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Introduction: The Center for Medicare and Medicaid Services introduced an End-Stage Renal Disease Prospective Payment System (PPS) in 2011 to increase the utilization of home dialysis modalities, including peritoneal dialysis (PD). Several studies have shown a significant increase in PD utilization after PPS implementation. However, its impact on patients with kidney allograft failure remains unknown. Methods: We conducted an interrupted time series analysis using data from the US Renal Data System (USRDS) that include all adult kidney transplant recipients with allograft failure who started dialysis between 2005 and 2019. We compared the PD utilization in the pre-PPS period (2005–2010) to the fully implemented post-PPS period (2014–2019) for early (within 90 days) and late (91–365 days) PD experience. Results: A total of 27,507 adult recipients with allograft failure started dialysis during the study period. There was no difference in early PD utilization between the pre-PPS and the post-PPS period in either immediate change (0.3% increase; 95% CI: −1.95%, 2.54%; p = 0.79) or rate of change over time (0.28% increase per year; 95% CI: −0.16%, 0.72%; p = 0.18). Subgroup analyses revealed a trend toward higher PD utilization post-PPS in for-profit and large-volume dialysis units. There was a significant increase in PD utilization in the post-PPS period in units with low PD experience in the pre-PPS period. Similar findings were seen for the late PD experience. Conclusion: PPS did not significantly increase the overall utilization of PD in patients initiating dialysis after allograft failure. [ABSTRACT FROM AUTHOR]

Background: In the development of prediction models for a clinical event, it is common to use the static prediction modeling (SPM), a regression model that relates baseline predictors to the time to event. In many situations, the data used in training and validation are from longitudinal studies, where predictor variables are time-varying and measured at clinical visits. But these data are not used in SPM. The landmark analysis (LA), previously proposed for dynamic prediction with longitudinal data, has interpretational difficulty when the baseline is not a risk-changing clinical milestone, as is often the case in observational studies of chronic disease without intervention. Methods: This paper studies the generalized landmark analysis (GLA), a statistical framework to develop prediction models for longitudinal data. The GLA includes the LA as a special case, and generalizes it to situations where the baseline is not a risk-changing clinical milestone with a more useful interpretation. Unlike the LA, the landmark variable does not have to be time since baseline in the GLA, but can be any time-varying prognostic variable. The GLA can also be viewed as a longitudinal generalization of localized prediction, which has been studied in the context of low-dimensional cross-sectional data. We studied the GLA using data from the Chronic Renal Insufficiency Cohort (CRIC) Study and the Wisconsin Allograft Replacement Database (WisARD) and compared the prediction performance of SPM and GLA. Results: In various validation populations from longitudinal data, the GLA generally had similarly or better predictive performance than SPM, with notable improvement being seen when the validation population deviated from the baseline population. The GLA also demonstrated similar or better predictive performance than LA, due to its more general model specification. Conclusions: GLA is a generalization of the LA such that the landmark variable does not have to be the time since baseline. It has better interpretation when the baseline is not a risk-changing clinical milestone. The GLA is more adaptive to the validation population than SPM and is more flexible than LA, which may help produce more accurate prediction. [ABSTRACT FROM AUTHOR]

Background Hyperkalemia is a modifiable risk factor for sudden cardiac death, a leading cause of mortality in hemodialysis (HD) patients. The optimal treatment of hyperkalemia in hospitalized end-stage renal disease (ESRD) patients is nonexistent in literature, which has prompted studies from outpatient dialysis to be extrapolated to inpatient care. The goal of this study was to determine if low-potassium dialysate 1 mEq/L is associated with higher mortality in hospitalized ESRD patients with severe hyperkalemia (serum potassium >6.5 mmol/L). Methods We conducted a retrospective study of all adult ESRD patients admitted with severe hyperkalemia between January 2011 and August 2016. Results There were 209 ESRD patients on HD admitted with severe hyperkalemia during the study period. Mean serum potassium was 7.1 mmol/L. In-hospital mortality or cardiac arrest in ESRD patients with severe hyperkalemia was 12.4%. Median time to dialysis after serum potassium result was 2.0 h (25, 75 interquartile range 0.9, 4.2 h). Totally, 47.4% of patients received dialysis with 1 mEq/L concentration potassium bath. The use of 1 mEq/L potassium bath was associated with significantly lower mortality or cardiac arrest in ESRD patients admitted with severe hyperkalemia (odds ratio 0.27, 95% confidence interval 0.09–0.80, P = 0.01). Conclusion We conclude that use of 1 mEq/L potassium bath for treatment of severe hyperkalemia (>6.5 mmol/L) in hospitalized ESRD patients is associated with decreased in-hospital mortality or cardiac arrest. [ABSTRACT FROM AUTHOR]

