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Patients with type 2 diabetes at high risk for cardiovascular disease who were already taking a renin–angiotensin system blocker were randomly assigned to the direct renin inhibitor aliskiren or placebo. The study was discontinued early for no benefit, or even possible harm. Mortality associated with type 2 diabetes remains nearly twice that when diabetes is absent. 1 Complications of diabetes, particularly renal and cardiovascular disease, substantially increase the risk of subsequent severe illness and death. When a patient has both renal and cardiovascular disease, the risk is magnified further. 2 , 3 Blood-pressure lowering is beneficial in slowing renal-disease progression, reducing cardiovascular disease events, and preventing premature death. 4 Renin–angiotensin–aldosterone system (RAAS) blockers are highly effective, with apparent benefits extending beyond simple blood-pressure lowering 5 – 8 ; such agents have become the preferred first-line interventions in high-risk persons with diabetes. Theoretically, dual RAAS blockade should be more . . .

Recent studies suggest that correcting low serum bicarbonate levels may reduce the progression of kidney disease; however, few patients with chronic kidney disease have low serum bicarbonate. Therefore, we examined whether higher levels of serum bicarbonate within the normal range (20–30mmol/l) were associated with better kidney outcomes in the African American Study of Kidney Disease and Hypertension (AASK) trial. At baseline and during follow-up of 1094 patients, the glomerular filtration rates (GFR) were measured by iothalamate clearances and events were adjudicated by the outcomes committee. Mean baseline serum bicarbonate, measured GFR, and proteinuria were 25.1mmol/l, 46ml/min per 1.73m2, and 326mg/g of creatinine, respectively. Each 1mmol/l increase in serum bicarbonate within the normal range was associated with reduced risk of death, dialysis, or GFR event and with dialysis or GFR event (hazard ratios of 0.942 and 0.932, respectively) in separate multivariable Cox regression models that included errors-in-variables calibration. Cubic spline regression showed that the lowest risk of GFR event or dialysis was found at serum bicarbonate levels near 28–30mmol/l. Thus, our study suggests that serum bicarbonate is an independent predictor of CKD progression. Whether increasing serum bicarbonate into the high-normal range will improve kidney outcomes during interventional studies will need to be considered.

In this study, consecutive patients with acute myocardial infarction who were undergoing primary angioplasty were randomly assigned to N -acetylcysteine at standard or double doses or to placebo. Creatinine concentrations increased after primary angioplasty in 33 percent of the patients in the control group, 15 percent of those in the standard-dose group, and 8 percent of those in the high-dose group (P<0.001). Intravenous N -acetylcysteine followed by oral N -acetylcysteine may prevent contrast-medium–induced nephropathy in patients undergoing angioplasty. Intravenous N -acetylcysteine followed by oral N -acetylcysteine may prevent contrast-medium–induced nephropathy in patients undergoing angioplasty. Contrast-medium–induced nephropathy is a recognized complication in coronary diagnostic and interventional procedures and is associated with prolonged hospitalization and adverse clinical outcomes. 1 – 5 Patients with acute myocardial infarction treated with primary angioplasty are at higher risk of contrast-medium–induced nephropathy than are those undergoing elective interventions. 6 , 7 In patients with acute myocardial infarction, several conditions may contribute to the development of renal dysfunction. Impaired systemic perfusion due to left ventricular dysfunction, a large volume of contrast medium, and the impossibility of starting renal prophylactic therapies before exposure to contrast medium are among the major factors that seem to be involved. Indeed, . . .

To investigate the role of hydration to prevent contrast-induced nephropathy (CIN) in patients with ST-segment elevation myocardial infarction (STEMI) who underwent primary percutaneous coronary intervention (PPCI), we prospectively included 408 consecutive patients who were randomly assigned to receive either hydration with isotonic saline (1 ml/kg/h since the beginning of the procedure and for 24 hours after it: NS+ group) or not (NS− group). All patients received an iso-osmolar nonionic contrast medium. The primary end point was the development of CIN: ≥25% or ≥0.5 mg/dl increase in serum creatinine within 3 days after the procedure. CIN was observed in 14% of patients: 21% in the NS− group and 11% in the NS+ group (p = 0.016). CIN was significantly associated with death (15.2% vs 2.8%; p <0.0001) and need for dialysis (13.4% vs 0%; p <0.0001). In multivariate analysis, the only predictors of CIN were hydration (OR = 0.29 [0.14 to 0.66]; p = 0.003) and the hemoglobin before the procedure (OR = 0.69 [0.59 to 0.88]; p <0.0001). In conclusion, intravenous saline hydration during PPCI reduced the risk of CIN to 48%. Patients with CIN had increased mortality and need for dialysis. Given the higher incidence of CIN in emergent procedures, and its morbidity and mortality, preventive hydration should be mandatory in them unless contraindicated.

