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.

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.

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.

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.

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.

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.

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.

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.

SCreening for Occult REnal Disease (SCORED): a simple prediction model for chronic kidney disease.

BACKGROUND: Despite the wide availability and low cost of serum creatinine measurement, at-risk populations are not routinely tested for chronic kidney disease (CKD). METHODS: We used a cross-sectional analysis of a nationally representative, population-based survey to develop a system, SCORED (SCreening for Occult REnal Disease), that uses routinely available demographic and medical information to identify individuals with an increased likelihood of CKD. The analysis included 8530 adult participants in the National Health and Nutrition Examination Surveys conducted from 1999 to 2000 and 2001 to 2002 in the United States. Chronic kidney disease was defined as a glomerular filtration rate less than 60 mL/min per 1.73 m(2). Univariate and multivariate associations between a comprehensive set of risk factors and CKD were examined to develop a prediction model. The optimal characteristics of the model were examined with internal measures. External validation was performed using the Atherosclerosis Risk in Communities study. A model-based numeric scoring system was developed. RESULTS: Age (P<.001), female sex (P = .02), and various health conditions (hypertension [P = .03], diabetes [P = .03], and peripheral vascular disease [P = .008]; history of cardiovascular disease [P = .001] and congestive heart failure [P = .04]; and proteinuria [P<.001] and anemia [P = .003]) were associated with CKD. The multivariate model was well validated in the internal and external data sets (area under the receiver operating characteristic curve of 0.88 and 0.71, respectively). A score of 4 or greater was chosen by internal validation as a cutoff point for screening based on the diagnostic characteristics (sensitivity, 92%; specificity, 68%; positive predictive value, 18%; and negative predictive value, 99%). CONCLUSION: This scoring system, weighted toward common variables associated with CKD, may be a useful tool to identify individuals with a high likelihood of occult kidney disease.

The incidence and implications of aldosterone breakthrough.

Interruption of the renin-angiotensin-aldosterone system has become a leading therapeutic strategy in the treatment of chronic heart and kidney disease. Angiotensin-converting-enzyme inhibitors and angiotensin-receptor blockers do not, however, uniformly suppress the renin-angiotensin-aldosterone system. Plasma aldosterone levels are elevated in a subset of patients despite therapy. This phenomenon, known as 'aldosterone escape' or 'aldosterone breakthrough', has only been directly examined in small numbers of patients. The key questions of how often breakthrough occurs and whether breakthrough leads to worse outcomes have yet to be definitively answered. In this Review, we summarize the reported data on the incidence and clinical implications of aldosterone breakthrough, and highlight areas of uncertainty that have yet to be adequately addressed in the literature. Although the available evidence is not strong enough to support widespread screening for aldosterone breakthrough, our findings should prompt physicians to consider the phenomenon in select patients as well as guide future research efforts.

Preexisting crescentic glomerulonephritis in the renal allograft.

Two patients who received cadaveric renal transplants from the same donor were found to have similar diffuse proliferative glomerular lesions on renal biopsies performed for delayed graft function. The donor had no known disease, but had subtle abnormalities on preprocurement urinalysis. In retrospect, lupus nephritis is suspected in the donor. The authors detail the course of these 2 patients, review the literature on preexisting glomerular lesions, and address issues with regard to donor selection.

Plasmapheresis therapy for diffuse alveolar hemorrhage in patients with small-vessel vasculitis.

BACKGROUND: Unlike Goodpasture's syndrome with diffuse alveolar hemorrhage (DAH), there are few studies examining therapy for patients with DAH associated with antineutrophil cytoplasmic antibody (ANCA)-associated small-vessel vasculitis (SVV). METHODS: We performed a retrospective review of all such patients presenting to our institution between 1995 and 2001. All patients were treated with apheresis and induction immunosuppressive therapy; namely, intravenous methylprednisolone and/or intravenous cyclophosphamide. RESULTS: DAH resolved with apheresis in 20 of 20 patients (100%) with 6.4 (average) treatments. There were no complications of therapy. Half the patients (7 of 14) who also presented with azotemia were discharged with improved renal function. CONCLUSION: Patients with ANCA-related SVV and DAH benefit from prompt initiation of apheresis coupled with aggressive immunosuppressive therapy. Such therapy can be lifesaving with respect to the pulmonary component of this syndrome.

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.