Anti‐glomerular basement membrane (GBM) disease causes rapidly progressive glomerulonephritis and end‐stage kidney disease (ESKD). Studies of post‐transplant outcomes in patients with ESKD due to anti‐GBM disease in the United States are lacking. To better characterize outcomes of transplant recipients with a history of anti‐GBM disease, we examined patient survival and graft survival among recipients with anti‐GBM disease compared with IgA nephropathy at a single center in the United States. We analyzed patient survival, graft survival, disease recurrence, and malignancy rates for kidney transplant recipients with ESKD due to biopsy‐proven anti‐GBM disease who underwent kidney transplantation at our center between 1994 and 2015. 26 patients with biopsy‐proven anti‐GBM disease and 314 patients with IgAN underwent kidney transplantation from 1994 to 2015. The incidence of graft loss was 6.2 per 100 person‐years for anti‐GBM disease, which was similar to IgAN (4.08 per 100 person‐years, p =.09). Patient mortality for anti‐GBM was 0.03 per 100 person‐years, similar to IgAN (0.02 per 100 person‐years, p =.12). Disease recurrence occurred in one of the 26 anti‐GBM patients. Four out of 26 patients (15%) developed malignancy, most commonly skin cancer. Long‐term graft and patient survival for patients with ESKD due to anti‐GBM was similar to IgAN after kidney transplantation. [ABSTRACT FROM AUTHOR]

Background: The incidence of renal cell carcinoma (RCC) is higher in kidney transplant recipients (KTRs) compared to the general population. However, the risk factors and outcomes based on the diagnosis of RCC after kidney transplantation are limited. Methods: We analyzed risk factors for the development of RCC in KTRs transplanted at our institution between 1994 and 2016. We compared the incidence of graft failure and mortality in KTRs with RCC to matched controls using 5:1 event density sampling. Identifying the risk factors of RCC and patient and graft survival were outcomes of interest. Results: There were 4,178 KTRs performed at our institution during the study period, and 51 patients were diagnosed with RCC. Recipients were followed until graft failure or death. We did not identify commonly looked at baseline characteristics associated with the risk of RCC. Comparing KTRs with RCC to matched controls, RCC patients were younger (47.5 vs. 49.6 years, p < 0.01), received basiliximab induction more commonly (p = 0.01), had hypertension and glomerulonephritis as causes of end-stage renal disease (p = 0.01), and were more likely to be smokers (p < 0.01). RCC was significantly associated with death-censored graft failure (adjusted hazard ratio [HR]: 1.76; 95% CI: 1.02–3.03; p = 0.04) but not patient death (adjusted HR: 0.95; 95% CI: 0.50–1.83; p = 0.89). Conclusion: In our experience, RCC had a detrimental impact on graft survival among KTRs, highlighting the potential benefit of early diagnosis and optimal immunosuppression management in optimizing graft survival. [ABSTRACT FROM AUTHOR]

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 (<11 ng/mL) had an increased risk of AVF intervention compared to those with higher 25(OH)D levels (adjusted relative hazard [aHR] = 3.28; 95% confidence interval [CI]: 1.31, 8.20). The highest tertile of FGF‐23 (>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. [ABSTRACT FROM AUTHOR]

Background. Anemia is common in chronic kidney disease (CKD) and associated with poor outcomes. In cross-sectional studies, lower estimated glomerular filtration rate (eGFR) has been associated with increased risk for anemia. The aim of this study was to determine how hematocrit changes as eGFR declines and what factors impact this longitudinal association. Methods. We followed 1094 African-Americans with hypertensive nephropathy who participated in the African- American Study of Kidney Disease and Hypertension. Mixed effects models were used to determine longitudinal change in hematocrit as a function of eGFR. Interaction terms were used to assess for differential effects of age, gender, baseline eGFR, baseline proteinuria, malnutrition and inflammation on eGFR-associated declines in hematocrit. In sensitivity analyses, models were run using iGFR (by renal clearance of I125 iothalamate) in place of eGFR. Results. At baseline, mean hematocrit was 39% and 441 (40%) individuals had anemia. The longitudinal relationship between eGFR and hematocrit differed by baseline eGFR and was steeper when baseline eGFR was <45 mL/min/1.73 m². For example, the absolute decline in hematocrit per 10 mL/min/1.73 m2 decline in longitudinal eGFR was -3.7, -1.3 and -0.5% for baseline eGFR values of 20, 40 and 60 mL/min/1.73 m², respectively (P < 0.001 comparing the longitudinal association between baseline eGFR = 40 or 60 versus baseline eGFR = 20 mL/min/1.73 m²). Similarly, male sex, younger age (<65 years) and higher baseline proteinuria (protein-tocreatinine ratio >0.22) were associated with greater hematocrit declines per unit decrease in longitudinal eGFR compared with female sex, older age and low baseline proteinuria, respectively (P-interaction <0.05 for each comparison). The longitudinal eGFR-hematocrit association did not differ by body mass index, serum albumin or C-reactive protein. Conclusions. Men, younger individuals and those with low baseline eGFR (<45 mL/min/1.73 m2) or baseline proteinuria are particularly at risk for eGFR-related declines in hematocrit. [ABSTRACT FROM AUTHOR]