We performed a double-blind placebo-controlled trial to study whether early treatment with erythropoietin could prevent the development of acute kidney injury in patients in two general intensive care units. As a guide for choosing the patients for treatment we measured urinary levels of two biomarkers, the proximal tubular brush border enzymes γ-glutamyl transpeptidase and alkaline phosphatase. Randomization to either placebo or two doses of erythropoietin was triggered by an increase in the biomarker concentration product to levels above 46.3, with a primary outcome of relative average plasma creatinine increase from baseline over 4 to 7 days. Of 529 patients, 162 were randomized within an average of 3.5 h of a positive sample. There was no difference in the incidence of erythropoietin-specific adverse events or in the primary outcome between the placebo and treatment groups. The triggering biomarker concentration product selected patients with more severe illness and at greater risk of acute kidney injury, dialysis, or death; however, the marker elevations were transient. Early intervention with high-dose erythropoietin was safe but did not alter the outcome. Although these two urine biomarkers facilitated our early intervention, their transient increase compromised effective triaging. Further, our study showed that a composite of these two biomarkers was insufficient for risk stratification in a patient population with a heterogeneous onset of injury.

Background Neonates with hypoxic–ischemic encephalopathy (HIE) frequently develop acute kidney injury (AKI). Aminophylline has been shown to reduce severe renal dysfunction in neonates after perinatal asphyxia. However, the effect of aminophylline on renal function in neonates undergoing hypothermia has not been studied. Methods A single-center, retrospective chart review of neonates cooled for moderate/severe HIE who received aminophylline for AKI was conducted to assess changes in urine output (UOP) and serum creatinine (SCr). Comparisons were also made to control neonates matched for hours of life who were cooled but unexposed to aminophylline. Results Sixteen neonates cooled for HIE received aminophylline starting at 25 ± 14 h of life. Within 12 h of starting aminophylline, UOP increased by 2.6 ± 1.9 mL/kg/h. SCr declined by 0.4 ± 0.2 mg/dL in survivors over the first 4 days. When compared to control neonates, UOP increase was greater in the aminophylline group ( p  < 0.001). SCr declined in survivors in both groups, although baseline SCr was higher in the aminophylline group. Conclusions Aminophylline use in neonates with HIE undergoing hypothermia was associated with an increase in UOP and a decline in SCr. A randomized trial will be needed to establish a potential renal protective role of aminophylline. Impact The renal protective effect of aminophylline in neonates with HIE has not yet been studied in the context of therapeutic hypothermia. Aminophylline exposure in neonates cooled for HIE was associated with increased UOP and a similar decline in SCr when compared to control infants unexposed to aminophylline. Improved renal function after receiving aminophylline in this observational cohort study suggests the need for future randomized trials to establish the potential benefit of aminophylline in the HIE population undergoing hypothermia.

This randomized study of patients in a medical ICU compared insulin infusion to normalize the blood glucose level with conventional therapy. Overall, insulin infusion was associated with decreased morbidity but not decreased mortality. However, a lower relative risk of both was observed among patients receiving insulin who remained in the ICU for more than three days, although predicting length of stay on admission to the ICU is not possible. Further studies are needed to confirm these data. In a medical ICU, insulin infusion was associated with decreased morbidity but not decreased mortality. However, a lower relative risk of both was observed among patients receiving insulin who remained in the ICU for more than three days. Hyperglycemia and insulin resistance are common in severe illness and are associated with adverse outcomes. 1 – 4 In a previous randomized, controlled study conducted in a surgical intensive care unit (ICU), strict control of blood glucose levels with insulin reduced morbidity and mortality, 5 , 6 significantly reducing in-hospital mortality from 11 to 7 percent in the entire study population. In a subgroup of patients who stayed in the ICU for three or more days, however, the benefit was much more pronounced, reducing mortality from 21 to 14 percent among patients treated for at least three days and from 26 to 17 percent . . .

