Sodium zirconium cyclosilicate in hyperkalemia.

BACKGROUND: Hyperkalemia (serum potassium level, >5.0 mmol per liter) is associated with increased mortality among patients with heart failure, chronic kidney disease, or diabetes. We investigated whether sodium zirconium cyclosilicate (ZS-9), a novel selective cation exchanger, could lower serum potassium levels in patients with hyperkalemia. METHODS: In this multicenter, two-stage, double-blind, phase 3 trial, we randomly assigned 753 patients with hyperkalemia to receive either ZS-9 (at a dose of 1.25 g, 2.5 g, 5 g, or 10 g) or placebo three times daily for 48 hours. Patients with normokalemia (serum potassium level, 3.5 to 4.9 mmol per liter) at 48 hours were randomly assigned to receive either ZS-9 or placebo once daily on days 3 to 14 (maintenance phase). The primary end point was the exponential rate of change in the mean serum potassium level at 48 hours. RESULTS: At 48 hours, the mean serum potassium level had decreased from 5.3 mmol per liter at baseline to 4.9 mmol per liter in the group of patients who received 2.5 g of ZS-9, 4.8 mmol per liter in the 5-g group, and 4.6 mmol per liter in the 10-g group, for mean reductions of 0.5, 0.5, and 0.7 mmol per liter, respectively (P<0.001 for all comparisons) and to 5.1 mmol per liter in the 1.25-g group and the placebo group (mean reduction, 0.3 mmol per liter). In patients who received 5 g of ZS-9 and those who received 10 g of ZS-9, serum potassium levels were maintained at 4.7 mmol per liter and 4.5 mmol per liter, respectively, during the maintenance phase, as compared with a level of more than 5.0 mmol per liter in the placebo group (P<0.01 for all comparisons). Rates of adverse events were similar in the ZS-9 group and the placebo group (12.9% and 10.8%, respectively, in the initial phase; 25.1% and 24.5%, respectively, in the maintenance phase). Diarrhea was the most common complication in the two study groups. CONCLUSIONS: Patients with hyperkalemia who received ZS-9, as compared with those who received placebo, had a significant reduction in potassium levels at 48 hours, with normokalemia maintained during 12 days of maintenance therapy. (Funded by ZS Pharma; ClinicalTrials.gov number, NCT01737697.).

Dyslipidemia in Dialysis Patients.

Dyslipidemia is a well-established traditional risk factor for cardiovascular events in the general population, particularly those with preexisting cardiovascular disease (CVD). In this population, reductions in total and low density lipoprotein cholesterol (LDL-C) levels are effective in reducing coronary artery events and mortality. Dyslipidemia is more common in patients with chronic kidney disease (CKD) and is believed to contribute to the high prevalence of CVD in these patients. To date, the treatment of dyslipidemia in patients with CKD followed the guidelines recommended by the US National Cholesterol Education Program Adult Treatment Panel III (ATP III) for the treatment of lipid abnormalities. These guidelines recommend that initiation of lipid-lowering therapy be based on LDL-C level and the projected 10-year risk for coronary artery disease (CAD). However, we now recognize that the relationship between serum cholesterol and CVD is more complex in patients with CKD, particularly those receiving maintenance hemodialysis. This has been demonstrated by the failure of three large randomized clinical trials to show a beneficial effect of lipid-lowering therapy in reducing mortality in dialysis patients despite significant reduction in LDL-C levels. These results have caused uncertainty among nephrologists about how best to manage dyslipidemia in their patients. In this review, the role of dyslipidemia as a risk factor for atherosclerosis in ESRD patients and the results of the 3 clinical trials and other studies, including their limitations will be discussed, and a schema for treating dyslipidemia in dialysis patients will be proposed.

Ferric carboxymaltose in patients with iron-deficiency anemia and impaired renal function: the REPAIR-IDA trial.