Background. Advanced glycation end products and their cell-bound receptors are thought to mediate the adverse effects of vascular disease through oxidative stress, inflammation and endothelial dysfunction. We examined the association between the soluble form of receptor for advanced glycation end products (sRAGE) and kidney disease. Methods. In this case-cohort study nested within the Atherosclerosis Risk in Communities (ARIC) study, baseline sRAGE levels were measured in a cohort random sample of participants without kidney disease (n= 1218), and among participants who developed incident chronic kidney disease (CKD) [estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 and ≥25% eGFR decline, n = 151] and end-stage renal disease (ESRD) [entry in the US Renal Data System (USRDS) registry, n = 152]. Results. Baseline sRAGE levels were inversely related to baseline eGFR (r = −0.13). After adjusting for age, sex and race, one interquartile range higher log10-transformed sRAGE was associated with development of CKD [odds ratio: 1.39; 95% confidence interval (95% CI) 1.06–1.83; P = 0.02] and ESRD (hazard ratio: 1.97; 95% CI 1.47–2.64; P < 0.001). These associations were not significant after eGFR adjustment. Conclusions. High sRAGE levels are associated with incident CKD and ESRD risk, but not after adjustment for kidney function at baseline. Future studies are needed to investigate specific mechanisms underlying the association of sRAGE with kidney disease risk. [ABSTRACT FROM AUTHOR]

The rope-ladder ( RL) technique is the most common technique used for cannulation of arteriovenous fistulae ( AVF). Buttonhole cannulation ( BHC), or constant-site technique, is recommended by the National Kidney Foundation's Kidney Disease Outcome Quality Initiative ( NKF/ KDOQI) vascular access guidelines. We compared outcomes of primary patency, episodes of bacteremia, access blood flow (Qa), and quality of life (QoL) scores between RL and BHC patients. Using a prospectively collected, vascular access database, a total of 45 prevalent dialysis patients using BHC were compared with 38 patients using the RL technique over a median of 12 months (inter-quartile range: 4-27 months). The two groups did not differ significantly in demographics except that diabetes was more common in those using BHC as compared to rope-ladder (69% vs. 34%; p = 0.002). Risk factors associated with lack of primary patency were age (hazards ratio [ HR] = 1.02 per decade; 95% CI: 1.00-1.03; p = 0.04) and female gender ( HR = 1.92; 95% CI: 1.08-3.40; p = 0.03). Use of the buttonhole technique was not associated with improved primary patency ( HR = 1.22, 95% CI: 0.65-2.28; p = 0.53). Episodes of bacteremia and mean scores from KDQOL-36 did not differ significantly between the groups. This study demonstrates for the first time that BHC use is not associated with improved access patency. [ABSTRACT FROM AUTHOR]

