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Item does not contain fulltext, IMPORTANCE: The established chronic kidney disease (CKD) progression end point of end-stage renal disease (ESRD) or a doubling of serum creatinine concentration (corresponding to a change in estimated glomerular filtration rate [GFR] of -57% or greater) is a late event. OBJECTIVE: To characterize the association of decline in estimated GFR with subsequent progression to ESRD with implications for using lesser declines in estimated GFR as potential alternative end points for CKD progression. Because most people with CKD die before reaching ESRD, mortality risk also was investigated. DATA SOURCES AND STUDY SELECTION: Individual meta-analysis of 1.7 million participants with 12,344 ESRD events and 223,944 deaths from 35 cohorts in the CKD Prognosis Consortium with a repeated measure of serum creatinine concentration over 1 to 3 years and outcome data. DATA EXTRACTION AND SYNTHESIS: Transfer of individual participant data or standardized analysis of outputs for random-effects meta-analysis conducted between July 2012 and September 2013, with baseline estimated GFR values collected from 1975 through 2012. MAIN OUTCOMES AND MEASURES: End-stage renal disease (initiation of dialysis or transplantation) or all-cause mortality risk related to percentage change in estimated GFR over 2 years, adjusted for potential confounders and first estimated GFR. RESULTS: The adjusted hazard ratios (HRs) of ESRD and mortality were higher with larger estimated GFR decline. Among participants with baseline estimated GFR of less than 60 mL/min/1.73 m2, the adjusted HRs for ESRD were 32.1 (95% CI, 22.3-46.3) for changes of -57% in estimated GFR and 5.4 (95% CI, 4.5-6.4) for changes of -30%. However, changes of -30% or greater (6.9% [95% CI, 6.4%-7.4%] of the entire consortium) were more common than changes of -57% (0.79% [95% CI, 0.52%-1.06%]). This association was strong and consistent across the length of the baseline period (1 to 3 years), baseline estimated GFR, age, diabetes status, or al

Item does not contain fulltext, BACKGROUND: As yet little is known about the effect of delayed separation of whole blood stored at room temperature on the stability of the kidney function markers creatinine and cystatin C. METHODS: We used plasma samples of 45 patients with a wide range of creatinine and cystatin C concentration. Samples were sent by post as whole blood, and differences in creatinine and cystatin C concentrations when measured (by enzymatic assay and PETIA, respectively) in plasma separated shortly after blood withdrawal or in plasma obtained after delayed separation at 24, 48 and 72 h. Intra- and inter-assay variability was assessed and total change limit was calculated to assess analyte stability. RESULTS: Total change limit was 3.3% for creatinine and 3.9% for cystatin C. In whole blood creatinine and cystatin C remained stable up to 48 h. Delayed separation of whole blood did not induce more variability in measured concentrations of both analytes. Glomerular filtration rate estimated with the CKD-EPI equations showed less than 3 mL/min/1.73 m(2) difference when using creatinine or cystatin C concentration measured in plasma separated up to 48 h after blood withdrawal compared to plasma separated shortly after blood withdrawal. The new CKD-EPI equation that uses creatinine as well as cystatin C to estimate GFR showed even at 72 h less than 3 mL/min/1.73 m(2) difference. CONCLUSIONS: Creatinine and cystatin C remain stable in whole blood stored at room temperature up to 48 h before separation, and changes in these analytes during this time period do not affect variability and eGFR.