BACKGROUND: Iron-deficiency anemia in non-dialysis-dependent chronic kidney disease (NDD-CKD) frequently requires parenteral iron replacement, but existing therapies often require multiple administrations. We evaluated the efficacy and cardiovascular safety of ferric carboxymaltose (FCM), a non-dextran parenteral iron permitting large single-dose infusions, versus iron sucrose in patients with iron-deficiency anemia and NDD-CKD. METHODS: A total of 2584 participants were randomized to two doses of FCM 750 mg in one week, or iron sucrose 200 mg administered in up to five infusions in 14 days. The primary efficacy endpoint was the mean change to highest hemoglobin from baseline to Day 56. The primary composite safety endpoint included all-cause mortality, nonfatal myocardial infarction, nonfatal stroke, unstable angina, congestive heart failure, arrhythmias and hyper- and hypotensive events. RESULTS: The mean hemoglobin increase was 1.13 g/dL in the FCM group and 0.92 g/dL in the iron sucrose group (95% CI, 0.13-0.28). Similar results were observed across all subgroups, except Stage 2 CKD. More subjects in the FCM group achieved a hemoglobin increase of ≥ 1.0 g/dL between baseline and Day 56 (48.6 versus 41.0%; 95% CI, 3.6-11.6%). There was no significant difference between FCM and iron sucrose recipients with respect to the primary composite safety endpoint, including the major adverse cardiac events of death, myocardial infarction, or stroke. A significant difference in the number of protocol-defined, predominantly transient hypertensive episodes was observed in the FCM group. CONCLUSIONS: Two 750-mg infusions of FCM are a safe and effective alternative to multiple lower dose iron sucrose infusions in NDD-CKD patients with iron-deficiency anemia.

Effect of sodium zirconium cyclosilicate on potassium lowering for 28 days among outpatients with hyperkalemia: the HARMONIZE randomized clinical trial.

IMPORTANCE: Hyperkalemia is a common electrolyte abnormality that may be difficult to manage because of a lack of effective therapies. Sodium zirconium cyclosilicate is a nonabsorbed cation exchanger that selectively binds potassium in the intestine. OBJECTIVE: To evaluate the efficacy and safety of zirconium cyclosilicate for 28 days in patients with hyperkalemia. DESIGN, SETTING, AND PARTICIPANTS: HARMONIZE was a phase 3, multicenter, randomized, double-blind, placebo-controlled trial evaluating zirconium cyclosilicate in outpatients with hyperkalemia (serum potassium ≥5.1 mEq/L) recruited from 44 sites in the United States, Australia, and South Africa (March-August 2014). INTERVENTIONS: Patients (n = 258) received 10 g of zirconium cyclosilicate 3 times daily in the initial 48-hour open-label phase. Patients (n = 237) achieving normokalemia (3.5-5.0 mEq/L) were then randomized to receive zirconium cyclosilicate, 5 g (n = 45 patients), 10 g (n = 51), or 15 g (n = 56), or placebo (n = 85) daily for 28 days. MAIN OUTCOMES AND MEASURES: The primary end point was mean serum potassium level in each zirconium cyclosilicate group vs placebo during days 8-29 of the randomized phase. RESULTS: In the open-label phase, serum potassium levels declined from 5.6 mEq/L at baseline to 4.5 mEq/L at 48 hours. Median time to normalization was 2.2 hours, with 84% of patients (95% CI, 79%-88%) achieving normokalemia by 24 hours and 98% (95% CI, 96%-99%) by 48 hours. In the randomized phase, serum potassium was significantly lower during days 8-29 with all 3 zirconium cyclosilicate doses vs placebo (4.8 mEq/L [95% CI, 4.6-4.9], 4.5 mEq/L [95% CI, 4.4-4.6], and 4.4 mEq/L [95% CI, 4.3-4.5] for 5 g, 10 g, and 15 g; 5.1 mEq/L [95% CI, 5.0-5.2] for placebo; P < .001 for all comparisons). The proportion of patients with mean potassium <5.1 mEq/L during days 8-29 was significantly higher in all zirconium cyclosilicate groups vs placebo (36/45 [80%], 45/50 [90%], and 51/54 [94%] for the 5-g, 10-g, and 15-g groups, vs 38/82 [46%] with placebo; P < .001 for each dose vs placebo). Adverse events were comparable between zirconium cyclosilicate and placebo, although edema was more common in the 15-g group (edema incidence: 2/85 [2%], 1/45 [2%], 3/51 [6%], and 8/56 [14%] patients in the placebo, 5-g, 10-g, and 15-g groups). Hypokalemia developed in 5/51 (10%) and 6/56 patients (11%) in the 10-g and 15-g zirconium cyclosilicate groups, vs none in the 5-g or placebo groups. CONCLUSIONS AND RELEVANCE: Among outpatients with hyperkalemia, open-label sodium zirconium cyclosilicate reduced serum potassium to normal levels within 48 hours; compared with placebo, all 3 doses of zirconium cyclosilicate resulted in lower potassium levels and a higher proportion of patients with normal potassium levels for up to 28 days. Further studies are needed to evaluate the efficacy and safety of zirconium cyclosilicate beyond 4 weeks and to assess long-term clinical outcomes. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT02088073.

