prescribed in 50% to 80% of patients admitted to geriatric and internal medicine wards in acute care hospitals.In chronic kidney diseases patients, different authors concluded that PPIs was prescribed often without adequate indication (41%) compared with hospitalized patients (13%) and patients with a chronic lung disease (18%).The risk of PPIs treatment in hemodialysis patients is unexplored.We assessed the relationship between the use of PPIs, hypomagnesemia and the risk of death in hemodialysis patients.METHODS: A retrospective multicentre propensity score-matched study to analyse the effect of PPIs on serum magnesium and mortality was designed.Information about demography, haemodialysis treatment, laboratory data and concomitant medication was obtained from the EuCliD database (FMC).We studied 1776 haemodialysis patients under PPI therapy compared to 466 patients not receiving PPIs.Further resulting population formed by two groups of 410 matched patients was explored.RESULTS: PPI use was associated with hypomagnesemia (Mg <1.8 mmol/L; OR= 2.70; 95% CI: 1.38-5.27;P=0.004).The exposure to PPIs in the full patient cohort, was identified as an independent predictor for all-cause mortality in both univariate (HR 3.16; 95% CI: 1.69-5.90,P<0.001) and multivariate (HR 2.70; 95% CI: 1.38-5.27P=0.004) Cox regression models.Moreover was identified as a predictor of CV mortality (HR 1.51; 95% CI: 1.05-2.20;P=0.028)Of the 820 patients matched throughout the propensity score analysis, the hazard ratios for all-cause mortality (HR 1.412; 95% CI: 1.04-1.93,P=0.030) and CV mortality (HR 1.67; 95% CI: 1.03-2.71;P=0.041) were higher among patients taken PPIs versus those not on PPIs.

BACKGROUND AND OBJECTIVES:High levels of serum polyclonal combined Ig free light chains are associated with inflammation and decreased excretory kidney function, and they are an independent risk factor for mortality. Whether combined Ig free light chain predicted mortality and progression to ESRD in a stages 3-5 CKD cohort was assessed. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:This was a prospective cohort study of 872 patients with stages 3-5 CKD (nondialysis) recruited into the Chronic Renal Insufficiency Standards Implementation Study. Patients were recruited to the Chronic Renal Insufficiency Standards Implementation Study in an unselected manner from secondary care nephrology clinics between 2004 and 2010. Combined Ig free light chain was measured at recruitment and analyzed by quartiles. The cohort was followed up for a median of 41.4 months (interquartile range =28.3-68.0 months). Cox regression analysis was undertaken to determine the variables associated with mortality and progression to ESRD. RESULTS:Combined Ig free light chain quartiles were <49.4, 49.4-68.8, 68.9-100.7, and >100.7 mg/L. An independent association with death and progression to ESRD was associated with the third and fourth combined Ig free light chain quartiles (quartile 3: death: hazard ratio, 1.49; 95% confidence interval, 1.02 to 2.18; P=0.04; ESRD: hazard ratio, 1.72; 95% confidence interval, 1.0 to 2.97; P=0.05; quartile 4: death: hazard ratio, 1.99; 95% confidence interval, 1.34 to 2.93; P<0.001; ESRD: hazard ratio, 3.73; 95% confidence interval, 2.1 to 6.3; P<0.001). The other independent risk factors were (1) preexisting cardiovascular disease, age >65 years old, and eGFR=15-30 ml/min per 1.73 m(2) for death and (2) age ≤65 years old, eGFR<30 ml/min per 1.73 m(2), urinary protein-to-creatinine ratio >30 mg/mmol, and serum phosphate level >4.65 mg/dl for progression to ESRD. CONCLUSIONS:An elevated serum combined Ig free light chain level is an independent risk factor for mortality and progression to ESRD in patients with stages 3-5 CKD managed in secondary care.