Item does not contain fulltext, BACKGROUND: Hypertension is the most prevalent comorbidity in individuals with chronic kidney disease. However, whether the association of the kidney disease measures, estimated glomerular filtration rate (eGFR) and albuminuria, with mortality or end-stage renal disease (ESRD) differs by hypertensive status is unknown. METHODS: We did a meta-analysis of studies selected according to Chronic Kidney Disease Prognosis Consortium criteria. Data transfer and analyses were done between March, 2011, and June, 2012. We used Cox proportional hazards models to estimate the hazard ratios (HR) of mortality and ESRD associated with eGFR and albuminuria in individuals with and without hypertension. FINDINGS: We analysed data for 45 cohorts (25 general population, seven high-risk, and 13 chronic kidney disease) with 1,127,656 participants, 364,344 of whom had hypertension. Low eGFR and high albuminuria were associated with mortality irrespective of hypertensive status in the general population and high-risk cohorts. All-cause mortality risk was 1.1-1.2 times higher in individuals with hypertension than in those without hypertension at preserved eGFR. A steeper relative risk gradient in individuals without hypertension than in those with hypertension at eGFR range 45-75 mL/min per 1.73 m(2) led to much the same mortality risk at lower eGFR. With a reference eGFR of 95 mL/min per 1.73 m(2) in each group to explicitly assess interaction, adjusted HR for all-cause mortality at eGFR 45 mL/min per 1.73 m(2) was 1.77 (95% CI 1.57-1.99) in individuals without hypertension versus 1.24 (1.11-1.39) in those with hypertension (p for overall interaction=0.0003). Similarly, for albumin-creatinine ratio of 300 mg/g (vs 5 mg/g), HR was 2.30 (1.98-2.68) in individuals without hypertension versus 2.08 (1.84-2.35) in those with hypertension (p for overall interaction=0.019). We recorded much the same results for cardiovascular mortality. The associations of eGFR and albuminuria with ESRD, however, d

1 februari 2012, Item does not contain fulltext, AIM: This study investigates the difference in the incidence of renal replacement therapy (RRT) between Flanders and the Netherlands and possible explanations for this difference. METHODS: End-stage renal disease incidence data were obtained from the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA). Additional sources were the National Institute of Statistics (NIS), the Central Bureau of Statistics (CBS), the Organisation for Economic Cooperation and Development (OECD) health data and the WHO Health For All database (WHO-HFA). RESULTS: There is remarkable difference in incidence rate of RRT between Flanders and the Netherlands, with a higher rate in Flanders. This difference is already present in patients aged 45-64 years and increases with age, being >2-fold higher in subjects of >/= 75 years. With respect to the renal diagnoses leading to need for RRT, a higher share of especially diabetes mellitus type 2 and renovascular disease was observed in Flanders. Remarkably, the difference in incidence rate of RRT is not associated with a difference in survival on RRT, not even in the elderly, arguing against a restricted access to RRT in the Netherlands. In the general population, the expected number of healthy life years at birth is lower in Belgium than in the Netherlands, and in Belgium, the hospital discharge rates for diabetes, acute myocardial infarction and cerebrovascular accident and the number of coronary bypass procedures and percutaneous coronary interventions per capitum is higher, as is the prevalence of obesity. CONCLUSION: Our data do not support the assumption that the differences in RRT incidence in the elderly between Flanders and the Netherlands are due to a more restricted access to RRT in the Netherlands but may be due to differences in underlying comorbidity and life style between the two populations.

Item does not contain fulltext, We studied here the independent associations of estimated glomerular filtration rate (eGFR) and albuminuria with mortality and end-stage renal disease (ESRD) in individuals with chronic kidney disease (CKD). We performed a collaborative meta-analysis of 13 studies totaling 21,688 patients selected for CKD of diverse etiology. After adjustment for potential confounders and albuminuria, we found that a 15 ml/min per 1.73 m(2) lower eGFR below a threshold of 45 ml/min per 1.73 m(2) was significantly associated with mortality and ESRD (pooled hazard ratios (HRs) of 1.47 and 6.24, respectively). There was significant heterogeneity between studies for both HR estimates. After adjustment for risk factors and eGFR, an eightfold higher albumin- or protein-to-creatinine ratio was significantly associated with mortality (pooled HR 1.40) without evidence of significant heterogeneity and with ESRD (pooled HR 3.04), with significant heterogeneity between HR estimates. Lower eGFR and more severe albuminuria independently predict mortality and ESRD among individuals selected for CKD, with the associations stronger for ESRD than for mortality. Thus, these relationships are consistent with CKD stage classifications based on eGFR and suggest that albuminuria provides additional prognostic information among individuals with CKD.