A randomized controlled trial comparing intravenous ferric carboxymaltose with oral iron for treatment of iron deficiency anaemia of non-dialysis-dependent chronic kidney disease patients.

BACKGROUND: Iron deficiency is a common cause of anaemia and hyporesponsiveness to erythropoiesis-stimulating agents (ESAs) in non-dialysis-dependent chronic kidney disease (ND-CKD) patients. Current intravenous iron agents cannot be administered in a single high dose because of adverse effects. Ferric carboxymaltose, a non-dextran parenteral iron preparation, can be rapidly administered in high doses. METHODS: This open-label trial randomized 255 subjects with glomerular filtration rates ≤ 45 mL/min/1.73 m(2), haemoglobin ≤ 11 g/dL, transferrin saturation ≤ 25%, ferritin ≤ 300 ng/mL, and stable ESA dose to either intravenous ferric carboxymaltose 1000 mg over 15 min (with up to two additional doses of 500 mg at 2-week intervals) or oral ferrous sulphate 325 mg thrice daily for a total of 195 mg elemental iron daily for 56 days. RESULTS: In the modified intent-to-treat population, the proportion of subjects achieving a haemoglobin increase ≥ 1 g/dL at any time was 60.4% with ferric carboxymaltose and 34.7% with oral iron (P < 0.001). At Day 42, mean increase in haemoglobin was 0.95 ± 1.12 vs 0.50 ± 1.23 g/dL (P = 0.005), mean increase in ferritin was 432 ± 189 ng/mL vs 18 ± 45 ng/mL (P < 0.001) and mean increase in transferrin saturation was 13.6 ± 11.9% vs 6.1 ± 8.1% (P < 0.001). Treatment-related adverse events were significantly fewer with ferric carboxymaltose than with oral iron (2.7% and 26.2%, respectively; P < 0.0001). CONCLUSIONS: We conclude that 1000 mg ferric carboxymaltose can be rapidly administered, is more effective and is better tolerated than oral iron for treatment of iron deficiency in ND-CKD patients.

A randomized, double-blind, placebo-controlled trial of calcium acetate on serum phosphorus concentrations in patients with advanced non-dialysis-dependent chronic kidney disease.

