Sodium phosphate does not increase risk for acute kidney injury after routine colonoscopy, compared with polyethylene glycol.

BACKGROUND & AIMS: Oral sodium phosphate (OSP) is a common bowel purgative administered before colonoscopy; the Food and Drug Administration has warned against its use because of concerns about acute kidney injury (AKI) from the absorbed phosphate and dystrophic calcification. However, it is not clear if OSP is associated with AKI in the general population or in high-risk subgroups undergoing colonoscopy. We estimated the risk of AKI among patients undergoing a screening colonoscopy using OSP vs polyethylene glycol (PEG) for bowel cleansing in a large, US-based claims database. METHODS: We used an insurance database to identify a cohort of patients ages 50 to 75 years who underwent screening colonoscopies as outpatients from January 2000 through November 2008 (before the Food and Drug Administration warning), receiving OSP (n = 121,266) or PEG (n = 429,430) within 30 days beforehand, without prior use of either drug. We collected data from patients for 6 months afterward to identify those who developed AKI or renal failure, or received dialysis. Adjusted and propensity score-matched hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox proportional hazards models. We investigated the effects in subgroups with higher AKI risk (patients with chronic kidney disease, kidney stones, hypertension, or diabetes, or using antihypertensive or nonsteroidal anti-inflammatory drugs). RESULTS: AKI occurred in 0.2% of OSP users and in 0.3% of PEG users (adjusted HR, 0.86; 95% CI, 0.75-0.99). OSP users matched well with PEG users, producing similar estimates (HR, 0.85; 95% CI, 0.72-1.01). We did not observe a consistent increase in the risk of AKI or other outcomes in any subgroups analyzed. CONCLUSIONS: In a large database analysis, we did not associate administration of OSP before colonoscopy with increased risk of postprocedure AKI, even in high-risk clinical subgroups.

Risk of high dietary calcium for arterial calcification in older adults.

Concern has recently arisen about the potential adverse effects of excessive calcium intakes, i.e., calcium loading from supplements, on arterial calcification and risks of cardiovascular diseases (CVD) in older adults. Published reports that high calcium intakes in free-living adults have relatively little or no beneficial impact on bone mineral density (BMD) and fracture rates suggest that current recommendations of calcium for adults may be set too high. Because even healthy kidneys have limited capability of eliminating excessive calcium in the diet, the likelihood of soft-tissue calcification may increase in older adults who take calcium supplements, particularly in those with age or disease-related reduction in renal function. The maintenance of BMD and bone health continues to be an important goal of adequate dietary calcium consumption, but eliminating potential risks of CVDs from excessive calcium intakes needs to be factored into policy recommendations for calcium by adults.

Aldosterone breakthrough during aliskiren, valsartan, and combination (aliskiren + valsartan) therapy.

Aldosterone levels increase in 30%-40% of patients on angiotensin-converting enzyme inhibitors and/or angiotensin receptor blockers over the long term. This "aldosterone breakthrough" may carry important clinical consequences given aldosterone's nonepithelial, pro-fibrotic actions. The renin inhibitor, aliskiren, by suppressing the renin-angiotensin-aldosterone system (RAAS) proximally, may limit breakthrough compared to conventional RAAS blockade. This open-label study (NCT01129557) randomized subjects to aliskiren 300 mg daily (A), valsartan 320 mg daily (V), or aliskiren 150 mg + valsartan 160 mg daily (A+V) for 9 months. Eligible subjects had proteinuria >300 mg/day, estimated glomerular filtration rate (eGFR) >45 mL/min/1.73 m(2), and systolic blood pressure (BP) >130 or diastolic BP >80 mm Hg. Serum and 24-hour urine aldosterone (indexed to 24-hour urine Na) were checked before initiation of therapy and at 3, 6, and 9 months. Aldosterone breakthrough was defined as a sustained increase from baseline aldosterone by study end. The study was intended to enroll 120 subjects but was terminated early by the sponsor. We present here the results of 33 subjects who completed the protocol, of which 12 were randomized to A, 11 were randomized to V, and 10 were randomized to A+V. Mean baseline eGFR was 75.5 (±23.3) mL/min/1.73 m(2); baseline proteinuria was 3104 (±2943) mg/day; and baseline BP was 134.7 (±10.5)/84.8 (±8.4) mm Hg. Three (27%) subjects on V, three (25%) subjects on A, and three (30%) subjects on A+V had aldosterone breakthrough. Mean proteinuria reduction was 31% from baseline in all subjects: 30% in subjects with breakthrough vs. 32% in subjects without breakthrough. Mean BP reduction was 11.0/8.8 mm Hg in all subjects: 8.4/6.1 mm Hg in subjects with breakthrough vs. 12.0/9.8 mm Hg in subjects without breakthrough. Aliskiren, alone or in combination with valsartan, did not reduce the incidence of aldosterone breakthrough in subjects with hypertension and proteinuria compared with conventional RAAS blockade.

