Cigarette smoking and cardio-renal events in patients with atherosclerotic renal artery stenosis.

Cigarette smoking causes cardiovascular disease and is associated with poor kidney function in individuals with diabetes mellitus and primary kidney diseases. However, the association of smoking on patients with atherosclerotic renal artery stenosis has not been studied. The current study utilized data from the Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL, NCT00081731) clinical trial to evaluate the effects of smoking on the risk of cardio-renal events and kidney function in this population. Baseline data showed that smokers (n = 277 out of 931) were significantly younger at enrollment than non-smokers (63.3±9.1 years vs 72.4±7.8 years; p<0.001). In addition, patients who smoke were also more likely to have bilateral renal artery stenoses and peripheral vascular disease (PVD). Longitudinal analysis showed that smokers experienced composite endpoint events (defined as first occurrence of: stroke; cardiovascular or renal death; myocardial infarction; hospitalization for congestive heart failure; permanent renal replacement; and progressive renal insufficiency defined as 30% reduction of GFR from baseline sustained for ≥ 60 days) at a substantially younger age compared to non-smokers (67.1±9.0 versus 76.1±7.9, p<0.001). Using linear regression and generalized linear modeling analysis controlled by age, sex, and ethnicity, smokers had significantly higher cystatin C levels (1.3±0.7 vs 1.2±0.9, p<0.01) whereas creatinine and estimated glomerular filtration rate (eGFR) were not different from non-smokers. From these data we conclude that smoking has a significant association with deleterious cardio-renal outcomes in patients with renovascular hypertension.

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 ß-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). Primary outcome was all-cause mortality. Secondary outcomes included cardiovascular mortality, HF mortality, first HF hospitalization, the composite of cardiovascular mortality or first HF hospitalization, and sudden cardiac death. Non-dialysis-dependent CKD was defined by estimated glomerular filtration rate ≤60 mL/min/1.73 m(2), using the abbreviated Modification of Diet in Renal Disease equation. CKD was present in 2566 of 4217 (60.8%) of the cohort, 50.4% of whom were randomly assigned to carvedilol therapy. Within the CKD group, treatment with carvedilol decreased the risks of all-cause mortality (hazard ratio [HR], 0.76; 95% confidence interval [CI], 0.63 to 0.93; P=0.007), cardiovascular mortality (HR, 0.76; 95% CI, 0.62 to 0.94; P=0.011), HF mortality (HR, 0.68; 95% CI, 0.52 to 0.88; P=0.003), first hospitalization for HF (HR, 0.74; 95% CI, 0.61 to 0.88; P=0.0009), and the composite of cardiovascular mortality or HF hospitalization (HR, 0.75; 95% CI, 0.65 to 0.87; P<0.001) but was without significant effect on sudden cardiac death (HR, 0.76; 95% CI, 0.56 to 1.05; P=0.098). There was no significant interaction between treatment arm and study type. Carvedilol was generally well tolerated by both groups of patients, with an increased relative incidence in transient increase in serum creatinine without need for dialysis and other electrolyte changes in the CKD patients. However, in a sensitivity analysis among HF subjects with estimated glomerular filtration rate <45 mL/min/1.73 m(2) (CKD stage 3b), the efficacy of carvedilol was not significantly different from placebo. CONCLUSIONS: This analysis suggests that the benefits of carvedilol therapy in patients with systolic left ventricular dysfunction with or without symptoms of HF are consistent even in the presence of mild to moderate CKD. Whether carvedilol therapy is similarly efficacious in HF patients with more advanced kidney disease requires further study.

Optimal cardiovascular therapy for patients with ESRD over the next several years.

This review points out the high morbidity and mortality associated with cardiovascular disease in patients with ESRD. Although there have been few randomized controlled trials that have examined this clinical problem in the population of patients with ESRD, there is a growing appreciation of the presentations and consequences of cardiovascular disease in this cohort. The etiology of this disease is multifactorial and the consequences include sudden death, coronary artery disease, and heart failure. The sudden death associated with ESRD has been linked to a progressive cardiac fibrosis that also accompanies left ventricular hypertrophy. Ischemic coronary disease is also common in this population. With regard to new therapy, efforts to control extracellular fluid volume and thereby control blood pressure are important. Two randomized trials have not shown the benefit of lowering low-density lipoprotein cholesterol concentrations in patients with ESRD, but such a strategy is thought to be beneficial in patients with chronic kidney disease. Efforts to optimally control calcium and phosphate concentrations are also beneficial, because vessel calcification remains a major problem for ESRD patients. The increase in vessel calcification leads to an increase in arterial stiffness and an increase in pulse wave velocity, which, in turn, increases cardiovascular morbidity and mortality. Additional recommendations are provided in this review including the use of erythrocyte stimulating agents, the cautious use of beta blockers with patients with a low ejection fraction systolic failure, and drugs that block the renin-angiotensin-alderosterone system.

Recent advances in the prevention and management of intradialytic hypotension.