lipoprotein risk factors for atherosclerosis, i.e., increased LDL cholesterol, increased triglycerides and decreased HDL cholesterol, also are associated with progression of loss of kidney function...Goek and coworkers describe the association of the apoliproteins A1 and B and eGFR in two large cohorts derived from the general polulation [the NHANES III (N=7,023) and the ARIC study (n=10,292)]. The results were similar in both cohorts...Background Circulating lipoproteins and their protein constituents, apolipoproteins, are risk factors for chronic kidney disease (CKD). The associations between apolipoprotein A1, apolipoprotein B and their ratio with glomerular filtration rate estimated from the new CKD Epidemiology Collaboration (CKD-EPI) equation (eGFR) are not well studied in the general population. Methods Associations between apolipoprotein A1, B and their ratio with the outcomes of eGFR, CKD (eGFR <60 mL/min/1.73m2) and albuminuria were examined in the Atherosclerosis Risk in Communities study (ARIC, n = 10 292, 1996–98) and the Third National Health and Nutrition Examination Survey (NHANES III, n = 7023, 1988–91). Cross-sectional multivariable-adjusted analyses were performed using linear and logistic regression. Prospective analyses related baseline apolipoprotein levels to subsequent CKD incidence over 10 years using the ARIC Carotid MRI follow-up cohort (n = 1659). Results Higher apolipoprotein A1 quartiles were associated with a lower prevalence of CKD [Q4 versus Q1: odds ratio (OR) 0.73, P-trend = 0.02 in ARIC; Q4 versus Q1: OR 0.53, P-trend <0.01 in NHANES III] as well as with higher eGFR (P-trend <0.01 in ARIC and NHANES III). No consistent significant associations were found for apolipoprotein B in either study. The apolipoprotein B/A1 ratio was significantly associated with eGFR across quartiles in both studies (P-trend <0.01) and with CKD in ARIC (Q4 versus Q1: OR 1.23, P-trend = 0.01). Prospectively, there were trends for the association of apolipoproteins with incident CKD [Q4 versus Q1: incidence rate ratio (IRR) = 0.68 for apolipoprotein A1, P-trend = 0.1; Q4 versus Q1: IRR = 1.35 for apolipoprotein B, P-trend = 0.2]. Associations were not systematically stronger when comparing traditional lipids (total cholesterol, low-density lipoprotein or high-density lipoprotein) to apolipoproteins. Conclusions Higher serum apolipoprotein A1 was associated with lower prevalence of CKD and higher eGFR estimated by the CKD-EPI equation in two large multiethnic population-based samples. While apolipoprotein B showed no consistent associations, a higher apolipoprotein B/A1 ratio was significantly associated with lower eGFR in both studies. The direction and magnitude of the longitudinal associations between apolipoproteins and CKD incidence were overall similar to those observed cross-sectionally. No consistent differences became apparent between traditional lipids and apolipoproteins. [ABSTRACT FROM PUBLISHER]

Background: Early detection of individuals at high risk for chronic kidney disease (CKD) may aid prevention. Urinary levels of trefoil factor 3 (TFF3) are associated with acute kidney injury in animal models, but the association of TFF3 levels with incident CKD in humans is unknown.Methods: We conducted a case-control study nested within the Atherosclerosis Risk in Communities (ARIC) Study and the ARIC Carotid MRI Study to determine whether urinary TFF3 levels predict incident CKD over 8.6 years of follow-up. A total of 143 participants with incident CKD (eGFR decreasing by ≥25% to <60 ml/min/1.73 m(2)) were matched on age, sex and race to 143 non-cases.Results: Higher TFF3 levels at baseline were strongly associated with Black race, diabetes (both p = 0.002), and antihypertensive medication use (p = 0.02). Compared to participants with TFF3 levels in the lowest quartile, the odds ratio (OR) of incident CKD was 1.84 (95% confidence interval (CI): 0.80, 4.22) for individuals with TFF3 levels in the second quartile, 2.43 (95% CI: 1.06, 5.53) for the third quartile, and 2.77 (95% CI: 1.22, 6.28) for the fourth quartile (p trend = 0.02). Adjustment for covariates, including urinary albumin: creatinine ratio, did not markedly change the associations. Twofold higher TFF3 levels were strongly associated with incident CKD after adjustment for CKD risk factors (adjusted OR = 1.35; 95% CI: 1.11, 1.64).Conclusions: Higher urinary TFF3 levels may indicate ongoing repair of damage in the kidney. Additional studies are needed to confirm whether TFF3 can be useful as a marker of increased risk for CKD. [ABSTRACT FROM AUTHOR]

