Comparing the association of GFR estimated by the CKD-EPI and MDRD study equations and mortality: the third national health and nutrition examination survey (NHANES III)

BACKGROUND: The Chronic Kidney Disease Epidemiology Collaboration equation for estimation of glomerular filtration rate (eGFR(CKD-EPI)) improves GFR estimation compared with the Modification of Diet in Renal Disease Study equation (eGFR(MDRD)) but its association with mortality in a nationally representative population sample in the US has not been studied. METHODS: We examined the association between eGFR and mortality among 16,010 participants of the Third National Health and Nutrition Examination Survey (NHANES III). Primary predictors were eGFR(CKD-EPI) and eGFR(MDRD). Outcomes of interest were all-cause and cardiovascular disease (CVD) mortality. Improvement in risk categorization with eGFR(CKD-EPI) was evaluated using adjusted relative hazard (HR) and Net Reclassification Improvement (NRI). RESULTS: Overall, 26.9% of the population was reclassified to higher eGFR categories and 2.2% to lower eGFR categories by eGFR(CKD-EPI,) reducing the proportion of prevalent CKD classified as stage 3–5 from 45.6% to 28.8%(.) There were 3,620 deaths (1,540 from CVD) during 215,082 person-years of follow-up (median, 14.3 years). Among those with eGFR(MDRD) 30–59 ml/min/1.73 m(2), 19.4% were reclassified to eGFR(CKD-EPI) 60–89 ml/min/1.73 m(2) and these individuals had a lower risk of all-cause mortality (adjusted HR, 0.53; 95% CI, 0.34-0.84) and CVD mortality (adjusted HR, 0.51; 95% CI, 0.27-0.96) compared with those not reclassified. Among those with eGFR(MDRD) >60 ml/min/1.73 m(2), 0.5% were reclassified to lower eGFR(CKD-EPI) and these individuals had a higher risk of all-cause (adjusted HR, 1.31; 95% CI, 1.01-1.69) and CVD (adjusted HR, 1.42; 95% CI, 1.01-1.99) mortality compared with those not reclassified. Risk prediction improved with eGFR(CKD-EPI); NRI was 0.21 for all-cause mortality (p < 0.001) and 0.22 for CVD mortality (p < 0.001). CONCLUSIONS: eGFR(CKD-EPI) categories improve mortality risk stratification of individuals in the US population. If eGFR(CKD-EPI) replaces eGFR(MDRD) in the US, it will likely improve risk stratification

Change in Estimated GFR and Risk of Allograft Failure in Patients Diagnosed With Late Active Antibody-mediated Rejection Following Kidney Transplantation

Malaltia renal en fase terminal; Trasplantament de ronyóEnfermedad renal en etapa terminal; Transplante de riñónEnd-stage renal disease; Kidney TransplantBackground. There are challenges in designing adequate, well-controlled studies of patients with active antibody-mediated rejection (AMR) after kidney transplantation (KTx). Methods. We assessed the functional relationship between change in estimated glomerular filtration rate (eGFR) following the diagnosis of AMR and the risk of subsequent death-censored graft failure using the joint modeling framework. We included recipients of solitary KTx between 1995 and 2013 at 4 transplant centers diagnosed with biopsy-proven active AMR at least 1 year post-KTx, who had a minimum of 3-year follow-up. Results. A total of 91 patients across participating centers were included in the analysis. Of the 91 patients, n = 54 patients (59%) met the death-censored graft failure endpoint and n = 62 patients (68%) met the all-cause graft failure composite endpoint. Kaplan-Meier death-censored graft survival rates at 12, 36, and 60 months postdiagnosis of AMR pooled across centers were 88.9%, 58.9%, and 36.4%, respectively. Spaghetti plots indicated a linear trend in the change in eGFR, especially in the first 12 months postdiagnosis of active AMR. A significant change in eGFR was observed within the first 12 months postdiagnosis of active AMR, getting worse by a factor of −0.757 mL/min/1.73 m2 per month during the 12-month analysis period (a delta of −9.084 mL/min/1.73 m2 at 1 y). Notably, an extrapolated 30% improvement in the slope of eGFR in the first 12 months was associated with a 10% improvement in death-censored graft failure at 5 years. Conclusions. If prospectively validated, this study may inform the design of pivotal clinical trials for therapies for late AMR

