Identifying Clinical and Genomic Features Associated With Chronic Kidney Disease.

We apply a pattern-based classification method to identify clinical and genomic features associated with the progression of Chronic Kidney disease (CKD). We analyze the African-American Study of Chronic Kidney disease with Hypertension dataset and construct a decision-tree classification model, consisting 15 combinatorial patterns of clinical features and single nucleotide polymorphisms (SNPs), seven of which are associated with slow progression and eight with rapid progression of renal disease among African-American Study of Chronic Kidney patients. We identify four clinical features and two SNPs that can accurately predict CKD progression.

Author Correction: A new common functional coding variant at the DDC gene change renal enzyme activity and modify renal dopamine function.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Rationale and Strategies for Preserving Residual Kidney Function in Dialysis Patients.

Background: Residual kidney function (RKF) conveys a survival benefit among dialysis patients, but the mechanism remains unclear. Improved volume control, clearance of protein-bound and middle molecules, reduced inflammation and preserved erythropoietin and vitamin D production are among the proposed mechanisms. Preservation of RKF requires techniques to measure it accurately to be able to uncover factors that accelerate its loss and interventions that preserve it and ultimately to individualize therapy.

Cardiac risk assessment for end-stage renal disease patients on the renal transplant waiting list.

Cardiovascular disease is a leading cause of morbidity and mortality and is becoming more prevalent as the population ages and risk factors increase. This is most apparent in the end-stage renal disease (ESRD) patient population. In part, this is due to cofactors such as diabetes and hypertension commonly predisposing to progressive renal disease, as well as being a direct consequence of having renal failure.

Kidney Risk Variants and Cardiovascular Disease: An Individual Participant Data Meta-Analysis.

Background: Two coding variants in the apo L1 gene () are strongly associated with kidney disease in blacks. Kidney disease itself increases the risk of cardiovascular disease, but whether these variants have an independent direct effect on the risk of cardiovascular disease is unclear. Previous studies have had inconsistent results.

Magnitude of the Difference Between Clinic and Ambulatory Blood Pressures and Risk of Adverse Outcomes in Patients With Chronic Kidney Disease.

Background Obtaining 24-hour ambulatory blood pressure ( BP ) is recommended for the detection of masked or white-coat hypertension. Our objective was to determine whether the magnitude of the difference between ambulatory and clinic BP s has prognostic implications. Methods and Results We included 610 participants of the AASK (African American Study of Kidney Disease and Hypertension) Cohort Study who had clinic and ambulatory BPs performed in close proximity in time.

A new common functional coding variant at the DDC gene change renal enzyme activity and modify renal dopamine function.

The intra-renal dopamine (DA) system is highly expressed in the proximal tubule and contributes to Na+ and blood pressure homeostasis, as well as to the development of nephropathy. In the kidney, the enzyme DOPA Decarboxylase (DDC) originating from the circulation. We used a twin/family study design, followed by polymorphism association analysis at DDC locus to elucidate heritable influences on renal DA production.

Soluble Urokinase-Type Plasminogen Activator Receptor in Black Americans with CKD.

Background And Objectives: Black Americans with and without kidney disease risk variants face high risk of ESKD. Soluble urokinase-type plasminogen activator receptor (suPAR), a circulating signaling protein and marker of immune activation, constitutes a promising biomarker of CKD-associated risks. We aimed to quantify the associations between serum suPAR concentration and adverse outcomes in Black Americans with and without kidney disease risk variants, over and above iodine-125 iothalamate measured GFR and proteinuria.

Serum 6-Bromotryptophan Levels Identified as a Risk Factor for CKD Progression.

Metabolite levels reflect physiologic homeostasis and may serve as biomarkers of disease progression. Identifying metabolites associated with risk alleles-genetic variants associated with CKD risk commonly present in persons of African descent-may reveal novel markers of CKD progression relevant to other populations. We evaluated associations between the number of risk alleles and 760 serum metabolites identified untargeted profiling in participants of the African American Study of Kidney Disease and Hypertension (AASK) (=588; Bonferroni significance threshold <6.

