Role of the Funder/Sponsor: Drs Linder (NIH), Imperatore, and Saydah (CDC) were participating members of the study steering committee and the writing group for this manuscript because of the cooperative funding agreements. They were involved in the design of the study but not the conduct of the study; they were not involved in the collection, management, and analysis of the data, but were involved in interpretation of the data; they were involved in the preparation, review, and approval of the manuscript and the decision to submit the manuscript for publication.

Results of the main Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial indicate that intensive glucose lowering increases cardiovascular and all-cause mortality. As the contribution of mild-to-moderate chronic kidney disease (CKD) to these risks is not known, we assessed the impact on cardiovascular outcomes in this population. Renal function data were available on 10,136 patients of the original ACCORD cohort. Of those, 6,506 were free of CKD at baseline and 3,636 met the criteria for CKD. Participants were randomly assigned to a treatment strategy of either intensive or standard glycemic goal. The primary outcome, all-cause and cardiovascular mortality, and prespecified secondary outcomes were evaluated. Risk for the primary outcome was 87% higher in patients with than in those without CKD (hazard ratio of 1.866; 95% CI: 1.651-2.110). All prespecified secondary outcomes were 1.5 to 3 times more frequent in patients with than in those without CKD. In patients with CKD, compared with standard therapy, intensive glucose lowering was significantly associated with both 31% higher all-cause mortality (1.306: 1.065-1.600) and 41% higher cardiovascular mortality (1.412: 1.052-1.892). No significant effects were found in patients without CKD. Thus, in high-risk patients with type II diabetes, mild and moderate CKD is associated with increased cardiovascular risk. Intensive glycemic control significantly increases the risk of cardiovascular and all-cause mortality in this population.

Abstract. N-acetylcysteine has been recommended for patients with renal insufficiency who are to receive radiocontrast media. However, trials of oral N-acetylcysteine for the prevention of radiocontrast-induced nephropathy have yielded inconsistent results. A systematic review of patient and study characteristics was undertaken to discover possible explanations of the inconsistencies. The databases MEDLINE, EMBASE, and CENTRAL (1966 to March 2003) were searched in all languages, and conference proceedings from several professional societies from the years 1999 to 2003 were also searched. Only prospective controlled trials of oral N-acetylcysteine were included. Risk difference estimates and 95% confidence intervals were calculated. The estimates were examined for evidence of publication bias and heterogeneity. Stratified and meta-regression analyses were used to compare estimates by study and patient characteristics. Identified were 16 studies, 15 published and 1 unpublished. There was no evidence of publication bias, but there was substantial evidence of heterogeneity, thus precluding reliance on a meaningful summary effect estimate. Meta-regression identified several patient and study characteristics, with some evidence of association with study-specific estimates. None of these characteristics, however, formed subsets of studies with results that were homogeneous enough to aggregate. Research on N-acetylcysteine and the incidence of radiocontrast nephropathy is too inconsistent at present to warrant a conclusion on efficacy or a recommendation for its routine use. Identified patient and study characteristics may be responsible for some, but not all, of this inconsistency. A large, randomized, placebo-controlled trial, a pooled analysis of patient-level data, or both may resolve this issue.Over the last 3 yr, enthusiasm for the use of oral N-acetylcysteine to prevent radiocontrast-induced nephropathy has been growing (1). A breakthrough study (2) first reported a large and significant reduction in the risk of radiocontrast-induced nephropathy compared with placebo among patients with moderate renal dysfunction. Subsequent studies produced mixed results (3-6). Recently, a large study (7), arguably with a relatively high degree of power and sound methods, seemed to confirm the beneficial effect of this agent. N-acetylcysteine is now being routinely recommended as preventative therapy, as an additive to low-osmolar contrast media and intravenous hydration, for patients with reduced renal function who are to undergo a planned exposure to radiocontrast media (8,9). Yet the reasons for discrepant findings among the trials need investigation before the widespread use of N-acetylcysteine can be recommended.We therefore performed a systematic review and metaanalysis of available prospective controlled trials to quantify and compare reported associations of oral N-acetylcysteine with the incidence of nephropathy after exposure to radiocontrast media. For this review, we examined several key questions. Is there evidenc...

Background This study sought to compare the prevalence and modifying factors of normoalbuminuric (NA) versus albuminuric (ALB) CKD in the U.S. diabetic and nondiabetic populations. Methods NHANES 2001–2008 included 2798 diabetic and 15,743 nondiabetic participants. Age-specific prevalence of NA-CKD and ALB-CKD was calculated within each diabetes stratum and then stratified again according to gender, ethnicity, mean arterial pressure ≥105mmHg and HbA1c≥7%. Multivariate regression analyses were performed to determine odds ratios and 95% CI for NA-CKD. Results Prevalence of NA-CKD rose with age, with an overall mean of 9.7% in diabetic and 4.3% in nondiabetic participants. NA-CKD was less prevalent in diabetic men, OR=0.58 (95% CI: 0.39, 0.87). In comparison with whites, blacks and ‘other’ ethnic groups had an OR for NA-CKD of 0.44 (95% CI 0.29, 0.68) and 0.57 (95% CI: 0.34, 0.96), respectively. Poorly controlled blood pressure and glycemia resulted in a decreased OR for NA-CKD (OR=0.25, 95% CI: 0.13, 0.50) and (0.48, 95% CI: 0.31, 0.74), respectively. Similar results were obtained for nondiabetic participants. Conclusions NA-CKD is more common in people with diabetes, women, non-Hispanic whites, and in the setting of well controlled blood pressure and glycemia.

Diabetes is the most frequent cause of chronic kidney disease (CKD), leading to nearly half of all cases of kidney failure requiring replacement therapy. The principal cause of death among patients with diabetes and CKD is cardiovascular disease (CVD). Sodium/glucose cotransporter 2 (SGLT2) inhibitors were developed to lower blood glucose levels by inhibiting glucose reabsorption in the proximal tubule. In clinical trials designed to demonstrate the CVD safety of SGLT2 inhibitors in type 2 diabetes mellitus (T2DM), consistent reductions in risks for secondary kidney disease end points (albuminuria and a composite of serum creatinine doubling or 40% estimated glomerular filtration rate decline, kidney failure, or death), along with reductions in CVD events, were observed. In patients with CKD, the kidney and CVD benefits of canagliflozin were established by the CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation) trial in patients with T2DM, urinary albumin-creatinine ratio > 300 mg/g, and estimated glomerular filtration rate of 30 to <90 mL/min/1.73 m 2. To clarify and support the role of SGLT2 inhibitors for treatment of T2DM and CKD, the National Kidney Foundation convened a scientific workshop with an international panel of more than 80 experts. They discussed the current state of knowledge and unanswered questions to propose therapeutic approaches and delineate future research. SGLT2 inhibitors improve glomerular hemodynamic function and are thought to ameliorate other local and systemic mechanisms involved in the pathogenesis of CKD and CVD. SGLT2 inhibitors should be used when possible by people with T2DM to reduce risks for CKD and CVD in alignment with the clinical trial entry criteria. Important risks of SGLT2 inhibitors include euglycemic ketoacidosis, genital mycotic infections, and volume depletion. Careful consideration should be given to the balance of benefits and harms of SGLT2 inhibitors and risk mitigation strategies. Effective implementation strategies are needed to achieve widespread use of these life-saving medications. Complete author and article information provided before references.