MRI measurements of carotid plaque in the atherosclerosis risk in communities (ARIC) study: Methods, reliability and descriptive statistics

To measure carotid plaque components using MRI and estimate reliability in the population-based Atherosclerosis Risk in Communities (ARIC) study

Net endogenous acid production is associated with a faster decline in GFR in African Americans

Increased acid excretion may promote renal injury. To evaluate this in African Americans with hypertensive nephrosclerosis, we studied the association between the net endogenous acid production and progression of kidney disease in 632 patients in the AASK trial. Protein and potassium intakes were estimated from 24h urea nitrogen and potassium excretion, and used to estimate net endogenous acid production, averaged over 2 years, approximating routine intake. The link between net endogenous acid production and the I125iothalamate glomerular filtration rate (iGFR) and time to end-stage renal disease or doubling of serum creatinine was analyzed using mixed models and Cox proportional hazards regressions. The trend in higher net endogenous acid production was significantly associated with a faster decline in iGFR over a median of 3.2 years. After adjustment for age, body mass index, baseline iGFR, urine protein-to-creatinine ratio, and randomized treatment group, the trend in higher net endogenous acid production remained significantly associated with a faster decline in iGFR at a rate of 1.01ml/min per 1.73m2 per year faster in the highest compared to the lowest quartile. However, in time-to-event analyses over a median of 7.7 years, the adjusted hazard ratio (1.10) for composite renal events per 25mEq/day higher net endogenous acid production was not significant. Hence, our findings implicate endogenous acid production as a potential modifiable risk factor for progressive kidney disease

Association of rs780094 in \u3ci\u3eGCKR\u3c/i\u3e with Metabolic Traits and Incident Diabetes and Cardiovascular Disease: The ARIC Study

Objective: The minor T-allele of rs780094 in the glucokinase regulator gene (GCKR) associates with a number of metabolic traits including higher triglyceride levels and improved glycemic regulation in study populations of mostly European ancestry. Using data from the Atherosclerosis Risk in Communities (ARIC) Study, we sought to replicate these findings, examine them in a large population-based sample of African American study participants, and to investigate independent associations with other metabolic traits in order to determine if variation in GKCR contributes to their observed clustering. In addition, we examined the association of rs780094 with incident diabetes, coronary heart disease (CHD), and stroke over up mean follow-up times of 8, 15, and 15 years, respectively. Research Design and Methods: Race-stratified analyses were conducted among 10,929 white and 3,960 black participants aged 45–64 at baseline assuming an additive genetic model and using linear and logistic regression and Cox proportional hazards models. Results: Previous findings replicated among white participants in multivariable adjusted models: the T-allele of rs780094 was associated with lower fasting glucose (p = 10-7) and insulin levels (p = 10-6), lower insulin resistance (HOMA-IR, p=10-9), less prevalent diabetes (p = 10-6), and higher CRP (p = 10-8), 2-h postprandial glucose (OGTT, p = 10-6), and triglyceride levels (p = 10-31). Moreover, the T-allele was independently associated with higher HDL cholesterol levels (p = 0.022), metabolic syndrome prevalence (p = 0.043), and lower beta-cell function measured as HOMA-B (p = 0.011). Among black participants, the T-allele was associated only with higher triglyceride levels (p = 0.004) and lower insulin levels (p = 0.002) and HOMA-IR (p = 0.013). Prospectively, the T-allele was associated with reduced incidence of diabetes (p = 10-4) among white participants, but not with incidence of CHD or stroke. Conclusions: Our findings indicate rs780094 has independent associations with multiple metabolic traits as well as incident diabetes, but not incident CHD or stroke. The magnitude of association between the SNP and most traits was of lower magnitude among African American compared to white participants

The definition, classification, and prognosis of chronic kidney disease: a KDIGO Controversies Conference report

