Bardoxolone Methyl and Kidney Function in CKD with Type 2 Diabetes

Bardoxolone Methyl and Kidney Function in CKD with Type 2 Diabetes: (N Engl J Med 2011)

Pablo E. Pergola, M.D., Ph.D., Philip Raskin, M.D., Robert D. Toto, M.D., Colin J. Meyer, M.D., J. Warren Huff, J.D., Eric B. Grossman, M.D., Melissa Krauth, M.B.A., Stacey Ruiz, Ph.D., Paul Audhya, M.D., Heidi Christ-Schmidt, M.S.E., Janet Wittes, Ph.D., and David G. Warnock, M.D. for the BEAM Study Investigators

June 24, 2011 (10.1056/NEJMoa1105351)

BACKGROUND

Chronic kidney disease (CKD) associated with type 2 diabetes is the leading cause of kidney failure, with both inflammation and oxidative stress contributing to disease progression. Bardoxolone methyl, an oral antioxidant inflammation modulator, has shown efficacy in patients with CKD and type 2 diabetes in short-term studies, but longer-term effects and dose response have not been determined.

Pirfenidone for Diabetic Nephropathy

Pirfenidone for Diabetic Nephropathy: "
Pirfenidone is an oral antifibrotic agent that benefits diabetic nephropathy in animal models, but whether it is effective for human diabetic nephropathy is unknown. We conducted a randomized, double-blind, placebo-controlled study in 77 subjects with diabetic nephropathy who had elevated albuminuria and reduced estimated GFR (eGFR) (20 to 75 ml/min per 1.73 m²). The prespecified primary outcome was a change in eGFR after 1 year of therapy. We randomly assigned 26 subjects to placebo, 26 to pirfenidone at 1200 mg/d, and 25 to pirfenidone at 2400 mg/d.

Early Reduction of Serum-Free Light Chains Associates with Renal Recovery in Myeloma Kidney

Early Reduction of Serum-Free Light Chains Associates with Renal Recovery in Myeloma Kidney: "
Myeloma kidney is the major cause of severe irreversible renal failure in patients with multiple myeloma. This tubulointerstitial injury is a direct consequence of high concentrations of circulating monoclonal free light chains (FLCs) produced by a clonal expansion of plasma cells. Early reduction of serum FLCs associates with renal recovery, but the target threshold of reduction to facilitate renal recovery is unknown. To determine the relationship between the achieved FLC reduction and renal recovery, we identified 39 patients with biopsy-proven myeloma kidney, the majority of whom had severe renal failure at presentation (median estimated GFR 9 ml/min per 1.73 m²).

ACE Inhibition Is Renoprotective among Obese Patients with Proteinuria

ACE Inhibition Is Renoprotective among Obese Patients with Proteinuria: "
Obesity may increase the risk for progression of CKD, but the effect of established renoprotective treatments in overweight and obese patients with CKD is unknown. In this post hoc analysis of the Ramipril Efficacy In Nephropathy (REIN) trial, we evaluated whether being overweight or obese influences the incidence rate of renal events and affects the response to ramipril. Of the 337 trial participants with known body mass index (BMI), 105 (31.1%) were overweight and 49 (14.5%) were obese. Among placebo-treated patients, the incidence rate of ESRD was substantially higher in obese patients than overweight patients (24 versus 11 events/100 person-years) or than those with normal BMI (10 events/100 person-years);

Hemodialysis Vascular Access Modifies the Association between Dialysis Modality and Survival

Hemodialysis Vascular Access Modifies the Association between Dialysis Modality and Survival: "
Several comparisons of peritoneal dialysis (PD) and hemodialysis (HD) in incident patients with ESRD demonstrate superior survival in PD-treated patients within the first 1 to 2 years. These survival differences may be due to higher HD-related mortality as a result of high rates of incident central venous catheter (CVC) use or due to an initial survival advantage conferred by PD. We compared the survival of incident PD patients with those who initiated HD with a CVC (HD-CVC) or with a functional arteriovenous fistula or arteriovenous graft (HD-AVF/AVG). We used multivariable piece-wise exponential nonproportional and proportional hazards models to evaluate early (1 year) mortality as well as overall mortality during the period of observation using an intention-to-treat approach.

