Modulation of endogenous antioxidant defense and the progression of kidney disease in multi-heritage groups of patients with type 2 diabetes: PRospective EValuation of Early Nephropathy and its Treatment (PREVENT).

BACKGROUND: Diabetes is the western world's leading cause of end-stage renal disease. Glucose-dependent, oxidative stress is linked to the development of renal inflammation and sclerosis, which, in animal models of diabetes, can be prevented by anti-oxidative treatment. Patients of non-Caucasian heritage have low activity of the selenoprotein, antioxidant enzyme, glutathione peroxidase (GPx) and its co-factor vitamin E, which may be linked to their increased propensity to developing end-stage renal disease. RESEARCH DESIGN AND METHODS: We have designed a double-blind, randomized, placebo controlled study with selenium and/or vitamin E versus placebo as the interventions for patients with type 2 diabetes and chronic kidney disease (CKD) stages 1-3. A 2 × 2 factorial design will allow a balanced representation of the heritage groups exposed to each intervention. The primary biochemical outcome is change in GPx activity, and clinical outcome measure is the actual, rate of-and/or percentage change in estimated glomerular filtration rate (eGFR) from baseline. Analysis will be with a marginal model for longitudinal data using Generalized Estimating Equations corrected for measures of baseline serum antioxidant enzyme activities (GPx, superoxide dismutase and catalase), micronutrient levels (vitamins E and C), measures of inflammation (interleukin 6, c-reactive protein and monocyte chemoattractant protein-1) and markers of oxidative damage (plasma 8-isoprostaglandin F2α and urinary 8-hydroxydeoxyguanosine). EXPECTED RESULTS: The study will assess the relationship between GPx activity, oxidative stress, inflammation and eGFR. It will test the null hypothesis that antioxidant therapy does not influence the activity of GPx or other antioxidant enzymes and/or alter the rate of change in eGFR in these patient groups. CONCLUSIONS: Outcome data on the effect of antioxidants in human diabetic renal disease is limited. Previous post hoc analyses have not shown a beneficial effect of vitamin E on renal function. A recent trial of a pharmaceutical antioxidant agent, improved eGFR, but in patients with advanced diabetes-related chronic kidney disease its use was associated with an increased incidence of cardiovascular events. We will explore whether the nutritional antioxidants, vitamin E and selenium alone, or in combination in patients at high risk of renal disease progression, forestalls a reduction in eGFR. The study will describe whether endogenous antioxidant enzyme defenses can be safely modified by this intervention and how this is associated with changes in markers of oxidative stress. Trial registration ISRCTN 97358113. Registered 21st September 2009.

Use of continuous venovenous hemofiltration for acute renal failure due to multiple myeloma cast nephropathy.

Renal insufficiency is associated with high morbidity and mortality in multiple myeloma. One of the common causes for acute renal failure in multiple myeloma is cast nephropathy. It is important to reduce the levels of light chains to improve renal failure and also the overall outcome. Plasmapheresis has failed to show any significant improvement in renal failure due to cast nephropathy as demonstrated in a recent randomized control trial. Here, we present a case series of three patients who were treated with continuous venovenous hemofiltration as a modality to remove these free light chains. There was improvement in renal failure in these patients with decrease in the levels of free light chains. These patients remained off hemodialysis on follow-up and two of them were able to undergo hematopoietic stem cell transplantation.

Adherence to K/DOQI guidelines for calcium-based phosphate binders in clinical practice.

OBJECTIVE: The Kidney Disease Outcomes Quality Initiative (K/DOQI) clinical practice guidelines for bone metabolism in chronic kidney disease recommend that calcium-based phosphate binders (CBPBs) be used in limited doses and be reduced or withheld when albumin-adjusted serum calcium exceeds target values, or when parathyroid hormone is below the target range. We sought to assess the pattern of CBPB use in a clinical practice setting. DESIGN: This was a retrospective review. PATIENTS: We reviewed 283 patients at three hemodialysis units in New York and New Jersey in which 39 physicians practice. METHODS: Data collected included intact parathyroid hormone levels (from February and May, 2006), blood chemistries (from April and May, 2006), and the use of CBPBs, vitamin D, and cinacalcet. The use of CBPBs was classified as "consistent" or "inconsistent" with the guidelines 1 month after the blood tests of May 2006 (to allow time for dosing adjustments). Because cinacalcet was not available when the K/DOQI guidelines were published, a failure to reduce or stop CBPBs in the presence of elevated calcium levels was still considered to be "consistent" use if cinacalcet was initiated in the appropriate time frame (5 patients). RESULTS: CBPBs were used in 172 of 283 patients (61%). In 10% (17 patients), doses exceeded the 1500-mg limit for calcium. Adjusted serum calcium levels exceeded 2.5 mmol/L (10.2 mg/dL) in 8 cases; CBPBs were not reduced or stopped in any of these. Similarly, CBPBs were reduced in only 2 of 27 patients on vitamin D, with an adjusted serum calcium level of 2.38 to 255 mmol/L (9.5 to 10.2 mg/dL). In all 10 patients with consecutive intact parathyroid hormone values of less than 150 ng/L (150 pg/mL), CBPBs were not discontinued or reduced. CONCLUSIONS: Overall, 50 of 172 patients (29%) receiving CBPBs did so in a manner inconsistent with K/DOQI guidelines. The reasons for this inconsistency are speculative, and may include disagreement with the opinion-based recommendations, insufficient knowledge of the guidelines, or individual patient considerations (including cost, tolerance, and effectiveness).