Background. The incidence of venous thromboembolism (VTE) is increased with severe kidney disease, but whether less-severe chronic kidney disease (CKD) increases the risk of VTE is less certain.Methods. We studied this in a prospective cohort of 10 700 whites and African Americans, aged 53–75 years, attending Visit 4 (1996–98) of the Atherosclerosis Risk in Communities Study. Estimated glomerular filtration rate (eGFR) values were estimated from prediction equations based on serum creatinine (eGFRcreat) or cystatin C (eGFRcys). Normal kidney function was defined as eGFR ≥90 ml/min/1.73 m2, mildly decreased kidney function as eGFR between 60 and 89 ml/min/1.73 m2 and Stage 3 to 4 CKD as eGFR between 15 and 59 ml/min/1.73 m2. VTE occurrence (n = 228) was ascertained over a median of 8.3 years.Results. For eGFRcys, the age-, race- and sex-adjusted hazard ratios of total VTE were 1.0, 1.40 and 1.94 (P trend = 0.003) for normal kidney function, mildly impaired kidney function and Stage 3 to 4 CKD, respectively. These respective hazard ratios were moderately attenuated to 1.0, 1.26 and 1.60 (P trend = 0.04) with adjustment for hormone replacement therapy, diabetes and body mass index. Associations between CKD based on eGFRcys and VTE were slightly stronger for idiopathic VTE than for secondary VTE. In contrast, CKD based on eGFRcreat was not associated with total VTE occurrence.Conclusions. Stage 3 to 4 CKD, based on eGFRcys but not eGFRcreat, was associated with an approximately 1.6-fold increased risk of VTE. [ABSTRACT FROM AUTHOR]

Background. Anaemia worsens as kidney function declines. Both conditions are associated with increased mortality. Serum cystatin C is purportedly a more sensitive marker of kidney disease and a better predictor of mortality than serum creatinine. However, studies suggest that extrarenal factors also influence cystatin C levels. [ABSTRACT FROM PUBLISHER]

Presents several studies on renal disease and failure. Effectiveness of trimethoprim-sulfamethoxazole for the treatment of uncomplicated urinary tract infections; Effects of acute renal failure on in-hospital mortality in patients with cardiogenic shock; Clinical significance of creatine kinase-MB elevation after percutaneous coronary intervention in patients with renal insufficiency; Relationship between mild renal insufficiency and atherosclerotic coronary heart disease in women.

Race-specific association of lipoprotein(a) with vascular access interventions in hemodialysis patients: The CHOICE Study. Background. Elevated serum levels of lipoprotein(a) [Lp(a)] and low molecular weight apolipoprotein(a) [apo(a)] isoforms are associated with atherothrombotic disease in the general population and in patients with kidney failure. Lp(a) may be more atherothrombotic in whites than in blacks. Data on the relation of Lp(a) and apo(a) isoform size to hemodialysis vascular access complications are limited. Methods. We analyzed the intervention-free survival of the first arteriovenous (AV) access among 215 white and 112 black incident hemodialysis patients participating in the CHOICE Study, a national multicenter prospective cohort study. Results. Median levels of Lp(a) protein were higher among blacks than whites (81.0 versus 37.5 nmol/L; P < 0.001) and inversely correlated with apo(a) isoform size (r = -0.57; P < 0.001). The incidence rate of access interventions was much higher in synthetic grafts (N = 193) than native fistulae (N = 134; 1.0 vs. 0.5 interventions per access-year; P < 0.001) and in patients with kidney failure primarily due to diabetes mellitus (N = 161) than others (N = 166; 0.9 vs. 0.6; P < 0.01), but did not differ by race. Blacks in the highest race-specific Lp(a) quartile (>145 nmol/L) had a significantly higher incidence rate than other blacks (1.4 vs. 0.7; P = 0.04), whereas no association was found in whites. The association in blacks remained after adjustment for access type and other characteristics (relative hazard = 1.68; 95% confidence interval: 0.98 to 2.86). No association was found with apo(a) isoform size in either race. Conclusions. Elevated Lp(a) may be a risk factor for arteriovenous access complications among black hemodialysis patients. Future studies should explore this possibility and be adequately powered to allow race-specific analyses. [ABSTRACT FROM AUTHOR]

