A critical evaluation of chronic kidney disease--should isolated reduced estimated glomerular filtration rate be considered a 'disease'?

The definition and classification of chronic kidney disease (CKD) as adopted by the National Kidney Foundation and by the Kidney Disease: Improving Global Outcomes [1,2] has generated new interest in nephrology. A consistent classification is necessary to develop a coherent literature on the natural history, risk factors and outcomes of a disease. A primary goal with CKD classification has been to identify an earlier, often asymptomatic stage where interventions may prevent the progression to end-stage renal disease. Interventions only at late stages of disease are not desirable given the high morbidity, mortality and societal costs associated with dialysis and transplantation. The current classification of CKD is based on three fundamental components: (1) damaged renal parenchyma for stages 1 and 2 (e.g. proteinuria or polycystic kidneys); (2) decreased function as determined by glomerular filtration rate (GFR) regardless of damaged renal parenchyma for stages 3 and higher; and (3) chronicity to distinguish these parenchymal and functional changes from acute states. Unfortunately, recent data suggest that this classification system for CKD is not adequate as currently applied. Serum creatinine has been pivotal for diagnosing and staging CKD because it is an inexpensive, common test in clinical practice. Unfortunately, serum creatinine is not just a marker of GFR, but also a marker of creatinine generation rate from muscle mass and dietary protein. Since direct GFR measurement is expensive and inconvenient, estimated GFR (eGFR) by the Modification of Diet in Renal Disease (MDRD) equation has been used to transform serum creatinine into a screening tool for CKD (defined by an eGFR <60 ml/min/1.73 m2) [1]. However, us-