The definition and classification for chronic kidney disease was proposed by the National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF-KDOQI) in 2002 and endorsed by the Kidney Disease: Improving Global Outcomes (KDIGO) in 2004. This framework promoted increased attention to chronic kidney disease in clinical practice, research and public health, but has also generated debate. It was the position of KDIGO and KDOQI that the definition and classification should reflect patient prognosis and that an analysis of outcomes would answer key questions underlying the debate. KDIGO initiated a collaborative meta-analysis and sponsored a Controversies Conference in October 2009 to examine the relationship of estimated glomerular filtration rate (GFR) and albuminuria to mortality and kidney outcomes. On the basis of analyses in 45 cohorts that included 1,555,332 participants from general, high-risk, and kidney disease populations, conference attendees agreed to retain the current definition for chronic kidney disease of a GFR <60ml/min per 1.73m2 or a urinary albumin-to-creatinine ratio >30mg/g, and to modify the classification by adding albuminuria stage, subdivision of stage 3, and emphasizing clinical diagnosis. Prognosis could then be assigned based on the clinical diagnosis, stage, and other key factors relevant to specific outcomes. KDIGO has now convened a workgroup to develop a global clinical practice guideline for the definition, classification, and prognosis of chronic kidney disease

Markers of mineral metabolism and vascular access complications: The Choices for Healthy Outcomes in Caring for ESRD (CHOICE) study

Introduction: Vascular access dysfunction is a major cause of morbidity in patients with end‐stage renal disease (ESRD) on chronic hemodialysis. The effects of abnormalities in mineral metabolism on vascular access are unclear. In this study, we evaluated the association of mineral metabolites, including 25‐hydroxy vitamin D (25(OH)D) and fibroblast growth factor‐23 (FGF‐23), with vascular access complications.Methods: We included participants from the Choices for Healthy Outcomes in Caring for ESRD (CHOICE) Study who were using an arteriovenous fistula (AVF; n = 103) or arteriovenous graft (AVG; n = 116). Serum levels of 25(OH)D, FGF‐23, parathyroid hormone (PTH), calcium, phosphorus, C‐reactive protein (CRP) and interleukin‐6 (IL‐6) were assessed from stored samples. Participants were followed for up to 1 year or until a vascular access intervention or replacement.Findings: A total of 24 participants using an AVF and 43 participants using an AVG experienced access intervention. Those with 25(OH)D level in the lowest tertile (3750 RU/mL) was associated with greater risk of AVF intervention (aHR = 2.56; 95% CI: 1.06, 6.18). Higher PTH was associated with higher risk of AVF intervention (aHR = 1.64 per SD of log(PTH); 95% CI: 1.02, 2.62). These associations were not observed in participants using an AVG. None of the other analytes were significantly associated with AVF or AVG intervention.Discussion: Low levels of 25(OH)D and high levels of FGF‐23 and PTH are associated with increased risk of AVF intervention. Abnormalities in mineral metabolism are risk factors for vascular access dysfunction and potential therapeutic targets to improve outcomes.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153726/1/hdi12798_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/153726/2/hdi12798.pd

Diabetes medication use and blood lactate level among participants with type 2 diabetes : the atherosclerosis risk in communities carotid MRI study

Background: The objective of this study is to compare lactate levels between users and non-users of diabetes medications under the hypothesis that the level of lactate is a marker of oxidative capacity. Methods: The cross-sectional data of 493 participants aged 61–84 with type 2 diabetes who participated in the Atherosclerosis Risk in Communities Carotid MRI study were analyzed using survey weighted linear regression. Results: Median plasma lactate level was 8.58 (95% CI: 8.23, 8.87) mg/dl. Comparing users of diabetic medications with nonusers, thiazolidinedione use was significantly associated with lower lactate level (7.57 (6.95–8.25) mg/dL vs. 8.78 (8.43–9.14) mg/dL), metformin use with a slightly higher lactate level (9.02 (8.51–9.58) mg/dL vs. 8.36 (7.96–8.77) mg/dL), and sulfonylurea and insulin use were not associated with lactate level. After adjustment for demographic and lifestyle factors, the plasma lactate level for thiazolidinedione users was 15.78% lower than that for non-users (p,0.001). Considering use of each medication separately and in combination did not change the results. Conclusion: In conclusion, thiazolidinedione use was associated with lower plasma lactate level compared to non-use and metformin use was only marginally associated with a slightly higher lactate level. These results are consistent with the previously demonstrated effects of diabetes medications on oxidative metabolism. Further investigation of the role that diabetes medications play in improvement of oxidative metabolism is warrante