BACKGROUND: Hyperphosphatemia in patients with chronic kidney disease (CKD) contributes to secondary hyperparathyroidism, soft tissue calcification, and increased mortality risk. This trial was conducted to examine the efficacy and safety of calcium acetate in controlling serum phosphorus in pre-dialysis patients with CKD. METHODS: In this randomized, double-blind, placebo-controlled trial, 110 nondialyzed patients from 34 sites with estimated GFR < 30 mL/min/1.73 m² and serum phosphorus > 4.5 mg/dL were randomized to calcium acetate or placebo for 12 weeks. The dose of study drugs was titrated to achieve target serum phosphorus of 2.7-4.5 mg/dL. Serum phosphorus, calcium, iPTH, bicarbonate and serum albumin were measured at baseline and every 2 weeks for the 12 week study period. The primary efficacy endpoint was serum phosphorus at 12 weeks. Secondary endpoints were to measure serum calcium and intact parathyroid hormone (iPTH) levels. RESULTS: At 12 weeks, serum phosphorus concentration was significantly lower in the calcium acetate group compared to the placebo group (4.4 ± 1.2 mg/dL vs. 5.1 ± 1.4 mg/dL; p = 0.04). The albumin-adjusted serum calcium concentration was significantly higher (9.5 ± 0.8 vs. 8.8 ± 0.8; p < 0.001) and iPTH was significantly lower in the calcium acetate group compared to placebo (150 ± 157 vs. 351 ± 292 pg/mL respectively; p < 0.001). At 12 weeks, the proportions of subjects who had hypocalcemia were 5.4% and 19.5% for the calcium acetate and the placebo groups, respectively, while the proportions of those with hypercalcemia were 13.5% and 0%, respectively. Adverse events did not differ between the treatment groups. CONCLUSIONS: In CKD patients not yet on dialysis, calcium acetate was effective in reducing serum phosphorus and iPTH over a 12 week period. TRIAL REGISTRATION: www.clinicaltrials.gov NCT00211978.

An evaluation of sodium zirconium cyclosilicate as a treatment option for hyperkalemia.

INTRODUCTION: Hyperkalemia, defined as serum potassium level > 5.0 mEq/l, is associated with serious cardiac dysrhythmias, sudden death and increased mortality risk. It is common in patients with chronic kidney disease (CKD), diabetes (DM) and heart failure (HF), particularly in those treated with the renin-angiotensin-aldosterone system (RAAS) inhibitors or potassium-sparing diuretics. Although these drugs have documented renal and cardiac protective benefits, frequent hyperkalemia associated with their use often dictates administration of suboptimal doses or their discontinuation altogether. Treatment for chronic hyperkalemia in these settings has been challenging; however, the recent introduction of two new potassium-binding resins has revolutionized our approach to treating hyperkalemia. AREAS COVERED: We review key clinical data relating to the pharmacokinetics, efficacy and safety of sodium zirconium cyclosilicate (SZC) as a treatment option for hyperkalemia. EXPERT OPINION: SZC and Patiromer are promising new agents for lowering serum potassium in hyperkalemic patients, including those with CKD, with and without DM or HF, facilitating the use of the RAAS inhibitors for renal and cardiac protection. Recent randomized clinical trials have shown that SZC effectively lowers serum potassium and maintains normokalemia in most hyperkalemic patients. Clinical trials showed that SZC lowers serum potassium within 1 h, although it is not approved for treating acute hyperkalemia. SZC was well tolerated and associated with minimal adverse effects.

AKI Associated with Acute Pancreatitis.

Acute pancreatitis is a common disorder of the pancreas. It is the most frequent gastrointestinal cause for hospitalization and one of the leading causes of in-hospital deaths. Its severity ranges from mild self-limited disease to severe acute necrotizing pancreatitis characterized by systemic complications and multiorgan failure. Severe acute pancreatitis develops in about 20% of patients with acute pancreatitis and may be associated with multiorgan failure (respiratory, cardiovascular, and kidney). AKI is a frequent complication of severe acute pancreatitis and develops late in the course of the disease, usually after the failure of other organs. It carries a very poor prognosis, particularly if kidney replacement therapy is required, with mortality rates exceeding 75%. The exact pathophysiology of AKI in acute pancreatitis remains unclear but appears to result from initial volume depletion followed by complex vascular and humoral factors. Here, we provide an overview of the epidemiology, pathogenesis, causes, and management of AKI in patients with severe acute pancreatitis.

A 1-year randomized trial of calcium acetate versus sevelamer on progression of coronary artery calcification in hemodialysis patients with comparable lipid control: the Calcium Acetate Renagel Evaluation-2 (CARE-2) study.

