A randomized controlled pilot trial of anakinra for hemodialysis inflammation.

Chronic inflammation is highly prevalent among patients receiving maintenance hemodialysis and is associated with morbidity and mortality. Inhibiting inflammation with anti-cytokine therapy has been proposed but not well studied in this population. Therefore, we conducted the ACTION trial, a pilot, multicenter, randomized, placebo-controlled trial of an IL-1 receptor antagonist, anakinra, to evaluate safety, tolerability, and feasibility, and explore efficacy. Eighty hemodialysis patients with plasma concentrations of high sensitivity C-reactive protein (hsCRP) 2 mg/L and above were randomized 1:1 to placebo or anakinra 100 mg, three times per week via the hemodialysis circuit for 24 weeks, with an additional 24 weeks of post-treatment safety monitoring. Efficacy outcomes included changes in hsCRP (primary), cytokines, and patient-reported outcomes. Rates of serious adverse events and deaths were similar with anakinra and placebo (serious adverse events: 2.71 vs 2.74 events/patient-year; deaths: 0.12 vs 0.22 events/patient-year). The rate of adverse events of interest (including infections and cytopenias) was significantly lower with anakinra than placebo (0.48 vs 1.40 events/patient-year). Feasibility was demonstrated by attaining the enrollment target, a retention rate of 80%, and administration of 72% of doses. The median decrease in hsCRP from baseline to Week 24 was 41% in the anakinra group and 6% in the placebo group, a between-group difference that was not statistically significant. For IL-6, the median decreases were significant: 25% and 0% in the anakinra and placebo groups, respectively. An effect of anakinra on patient-reported outcomes was not evident. Thus, anakinra was well tolerated and did not increase infections or cytopenias. The promising safety data and potential efficacy on CRP and IL-6 provide support for conducting definitive trials of IL-1 inhibition to improve outcomes in hemodialysis patients.

Calculating estimated glomerular filtration rate without the race correction factor: Observations at a large academic medical system.

BACKGROUND AND AIMS: Creatinine-based MDRD and CKD-EPI equations include a race correction factor, which results in higher eGFR in Black patients. We evaluated the impact on our patient population upon adoption of the CKD-EPI equation and the removal of the race correction factor from the equation. MATERIALS AND METHODS: Retrospective analysis of blood creatinine results and respective eGFR values calculated by the MDRD or CKD-EPI equation without the race correction factor (CKD-EPINoRace) in a large academic medical system over a 20.5-month period. RESULTS: In our population, when changing from MDRD to CKD-EPINoRace, we observed that 3.5% of all patients were reclassified to categorically have worse kidney function. However, we also observed fewer patients overall with eGFR below 60 mL/min/1.73 m2. Around 60 and 20 mL/min/1.73 m2, 2.96% and 0.16% of all patients > 65 years of age were reclassified, as were 4.29% and 0.03% of all Black patients, respectively. When calculated with CKD-EPINoRace, median eGFR was not meaningfully different between Black and non-Black patients (p = 0.02). CONCLUSIONS: Changing from MDRD to CKD-EPINoRace could lead to a lower referral rate to nephrology. The distributions of creatinine and eGFR calculated with CKD-EPINoRace were not meaningfully different in Black and non-Black patients.

KDOQI US Commentary on the 2020 ISPD Practice Recommendations for Prescribing High-Quality Goal-Directed Peritoneal Dialysis.

The recently published 2020 International Society for Peritoneal Dialysis (ISPD) practice recommendations regarding prescription of high-quality goal-directed peritoneal dialysis differ fundamentally from previous guidelines that focused on "adequacy" of dialysis. The new ISPD publication emphasizes the need for a person-centered approach with shared decision making between the individual performing peritoneal dialysis and the clinical care team while taking a broader view of the various issues faced by that individual. Cognizant of the lack of strong evidence for the recommendations made, they are labeled as "practice points" rather than being graded numerically. This commentary presents the views of a work group convened by the National Kidney Foundation's Kidney Disease Outcomes Quality Initiative (KDOQI) to assess these recommendations and assist clinical providers in the United States in interpreting and implementing them. This will require changes to the current clinical paradigm, including greater resource allocation to allow for enhanced services that provide a more holistic and person-centered assessment of the quality of dialysis delivered.