Cytomegalovirus infection (CMV) after kidney transplantation leads to increased morbidity and mortality. Whether the cause of end-stage renal disease (ESRD) influences the risk of CMV infection post-transplant is not known. We analyzed data from 2741 adult kidney transplant recipients from January 1993 through December 2014. The causes of ESRD included diabetes mellitus (n = 947), hypertension (n = 442), polycystic kidney disease (n = 549), and glomerulonephritis (GN) (n = 803). The primary outcome was incidence of CMV infection, defined as the first episode of detectable CMV DNA in the blood following transplant. Three hundred and thirty patients developed a CMV infection over a median follow-up of 4.5 years. Patients with diabetes mellitus (DM) as the cause of ESRD had a higher incidence of CMV infection post-transplant compared to patients with GN (2.37 vs 1.58/100 person-years, P <.005) whereas hypertension (HTN) and autosomal dominant polycystic kidney disease (PKD) were similar (2.17 and 2.07/100 person-years). DM was associated with a 35% higher risk of CMV infection compared to GN in unadjusted analyses [hazard ratio=1.35 [95% confidence interval 1.02–1.78], P =.04). However, after adjustment for age, the risk of CMV infection was similar in all groups (DM: age-adjusted hazard ratio 1.02 [0.78–1.39]; HTN: 0.96 (0.67–1.36); PKD: 1.08 [0.78–1.48]; compared to GN). The risk of CMV infection increased with age (adjusted hazard ratio=1.32 [1.18–1.47] for every decade of life, P <.001). Our study demonstrates that the cause of ESRD is not a significant risk factor for CMV infection in kidney transplant recipients once adjusted for age. Future studies are needed to identify risk factors for CMV infection to define patient-centered monitoring and prevention. • Kidney transplant recipients with diabetes as the cause of ESRD have higher incidence of CMV post-transplant. • Cause of ESRD is not a significant risk factor for CMV infection in kidney transplant recipients once adjusted for age. • The age of 50 years is a cutoff for kidney transplant recipients after which the risk of CMV infection increases significantly. [ABSTRACT FROM AUTHOR]

The article discusses the results of a clinical study investigating the connection between glycemic control and chronic kidney disease (CKD) in diabetic adults who were followed for 10 years through the Atherosclerosis Risk in Communities study. It mentions that hypertension and dyslipidemia are among the many common risk factors shared by diabetes and CKD. The study concludes that glycemic control is the primary factor in reduced kidney function in diabetes mellitus.

Some suggest race-specific cutpoints for kidney measures to define and stage chronic kidney disease (CKD), but evidence for race-specific clinical impact is limited. To address this issue, we compared hazard ratios of estimated glomerular filtration rates (eGFR) and albuminuria across races using meta-regression in 1.1 million adults (75% Asians, 21% Whites, and 4% Blacks) from 45 cohorts. Results came mainly from 25 general population cohorts comprising 0.9 million individuals. The associations of lower eGFR and higher albuminuria with mortality and end-stage renal disease (ESRD) were largely similar across races. For example, in Asians, Whites, and Blacks, the adjusted hazard ratios (95% confidence interval) for eGFR 45-59 versus 90-104 ml/min per 1.73 m2 were 1.3 (1.2-1.3), 1.1 (1.0-1.2), and 1.3 (1.1-1.7) for all-cause mortality, 1.6 (1.5-1.7), 1.4 (1.2-1.7), and 1.4 (0.7-2.9) for cardiovascular mortality, and 27.6 (11.1-68.7), 11.2 (6.0-20.9), and 4.1 (2.2-7.5) for ESRD, respectively. The corresponding hazard ratios for urine albumin-to-creatinine ratio 30-299 mg/g or dipstick 1+ versus an albumin-to-creatinine ratio under 10 or dipstick negative were 1.6 (1.4-1.8), 1.7 (1.5-1.9), and 1.8 (1.7-2.1) for all-cause mortality, 1.7 (1.4-2.0), 1.8 (1.5-2.1), and 2.8 (2.2-3.6) for cardiovascular mortality, and 7.4 (2.0-27.6), 4.0 (2.8-5.9), and 5.6 (3.4-9.2) for ESRD, respectively. Thus, the relative mortality or ESRD risks of lower eGFR and higher albuminuria were largely similar among three major races, supporting similar clinical approach to CKD definition and staging, across races. [ABSTRACT FROM AUTHOR]