BACKGROUND: Previous clinical trials showed that progression of coronary artery calcification (CAC) may be slower in hemodialysis patients treated with sevelamer than those treated with calcium-based phosphate binders. Because sevelamer decreases low-density lipoprotein cholesterol (LDL-C) levels, we hypothesized that intensive lowering of LDL-C levels with atorvastatin in hemodialysis patients treated with calcium acetate would result in CAC progression rates similar to those in sevelamer-treated patients. STUDY DESIGN: Randomized, controlled, open-label, noninferiority trial with an upper bound for the noninferiority margin of 1.8. SETTING & PARTICIPANTS: 203 prevalent hemodialysis patients at 26 dialysis centers with serum phosphorus levels greater than 5.5 mg/dL, LDL-C levels greater than 80 mg/dL, and baseline CAC scores of 30 to 7,000 units assessed by means of electron-beam computed tomography. INTERVENTIONS: 103 patients were randomly assigned to calcium acetate, and 100 patients to sevelamer for 12 months to achieve phosphorus levels of 3.5 to 5.5 mg/dL. Atorvastatin was added to achieve serum LDL-C levels less than 70 mg/dL in both groups. OUTCOMES & MEASUREMENTS: The primary end point was change in CAC score assessed by means of electron-beam computed tomography. RESULTS: After 12 months, mean serum LDL-C levels decreased to 68.8 +/- 22.0 mg/dL in the calcium-acetate group and 62.4 +/- 23.0 mg/dL in the sevelamer group (P = 0.3). Geometric mean increases in CAC scores were 35% in the calcium-acetate group and 39% in the sevelamer group, with a covariate-adjusted calcium acetate-sevelamer ratio of 0.994 (95% confidence interval, 0.851 to 1.161). LIMITATIONS: Treatment assignment was not blinded. The 1.8 a priori margin is large, CAC is a surrogate outcome, duration of treatment was short, and dropout rate was high. CONCLUSIONS: With intensive lowering of LDL-C levels for 1 year, hemodialysis patients treated with either calcium acetate or sevelamer experienced similar progression of CAC.

The interscan variation of CT coronary artery calcification score: analysis of the Calcium Acetate Renagel Comparison (CARE)-2 study.

RATIONALE AND OBJECTIVES: In the Calcium Acetate Renagel Evaluation (CARE)-2 study, the effects of calcium acetate plus atorvastatin (Lipitor) on the progression of coronary artery calcifications (CACs) are evaluated versus those of Renagel, monitored using dual electron beam tomography (EBT) scans (two scans at study initiation and two at follow up). The aim of this study is to estimate the interscan variation for the Agatston score and for the volume score determined in patients with end-stage renal disease (ESRD) in the CARE-2 study. MATERIALS AND METHODS: CAC score and volume were measured at study initiation in 463 ESRD subjects (mean age: 59.4 +/- 12.5 years, 48.3% female). All patients underwent dual scanning using an EBT, as first scan of two needed to measure the progression of CAC when treated with sevelamer (Renagel) compared with calcium acetate with or without atorvastatin. All scans in all participants were completed by using an EBT system (GE Imatron, South San Francisco, CA). Interscan variability was defined by the following formula: abs (scan A - scan B) / (0.5 x scan A + 0.5 x scan B) x 100%, where A and B denote the first and second scan, respectively, of the dual scan procedure performed before treatment. We evaluated the reproducibility of the cutpoints commonly used for calcium scores clinically, namely 1-30, 31-100, 101-400, and >400. RESULTS: The CAC interscan variability was 11.8% using the Agatston score and 10.3% using the volume score. The reproducibility was then assessed using cutpoints 1-30, 31-100, 101-400, and >400. Agatston score variability for the four subgroups was 61.3%, 23%, 16.1%, and 8.2%, respectively (mean variability, 11.8%). Volume score variability was 60.0%, 14.4%, 14.6%, and 7.7%, respectively (mean variability, 10.3%). The correlation coefficient for scan A to scan B goes up significantly with increasing calcium scores and reaches 0.99 for scores greater than 400 (P < .0001). CONCLUSION: Interscan variability was sufficiently small for patients with calcium scores greater than 30. Our study thus demonstrates a sufficient reproducibility of the calcium score using EBT. This score allows for accurate serial assessment of these patients and for comparing different therapies.