Safety and cardiovascular efficacy of spironolactone in dialysis-dependent ESRD (SPin-D): a randomized, placebo-controlled, multiple dosage trial.

The safety and efficacy of spironolactone is uncertain in end-stage renal disease. We randomized 129 maintenance hemodialysis patients to placebo (n=51) or spironolactone 12.5 mg (n=27), 25 mg (n=26), or 50 mg (n=25) daily for 36 weeks in a double-blind, placebo-controlled, multiple dosage trial to assess safety, tolerability and feasibility and to explore cardiovascular efficacy. The primary safety endpoints were hyperkalemia (potassium > 6.5 mEq/L) and hypotension requiring emergency department visit or hospitalization. Diastolic function was assessed by Doppler echocardiography. 125 participants (97%) completed dose escalation, with no significant difference in permanent study drug discontinuation between the groups (27.5% in placebo versus 16.7% in the combined spironolactone groups and 28% in the 50 mg group). Hyperkalemia frequency was similar between spironolactone and placebo (0.49 versus 0.50 events per patient-year) but demonstrated a significant linear trend due primarily to an increased event rate at the 50 mg dose (0.89 events per patient-year). The primary hypotension outcome was infrequent and similar with spironolactone and placebo (0.11 versus 0 events per patient-year). Gynecomastia was rare and did not differ significantly between groups. Change in diastolic function was similar with spironolactone and placebo. Spironolactone appears safe in carefully monitored maintenance hemodialysis patients, but did not affect cardiovascular parameters in this small study. Hyperkalemia occurs more frequently as dosage increases to 50 mg daily.

Predictors of early mortality and readmissions among dialysis patients undergoing lower extremity amputation.

OBJECTIVE: Patients receiving dialysis are at increased risk for lower extremity amputations (LEAs) and postoperative morbidity. Limited studies have examined differences in 30-day outcomes of mortality and health care use after amputation or the preoperative factors that relate to worsened outcomes in dialysis patients. Our objective was to examine dialysis dependency and other preoperative factors associated with readmission or death after LEA. METHODS: A retrospective cohort study was conducted of dialysis-dependent and nondialysis patients undergoing major LEA in the 2012 to 2013 American College of Surgeons National Surgical Quality Improvement Program. Primary outcomes included death and hospital readmission within 30 days of amputation. RESULTS: Of 6468 patients, 1166 (18%) were dialysis dependent. The dialysis cohort had more blacks (39% vs 23%), diabetes (76% vs 58%), below-knee amputations (62% vs 55%), and in-hospital deaths (8% vs 3%; all P < .001). The 30-day postoperative death rates (15% vs 7%) and readmission rates (35% vs 20% per 30 person-days; both P < .001) were higher in dialysis patients. Among the live discharges, the rate of any readmission or death within 30 days from amputation was highest in those aged ≥50 years (40% per 30 person-days). Multivariable analyses in the dialysis cohort revealed increased age, above-knee amputation, decreased physical status, heart failure, high preoperative white blood cell count, and low platelet count to be associated with death (P < .05; C statistic, 0.75). The only preoperative factor associated with readmission in dialysis patients was race (P = .04; C statistic, 0.58). CONCLUSIONS: Readmission or death after amputation is increased among dialysis patients. Predicting which dialysis patients are at highest risk for death is feasible, whereas predicting which will require readmission is less so. Risk factor identification may improve risk stratification, inform reimbursement policies, and allow targeted interventions to improve outcomes.

ISPD Cardiovascular and Metabolic Guidelines in Adult Peritoneal Dialysis Patients Part II - Management of Various Cardiovascular Complications.

Cardiovascular mortality has remained high in patients on peritoneal dialysis (PD) due to the high prevalence of various cardiovascular complications including coronary artery disease, left ventricular hypertrophy and dysfunction, heart failure, arrhythmia (especially atrial fibrillation), cerebrovascular disease, and peripheral arterial disease. In addition, nearly a quarter of PD patients develop sudden cardiac death as the terminal life event. Thus, it is essential to identify effective treatment that may lower cardiovascular mortality and improve survival of PD patients. The International Society for Peritoneal Dialysis (ISPD) commissioned a global workgroup in 2012 to formulate a series of recommendation statements regarding lifestyle modification, assessment and management of various cardiovascular risk factors, and management of the various cardiovascular complications to be published in 2 guideline documents. This publication forms the second part of the guideline documents and includes recommendation statements on the management of various cardiovascular complications in adult chronic PD patients. The documents are intended to serve as a global clinical practice guideline for clinicians who look after PD patients. We also define areas where evidence is clearly deficient and make suggestions for future research in each specific area.