Chronic kidney disease, kidney transplantation and oxidative stress: a new look to successful kidney transplantation.

Oxidative stress plays a key role in the pathophysiological process of uremia and its complications, particularly in cardiovascular disease. The level of oxidative stress markers is known to increase as chronic kidney disease progresses and correlates significantly with the level of renal function. Hemodialysis and peritoneal dialysis are major modes of renal replacement therapy for end-stage renal disease patients, but unfortunately they are also accompanied by increased oxidative stress.

Risk Variants, Incident Proteinuria, and Subsequent eGFR Decline in Blacks with Hypertension-Attributed CKD.

Background And Objectives: The natural history of kidney disease among blacks who carry the high-risk variants varies, with only a subgroup progressing to ESRD. We aimed to determine whether the risk variants are associated with incident proteinuria in the context of hypertension-attributed CKD, and whether subsequent kidney function decline after the onset of proteinuria differs by risk status.

Design, Setting, Participants, & Measurements: Using Cox models, we studied the association between risk status and incident proteinuria (defined as a doubling of urine protein-to-creatinine ratio to a level ≥0.

A Classification Model to Predict the Rate of Decline of Kidney Function.

The African American Study of Kidney Disease and Hypertension (AASK), a randomized double-blinded treatment trial, was motivated by the high rate of hypertension-related renal disease in the African-American population and the scarcity of effective therapies. This study describes a pattern-based classification approach to predict the rate of decline of kidney function using surface-enhanced laser desorption ionization/time of flight proteomic data from rapid and slow progressors classified by rate of change in glomerular filtration rate. An accurate classification model consisting of 7 out of 5,751 serum proteomic features is constructed by applying the logical analysis of data (LAD) methodology.

A tripartite complex of suPAR, APOL1 risk variants and αβ integrin on podocytes mediates chronic kidney disease.

Soluble urokinase plasminogen activator receptor (suPAR) independently predicts chronic kidney disease (CKD) incidence and progression. Apolipoprotein L1 (APOL1) gene variants G1 and G2, but not the reference allele (G0), are associated with an increased risk of CKD in individuals of recent African ancestry. Here we show in two large, unrelated cohorts that decline in kidney function associated with APOL1 risk variants was dependent on plasma suPAR levels: APOL1-related risk was attenuated in patients with lower suPAR, and strengthened in those with higher suPAR levels.

Risk Variants and Cardiovascular Disease: Results From the AASK (African American Study of Kidney Disease and Hypertension).

Objective: Among African Americans, the apolipoprotein L1 () risk variants have been associated with various types of kidney disease and chronic kidney disease progression. We aimed to determine whether these same risk variants also confer an increased risk for cardiovascular disease.

Approach And Results: In a cohort of African Americans with hypertension-attributed chronic kidney disease followed for up to 12 years, we used Cox proportional hazards models to estimate the relative hazard of a composite cardiovascular disease outcome (cardiovascular death or hospitalization for myocardial infarction, cardiac revascularization procedure, heart failure, or stroke) for the high- (2 risk variants) versus low-risk (0-1 risk variant) genotypes.

In-Hospital Mortality in Cirrhotic Patients with End-Stage Renal Disease Treated with Hemodialysis Versus Peritoneal Dialysis: A Nationwide Study.

Background: Cirrhotic patients often develop end-stage renal disease (ESRD) requiring renal replacement therapy in the form of hemodialysis (HD) or peritoneal dialysis (PD). Studies comparing the outcomes and difference in in-hospital mortality between these 2 groups, particularly among those with ascites, are sparse. We set our objective to determine the dialysis modality with a better in-hospital survival rate among cirrhotic patients with ESRD (ESRD-cirrhosis).

Acute Kidney Injury and In-Hospital Mortality after Coronary Artery Bypass Graft versus Percutaneous Coronary Intervention: A Nationwide Study.

Background: Post-procedural acute kidney injury (AKI) is associated with significantly increased short- and long-term mortalities, and renal loss. Few studies have compared the incidence of post-procedural AKI and in-hospital mortality between 2 major modalities of revascularization - coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) - and results have been inconsistent.