Vascular access mortality and hospitalization among hemodialysis patients in Palestine.

Vascular access complications are common in patients with end-stage kidney disease who are receiving maintenance hemodialysis (HD) and are responsible for an enormous burden of morbidity and mortality among these patients. Differences in the all-cause mortality rate and hospitalization between dialysis catheter use and arteriovenous (AV) vascular access use have not been documented in our HD population. We performed a 12-month prospective analysis of our HD patients from four dialysis centers. We examined all-cause mortality and hospitalization in patients being dialyzed through HD catheters as compared to patients with AV access. A total of 382 patients were included in the study. Of these, 88 had catheters and 294 had AV accesses. Seventy-eight percent of all catheters were temporary nontunneled dialysis catheters. The overall gross mortality rate for all patients was 14.7%. Gross mortality was significantly lower among AV access group compared to the catheter group (12.2% vs. 22.7%; P = 0.015). Catheter use was associated with a relative hazard ratio (HR) of 1.85 [95% confidence interval (CI), 1.13-3.03] compared with use of an AV access. Hospitalization rate was also significantly lower among patients with AV access versus patients who used catheters (27.6% vs. 46.6%; P = 0.006). The risk of hospitalization was also higher in catheter users with a relative HR of 1.69 (95% CI, 1.26-2.26) compared with use of AV access. In our HD population where the majority of catheters were temporary nontunneled catheters, dialysis catheter use was associated with higher mortality and increased hospitalization rates compared with AV access. These results emphasize the urgent need to minimize the use of dialysis catheters, in order to reduce mortality and hospitalization rates among HD patients.

Delayed Manifestation of Shunt Nephritis: A Case Report and Review of the Literature.

We present an unusual case of shunt nephritis in a 39-year-old male who presented 21 years after placement of a ventriculoperitoneal (VP) shunt. He complained of fevers, headaches, dizziness, and urticarial plaques on arms, trunks, and legs and was found to have anemia, low complement levels, elevated serum creatinine, proteinuria, and new onset microhematuria. Blood and urine cultures were negative. Renal biopsy showed features of acute tubulointerstitial nephritis attributed to vancomycin use. Glomeruli showed increased mesangial hypercellularity and segmental endocapillary proliferation. Immunofluorescence showed focal IgM and C3 staining. Electron microscopy revealed small subendothelial electron-dense deposits. Symptoms and renal insufficiency appeared to improve with antibiotic therapy. He was discharged and readmitted 2 months later with similar presentation. CSF grew Propionibacterium acnes and shunt hardware grew coagulase-negative Staphylococcus. He completed an intravenous antibiotic course and was discharged. On 1-month follow-up, skin lesions persisted but he was otherwise asymptomatic. Follow-up labs showed significant improvement. We did a brief systematic review of the literature on shunt nephritis and report our findings on 79 individual cases. In this review, we comment on the presentation, lab findings, pathological features, and management of this rare, potentially fatal, but curable disease entity.

The CARE study and cardiovascular calcification.

Cardiovascular disease (CVD) remains the major mortality risk in dialysis patients, accounting for almost 50 percent of deaths. Risk is related to the increased prevalence of traditional risk factors for CVD and to the contribution of abnormalities in mineral metabolism as well as cardiovascular calcification. Hyperphosphatemia invariably is present among patients with end-stage renal disease and is becoming an increasingly important clinical entity. In addition to its role in the pathogenesis of secondary hyperparathyroidism, elevated serum phosphorus increases the mortality risk among these patients. The pathophysiologic mechanisms by which persistent hyperphosphatemia enhances mortality risk in dialysis patients are not yet completely understood. Given that inadequate control of serum phosphorus contributes to elevated calcium-phosphorus (Ca x P) product, hyperphosphatemia may play a key role in cardiovascular calcification. The National Kidney Foundation's Kidney Disease Outcomes Quality Initiative (K/DOQI) "Clinical Practice Guidelines for Bone Metabolism and Disease in Chronic Kidney Disease" recommends more stringent levels for controlling serum phosphorus and Ca x P product to improve patients' quality of life and longevity. Several studies, including the CARE study, have shown that calcium acetate is more cost-effective than sevelamer as a phosphate binder. Although concern has been raised about its purported link to cardiovascular calcification, the author demonstrates in this review that calcium acetate can be used effectively with doses of elemental calcium that meet the K/DOQI guidelines.