Mineralocorticoid receptor blockade in chronic kidney disease.

Mineralocorticoid receptor blockers (MRBs) have proven highly successful in the treatment of congestive heart failure and resistant hypertension. In contrast, their use in chronic kidney disease (CKD) has lagged due to the concern of hyperkalemia and, possibly, because of the incorrect assumption that traditional therapy with angiotensin-converting enzyme inhibitors and/or angiotensin receptor blockers consistently reduce aldosterone activity in all patients. Low-dose MRB therapy may offer additional antihypertensive and unique anti-inflammatory benefits in select CKD populations.

Mineralocorticoid receptor blockade in chronic kidney disease.

Aldosterone antagonists have been highly successful in treating congestive heart failure and resistant hypertension. Until recently, therapies targeting the mineralocorticoid receptor in chronic kidney disease (CKD) have received little attention, largely because of the risk of hyperkalemia and the incorrect assumption that traditional therapy with angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or both consistently reduces activity of the renin-angiotensin system in all patients. Control of extracellular volume and low-dose mineralocorticoid receptor blocker therapy may offer additional antihypertensive and anti-inflammatory benefits in select CKD populations.

High-output heart failure secondary to arteriovenous fistula.

In the hemodialysis patient population, a surgically created arteriovenous fistula is the preferred vascular access option. Development of high-output heart failure may be an underappreciated complication in patients who have undergone this procedure. When a large proportion of arterial blood is shunted from the left-sided circulation to the right-sided circulation via the fistula, the increase in preload can lead to increased cardiac output. Over time, the demands of an increased workload may lead to cardiac hypertrophy and eventual heart failure. Patients may present with the usual signs of high-output heart failure including tachycardia, elevated pulse pressure, hyperkinetic precordium, and jugular venous distension. Typically, the AV fistula is quite large and is likely located in the upper arm, more proximal to the heart. Routine access flow monitoring should demonstrate blood flows (Qa) >2000 ML/min. Echocardiogram may reveal either a low or high left ventricular ejection fraction, and right-heart catheterization demonstrates an elevated cardiac output with a low to normal systemic vascular resistance. When addressing the problem of high-output heart failure, the nephrologist is faced with the dilemma of preventing progression of heart failure at the expense of loss of vascular access. Nevertheless, treatment should be directed at correcting the underlying problem by surgical banding or ligation of the fistula.

Racial differences in kidney function among individuals with obesity and metabolic syndrome: results from the Kidney Early Evaluation Program (KEEP).

BACKGROUND: Obesity and metabolic syndrome may differ by race. For participants in the National Kidney Foundation's Kidney Early Evaluation Program (KEEP), we examined whether African American and white participants with obesity and metabolic syndrome differ regarding albuminuria, estimated glomerular filtration rate (eGFR), anemia, and bone/mineral metabolism derangements in chronic kidney disease (CKD). METHODS: 3 study cohorts were assembled: (1) eligible African American and white KEEP participants with body mass index > or = 30 kg/m(2), (2) a subgroup meeting criteria for metabolic syndrome, and (3) a subgroup with eGFR < 60 mL/min/1.73 m(2) and laboratory measurements for hemoglobin, parathyroid hormone, calcium, and phosphorus. Patient characteristics and kidney function assessments were compared and tested using chi(2) (categorical variables) and t test (continuous variables). Univariate and multivariate logistic regression analyses were performed to evaluate associations of race with kidney disease measures. RESULTS: Of 37,107 obese participants, 48% were African American and 52% were white. Whites were more likely to have metabolic syndrome components (hypertension, 87.1% vs 84.8%; dyslipidemia, 81.6% vs 66.7%; diabetes, 42.7% vs 34.9%) and more profoundly decreased eGFR than African Americans (CKD stages 3-5 prevalence, 23.6% vs 13.0%; P < 0.001). African Americans were more likely to have abnormal urinary albumin excretion (microalbuminuria, 12.5% vs 10.2%; OR, 1.60 [95% CI, 1.45-1.76]; macroalbuminuria, 1.3% vs 1.2%; OR, 1.61 [95% CI, 1.23-2.12]) and CKD stages 1-2 (10.3% vs 7.1%; OR, 1.54 [95% CI, 1.38-1.72]). For participants with CKD stages 3-5, anemia prevalence was 32.4% in African Americans and 14.1% in whites; corresponding values for secondary hyperparathyroidism were 66.2% and 46.6%, respectively. CONCLUSIONS: Obesity and metabolic syndrome may be heterogeneous disease states in African Americans and whites, possibly explaining differences in long-term kidney and cardiovascular outcomes.

