Does reduced glomerular filtration rate equate to chronic kidney disease?BMJ 2012; 344 doi: http://dx.doi.org/10.1136/bmj.e1167 (Published 01 March 2012) Cite this as: BMJ 2012;344:e1167
- Sarah White, adjunct research investigator,
- Alan Leichtman, professor
- 1University of Michigan, Department of Internal Medicine and Kidney Epidemiology and Cost Center, Ann Arbor, MI 48109-2029, USA
An estimated 32 201 living donor kidney transplants were performed worldwide in 2010.1 This number will undoubtedly increase in coming years as demand for kidney transplantation grows and strategies to meet this demand, such as paired kidney exchange, gather momentum. Although living kidney donors have mortality outcomes and quality of life scores above population norms,2 3 donor nephrectomy will always entail some degree of medical, social, financial, or psychological risk to the donor, and the transplantation community and the public must be satisfied that any risks are explicit and minimal.
The linked research paper by Garg and colleagues (doi:10.1136/bmj.e1113) makes an important contribution to our understanding of the long term consequences of living kidney donation.4 In patients with chronic kidney disease, there is an established association between reduced kidney function and cardiovascular events. Although donor uninephrectomy also results in a sizable decrease in glomerular filtration rate (GFR), evidence of an association between reduced GFR and cardiovascular events in living kidney donors is limited.5 6 Long term data on outcomes for donors have been scarce,3 and the identification of appropriate control groups against which to compare rigorously selected, highly screened living kidney donors has posed methodological difficulties. Garg and colleagues’ population based matched cohort study explores the association between living kidney donation and risk of major cardiovascular events or death. The authors apply a careful restriction matching protocol to define a comparator group that, as far as possible, satisfies acceptance criteria for kidney donation. Despite reduced GFR in the donors, they found no evidence that living kidney donors had increased cardiovascular risk in the first 10 years after transplantation compared with the healthiest segment of the general population.
How can the findings of the current study, that an acute 50% reduction in GFR as a result of kidney donation does not increase cardiovascular risk, be reconciled with the well established observation that an estimated glomerular filtration rate (eGFR) of less than 60 mL/min/1.73 m2 is an independent risk factor for cardiovascular and all cause mortality in the general population?7 A possible explanation, which the authors discuss, is that the association between chronic kidney disease and cardiovascular disease seen in epidemiological studies might not be causal but a consequence of the shared risk factors for both conditions. In contrast, living kidney donors are healthy people who develop reduced GFR in the absence of nephropathological and presumably cardiopathological processes. Furthermore, the observation that the outcomes for donors are superior to those for non-donors may be attributed to the quality of pre-donation screening for both renal and cardiovascular disease, and the difficulty of replicating all aspects of the donor selection process when trying to identify appropriate controls retrospectively. In addition, risks associated with uninephrectomy might be mitigated in Canadian donors whose ongoing management of risk factors for cardiovascular and chronic kidney disease through routine follow-up with primary care practitioners may be better than that received by donors in nations without universal health coverage.
The current study’s findings are a reminder of our limited understanding of the natural course of early chronic kidney disease and of the need for more data on how age, albuminuria, GFR, diabetes, and blood pressure combine to predict progression to end stage disease, cardiovascular events, or death in the general population. Predictive instruments for chronic kidney disease are still in their infancy, and the current staging system based on eGFR is limited as a tool for clinical decision making.7 Renal specific risk scores would enable eGFR to be interpreted in the context of individual patient characteristics, so that patients at greatest risk of progressive disease, cardiovascular events, and death can be distinguished from those more likely to follow a benign course. The ongoing refinement of existing markers of chronic kidney disease—such as combinations of eGFR, cystatin C, and microalbuminuria8—and the identification of new biomarkers with higher predictive accuracy for adverse outcomes—such as urinary podocyte loss, neutrophil gelatinase associated lipocalin, and fibroblast growth factor 23—have the potential to enhance the clinical management of chronic kidney disease through more accurate classification and assessment of prognosis.9 10 11
Although difficult to quantify, the excellent cardiovascular outcomes seen for this cohort of living donors might be attributable to regular medical follow-up and meticulous risk management as much as to careful donor screening and selection. What outcomes might patients with chronic kidney disease expect in a scenario of similarly rigorous medical management and optimal access to healthcare? Some indication is given by international comparisons of the association between the prevalence of chronic kidney disease and that of end stage disease. Despite a similar prevalence of chronic kidney disease in Norway and the United States, US patients have about twice the risk of progression to end stage disease after accounting for patient level factors.12
Recent years have seen a trend towards accepting living donors with less than optimal kidney function, mild glucose intolerance, hypertension treated with a single drug, and nephrolithiasis. Garg and colleagues’ findings may not generalise to donors at and beyond the margins of current acceptance criteria, and this should be the subject of further investigation.
Living donor transplantation will always entail ethical tensions between the doctor’s duty to do no harm, donor autonomy, and the unmistakable benefit to the recipient. Informed consent relies on explicit communication of the risks of donation, yet a lack of comprehensive data on long term outcomes has meant that some uncertainty about the full extent of risks assumed by living kidney donors has persisted. Garg and colleagues’ findings are a important step towards resolving this uncertainty, which undermines the quality of donor consent.
Cite this as: BMJ 2012;344:e1167
Competing interests: The author has completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declares: no support from any organisation for the submitted work; AL has received funding from the National Institute of Allergy and Infectious Diseases and from the Health Resources and Services Administration to study US living donor lung and living donor kidney outcomes; no other relationships or activities that could appear to have influenced the submitted work.
Provenance and peer review: Commissioned; not externally peer reviewed.