Hypomagnesemia and Mortality in Incident Hemodialysis Patients.

BACKGROUND: In the general population, low serum magnesium levels are associated with poor outcomes and death. While limited data suggest that low baseline magnesium levels may be associated with higher mortality in hemodialysis (HD) patients, the impact of changes in magnesium levels over time is unknown. STUDY DESIGN: We examined the association of time-varying serum magnesium levels with all-cause mortality using multivariable time-varying survival models adjusted for clinical characteristics and other time-varying laboratory measures. SETTING & PARTICIPANTS: 9,359 maintenance HD patients treated in a large dialysis organization between 2007 and 2011. PREDICTOR: Time-varying serum magnesium levels across 5 magnesium increments (<1.8, 1.8-<2.0, 2.0-<2.2, 2.2-<2.4, and ≥2.4mg/dL). OUTCOME: All-cause mortality. RESULTS: 2,636 individuals died over 5 years. Time-varying serum magnesium levels < 2.0mg/dL were associated with higher mortality after adjustment for demographics and comorbid conditions, including hypertension, diabetes, and malignancies (reference: magnesium, 2.2-<2.4mg/dL): adjusted HRs for serum magnesium level < 1.8 and 1.8 to <2.0mg/dL were 1.39 (95% CI, 1.23-1.58; P<0.001) and 1.20 (95% CI, 1.06-1.36; P=0.004), respectively. Some associations were attenuated to the null after incremental adjustment for laboratory test results, particularly serum albumin. However, among patients with serum albumin measurements, low albumin level (<3.5g/dL) and magnesium level < 2.0mg/dL were associated with an additional death risk (adjusted HR, 1.17; 95% CI, 1.05-1.31; P=0.004), whereas patients with high serum albumin levels (≥3.5g/dL) exhibited low death risk (adjusted HRs of 0.53 and 0.53 [P≤0.001] for magnesium < 2.0 and ≥2.0mg/dL, respectively; reference: albumin < 3.5g/dL and magnesium ≥ 2.0mg/dL). LIMITATIONS: Causality cannot be determined, and residual confounding cannot be excluded given the observational study design. CONCLUSIONS: Lower serum magnesium levels are associated with higher mortality in HD patients, including those with hypoalbuminemia. Interventional studies are warranted to examine whether correction of hypomagnesemia ameliorates adverse outcomes in this population.

Association of plasma F2-isoprostanes and isofurans concentrations with erythropoiesis-stimulating agent resistance in maintenance hemodialysis patients.

BACKGROUND: In patients undergoing maintenance hemodialysis (HD), hyporesponsiveness to erythropoiesis stimulating agents (ESAs) is associated with adverse clinical outcomes. Systemic inflammation is highly prevalent in HD patients and is associated with ESA hyporesponsiveness. Oxidative stress is also highly prevalent in HD patients, but no previous study has determined its association with ESA response. This study assessed the association of plasma markers of oxidative stress and inflammation with ESA resistance in patients undergoing maintenance HD. METHODS: We analyzed data from 165 patients enrolled in the Provision of Antioxidant Therapy in Hemodialysis study, a randomized controlled trial evaluating antioxidant therapy in prevalent HD patients. Linear and mixed-effects regression were used to assess the association of baseline and time-averaged high sensitivity F2-isoprostanes, isofurans, C-reactive protein (hsCRP), and interleukin-6 (IL-6) with ESA resistance index (ERI), defined as the weekly weight-adjusted ESA dose divided by blood hemoglobin level. Unadjusted models as well as models adjusted for potential confounders were examined. Predicted changes in ERI per month over study follow-up among baseline biomarker quartiles were also assessed. RESULTS: Patients with time-averaged isofurans in the highest quartile had higher adjusted mean ERI compared with patients in the lowest quartile (ß = 14.9 ng/ml; 95% CI 7.70, 22.2; reference group <0.26 ng/ml). The highest quartiles of hsCRP and IL-6 were also associated with higher adjusted mean ERI (ß = 10.8 mg/l; 95% CI 3.52, 18.1 for hsCRP; ß = 10.2 pg/ml; 95% CI 2.98, 17.5 for IL-6). No significant association of F2-isoprostanes concentrations with ERI was observed. Analyses restricted to baseline exposures and ERI showed similar results. Baseline hsCRP, IL-6, and isofurans concentrations in the highest quartiles were associated with greater predicted change in ERI over study follow-up compared to the lowest quartiles (P = 0.008, P = 0.004, and P = 0.04, respectively). There was no association between baseline F2-isoprostanes quartile and change in ERI. CONCLUSIONS: In conclusion, higher concentrations of isofurans, hsCRP and IL-6, but not F2-isoprostanes, were associated with greater resistance to ESAs in prevalent HD patients. Further research is needed to test whether interventions that successfully decrease oxidative stress and inflammation in patients undergoing maintenance HD improve ESA responsiveness.

