developing pathological processes can then be targeted, prior to that edge. For example, considering renal transplantation as the only modality among RRT modalities that can truly reverse this uraemic milieu, we might be justified in considering the introduction of this modality, not as a RRT, but as a mean to save patients organs and lives prior to that lethal edge. Prospective studies for such utilization of renal transplantation or any other therapeutic maneuvers directed to stage 3 will of course be needed. This hypothesis concerns the existence of an edge or a jump in mortality rate within stage 3, that is expected to be within the latter part of stage 3 (3b). Defining that point might help in directing our intervention more appropriately. In addition, as CKD is essentially defined by estimated GFR below 60 ml/min, having our data on CKD patients, reported on equally divided stages (each of 15 ml/min range) would allow for better comprehension and comparative evaluation of the changing trends of morbidity and mortality during the CKD journey.
Conflict of interest statement. None declared.
Consultant Nephrologist
KFSHD Government hospital
Saudi Arabia
References
- Foley RN, Murray AM Li S, et al. Chronic kidney disease and the risk for cardiovascular disease, renal replacement, and death in the United States Medicare population, 1998 to 1999. J Am Soc Nephrol (2005) 16:489.
[Abstract/Free Full Text] - Keith DS, Nichols GA, Gullion CM, et al. Longitudinal follow-up and outcomes among a population with chronic kidney disease in a large managed care organization. Arch Intern Med (2004) 164:659–663.
[Abstract/Free Full Text] - USRDS 2003.
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