Disordered aldosterone-volume relationship in end-stage kidney disease.

INTRODUCTION: Sodium loading, and subsequent volume expansion, suppresses aldosterone levels in individuals with normal renal function. We hypothesised that loss of renal function impairs this volume-aldosterone relationship. MATERIALS AND METHODS: With multifrequency bioimpedance spectroscopy, we measured total body water (TBW), extracellular volume (ECV), and intracellular volume in five haemodialysis patients at varied states of hydration and in five healthy volunteers during low-, normal-, and high-salt diets. Serum aldosterone, potassium, and C-reactive protein were measured simultaneously. Scatterplots and general estimating equations were used to examine the relationship among these variables. RESULTS: In healthy volunteers with salt loading, and in haemodialysis subjects with increased inter-dialytic weight gain, expansion of ECV led to reciprocal declines in serum aldosterone concentrations. The relationship was more profound in healthy volunteers (p<0.001) than in haemodialysis subjects (p=0.1). Notably, haemodialysis subjects posted consistently higher levels of ECV (median 49.6% TBW, IQR 43.9-51.8% compared to 41.1%, 39.9-42.8% in volunteers) and serum aldosterone (median 26.7 ng/dl, IQR 19.8-29.6 compared to 12.4 ng/dl, 8.8-16.0 in volunteers). Serum potassium did not appear to influence aldosterone concentration (p=0.9). CONCLUSIONS: The shift of the volume-aldosterone curve in haemodialysis subjects suggests that end-stage kidney disease is a state of high volume and inappropriately high aldosterone. These data have important clinical implications, as dialysis patients may benefit from both volume reduction and mineralocorticoid receptor blockade.

Sugar-sweetened beverage consumption and the progression of chronic kidney disease in the Multi-Ethnic Study of Atherosclerosis (MESA).

BACKGROUND: Recent studies have examined sugar-sweetened soda consumption in relation to early markers of kidney disease, but to date there have been no investigations of whether sugar-sweetened beverage consumption affects preexistent chronic kidney disease (CKD). OBJECTIVE: This prospective cohort study of 447 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) with preexistent CKD examined the association between sugar-sweetened beverage consumption (<1 drink/wk, 1-6 drinks/wk, and > or =1 drink/d) and progression of CKD. DESIGN: beta-Coefficients for continuous outcomes of changes in estimated glomerular filtration rate (eGFR) and urinary albumin to creatinine ratio (UACR) were calculated by using linear regression. Odds ratios for binary outcomes of accelerated decline in eGFR, defined as >2 mL x min(-1) x 1.73 m(-2) per year, and clinically significant progression of albuminuria (defined as attainment of UACR > or =30 mg/g for participants without microalbuminuria at visit 1 or a > or =25% increase in UACR for participants with baseline microalbuminuria) were evaluated by using logistic regression. RESULTS: The mean (+/-SD) baseline eGFR was 52 +/- 6 mL x min(-1) x 1.73 m(-2) per year, and median baseline UACR was 6.3 mg/g (interquartile range: 3.5-17.6). Univariate and multivariate analyses showed no association between sugar-sweetened beverage consumption and rate of eGFR decline or changes in urinary albumin to creatinine ratio. The multivariate odds ratios comparing participants who drank > or =1 sugary beverage daily with those who drank < or =1 beverage weekly were 0.62 (95% CI: 0.27, 1.41) for accelerated eGFR decline and 1.51 (95% CI: 0.49, 4.62) for clinically significant progression of albuminuria. CONCLUSION: A higher consumption of sugar-sweetened beverages was not associated with disease progression, on the basis of either eGFR or the urinary albumin to creatinine ratio, in MESA participants with preexistent CKD.