Dyslipidemia and progression of cardiovascular calcification (CVC) in patients with end-stage renal disease (ESRD).

Dyslipidemia and progression of cardiovascular calcification (CVC) in patients with end-stage renal disease (ESRD). Cardiovascular calcification (CVC) is commonly encountered both in the general population as well as in patients with end-stage renal disease (ESRD). The etiology of CVC in patients with ESRD is multifactorial. Despite that, current debate remains narrowly focused on the role of calcium loading from calcium-based phosphate binders (CBPB) in the pathogenesis and progression of CVC. Yet, the alleged link between these binders and CVC has not been substantiated in well-designed controlled trials. In contrast, the purported role of sevelamer, a non-calcium-based phosphate binder, in slowing the progression of CVC in dialysis patients has attracted widespread attention. The beneficial effect of sevelamer on progression of calcification was thought to be due to lower calcium loading during its use. However, an alternative and possibly more likely mechanism involves sevelamer-induced lowering of LDL cholesterol. In this context, previous studies in individuals with normal renal function have documented amelioration of coronary artery calcification (CAC) with reduction of LDL-cholesterol by treatment with HMG-CoA reductase inhibitors (statins). Given that CAC is a well-accepted marker of atherosclerosis, and that high plasma cholesterol concentration is one of the main risk factors for atherosclerosis, then it is not unreasonable to suspect that CAC may be halted or even reversed by lowering of LDL cholesterol level with statin therapy. Unfortunately, the effect of lowering the LDL-cholesterol level on CAC has not been studied in patients with ESRD. Therefore, conclusions about this important topic should await the results of well-designed clinical studies that control for all factors potentially implicated in the CVC burden of patients with ESRD. In this review, I will discuss the role of various potential mechanisms involved in the pathogenesis of CVC in patients with ESRD, and emphasize the role of dyslipidemia and its treatment in this important clinical entity.

Treatment of hyperphosphatemia in patients with chronic kidney disease on maintenance hemodialysis.

Treatment of hyperphosphatemia in patients with chronic kidney disease on maintenance hemodialysis. Hyperphosphatemia in patients with ESRD leads to secondary hyperparathyroidism, renal osteodystrophy, and is independently associated with mortality risk. The exact mechanism by which hyperphosphatemia increases mortality risk is unknown, but it may relate to enhanced cardiovascular calcification. National Kidney Foundation K/DOQI bone metabolism and disease guidelines recommend maintenance of serum phosphorus (P) below 5.5 mg/dL, and Ca x P product less than 55 mg(2)/dL(2). Although calcium-based phosphate binders (CBPB) are cost effective, long-term safety concerns relate to their postulated role in progression of cardiovascular calcification. Sevelamer hydrochloride has been recommended as an alternative noncalcium phosphate binder. Results from the Calcium Acetate Renagel Evaluation (CARE study) indicate that calcium acetate is more effective than sevelamer in controlling serum phosphorous and Ca x P product in hemodialysis patients. In the Treat-to-Goal study, dialysis patients treated with sevelamer had slower progression of coronary and aortic calcification than patients treated with CBPB. The mechanism underlying the beneficial effect of sevelamer is unknown, but may relate to decreased calcium loading or to dramatic reductions in LDL cholesterol in sevelamer-treated patients. At present, evidence incriminating CBPB in the progression of cardiovascular calcification in ESRD remains largely circumstantial. As calcium acetate is more efficacious and cost effective than sevelamer, it remains an accepted first-line phosphate binder. In this review, we will examine these issues and provide rational guidelines for the use of calcium-based phosphate binders in patients on maintenance hemodialysis.