Intradialytic hypotension continues to play a significant role in the morbidity and in some cases the mortality associated with maintenance hemodialysis. Greater precision in the determination of dry weight using bioimpedance technology and biofeedback systems designed to prevent rapid fluctuations in blood volume have recently been shown to decrease the frequency of this complication. Pharmacologic strategies designed to maintain peripheral vascular resistance in patients with insufficient release of endogenous vasoconstrictors continue to be explored. The sudden development of intradialytic hypotension may respond to specific antagonists to hypotensive mediators.

Non-contrast-enhanced computerized tomography and analgesic-related kidney disease: report of the national analgesic nephropathy study.

Previous studies suggested that the non-contrast-enhanced computerized tomography (CT) scan is a highly reliable tool for the diagnosis of analgesic-associated renal disease. However, this issue has not been addressed in the US population. A total of 221 incident patients with ESRD from different regions of the United States underwent a helical CT scan and detailed questioning about drug history. Specific renal anatomic criteria were developed to determine whether a constellation of CT findings (small indented calcified kidneys [SICK]) is linked to analgesic ingestion. For approximating use before the onset of renal disease, only analgesic ingestion at least 9 yr before starting dialysis was considered relevant. Fifteen patients met the criteria for SICK. This represented 7% of the enrolled patients and approximately 1% of the total ESRD population. There was a significant increase in the estimated risk among patients with a history of heavy aspirin ingestion (odds ratio [OR] 7.4 [95% confidence interval (CI) 1.2 to 43] for > or =1 kg lifetime; OR 8.8 [95% CI 1.2 to 66] for > or =0.3 kg/yr). Total analgesic ingestion of > or =0.3 kg/yr also was significantly associated with SICK (OR 8.2; 95% CI 1.5 to 45). These findings were accounted for largely by combination products that contained aspirin and phenacetin (used by three patients with SICK), which are no longer available. In addition, the CT finding of SICK was present only in a minority of heavy analgesic users, yielding a sensitivity of 5 to 26%. Findings of SICK are infrequent in the US ESRD population and do not occur among a sufficient proportion of heavy analgesic users to render the non-contrast-enhanced CT scan a sensitive tool to detect analgesic-associated kidney injury.

Chronic kidney disease: a risk factor for cardiovascular disease.

The goal of risk stratification of CVD inpatients with CKD is to lead to effective and early intervention and to prevent the adverse outcomes associated with this complex multisystem disease that is characteristic of growing number of patients with CKD in the general population and of patients receiving dialysis therapy or kidney transplantation. By 2030, there will be 2.24 million patients with ESRD in the United States, and approximately 1.3 million of these cases of ESRD will be caused by diabetes mellitus. Thus, CVD in this high-risk population presents a challenge for the nephrology and the cardiology community.

Characterization of hepatic cytochrome p4503A activity in patients with end-stage renal disease.

BACKGROUND: The cytochrome p450 (CYP) oxidative enzyme system, located primarily in the liver and small intestine, is responsible for metabolism and detoxification of numerous endogenous and exogenous substances. The most abundant CYP enzyme, CYP3A, is known to be involved in the metabolism of more than 200 commonly used medications. In experimental models of renal failure, both hepatic function and CYP enzyme content are reduced; however, direct evidence in humans is lacking. Evaluation of drug metabolism in patients with end-stage renal disease is important because these patients use a large number of medications and are at risk of adverse reactions and drug-drug interactions. METHODS: We measured hepatic CYP3A activity at baseline and after rifampin (INN, rifampicin) enzyme induction in 12 patients with end-stage renal disease and 12 healthy, age-matched controls. Hepatic CYP3A phenotype was characterized with the erythromycin breath test, and enzyme induction capacity was evaluated with a short course of rifampin (600 mg/d for 6 days). RESULTS: The end-stage renal disease group had 28% lower baseline erythromycin breath test values than controls (P <.05); however, enzyme induction capacity after rifampin administration was similar between groups (P =.70). CONCLUSION: The findings suggested that one mechanism by which patients with end-stage renal disease are at increased risk of drug toxicity is reduced activity of the CYP3A enzyme pathway.

Recent developments in toxic nephropathy.

Toxic nephropathy is an important cause of reversible renal injury if detected early. Renal damage can be due to several different mechanisms affecting different segments of the nephron, renal microvasculature or interstitium. Clinical signs may not be apparent in the early stages and assessment of renal function should include thorough evaluation of glomerular filtration rate, proximal and distal tubular function. A kidney biopsy may be indicated to establish the cause and effect relationship. The presence of comorbid conditions such as older age, diabetes mellitus, hypertension and congestive heart failure have a significant influence on the patient's ability to recover from the toxic effects. A significant degree of drug-induced renal toxicity is only acceptable if the causative agent is used for the curative treatment of an underlying disease but not if the aim is the palliative or supportive therapy. The decision to reduce the dose or to stop the toxic agent must be based on the ultimate goal of therapy and the patient's baseline health status.