Item does not contain fulltext, In 2006, the Dutch Nierstichting (Kidney Foundation) provided people with urinary dipsticks to determine whether they suffered from urinary protein loss. It was suspected that 0.5% of adult inhabitants would have hidden renal disease. Within two weeks, more than one million people had applied to receive the dipsticks. They were advised to contact their general practitioner if they tested positive. Blockade of the renin-angiotensin-aldosterone system (RAAS) in subjects with known renal disease and proteinuria improves renal and cardiac survival. However, many patients currently develop end-stage renal disease without prior knowledge ofhaving chronic kidney disease. These patients can be detected by screening for proteinuria or albuminuria. Japanese studies showed that about 5% of the general population have positive dipstick tests. It is to be expected that about 1% will be truly macroalbuminuric and another 2-3% will be microalbuminuric. Macroalbuminuria is the consequence of manifest glomerular damage, while microalbuminuria is in most cases related to underlying diabetes or hypertension (which frequently are not yet diagnosed). In both conditions, treatment with RAAS blockade is indicated and is aimed at both cardiac and renal protection. There are arguments indicating that screening of the general population for urinary protein loss is cost-effective.

Item does not contain fulltext, Macroalbuminuria, erythrocyturia, and impaired renal function are strong predictors of poor renal outcome in patients with known renal disease. However, the yield of mass screening for these variables to identify individuals who are at risk for GFR loss is yet unknown in a Western population. With the use of data from the Prevention of Renal and Vascular End-Stage Disease (PREVEND) study, a prospective, population-based cohort study, the cardiovascular and renal prognosis was investigated in patients with classical renal risk markers: Macroalbuminuria (> or =300 mg albumin/24 h urine), erythrocyturia (> or =250 erythrocytes/L, without leukocyturia), and impaired renal function (both 24-h creatinine clearance and Modification of Diet in Renal Disease clearance below the fifth percentile of age- and gender-matched control subjects). The 8592 patients who were included in this study were followed for a 4-yr period. We identified 134 patients with macroalbuminuria, 128 with erythrocyturia, and 103 with impaired renal function. There was only a little overlap among the three groups. The prevalence of macroalbuminuria, erythrocyturia, and impaired renal function was calculated to be in the general population 0.6, 1.3, and 0.9%, respectively. In all three groups, fewer than 30% of patients were known to have this laboratory abnormality before screening. The incidence of cardiovascular disease was high in the macroalbuminuria group (e.g., the age- and gender-adjusted hazard ratio for mortality as a result of cardiovascular disease is 2.6 [1.1 to 6.0]) and for the impaired renal function group (3.4 [1.5 to 8.0]). After a mean follow-up of 4.2 yr, the macroalbuminuria group showed a -7.2 ml/min per 1.73 m2 estimated GFR (eGFR) loss, compared with -2.3 ml/min per 1.73 m2 in the control group (difference P < 0.001), whereas the rate of eGFR loss in the impaired renal function group (-0.2 ml/min per 1.73 m2; P = 0.18) and the erythrocyturia group (-2.6 ml/min per 1.73 m2) was no

Item does not contain fulltext, The gradual onset of the antiproteinuric effects of ACE inhibition suggests that structural effects on the glomerular basement membrane (GBM) may be involved in their renoprotective action. To test this hypothesis, we studied the effects of lisinopril (5 mg/kg/24 h) on proteinuria, focal glomerulosclerosis (FGS) and glomerular heparan sulfate (HS) proteoglycan (HSPG) GBM staining in rats with established Adriamycin nephrosis. Treatment was started 6 weeks after disease induction. As expected, lisinopril reduced blood pressure, proteinuria and the FGS score. In control rats, Adriamycin nephrosis was associated with significantly impaired GBM staining for both HSPG core protein (assessed from BL-31 staining) and HS staining (assessed from JM-403 staining) 12 weeks after disease induction. In rats treated with lisinopril (5 mg/kg/24 h) GBM staining was significantly better preserved for HS as well as for HSPG core protein. These data suggest that structural effects on the GBM, improving glomerular permselectivity, may be involved in the renoprotective effects of ACE inhibition in proteinuria-induced renal damage.