Interaction of aldosterone and extracellular volume in the pathogenesis of obesity-associated kidney disease: a narrative review.

Obesity and obesity-associated kidney injuries have played an important role in the rising prevalence of chronic kidney disease (CKD). The link between obesity and kidney disease begins with obesity's well-known associations with diabetes and hypertension, the two leading etiologies of CKD. However, a growing body of evidence suggests that elevated aldosterone levels and expanded extracellular volume are key components of obesity-induced renal disease via aldosterone's non-epithelial effects on the kidney. Highlighting these blood pressure- and diabetes-independent mechanisms of kidney injury in obesity allows an exploration of whether mineralocorticoid receptor blockade, coupled with weight loss and salt restriction, is an optimal treatment for overweight CKD patients.

Extracellular volume and aldosterone interaction in chronic kidney disease.

Since the advent of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, little attention has been given to the potential proinflammatory effects of aldosterone in high-volume states on the kidney and cardiovascular system. In order to be correctly interpreted, aldosterone levels require a volume cofactor which can now be determined by measurement of extracellular fluid volume by means of bioimpedance. Chronic kidney disease patients frequently have expanded extracellular volume (ECV) in the presence of elevated aldosterone levels. This combination may lead to cardiovascular and renal inflammation and fibrosis that can be mitigated by more precise control of ECV and/or blockade of the mineralocorticoid receptor.

Periodontal disease adversely affects the survival of patients with end-stage renal disease.

Periodontal disease is associated with cardiovascular disease and is thought to accelerate systemic atherosclerosis. Here we examined the relationship between periodontitis and cardiovascular disease mortality in outpatients on hemodialysis using a retrospective analysis of 168 adult patients in New York City and North Carolina. During 18 months of follow-up, cardiovascular disease and all-cause mortality were determined from a centralized dialysis registry. One hundred patients had mild or no periodontal disease but the remaining 68 had moderate-to-severe disease defined as 2 or more teeth with at least 6 mm of inter-proximal attachment loss. At baseline, the proportion of males was significantly lower in the moderate-to-severe group. Compared with mild or no periodontal disease, moderate-to-severe disease was significantly associated with death from cardiovascular causes. Adjustment for age, gender, center and dialysis vintage, smoking status, and history of diabetes mellitus or hypertension did not diminish the strength of this association. Our findings suggest a need for larger studies to confirm this connection, along with intervention trials to determine if treating periodontitis reduces cardiovascular disease mortality in dialysis patients.

A simple algorithm to predict incident kidney disease.

BACKGROUND: Despite the growing burden of chronic kidney disease (CKD), there are no algorithms (to our knowledge) to quantify the effect of concurrent risk factors on the development of incident disease. METHODS: A combined cohort (N = 14 155) of 2 community-based studies, the Atherosclerosis Risk in Communities Study and the Cardiovascular Health Study, was formed among men and women 45 years or older with an estimated glomerular filtration rate (GFR) exceeding 60 mL/min/1.73 m(2) at baseline. The primary outcome was the development of a GFR less than 60 mL/min/1.73 m(2) during a follow-up period of up to 9 years. Three prediction algorithms derived from the development data set were evaluated in the validation data set. RESULTS: The 3 prediction algorithms were continuous and categorical best-fitting models with 10 predictors and a simplified categorical model with 8 predictors. All showed discrimination with area under the receiver operating characteristic curve in a range of 0.69 to 0.70. In the simplified model, age, anemia, female sex, hypertension, diabetes mellitus, peripheral vascular disease, and history of congestive heart failure or cardiovascular disease were associated with the development of a GFR less than 60 mL/min/1.73 m(2). A numeric score of at least 3 using the simplified algorithm captured approximately 70% of incident cases (sensitivity) and accurately predicted a 17% risk of developing CKD (positive predictive value). CONCLUSIONS: An algorithm containing commonly understood variables helps to stratify middle-aged and older individuals at high risk for future CKD. The model can be used to guide population-level prevention efforts and to initiate discussions between practitioners and patients about risk for kidney disease.