Abstract: Background: Chronic kidney disease (CKD) is associated with elevated apolipoprotein B to A-1 ratio (ApoB/A1). It is not known whether these markers are more strongly associated with the risk of coronary heart disease (CHD) in CKD compared to traditionally measured lipids and lipoprotein cholesterol ratios. Methods: We studied the association of lipids and apolipoproteins including non-HDL-cholesterol to HDL-cholesterol ratio (NonHDLc/HDLc) and ApoB/A1 with incident CHD in 10,137 individuals free of CHD at baseline (visit four) in the Atherosclerosis Risk in Communities (ARIC) study. An estimated glomerular filtration rate of 15 to <60 ml/min/1.73 m2 based on a cystatin C measurement was used to define CKD (Stage 3–4). Cox proportional hazards regression models were used to determine the association of lipids and apolipoprotein measurements with the risk of CHD in those with and without CKD after adjustment for demographic and known clinical cardiovascular risk factors. Results: CKD was present in 1217 (12%) individuals free of CHD at baseline. The median follow-up time was 11.1 years. A CHD event developed in 498 out of 8920 individuals without CKD (incidence rate: 5.2 events per 1000 person-years) and in 138 out of 1217 individuals with CKD (incidence rate: 12.0 events per 1000 person–years; P < 0.001). Those with CKD had a lower concentration of ApoA1: median (in g/L) and interquartile range (IQR) = 1.40 (1.38–1.42) vs. 1.48 (1.47–1.49) P < 0.001; and a higher ApoB/A1 = 0.75 (0.73–0.77) vs. 0.71 (0.70–0.72) P < 0.001; than those without CKD (eGFR ≥ 60 ml/min/1.73 m2). Among individuals with CKD, ApoB/A1 and NonHDLc/HDLc were both associated with the risk of CHD: hazard ratios (HR) and 95% confidence intervals (CI) per one standard deviation increase = 1.22 (1.02–1.46) for ApoB/A1 and 1.30 (1.07–1.57) for NonHDLc/HDLc with no significant differences detected (P for interaction >0.1) when comparing these estimates to those of participants without CKD. Conclusions: Although CKD is associated with a lower ApoA1 concentration and with a higher ApoB/A1, we found no evidence that these apolipoproteins are more strongly associated with CHD incidence in CKD compared to NonHDLc/HDLc. [Copyright &y& Elsevier]

The article focuses on a meta-analysis of studies to assess whether hypertensive status modifies the association of decreased estimated glomerular filtration rate (eGFR) and increased albuminuria with all-cause mortality, cardiovascular mortality, and end-stage renal disease (ESRD). It analysed data for 45 cohorts with 1,127,656 participants using Cox proportional hazards models. The results indicated that chronic kidney disease should be an equally relevant risk factor for mortality and ESRD. INSET: Panel: Research in context.

Background--Recent findings suggest that chronic kidney disease (CKD) may be associated with an increased risk of venous thromboembolism (VTE). Given the high prevalence of mild-to-moderate CKD in the general population, in depth analysis of this association is warranted. Methods and Results--We pooled individual participant data from 5 community-based cohorts from Europe (second Nord-TrØndelag Health Study [HUNT2], Prevention of Renal and Vascular End-stage Disease [PREVEND], and the TromsØ study) and the United States (Atherosclerosis Risks in Communities [ARIC] and Cardiovascular Health Study [CHS]) to assess the association of estimated glomerular filtration rate (eGFR), albuminuria, and CKD with objectively verified VTE. To estimate adjusted hazard ratios for VTE, categorical and continuous spline models were fit by using Cox regression with shared-frailty or random-effect meta-analysis. A total of 1178 VTE events occurred over 599 453 person-years follow-up. Relative to eGFR 100 mL/min per 1.73 m², hazard ratios for VTE were 1.29 (95% confidence interval, 1.04-1.59) for eGFR 75, 1.31 (1.00-1.71) for eGFR 60, 1.82 (1.27-2.60) for eGFR 45, and 1.95 (1.26-3.01) for eGFR 30 mL/min per 1.73 m2. In comparison with an albumin-to-creatinine ratio (ACR) of 5.0 mg/g, the hazard ratios for VTE were 1.34 (1.04-1.72) for ACR 30 mg/g, 1.60 (1.08-2.36) for ACR 300 mg/g, and 1.92 (1.19-3.09) for ACR 1000 mg/g. There was no interaction between clinical categories of eGFR and ACR (P=0.20). The adjusted hazard ratio for CKD, defined as eGFR <60 mL/min per 1.73 m² or albuminuria ≥30 mg/g, (versus no CKD) was 1.54 (95% confidence interval, 1.15-2.06). Associations were consistent in subgroups according to age, sex, and comorbidities, and for unprovoked versus provoked VTE, as well. Conclusions--Both eGFR and ACR are independently associated with increased risk of VTE in the general population, even across the normal eGFR and ACR ranges. [ABSTRACT FROM AUTHOR]

