Temporal trends in the prevalence of diabetic kidney disease in the United States.

Context: Diabetes is the leading cause of kidney disease in the developed world. Over time, the prevalence of diabetic kidney disease (DKD) may increase due to the expanding size of the diabetes population or decrease due to the implementation of diabetes therapies.

Objective: To define temporal changes in DKD prevalence in the United States.

Use of aspirin associates with longer primary patency of hemodialysis grafts.

Extended-release dipyridamole plus low-dose aspirin (ERDP/ASA) prolongs primary unassisted graft patency of newly created hemodialysis arteriovenous grafts, but the individual contributions of each component are unknown. Here, we analyzed whether use of aspirin at baseline associated with primary unassisted graft patency among participants in a randomized trial that compared ERDP/ASA and placebo in newly created grafts. We used Cox proportional hazards regression, adjusting for prespecified baseline comorbidities and covariates.

Advances in understanding ischemic acute kidney injury.

Acute kidney injury (AKI) is independently associated with increased morbidity and mortality. Ischemia is the leading cause of AKI, and short of supportive measures, no currently available therapy can effectively treat or prevent ischemic AKI. This paper discusses recent developments in the understanding of ischemic AKI pathophysiology, the emerging relationship between ischemic AKI and development of progressive chronic kidney disease, and promising novel therapies currently under investigation.

Acute kidney injury in older adults.

Aging kidneys undergo structural and functional changes that decrease autoregulatory capacity and increase susceptibility to acute injury. Acute kidney injury associates with duration and location of hospitalization, mortality risk, progression to chronic kidney disease, and functional status in daily living. Definition and diagnosis of acute kidney injury are based on changes in creatinine, which is an inadequate marker and might identify patients when it is too late.

Effects of combination tocopherols and alpha lipoic acid therapy on oxidative stress and inflammatory biomarkers in chronic kidney disease.

Objective: Although increased oxidative stress and inflammation are highly prevalent in chronic kidney disease (CKD), few studies have investigated whether oral antioxidant therapy can alter markers of inflammation or oxidative stress in patients with CKD. The purpose of this study was to investigate whether a combination of mixed tocopherols and alpha lipoic acid (ALA) would alter biomarkers of oxidative stress and inflammation in subjects with stage 3 to 4 CKD.

Methods: This was a prospective, randomized, double-blind, placebo-controlled pilot trial.

Safety of low volume iodinated contrast administration for arteriovenous fistula intervention in chronic kidney disease stage 4 or 5 utilizing a bicarbonate prophylaxis strategy.

Efforts to increase the number of functioning arteriovenous fistulas in chronic kidney disease (CKD) stages 4 and 5 have been impacted by concerns about the risk for contrast-induced nephropathy during diagnostic and interventional procedures for poorly developed fistulas. We conducted a prospective observational study of low volume iodinated contrast administration for fistulography and angioplasty in a CKD stage 4 and stage 5 population pretreated with a sodium bicarbonate protocol. Acute kidney injury was assessed by change in serum creatinine and urinary neutrophil-gelatinase associated lipocalcin (NGAL).

Sepsis as a cause and consequence of acute kidney injury: Program to Improve Care in Acute Renal Disease.

Purpose: Sepsis commonly contributes to acute kidney injury (AKI); however, the frequency with which sepsis develops as a complication of AKI and the clinical consequences of this sepsis are unknown. This study examined the incidence of, and outcomes associated with, sepsis developing after AKI.

Methods: We analyzed data from 618 critically ill patients enrolled in a multicenter observational study of AKI (PICARD).

Effluent volume in continuous renal replacement therapy overestimates the delivered dose of dialysis.

Background And Objectives: Studies examining dose of continuous renal replacement therapy (CRRT) and outcomes have yielded conflicting results. Most studies considered the prescribed dose as the effluent rate represented by ml/kg per hour and reported this volume as a surrogate of solute removal. Because filter fouling can reduce the efficacy of solute clearance, the actual delivered dose may be substantially lower than the observed effluent rate.

MCP-1 gene activation marks acute kidney injury.

Monocyte chemoattractant protein 1 (MCP-1) mediates acute ischemic and toxic kidney injury, but whether this can be used as a biomarker of acute kidney injury (AKI) is unknown. We obtained kidney and urine samples from mice with intrarenal (maleate), prerenal (endotoxemia), or postrenal (ureteral obstruction) injury. We also studied the independent effects of uremia without concomitant kidney injury by performing bilateral ureteral transection in mice.

Efficacy and safety of carvedilol in treatment of heart failure with chronic kidney disease: a meta-analysis of randomized trials.

Background: The safety and efficacy of different types of β-blocker therapy in patients with non-dialysis-dependent chronic kidney disease (CKD) and systolic heart failure (HF) are not well described. We assessed whether treatment of systolic HF with carvedilol is efficacious and safe in adults with CKD.

Methods And Results: We performed a post hoc analysis of pooled individual patient data (n=4217) from 2 multinational, double-blinded, placebo-controlled, randomized trials, CAPRICORN (Carvedilol Postinfarct Survival Control in Left Ventricular Dysfunction Study) and COPERNICUS (Carvedilol Prospective Randomized, Cumulative Survival study).

Multiple-dose pharmacokinetics and pharmacodynamics of N-acetylcysteine in patients with end-stage renal disease.