Severe lactic acidosis associated with juice of the mangosteen fruit Garcinia mangostana.

The tropical mangosteen fruit has long been prized in Southeast Asia for its traditional healing properties. Mangosteen fruit juice is now available in the United States and marketed for its purported health benefits. We describe a case of severe lactic acidosis associated with the use of mangosteen juice as a dietary supplement.

Association of C-reactive protein and microalbuminuria (from the National Health and Nutrition Examination Surveys, 1999 to 2004).

Chronic kidney disease and cardiovascular disease share many risk factors. Injury to the vascular endothelium, measured by elevated levels of serum C-reactive protein (CRP), may play a role in kidney and cardiovascular disease. We therefore examined the association of CRP with microalbuminuria, a marker of early kidney injury. We conducted a cross-sectional analysis of a nationally representative, population-based survey. Weighted multiple logistic regression was used to study the association between CRP and microalbuminuria, adjusting for well-known risk factors. CRP was analyzed by a continuous variable and two categorized variables using quartiles and clinically recommended cutpoints. CRP concentration was positively associated with microalbuminuria. In the multivariate model, a one unit (in milligrams per liter) increase in CRP concentration was associated with a 2% increased odds of microalbuminuria (odds ratio 1.02, 95% confidence interval [CI] 1.01 to 1.02, p=0.0003). When CRP concentrations were stratified by clinically recommended cutpoints, compared with persons with CRP concentrations<1 mg/dl, persons with CRP concentrations between 1 and 3 mg/L and >3 mg/L were 1.15 times (95% CI 0.94 to 1.42) and 1.33 times (95% CI 1.08 to 1.65) more likely to have microalbuminuria, respectively. In subgroup analyses, the strength of association was comparable or stronger. In conclusion, elevated CRP levels were associated with microalbuminuria in a large, nationally representative data set. Vascular inflammation, as measured by CRP, may be a common contributor to early heart and kidney disease.

Change in proteinuria after adding aldosterone blockers to ACE inhibitors or angiotensin receptor blockers in CKD: a systematic review.

BACKGROUND: The use of mineralocorticoid receptor blockers (MRBs) in patients with chronic kidney disease is growing, but data for efficacy in decreasing proteinuria are limited by a relative paucity of studies, many of which are small and uncontrolled. STUDY DESIGN: We performed a systematic review using the MEDLINE database (inception to November 1, 2006), abstracts from national meetings, and selected reference lists. SETTING & POPULATION: Adult patients with chronic kidney disease and proteinuria. SELECTION CRITERIA FOR STUDIES: English-language studies investigating the use of MRBs added to long-term angiotensin-converting enzyme (ACE)-inhibitor and/or angiotensin receptor blocker (ARB) therapy in adult patients with proteinuric kidney disease. INTERVENTION: MRBs as additive therapy to conventional renin-angiotensin-aldosterone system blockade in patients with chronic kidney disease. OUTCOMES: Changes in proteinuria as the primary outcome; rates of hyperkalemia, changes in blood pressure, and changes in glomerular filtration rate as secondary outcomes. RESULTS: 15 studies met inclusion criteria for our review; 4 were parallel-group randomized controlled trials, 4 were crossover randomized controlled trials, 2 were pilot studies, and 5 were case series. When MRBs were added to ACE-inhibitor and/or ARB therapy, the reported proteinuria decreases from baseline ranged from 15% to 54%, with most estimates in the 30% to 40% range. Hyperkalemic events were significant in only 1 of 8 randomized controlled trials. MRB therapy was associated with statistically significant decreases in blood pressure and glomerular filtration rate in approximately 40% and 25% of included studies, respectively. LIMITATIONS: Reported results were insufficient for meta-analysis, with only 2 studies reporting sufficient data to calculate SEs of their published estimates. We were unable to locate studies that showed no effect of MRB treatment over placebo, raising concern for publication bias. CONCLUSIONS: Although data suggest that adding MRBs to ACE-inhibitor and/or ARB therapy yields significant decreases in proteinuria without adverse effects of hyperkalemia and impaired renal function, routine use of MRBs as additive therapy in patients with chronic kidney disease cannot be recommended yet. However, the findings of this review promote interesting hypotheses for future study.