Effect of Medicare dialysis payment reform on use of erythropoiesis stimulating agents.

OBJECTIVE: In 2011, the Centers for Medicare and Medicaid Services (CMS) replaced fee-for-service reimbursement for erythropoiesis stimulating agents (ESAs) with a fixed-sum bundled payment for all dialysis-related care and pay-for-performance incentives to discourage maintaining patients' hematocrits above 36 percent. We examined the impact of the new payment policy on the use of ESAs. DATA SOURCES: CMS's Renal Information Management System. STUDY DESIGN: Regression discontinuity design assessing the use of ESAs by hematocrit level before and after the implementation of the payment policy change. DATA EXTRACTION: Secondary data from 424,163 patients receiving hemodialysis treatment between January 2009 and June 2011. PRINCIPAL FINDINGS: The introduction of bundled payments with pay-for-performance initiatives was associated with an immediate and substantial decline in the use of ESAs among patients with hematocrit >36 percent and little change in the use of ESAs among patients with hematocrit ≤36 percent. In the first two quarters of 2011, the use of ESAs during dialysis fell by about 7-9 percentage points among patients with hematocrit levels >36 percent. No statistically significant differences in ESA use were observed at the thresholds of 30 or 33 percent. CONCLUSIONS: CMS's payment reform for dialysis care reduced the use of ESAs in patients who may not benefit from these agents.

A pilot randomized crossover trial assessing the safety and short-term effects of pomegranate supplementation in hemodialysis patients.

OBJECTIVE: Oxidative stress and systemic inflammation are highly prevalent in patients undergoing maintenance hemodialysis (MHD) and are linked to excess cardiovascular risk. This study examined whether short-term supplementation with pomegranate juice and extract is safe and well tolerated by MHD patients. The secondary aim was to assess the effect of pomegranate supplementation on oxidative stress, systemic inflammation, monocyte function, and blood pressure. DESIGN: Prospective, randomized, crossover, pilot clinical trial (NCT01562340). SETTING: The study was conducted from March to October 2012 in outpatient dialysis facilities in the Seattle metropolitan area. SUBJECTS: Twenty-four patients undergoing MHD (men, 64%; mean age, 61 ± 14 years) were randomly assigned to receive pomegranate juice or extract during a 4-week intervention period. After a washout period, all patients received the alternative treatment during a second 4-week intervention period. INTERVENTION: Patients assigned to receive pomegranate juice received 100 mL of juice before each dialysis session. Patients assigned to receive pomegranate extract were given 1,050 mg of extract daily. MAIN OUTCOME MEASURES: The main outcome measures were safety and tolerability of pomegranate juice and extract. Additional secondary outcomes assessed included serum lipids, laboratory biomarkers of inflammation (C-reactive protein and interleukin 6) and oxidative stress (plasma F2 isoprostanes and isofurans), monocyte cytokine production, and predialysis blood pressure. RESULTS: Both pomegranate juice and extract were safe and well tolerated by study participants. Over the study period, neither treatment had a significant effect on lipid profiles, plasma C-reactive protein, interleukin 6, F2-isoprostane or isofuran concentrations, predialysis systolic or diastolic blood pressure nor changed the levels of monocyte cytokine production. CONCLUSIONS: Both pomegranate juice and extract are safe and well tolerated by patients undergoing MHD but do not influence markers of inflammation or oxidative stress nor affect predialysis blood pressure.