Background And Objectives: ESRD is associated with systemic oxidative stress, an important nontraditional risk factor for the development of cardiovascular disease. Since interventions aimed at reducing oxidative stress may be beneficial, we examined the pharmacokinetics and pharmacodynamics of the widely used antioxidant N-acetylcysteine (NAC) after oral administration in patients with ESRD.

Design, Setting, Participants, & Measurements: Twenty-four ESRD patients were randomly assigned to receive 600 or 1200 mg of sustained-release NAC orally every 12 hours for 14 days.

Fluid accumulation, recognition and staging of acute kidney injury in critically-ill patients.

Introduction: Serum creatinine concentration (sCr) is the marker used for diagnosing and staging acute kidney injury (AKI) in the RIFLE and AKIN classification systems, but is influenced by several factors including its volume of distribution. We evaluated the effect of fluid accumulation on sCr to estimate severity of AKI.

Methods: In 253 patients recruited from a prospective observational study of critically-ill patients with AKI, we calculated cumulative fluid balance and computed a fluid-adjusted sCr concentration reflecting the effect of volume of distribution during the development phase of AKI.

Association of major depression and mortality in Stage 5 diabetic chronic kidney disease.

Objectives: Depression is the most common psychiatric disorder in patients with chronic kidney disease (CKD). We sought to determine the association of major depression with mortality among diabetic patients with late stage CKD.

Method: The Pathways Study is a longitudinal, prospective cohort study initiated to determine the impact of depression on outcomes among primary care diabetic patients.

Mechanisms of drug-induced nephrotoxicity.

Drug-induced nephrotoxicity is a common complication of several medications and diagnostic agents. It is seen in both inpatient and outpatient settings with variable presentations ranging from mild, reversible injury to advanced kidney disease. Manifestations of drug-induced nephrotoxicity include acid-base abnormalities, electrolyte imbalances, urine sediment abnormalities, proteinuria, pyuria, hematuria, and, most commonly, a decline in the glomerular filtration rate.

Tubular expression of KIM-1 does not predict delayed function after transplantation.

Injured epithelial cells of the proximal tubule upregulate the glycoprotein kidney injury molecule 1 (KIM-1), suggesting its potential as a biomarker of incipient kidney allograft injury. It is unknown whether KIM-1 expression changes in kidney allografts with delayed graft function (DGF), which often follows ischemia-reperfusion injury. Here, we prospectively measured KIM-1 RNA and protein expression in preperfusion biopsies of 30 living- and 85 deceased-donor kidneys and correlated the results with histologic and clinical outcomes after transplantation.

Uremic toxicity, oxidative stress, and hemodialysis as renal replacement therapy.

Patients with uremia are subject to greatly increased cardiovascular risk that cannot be completely explained by traditional cardiovascular risk factors. An increase in oxidative stress and inflammation has been proposed as contributory nontraditional uremic cardiovascular risk factors. Oxidative stress reflects the balance between oxidant generation and antioxidant defense mechanisms.

Acute kidney injury in the elderly: problems and prospects.

Acute kidney injury (AKI) usually is defined as a decline in glomerular filtration rate over hours to days that can occur either in a person with previously normal kidney function, or in the setting of pre-existing chronic kidney disease. The incidence of AKI has increased steadily in recent years, and this increase is associated strongly with advancing age in the population because epidemiologic data indicate that AKI is much more common in the elderly. In the aging population there is heightened susceptibility to drug toxicity, partially owing to altered drug pharmacokinetics and pharmacodynamics.

Preexisting chronic kidney disease: a potential for improved outcomes from acute kidney injury.

Background And Objectives: Acute kidney injury (AKI) is associated with adverse outcomes in critically ill patients. The influence of preexisting chronic kidney disease (CKD) on AKI outcomes is unclear.

Design, Setting, Participants, & Measurements: We analyzed data from a prospective observational cohort study of AKI in critically ill patients who received nephrology consultation: the Program to Improve Care in Acute Renal Disease.

Mapping of NRAGE domains reveals clues to cell viability in BMP signaling.

Bone morphogenetic signaling (BMP) is a key pathway during neurogenesis and depends on many downstream intermediators to carry out its signaling. One such signaling pathway utilizes neurotrophin receptor-interacting MAGE protein (NRAGE), a member of the melanoma-associated antigen (MAGE) family, to upregulate p38 mitogen activated protein kinase (p38(MAPK)) in response to cellular stress and activate caspases which are critical in leading cells to death. NRAGE consists of two conserved MAGE homology domains separated by a unique hexapeptide repeat domain.

Primary mouse renal tubular epithelial cells have variable injury tolerance to ischemic and chemical mediators of oxidative stress.

We have developed and evaluated an in vitro culture method for assessing ischemic injury in primary mouse renal tubular epithelial cells (RTEC) in which to explore the pathobiology underlying acute kidney injury. RTEC were predominately of proximal tubule origin which is most susceptible to ischemic injury as compared to other nephron segments. Oxidative stress was induced by chemically depleting ATP using Antimycin A and 2-Deoxy-D-Glucose and by exposing cells to a 1% oxygen environment.

Creating research infrastructure and functionality to address chronic kidney disease: the Kidney Research Institute.

An expanding proportion of people in the United States and worldwide are affected by kidney disease, leading to a growing concern over the public health implications. Despite the high prevalence and the considerable associated health risks of kidney disease, major gaps in our knowledge base hinder the delivery of optimal medical care to affected individuals. Moreover, research progress that translates into clinical benefit has been slow.