Methods: We generated a propensity score-matched cohort that includes a total of 286,670 hospitalizations with multi-vessel coronary disease undergoing CABG or PCI (2004-2012) from the National Inpatient Sample database.

Strict blood pressure control associates with decreased mortality risk by APOL1 genotype.

Although APOL1 high-risk genotype partially accounts for the increased susceptibility of blacks to chronic kidney disease (CKD), whether APOL1 associates differentially with mortality risk remains controversial. Here we evaluate the association between APOL1 genotype and risk of death and determine whether APOL1 status modifies the association between strict versus usual blood pressure control and mortality risk. We performed a retrospective analysis of the African American Study of Kidney Disease and Hypertension trial that randomized black participants with CKD to strict versus usual blood pressure control from 1995 to 2001.

Endocarditis and Pauci-Immune Glomerulonephritis: A Case Report and Review of the Literature.

Among culture-negative endocarditis in the United States, species are the most common cause, with and comprising the majority of cases. Kidney manifestations, particularly glomerulonephritis, are common sequelae of infectious endocarditis, with nearly half of all patients demonstrating renal involvement. Although a pauci-immune pattern is a frequent finding in infectious endocarditis-associated glomerulonephritis, it is rarely reported in endocarditis.

Genome-Wide Association of CKD Progression: The Chronic Renal Insufficiency Cohort Study.

The rate of decline of renal function varies significantly among individuals with CKD. To understand better the contribution of genetics to CKD progression, we performed a genome-wide association study among participants in the Chronic Renal Insufficiency Cohort Study. Our outcome of interest was CKD progression measured as change in eGFR over time among 1331 blacks and 1476 whites with CKD.

BP Control and Long-Term Risk of ESRD and Mortality.

We recently showed an association between strict BP control and lower mortality risk during two decades of follow-up of prior participants in the Modification of Diet in Renal Disease (MDRD) trial. Here, we determined the risk of ESRD and mortality during extended follow-up of the African American Study of Kidney Disease and Hypertension (AASK) trial. We linked 1067 former AASK participants with CKD previously randomized to strict or usual BP control (mean arterial pressure ≤92 mmHg or 102-107 mmHg, respectively) to the US Renal Data System and Social Security Death Index; 397 patients had ESRD and 475 deaths occurred during a median follow-up of 14.

Analysis of ABCG2 and other urate transporters in uric acid homeostasis in chronic kidney disease: potential role of remote sensing and signaling.

Background: In the setting of chronic kidney disease (CKD), altered extra-renal urate handling may be necessary to regulate plasma uric acid. The Remote Sensing and Signaling Hypothesis (Nigam S. What do drug transporters really do? Nat Rev Drug Discov 2015; 14: 29-44) suggests that multispecific solute carrier (SLC) and ATP-binding cassette (ABC) drug transporters in different tissues are part of an inter-organ communication system that maintains levels of urate and other metabolites after organ injury.

Patterns of Kidney Function Decline Associated with APOL1 Genotypes: Results from AASK.

Background And Objectives: Trajectories of eGFR in patients with CKD are highly variable. Only a subset of patients with CKD experiences a steady decline in eGFR. The objective of our study was to investigate whether eGFR trajectory patterns differ by APOL1 risk status.

Combined Effects of GSTM1 Null Allele and APOL1 Renal Risk Alleles in CKD Progression in the African American Study of Kidney Disease and Hypertension Trial.

Apolipoprotein L-1 (APOL1) high-risk alleles and the glutathione-S-transferase-μ1 (GSTM1) null allele have been shown separately to associate with CKD progression in the African American Study of Kidney Disease and Hypertension (AASK) trial participants. Here, we determined combined effects of GSTM1 null and APOL1 high-risk alleles on clinical outcomes in 682 AASK participants who were classified into four groups by GSTM1 null or active genotype and APOL1 high- or low-risk genotype. We assessed survival differences among these groups by log-rank test and Cox regression adjusted for important clinical variables for time to GFR event (change in GFR of 50% or 25-ml/min per 1.