Severe vascular calcification and tumoral calcinosis in a family with hyperphosphatemia: a fibroblast growth factor 23 mutation identified by exome sequencing.

BACKGROUND: Tumoral calcinosis is an autosomal recessive disorder characterized by ectopic calcification and hyperphosphatemia. METHODS: We describe a family with tumoral calcinosis requiring amputations. The predominant metabolic anomaly identified in three affected family members was hyperphosphatemia. Biochemical and phenotypic analysis of 13 kindred members, together with exome analysis of 6 members, was performed. RESULTS: We identified a novel Q67K mutation in fibroblast growth factor 23 (FGF23), segregating with a null (deletion) allele on the other FGF23 homologue in three affected members. Affected siblings had high circulating plasma C-terminal FGF23 levels, but undetectable intact FGF23 or N-terminal FGF23, leading to loss of FGF23 function. CONCLUSIONS: This suggests that in human, as in experimental models, severe prolonged hyperphosphatemia may be sufficient to produce bone differentiation proteins in vascular cells, and vascular calcification severe enough to require amputation. Genetic modifiers may contribute to the phenotypic variation within and between families.

A palliative approach to dialysis care: a patient-centered transition to the end of life.

As the importance of providing patient-centered palliative care for patients with advanced illnesses gains attention, standard dialysis delivery may be inconsistent with the goals of care for many patients with ESRD. Many dialysis patients with life expectancy of <1 year may desire a palliative approach to dialysis care, which focuses on aligning patient treatment with patients' informed preferences. This commentary elucidates what comprises a palliative approach to dialysis care and describes its potential and appropriate use. It also reviews the barriers to integrating such an approach into the current clinical paradigm of care and existing infrastructure and outlines system-level changes needed to accommodate such an approach.

Medication reconciliation and therapy management in dialysis-dependent patients: need for a systematic approach.

Patients with ESRD undergoing dialysis have highly complex medication regimens and disproportionately higher total cost of care compared with the general Medicare population. As shown by several studies, dialysis-dependent patients are at especially high risk for medication-related problems. Providing medication reconciliation and therapy management services is critically important to avoid costs associated with medication-related problems, such as adverse drug events and hospitalizations in the ESRD population. The Medicare Modernization Act of 2003 included an unfunded mandate stipulating that medication therapy management be offered to high-risk patients enrolled in Medicare Part D. Medication management services are distinct from the dispensing of medications and involve a complete medication review for all disease states. The dialysis facility is a logical coordination center for medication management services, like medication therapy management, and it is likely the first health care facility that a patient will present to after a care transition. A dedicated and adequately trained clinician, such as a pharmacist, is needed to provide consistent, high-quality medication management services. Medication reconciliation and medication management services that could consistently and systematically identify and resolve medication-related problems would be likely to improve ESRD patient outcomes and reduce total cost of care. Herein, this work provides a review of available evidence and recommendations for optimal delivery of medication management services to ESRD patients in a dialysis facility-centered model.

Mortality associated with dose response of erythropoiesis-stimulating agents in hemodialysis versus peritoneal dialysis patients.