BACKGROUND:Currently, most chronic kidney disease (CKD) classifications identify patients at different stages of CKD but do not identify risk of progression or adverse outcome. This analysis aims to describe associations between baseline characteristics and the evolution of estimated glomerular filtration rate (eGFR) and identify threshold values for clinical parameters that maximally discriminate progression to renal replacement therapy (RRT) in a referred cohort of patients with CKD stages 3-5.DESIGN AND METHODS:A longitudinal mixed-effect model was used to determine annualized estimated change in eGFR and classification tree analysis to identify threshold values that maximally discriminate progression to RRT.RESULTS:A total of 1316 patients were available for analysis with median follow-up of 33 months (interquartile range 20-60). Mixed model analysis suggested that the underlying diagnoses of autosomal dominant polycystic kidney disease and diabetic nephropathy exhibited on average a 2.7 (0.3) and 0.7 (0.3) ml/min/year faster rate of decline in eGFR, respectively, compared to those patients with biopsy-proven glomerulonephritis. In the regression tree analysis, we attempted to identify threshold values for clinical parameters that maximally discriminate progression to RRT. eGFR ≤24 ml/min was the first ranked discriminator, diastolic blood pressure appeared in the second and fourth rounds, eGFR appeared again in the third round together with cholesterol and systolic blood pressure, with basal metabolic index in the fourth.CONCLUSION:This analysis highlights risk factors for progressive kidney disease and demonstrates the variability in evolution of eGFR across the cohort as well as the importance of underlying renal disease type on the progression of CKD.

Rebecca Brown and colleagues examine the association between BMI and kidney disease progression among 499 adults with established stage 3-5 CKD in the absence of diabetes...the analysis showed no significant difference in annual eGFR decline by obesity status...Chronic kidney disease (CKD) is increasingly prevalent worldwide. Furthermore, obesity is now a global problem with major health implications. There is a clear association between obesity and the development of CKD but it is not known whether obesity is a risk factor for the progression of pre-existing kidney disease. We examined the relationship between the body mass index (BMI) and the rate of progression of CKD in non-diabetic adults.The Chronic Renal Insufficiency Standards Implementation Study (CRISIS) is a prospective observational study in a predominantly white population in Greater Manchester. From the CRISIS database, we assessed rate of progression of CKD in 499 adults attending the hospital. Baseline measurements including BMI were obtained and estimated glomerular filtration rate (eGFR) was monitored. The rate of deterioration of eGFR was derived over time, defined as eGFR (mL/min/1.73m(2)/year) and assessed using univariate analysis of variance.In the groups as a whole, no relationship between BMI and eGFR was shown. Dividing the subjects into obese (BMI epsilon 30) and non-obese (BMI 30) groups and further breakdown into CKD stages 3, 4 and 5, also showed no relationship between BMI and eGFR. Univariate analysis of variance was used.Neither BMI as a continuous variable nor obesity (BMI epsilon 30) as a categorical variable was associated with an increased rate of progression of existing CKD in this predominantly white population.

Background. There have been few attempts to estimate progression of kidney disease in people with diabetes in a single large population with predictive modelling. The aim of this study was to investigate the rate of progression of chronic kidney disease in people with diabetes according to their estimated glomerular filtration rate (eGFR) and presence of albuminuria.Methods. Data were collected on all people with diabetes in Salford, UK, where an eGFR could be calculated using the four-variable MDRD formula and urinary albumin-creatinine ratio (uACR) was available. All data between 2001 and 2007 were used in the model. Classification of albuminuria status was based on the average of their first two uACR measurements. A longitudinal mixed effect dynamic regression model was fitted to the data. Parameters were estimated by maximum likelihood.Results. For the analysis of the population, average progression of eGFR, uACR and drug prescribing were available in 3431 people. The regression model showed that in people with diabetes and macroalbuminuria, eGFR declined at 5.7% per annum, while the eGFR of those with microalbuminuria or without albuminuria declined at 1.5% and 0.3% per annum, respectively, independently of age (P < 0.0001).Conclusions. The longitudinal effect of time on eGFR showed that people with diabetes and macroalbuminuria have an estimated 19 times more rapid decline in renal function compared with those without albuminuria. This study demonstrates that the progression of kidney disease in diabetic people without albuminuria is relatively benign compared with those with albuminuria.