Antiproteinuric Response to Add-on Aliskiren in Proteinuric Patients Treated With Dual Blockade of the Renin-Angiotensin System: A 12-Month Prospective Uncontrolled Study

Antiproteinuric Response to Add-on Aliskiren in Proteinuric Patients Treated With Dual Blockade of the Renin-Angiotensin System: A 12-Month Prospective Uncontrolled Study: "Renin-angiotensin system (RAS) inhibition is the cornerstone treatment in proteinuric chronic kidney disease (CKD), but multiple escape mechanisms prevent adequate suppression. Compared with either monotherapy, dual blockade with an angiotensin-converting enzyme (ACE) inhibitor and angiotensin receptor blocker (ARB) improves proteinuria reduction by just 20%-30% on average. Consequently, many patients are left with residual proteinuria, which is still an important risk factor for end-stage renal disease. Recently, a synergistic antialbuminuric effect was evidenced when the direct renin inhibitor aliskiren was added to ARB therapy in diabetic patients with CKD. Here, we evaluate add-on aliskiren in proteinuric patients treated with an ACE inhibitor and ARB. Outcomes were proteinuria reduction after 6 months (primary) and maintenance at month 12, as well as safety (secondary)."

Fluid Balance, Diuretic Use, and Mortality in Acute Kidney Injury

Fluid Balance, Diuretic Use, and Mortality in Acute Kidney Injury: "SummaryBackground and objectives
Management of volume status in patients with acute kidney injury (AKI) is complex, and the role of diuretics is controversial. The primary objective was to elucidate the association between fluid balance, diuretic use, and short-term mortality after AKI in critically ill patients.
Design, setting, participants, & measurements
Using data from the Fluid and Catheter Treatment Trial (FACTT), a multicenter, randomized controlled trial evaluating a conservative versus liberal fluid-management strategy in 1000 patients with acute lung injury (ALI), we evaluated the association of post-renal injury fluid balance and diuretic use with 60-day mortality in patients who developed AKI, as defined by the AKI Network criteria.

Survival of elderly patients with stage 5 CKD: comparison of conservative management and renal replacement therapy

Survival of elderly patients with stage 5 CKD: comparison of conservative management and renal replacement therapy: "
Background. Elderly patients with end-stage renal disease and severe extra-renal comorbidity have a poor prognosis on renal replacement therapy (RRT) and may opt to be managed conservatively (CM). Information on the survival of patients on this mode of therapy is limited.
Methods. We studied survival in a large cohort of CM patients in comparison to patients who received RRT.

Cost-Effectiveness of Initiating Dialysis Early: A Randomized Controlled Trial

Cost-Effectiveness of Initiating Dialysis Early: A Randomized Controlled Trial: "Background: Planned early initiation of dialysis therapy based on estimated kidney function does not influence mortality and major comorbid conditions, but amelioration of symptoms may improve quality of life and decrease costs.Study Design: Patients with progressive chronic kidney disease and a Cockcroft-Gault estimated glomerular filtration rate of 10-15 mL/min/1.73 m2 were randomly assigned to start dialysis therapy at a glomerular filtration rate of either 10-14 (early start) or 5-7 mL/min/1.73 m2 (late start).Setting & Population: Of the original 828 patients in the IDEAL (Initiation of Dialysis Early or Late) Trial in renal units in Australia and New Zealand, 642 agreed to participate in this cost-effectiveness study.

Desmopressin Acetate in Percutaneous Ultrasound-Guided Kidney Biopsy: A Randomized Controlled Trial

Desmopressin Acetate in Percutaneous Ultrasound-Guided Kidney Biopsy: A Randomized Controlled Trial: "Background: Bleeding complications occur in one-third of percutaneous kidney biopsies and increase costs of the hospital stay. The aim of the study was to evaluate the effect of prebiopsy administration of desmopressin acetate versus placebo in the incidence of postbiopsy bleeding complications.Study Design: Double-blind randomized controlled clinical trial.Setting & Participants: We enrolled all patients with serum creatinine level ≤1.5 mg/dL and/or estimated glomerular filtration rate ≥60 mL/min/1.73 m2 and normal coagulation parameters undergoing ultrasound-guided biopsy of the native kidney in our unit from August 2008 to December 2009.Intervention: We examined prebiopsy subcutaneous administration of desmopressin acetate, 0.3 μg/kg, compared with placebo.

Olmesartan for the Delay or Prevention of Microalbuminuria in Type 2 Diabetes

Olmesartan for the Delay or Prevention of Microalbuminuria in Type 2 Diabetes: "Diabetic nephropathy is an increasingly common cause of end-stage renal disease, and the development and rate of renal deterioration are most closely related to the patient's blood pressure. Guideline committees worldwide concur that the blood pressure in patients with diabetes and chronic kidney…"