BACKGROUND: Several studies have shown an association between erythropoietin-stimulating agent (ESA) responsiveness and mortality in chronic kidney disease (CKD) patients. In our present study, we examined the association between prescribed ESA dose and mortality in peritoneal dialysis (PD) and hemodialysis (HD) patients. We hypothesized that PD patients received lower ESA dose for the same achieved hemoglobin compared to HD patients and that ESA dose-mortality associations were different between PD and HD patients. METHODS: We compared the prescribed doses of ESA between 139,103 HD and 10,527 PD patients treated in DaVita dialysis clinics from 7/2001 through 6/2006 using adjusted Poisson regression and examined mortality-predictability of prescribed ESA dose and ESA responsiveness index (ESA/hemoglobin) in PD and HD with follow-up through 6/2007 using Cox regression models. RESULTS: Poisson adjusted ratio of ESA dose of HD to PD was 3.6 (95% CI 3.5-3.7). In PD patients, adjusted all-cause death hazard ratios (HR) for ESA doses of 3,000-5,999, 6,000-8,999 and ≥9,000 U/week (reference <3,000 U/week) were 0.97 (0.87-1.07), 0.85 (0.76-0.95) and 1.08 (0.98-1.18), respectively; whereas in HD patients across commensurate ESA dose increments of 10,000-19,999, 20,000-29,999 and ≥30,000 U/week (reference <10,000 U/week) were 1.14 (1.11-1.17), 1.54 (1.50-1.58) and 2.15 (2.10-2.21), respectively. In PD and HD patients, the adjusted death HR of the 4th to 1st quartile of ESA responsiveness index were 1.14 (1.04-1.26) and 2.37 (2.31-2.43), respectively. CONCLUSIONS: Between 2001 and 2006, most PD patients received substantially lower ESA dose for same achieved hemoglobin levels, and low ESA responsiveness was associated with higher mortality in both HD and PD patients.

Association of hemoglobin and survival in peritoneal dialysis patients.

BACKGROUND AND OBJECTIVES: Interventional trials and some observational studies show target hemoglobin >13 g/dl to be associated with higher mortality in erythropoiesis-stimulating agent-treated (ESA-treated) hemodialysis patients; data for peritoneal dialysis (PD) patients are limited. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We tested our hypothesis that higher and lower achieved hemoglobin levels are associated with increased mortality in 9269 ESA-treated PD patients from all DaVita dialysis clinics during the time period July 2001 through June 2006 followed through June 2007 using a time-dependent analysis. RESULTS: Lower hemoglobin was associated with significantly higher all-cause mortality in ESA-treated PD patients: with hemoglobin of 11.0 to <12.0 g/dl as reference, the time-dependent adjusted death hazard ratios for hemoglobin levels of 10.0 to <11.0, 9.0 to <10.0, and ≤9.0 g/dl were 1.12 (1.00 to 1.24), 1.30 (1.12 to 1.50), and 1.38 (1.14 to 1.67), respectively. The time-dependent adjusted hazard ratios for cardiovascular death with hemoglobin levels of 10.0 to <11.0, 9.0 to <10.0, and ≤9.0 g/dl were 1.11 (0.93 to 1.32), 1.37 (1.09 to 1.72), and 1.12 (0.79 to 1.57), respectively. The same trend for association of lower hemoglobin level with higher mortality was seen in African-American and non-African American men and women. In contrast, there was no association between higher achieved hemoglobin and all-cause or cardiovascular mortality in ESA-treated PD patients. CONCLUSIONS: Lower, but not higher, achieved hemoglobin is associated with higher mortality in ESA-treated PD patients. Randomized controlled trials are needed to examine the target hemoglobin level with lowest mortality in PD patients.

Prevalence and prognostic significance of renal artery calcification in patients with diabetes and proteinuria.

BACKGROUND AND OBJECTIVES: Vascular calcification is common and severe in chronic kidney disease. Because the consequences of calcification may differ by vascular beds, we sought to test the hypothesis that patients who have diabetes with proteinuria and have significant renal artery calcification (RAC) have a higher risk for progression to ESRD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Using electron-beam computed tomography, RAC was computed as the sum of Agatston scores at each of the two renal ostia and renal arteries. Time-to-event analysis was conducted to compare the risk in individuals with or without significant RAC (total score >10). RESULTS: Of 172 patients with type 2 diabetes and overt proteinuria studied (estimated GFR 56 ± 25 ml/min per 1.73 m(2)), significant RAC was present in 31%. In 33 ± 21 months, 41 progressed to ESRD and 65 reached a composite outcome (ESRD or death). Serum phosphorus was a significant predictor of progression to ESRD but was replaced by the significant RAC in multivariate models that included the latter. Individuals with significant RAC had a higher risk for reaching the composite outcome. In contrast, there was no association between coronary artery calcification scores and progression to ESRD. CONCLUSIONS: Significant RAC was an independent predictor of progression to ESRD as well as reaching the composite outcome. Understanding the pathogenesis of RAC would allow determination of whether this risk is potentially modifiable.