Abstract: Background: Stratification of individuals at risk for chronic kidney disease may allow optimization of preventive measures to reduce disease incidence and complications. We sought to develop a risk score that estimates an individual''s absolute risk of incident chronic kidney disease. Methods: Framingham Heart Study participants free of baseline chronic kidney disease, who attended a baseline examination in 1995-1998 and follow-up in 2005-2008, were included in the analysis (n=2490). Chronic kidney disease was defined as an estimated glomerular filtration rate <60 mL/min/1.73m2 using the Modification of Diet in Renal Disease equation. Participants were assessed for the development of chronic kidney disease at 10 years follow-up. Stepwise logistic regression was used to identify chronic kidney disease risk factors, and these were used to construct a risk score predicting 10-year chronic kidney disease risk. Performance characteristics were assessed using calibration and discrimination measures. The final model was externally validated in the bi-ethnic Atherosclerosis Risk in Communities Study (n=1777). Results: There were 1171 men and 1319 women at baseline, and the mean age was 57.1 years. At follow-up, 9.2% (n=229) had developed chronic kidney disease. Age, diabetes, hypertension, baseline estimated glomerular filtration rate, and albuminuria were independently associated with incident chronic kidney disease (P <.05), and these covariates were incorporated into a risk function (c-statistic 0.813). In external validation in the ARIC study, the c-statistic was 0.74 in whites (n=1353) and 0.75 in blacks (n=424). Conclusion: Risk stratification for chronic kidney disease is achievable using a risk score derived from clinical factors that are readily accessible in primary care. The utility of this score in identifying individuals in the community at high risk of chronic kidney disease warrants further investigation. [Copyright &y& Elsevier]

Both a low estimated glomerular filtration rate (eGFR) and albuminuria are known risk factors for end-stage renal disease (ESRD). To determine their joint contribution to ESRD and other kidney outcomes, we performed a meta-analysis of nine general population cohorts with 845,125 participants and an additional eight cohorts with 173,892 patients, the latter selected because of their high risk for chronic kidney disease (CKD). In the general population, the risk for ESRD was unrelated to eGFR at values between 75 and 105 ml/min per 1.73 m2 but increased exponentially at lower levels. Hazard ratios for eGFRs averaging 60, 45, and 15 were 4, 29, and 454, respectively, compared with an eGFR of 95, after adjustment for albuminuria and cardiovascular risk factors. Log albuminuria was linearly associated with log ESRD risk without thresholds. Adjusted hazard ratios at albumin-to-creatinine ratios of 30, 300, and 1000 mg/g were 5, 13, and 28, respectively, compared with an albumin-to-creatinine ratio of 5. Albuminuria and eGFR were associated with ESRD, without evidence for multiplicative interaction. Similar associations were found for acute kidney injury and progressive CKD. In high-risk cohorts, the findings were generally comparable. Thus, lower eGFR and higher albuminuria are risk factors for ESRD, acute kidney injury and progressive CKD in both general and high-risk populations, independent of each other and of cardiovascular risk factors. [ABSTRACT FROM AUTHOR]

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 <60 ml/min per 1.73 m2 or a urinary albumin-to-creatinine ratio >30 mg/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. [ABSTRACT FROM AUTHOR]

Background: In observational studies, the relationship between blood pressure and end-stage renal disease (ESRD) is direct and progressive. The burden of hypertension-related chronic kidney disease and ESRD is especially high among black patients. Yet few trials have tested whether intensive blood-pressure control retards the progression of chronic kidney disease among black patients. Methods: We randomly assigned 1094 black patients with hypertensive chronic kidney disease to receive either intensive or standard blood-pressure control. After completing the trial phase, patients were invited to enroll in a cohort phase in which the blood-pressure target was less than 130/80 mm Hg. The primary clinical outcome in the cohort phase was the progression of chronic kidney disease, which was defined as a doubling of the serum creatinine level, a diagnosis of ESRD, or death. Follow-up ranged from 8.8 to 12.2 years. Results: During the trial phase, the mean blood pressure was 130/78 mm Hg in the intensive-control group and 141/86 mm Hg in the standard-control group. During the cohort phase, corresponding mean blood pressures were 131/78 mm Hg and 134/78 mm Hg. In both phases, there was no significant between-group difference in the risk of the primary outcome (hazard ratio in the intensive-control group, 0.91; P=0.27). However, the effects differed according to the baseline level of proteinuria (P=0.02 for interaction), with a potential benefit in patients with a protein-to-creatinine ratio of more than 0.22 (hazard ratio, 0.73; P=0.01). Conclusions: In overall analyses, intensive blood-pressure control had no effect on kidney disease progression. However, there may be differential effects of intensive blood-pressure control in patients with and those without baseline proteinuria. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases, the National Center on Minority Health and Health Disparities, and others.) N Engl J Med 2010;363:918-29. [ABSTRACT FROM AUTHOR]

Several letters to the editor, as well as the authors' reply on their article "Associations of Kidney Disease Measures With Mortality and End-Stage Renal Disease in Individuals With and Without Hypertension: A Meta-Analysis" published in the November 10, 2012 issue are presented.