Comparison of intravenous iron sucrose to oral iron in the treatment of anemic patients with chronic kidney disease not on dialysis.

BACKGROUND: Few studies compare oral to intravenous (IV) iron for managing anemia in patients with chronic kidney disease (CKD) not on dialysis. METHODS: We enrolled 96 CKD anemic patients on erythropoietin in a randomized, open-label, multicenter, controlled study. Patients received 29 days of oral FeSO4 (325 mg t.i.d.) or intravenous (IV) iron sucrose (5 doses of 200 mg weekly). Assessments were made up to 14 days after the last dose. Primary endpoints were changes in hemoglobin and ferritin, and clinical success was evaluated from the percent of patients with combined endpoints of rises in hemoglobin/ferritin, hemoglobin/ferritin/TSAT, and hemoglobin/TSAT. RESULTS: There was no significant difference in hemoglobin values between IV and oral therapy. IV iron patients had greater increases in mean serum ferritin (288 ng/ml, p < 0.0001) compared to oral iron patients (-5.1 ng/ml, p = NS). IV iron patients with baseline ferritin < 100 ng/ml had a greater increase in hemoglobin (1.4 g/dl) compared to oral iron patients (0.9 g/dl) (p < 0.05). More IV iron patients (54.2%) attained hemoglobin values > 11.0 g/dl compared to oral iron patients (31.3%, p = 0.028), and met hemoglobin/ferritin (62.5%), hemoglobin/TSAT (47.9%), hemoglobin/ferritin/TSAT (43.8%), and ferritin/TSAT criteria (54.2%) than oral iron patients (0, 22.9, 0, and 0%, respectively). There were no serious side effects. CONCLUSIONS: These CKD patients had increases in both hemoglobin and ferritin following IV iron therapy, whereas those treated with oral iron had increases in hemoglobin without increases in iron stores. Iron sucrose, given weekly as 200 mg IV push over 5 min is an effective and safe anemia treatment in this population.

Treatment of vitamin D deficiency/insufficiency with ergocalciferol is associated with reduced vascular access dysfunction in chronic hemodialysis patients.

Vitamin D deficiency or insufficiency is highly prevalent among patients with chronic kidney disease (CKD). This study aims to determine the relationship between vitamin D and frequency of vascular access dysfunction (VAD) in hemodialysis (HD) patients. We reviewed medical records of all HD patients who had serum 25-hydroxyvitamin D (25OHD) levels at 4 outpatient dialysis facilities between January 2011 and January 2012. Patients were included if they were ≥18 years of age, had been on maintenance dialysis for ≥3 months, and had native arteriovenous fistula or synthetic polytetrafluoroethylene grafts for dialysis access. Patients with catheters were excluded. 25-Hydroxyvitamin D levels <30 ng/mL were documented in 183 patients (86%). Median and interquartile range [Q1, Q3] of 25OHD level was 16 [11, 25] ng/mL. Among 213 dialysis patients, 102 had VAD. Median 25OHD level was significantly lower in patients who had VAD than in those without VAD (14.5 [10, 22] vs. 19 [12, 27.5] ng/mL; P = 0.003). There was significant association between VAD and the lowest quartile relative to the highest quartile of 25OHD level. A 25OHD level <12 ng/mL was associated with more than doubling of risk for VAD (OR 2.56; 95% CI [1.05-6.23], P < 0.05). Of 213 patients, 140 were treated with ergocalciferol and 73 were not treated. Treatment was associated with significant reduction in VAD (OR = 0.36; 95% CI [0.19-0.68], P = 0.002). Vitamin D deficiency or insufficiency is an independent risk factor for VAD in HD patients; its treatment with ergocalciferol is associated with decreased VAD.