Coronary artery calcification and mortality in diabetic patients with proteinuria.

Vascular calcification is one of the mechanisms mediating the higher mortality risk associated with the hyperphosphatemia of chronic kidney disease. Though common, and often severe in non-dialyzed proteinuric diabetics, there are no studies on the prognostic significance of coronary artery calcification in early stage type 2 diabetic nephropathy. Here we determine this significance in 225 proteinuric diabetic patients (mean age 57 years, mean estimated glomerular filtration rate (eGFR) 52 ml/min per 1.73 m(2) and a median urine protein-creatinine ratio of 2.7). Coronary artery calcification, measured by electron beam computed tomography, was diagnosed in 86% of the patients, the severity of which correlated with older age, male gender, and white ethnicity. However, no association was found between eGFR, serum calcium, phosphorus, parathyroid hormone, or 25-hydroxy vitamin D. Over an average follow-up of 39 months, 54 patients died. A graded relationship between the severity of calcification and all-cause mortality was consistently demonstrated on both univariate and multivariate analyses. Patients in the highest quartile of calcification score had a 2.5-fold higher risk for death. Our results show the severity of coronary artery calcification early in the course of chronic kidney disease is an independent predictor of all-cause mortality. Additional studies need to determine whether altering the natural history of coronary artery calcification in early chronic kidney disease prolongs survival.

Correction of metabolic acidosis to ameliorate wasting in chronic kidney disease: goals and strategies.

Metabolic acidosis is an important cause of protein-energy wasting, commonly observed in chronic kidney disease (CKD). This wasting is, in part, a result of the imbalance between protein degradation and synthesis induced by metabolic acidosis. The increase in protein degradation seen with metabolic acidosis is largely secondary to increased activities of the adenosine triphosphate-dependent, ubiquitin-proteasome system and branched-chain ketoacid dehydrogenase. Studies consistently have shown increased protein degradation with lower serum bicarbonate levels and/or arterial pH; however, the evidence for the anti-anabolic effects of metabolic acidosis is less consistent. In contrast to these metabolic studies, many cross-sectional studies have shown a direct relationship between the severity of metabolic acidosis and the adequacy of nutritional status in CKD patients. Moreover, lower serum bicarbonate levels have been associated with better survival in some epidemiologic studies of patients undergoing maintenance hemodialysis. It is likely that these relationships are confounded by the direct association of dietary protein intakes with metabolic acidosis-controlling the survival data for measures of dietary protein intakes, malnutrition, and inflammation shows a rather steep increase in the risk of death with lower serum bicarbonate levels. Two randomized controlled studies have shown that correction of metabolic acidosis is associated with reduction in risk for hospitalization in chronic peritoneal dialysis patients; the studies in maintenance hemodialysis patients have been small and inconsistent. For now, metabolic studies and data from clinical trials lend support to the recommendations made by the Nutrition Workgroup of the Kidney Disease Outcomes Quality Initiative to maintain serum bicarbonate levels of 22 mEq/L or greater in all CKD patients. Limited data suggest that a higher serum bicarbonate level (around 24 mEq/L) may be even more beneficial, particularly in chronic peritoneal dialysis patients.

Nodular glomerulosclerosis in a patient with metabolic syndrome without diabetes.

BACKGROUND: A 56-year-old man with previously treated hepatitis C presented to a nephrology clinic with hypertension, proteinuria and declining renal function. His medical history included previous smoking, prior hip replacements with prolonged osteomyelitis, and left renal artery stenosis. Diabetes mellitus was ruled out by a 2 h oral glucose tolerance test and two glycated hemoglobin (HbA 1c) measurements. A renal biopsy showed evidence of nodular glomerulosclerosis. INVESTIGATIONS: Physical examination, renal biopsy, and urine and blood analyses including an oral glucose tolerance test. DIAGNOSIS: Nodular glomerulosclerosis and metabolic syndrome. MANAGEMENT: Patients with metabolic syndrome should be screened for evidence of renal injury since clinical and histological nodular glomerulosclerosis identical to diabetic nephropathy can occur in this setting. Early diagnosis and treatment of albuminuria could alter the course of disease progression.