that they are not necessarily biologically linked. A patient in stage 1 is not bound to flow through 2, 3, and 4 and thus end up in stage 5. In fact, little is known about the natural history of stages 1 and 2 CKD. We all are familiar with the assumption that most patients with advanced renal insufficiency (stages 3–5) will eventually require RRT. While this might be true for most, it is not invariable; numerous analyses have shown that a sizable percentage of patients in stages 3 and 4 have stable renal function. In an analysis of the percentage of patients in different stages of CKD followed up at the Sheffield Kidney Institute, we found that as many as 27%, 34%, and 38% of patients in stages 3, 4, and 5, respectively, were non-progressors, based on an estimated GFR calculated from the MDRD 4 variables formula, over a retrospective observation period of approximately 5 years (Al Tahir G, Abdul Wahab H, MMed Sci Dissertations, University of Sheffield 2004, unpublished observations). It is unknown what proportion of patients classified as having stage 1 and 2 or even 3 will progress to ESRD (stage 5). More research is needed to validate modeled projections of future numbers of ESRD patients and relevance as well as cost-effectiveness of screening and intervention. Finally, this calls into question the wisdom of the K/DOQI definition of “stages” of CKD rather than “grades” or “classes”; a stage is by definition a transitory step toward an end (ESRD in this case), while a grade or a class does not have a connotation of progression. Are screening tests for CKD reliable? K/DOQI [23] and PARADE [13] have recommended that screening be undertaken by urine dipstick analysis. A positive test should be repeated within 3 months and subsequently confirmed by a quantitative estimation of albuminuria/proteinuria such as a urine albumin/creatinine ratio (ACR) [13]. Of note, different thresholds need to be defined for abnormal ACR in males (>2.5 mg/mmol) and females (>3.5 mg/mmol) [26]. A review of costeffectiveness of proteinuria dipstick tests concluded that their sensitivity averages 76% with a specificity of around 79% [27]. Such accuracy would be acceptable if, as recommended, positive tests are repeated and subsequently validated. Albuminuria also performs well as a screening test for proteinuria in the general population; the AusDiab study showed that albuminuria was highly sensitive (91.7%) and specific (95.3%) for detecting proteinuria in the general Australian population [28]. From the cost-effectiveness of screening for CKD viewpoint, only routine and cheap dipsticks are a realistic option. The more expensive and more sensitive and specific Albustix might not be a cost-effective option unless we take into consideration the cardiovascular implications of albuminuria detection. Therefore tools are available to us for screening for proteinuria at a relatively affordable cost and with an acceptable degree of accuracy. In NHANES III, serum creatinine measurements varied by as much as 25% [14]. Measurement of serum creatinine will have to undergo rigorous calibration and standardization to avoid inaccuracies and variability [14]. Also, estimation of renal function from serum creatinine should take into consideration all the confounding factors such as gender, age, race, muscle mass, timing, and diet. 2922 Nephrology Forum: Chronic CKD The calculation of GFR will have to rely on formulas validated for given subgroups of individuals depending on their stage of CKD and ethnicity [15]. Prognostic significance of albuminuria and proteinuria Little doubt exists that patients with established nephropathies have a worse prognosis in the presence of heavy and sustained proteinuria [29, 30], and evidence is emerging regarding the prognostic significance of proteinuria and albuminuria in the general population [10, 21]. Studies undertaken in Okinawa after 17 years of follow-up indicate that individuals with dipstick-positive proteinuria are at increased risk, proportional to the severity of proteinuria, of developing CKD [31]. Also, data derived from the Prevention of Renal and Vascular End-Stage Disease (PREVEND) study in Groningen revealed that albuminuria is associated with the subsequent development of CKD [32]. Furthermore, individuals with albuminuria in the PREVEND study were at increased risk of all-cause death as well as cardiovascular mortality [10, 21]. Similar observations were made in the EPIC-Norfolk study in the UK [33]. These findings support numerous reports linking albuminuria in the general population, hypertensive as well as diabetic individuals, with the subsequent development of cardiovascular disease (CVD) [33–36]. Albuminuria has been associated with the cardiometabolic syndrome predisposing patients to diabetes, hypertension, and CVD [37, 38]. Albuminuria might be a marker of vascular inflammation as well as endothelial damage and dysfunction with a resulting leakage of albumin from vascular and glomerular beds. Proteinuria is also one of the most predictive markers of CKD [22, 29–31]. The detection of CKD identifies patients at risk of cardiovascular complications; increasing evidence suggests that there is a steady increase in CVD morbidity and mortality with declining renal function [18–20, 39]. In some studies of hypertensive patients with and without leftventricular hypertrophy, proteinuria and raised serum creatinine were higher