BACKGROUNDKnowing how kidney disease progresses is important for decision making in patients with chronic kidney disease (CKD) and for designing clinical services.STUDY DESIGNProspective cohort study.SETTING & PARTICIPANTSWe examined renal function trajectories in CRISIS (Chronic Renal Insufficiency Standards Implementation Study), in which 1,325 patients with CKD stages 3-5 and mean age of 65.1 years were followed up prospectively for a median of 26 months after referral to a regional nephrology center in the United Kingdom. By protocol, estimated glomerular filtration rate was determined every 12 months.PREDICTORSCKD stage defined as estimated glomerular filtration rate ≥ 45 (stage 3a), 30-44 (3b), 15-29 (4), and < 15 (5) mL/min/1.73 m².OUTCOMESOnset of renal replacement therapy (RRT), death, the composite end point of RRT or death, or decreasing CKD stage.RESULTSDuring a median follow-up of 26 months, 13% reached the end point of RRT (5.1 events/100 patient-years), 20% died (9.6 deaths/100 patient-years), and 33% reached the combined end point of RRT or death (14.7 events/100 patient-years). For stage 3a, baseline prevalence and annual probabilities of decreasing CKD stage, RRT, and death were 18.0%, 0.41, 0.01, and 0.02, respectively. Corresponding values for stage 3b were 32.5%, 0.22, < 0.01, and 0.06; for stage 4, 36.5%, 0.17, 0.03, and 0.10; and for stage 5, 13.2%, zero (by definition), 0.31, and 0.08, respectively. Markov model projections suggested a steady decrease for proportions with stages 3a, 3b, and 4; a steady increase for death and RRT; and a biphasic pattern for (non-RRT) stage 5, with a plateau in the first 2 years followed by a steady decrease.LIMITATIONSSingle-center observational study.CONCLUSIONThis study suggests that death and RRT are the dominant outcomes in patients referred for management of CKD and that most patients spend comparatively little time in late stages without RRT.

In patients with chronic kidney disease, high plasma levels of the endogenous nitric oxide synthase inhibitor, asymmetric dimethylarginine, are thought to contribute to decline in renal function. Here we took a candidate gene approach to determine any causal role of asymmetric dimethylarginine in the progression of chronic kidney disease. The impact of single-nucleotide polymorphisms in the genes encoding the two isoforms of the asymmetric dimethylarginine-degrading enzyme, dimethylarginine dimethylaminohydrolase (DDAH1 and DDAH2), on enzyme expression, plasma asymmetric dimethylarginine levels, and longitudinal changes in estimated glomerular filtration rate were determined in various patient groups. There was evidence suggesting that the rs17384213 DDAH1 GG genotype was associated with increased expression of its mRNA in kidney allografts. Healthy subjects carrying the rs17384213 G allele had lower plasma asymmetric dimethylarginine, and a similar borderline association was found in patients with chronic kidney disease. This allele, however, was independently associated with a steeper decline in renal function in two separate cohorts of patients with chronic kidney disease. We conclude that polymorphisms in DDAH1 alter the rate of decline of glomerular filtration rate in subjects with chronic kidney disease. Our findings show that DDAH1 modulates plasma asymmetric dimethylarginine and contributes to the decline in renal function. However, it appears that increases in circulating methylarginine did not mediate progressive kidney injury.

BACKGROUND AND OBJECTIVES:Higher phosphate is associated with mortality in dialysis patients but few prospective studies assess this in nondialysis patients managed in an outpatient nephrology clinic. This prospective longitudinal study examined whether phosphate level was associated with death in a referred population. DESIGN, SETTING, PARTICIPANTS & MEASUREMENTS:Patients (1203) of nondialysis chronic kidney disease (CKD) in the Chronic Renal Insufficiency Standards Implementation Study were assessed. Survival analyses were performed for quartiles of baseline phosphate relative to GFR, 12-month time-averaged phosphate, and baseline phosphate according to published phosphate targets. RESULTS:Mean (SD) eGFR was 32 (15) ml/min per 1.73 m(2), age 64 (14) years, and phosphate 1.2 (0.30) mmol/L. Cox multivariate adjusted regression in CKD stages 3 to 4 patients showed an increased risk of all-cause and cardiovascular mortality in the highest quartile compared with that in the lowest quartile of phosphate. No association was found in CKD stage 5 patients. Patients who had values above recommended targets for phosphate control had increased risk of all-cause and cardiovascular death compared with patients below target. The highest quartile compared with the lowest quartile of 12-month time-averaged phosphate was associated with an increased risk of mortality. CONCLUSIONS:In CKD stages 3 to 4 patients, higher phosphate was associated with a stepwise increase in mortality. As phosphate levels below published targets (as opposed to within them) are associated with better survival, guidelines for phosphate in nondialysis CKD patients should be re-examined. Intervention trials are required to determine whether lowering phosphate will improve survival.