Background Cytomegalovirus (CMV) prophylaxis may prevent CMV indirect effects in renal transplant recipients. This study aimed to compare the efficacy of valganciclovir and valacyclovir prophylaxis for CMV after renal transplantation with the focus on chronic histologic damage within the graft. Methods From November 2007 through April 2012, adult renal transplant recipients were randomized, in an open-label, single-center study, at a 1:1 ratio to 3-month prophylaxis with valganciclovir ( n  = 60) or valacyclovir ( n  = 59). The primary endpoint was moderate-to-severe interstitial fibrosis and tubular atrophy assessed by protocol biopsy at 3 years evaluated by a single pathologist blinded to the study group. The analysis was conducted in an intention-to-treat population. Results Among the 101 patients who had a protocol biopsy specimen available, the risk of moderate-to-severe interstitial fibrosis and tubular atrophy was significantly lower in those treated with valganciclovir (22% versus 34%; adjusted odds ratio, 0.31; 95% confidence interval, 0.11–0.90; P  = 0.032 by multivariate logistic regression). The incidence of CMV disease (9% versus 2%; P  = 0.115) and CMV DNAemia (36% versus 42%; P  = 0.361) were not different at 3 years. Conclusions Valganciclovir prophylaxis, as compared with valacyclovir, was associated with a reduced risk of moderate-to-severe interstitial fibrosis and tubular atrophy in patients after renal transplantation. Trial registration Australian New Zealand Clinical Trials Registry ( ACTRN12610000016033 ). Registered on September 26, 2007

Purpose The contrast-induced nephropathy (CIN) rate is increasing globally and can increase the rate of mortality and long-term problems. This study aims to determine the effect of Nicorandil on preventing CIN among patients undergoing cardiac catheterization. Methods In a controlled randomized open-labeled clinical trial, all included patients undergoing cardiac catheterization due to coronary problems and possessing at least two risk factors of contrast nephropathy were divided into two groups of intervention and control. The intervention group received oral Nicorandil and normal saline, while the control group was treated with intravenous normal saline. Serum creatinine was measured before and 48 h after the procedure, and patients were assessed regarding CIN. Results In this study, 172 patients entered each group; 41.86% and 45.34% were male in the control and Nicorandil groups. We showed that the incidence of CIN was meaningfully lower in the Nicorandil group (12, 7%) than in the control group (34, 19.8%, P  = 0.001). Additionally, the incidence of CIN was notably lower in the female patients in the Nicorandil (85.7%) than in the control group (14.3%, P  = 0.001); however, these numbers were not significantly different among men (64.0% and 36.0%, respectively, P  = 0.850). After the injection of the contrast agent, the serum levels of blood urea nitrogen ( P  = 0.248), creatinine ( P  = 0.081), and glomerular filtration rate ( P  = 0.386) showed no significant differences between the control and Nicorandil groups. Multivariate regression analysis showed that Nicorandil significantly lowered the odds of CIN [odds ratio (OR) = 0.299, 95% confidence interval (CI) 0.149–0.602; P  = 0.001] after adjustment for baseline creatinine (OR = 1.404, 95% CI 0.431–4.572; P  = 0.574). Conclusion Our results indicate that pre-procedural treatment with Nicorandil may be effective against CIN in contrast to agent-exposed patients.

Background At present, the clinical methods for preventing and treating contrast-induced nephropathy (CIN) are limited, and statins can play a better role during this process. So, we aimed to assess the atorvastatin on renal function in nephropathy patients after percutaneous coronary intervention (PCI). Methods In this work, 100 elderly patients with coronary heart disease (CHD) were selected into an experimental group (Exp group, 50 cases, 40 mg/d po atorvastatin) and a control group (Ctrl group, 50 cases, 10 mg/d po atorvastatin). The renal function indicators, blood routine indicators, and the incidence of adverse reactions (ARs) were compared between patients in Exp and Ctrl groups. Results After surgery, the levels of serum creatinine (SCr), blood urea nitrogen (BUN), cystatin C (CysC), high-sensitivity C-reactive protein (hs-CRP), and interleukin (IL6) in patients in the Exp group were much lower, and the levels of estimated glomerular filtration rate (eGFR) and superoxide dismutase (SOD) were higher (all P  < 0.05). Meanwhile, the incidences of ARs during hospitalization between patients in the Exp and Ctrl groups were all 8%, showing no observable difference ( P  > 0.05). Compared with conventional doses of atorvastatin, high-dose atorvastatin can effectively prevent renal function damage in patients with CIN, decrease the inflammation and oxidative stress in patients, and will not increase the risk of ARs during hospitalization. Conclusion Taken together, high-dose atorvastatin can be applied in treating patients with CHD after PCI due to its excellent efficacy and high safety.