Itzchak Slotki

Iron management in chronic kidney disease: conclusions from a “Kidney Disease: Improving Global Outcomes” (KDIGO) Controversies Conference

Before the introduction of erythropoiesis-stimulating agents (ESAs) in 1989, repeated transfusions given to patients with end-stage renal disease caused iron overload, and the need for supplemental iron was rare. However, with the widespread introduction of ESAs, it was recognized that supplemental iron was necessary to optimize hemoglobin response and allow reduction of the ESA dose for economic reasons and recent concerns about ESA safety. Iron supplementation was also found to be more efficacious via intravenous compared to oral administration, and the use of intravenous iron has escalated in recent years. The safety of various iron compounds has been of theoretical concern due to their potential to induce iron overload, oxidative stress, hypersensitivity reactions, and a permissive environment for infectious processes. Therefore, an expert group was convened to assess the benefits and risks of parenteral iron, and to provide strategies for its optimal use while mitigating the risk for acute reactions and other adverse effects.

Effect of eplerenone on blood pressure and the renin-angiotensin-aldosterone system in oligo-anuric chronic hemodialysis patients - a pilot study.

INTRODUCTION AND AIMS Recent studies have suggested that aldosterone has many effects in addition to its ability to cause the kidney to retain sodium. To test the hypothesis that aldosterone can cause hypertension in a manner that does not involve renal sodium retention, we administered eplerenone, a specific aldosterone antagonist, to oligo-anuric chronic hemodialysis patients who had HTN. METHODS 220 chronic hemodialysis patients underwent initial screening. Of these, 8 patients were followed for 8 weeks and their blood pressure, weight, plasma potassium, aldosterone levels and plasma renin activity were recorded. After a 4 week run in period, each patient received eplerenone 25 mg twice daily for another 4 weeks. RESULTS Administration of eplerenone for 4 weeks decreased predialysis systolic blood pressure from 166 ± 14 to 153 ± 10 mmHg (p < 0.05). Eplerenone had no effect on diastolic blood pressure, potassium, predialysis weight, intradialytic weight gain, plasma aldosterone or PRA. CONCLUSION Eplerenone significantly reduces systolic blood pressure in oligo-anuric hypertensive hemodialysis patients without effect on plasma aldosterone concentrations or plasma renin activity. Plasma potassium increases minimally after 4 weeks of therapy, a finding that raises some concern for long-term eplerenone use in chronic hemodialysis.

The Agreement between Auscultation and Lung Ultrasound in Hemodialysis Patients: The LUST Study

BACKGROUND AND OBJECTIVES Accumulation of fluid in the lung is the most concerning sequela of volume expansion in patients with ESRD. Lung auscultation is recommended to detect and monitor pulmonary congestion, but its reliability in ESRD is unknown. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS In a subproject of the ongoing Lung Water by Ultra-Sound Guided Treatment to Prevent Death and Cardiovascular Complications in High Risk ESRD Patients with Cardiomyopathy Trial, we compared a lung ultrasound-guided ultrafiltration prescription policy versus standard care in high-risk patients on hemodialysis. The reliability of peripheral edema was tested as well. This study was on the basis of 1106 pre- and postdialysis lung ultrasound studies (in 79 patients) simultaneous with standardized lung auscultation (crackles at the lung bases) and quantification of peripheral edema. RESULTS Lung congestion by crackles, edema, or a combination thereof poorly reflected the severity of congestion as detected by ultrasound B lines in various analyses, including standard regression analysis weighting for repeated measures in individual patients (shared variance of 12% and 4% for crackles and edema, respectively) and κ-statistics (κ ranging from 0.00 to 0.16). In general, auscultation had very low discriminatory power for the diagnosis of mild (area under the receiver operating curve =0.61), moderate (area under the receiver operating curve =0.65), and severe (area under the receiver operating curve =0.68) lung congestion, and the same was true for peripheral edema (receiver operating curve =0.56 or lower) and the combination of the two physical signs. CONCLUSIONS Lung crackles, either alone or combined with peripheral edema, very poorly reflect interstitial lung edema in patients with ESRD. These findings reinforce the rationale underlying the Lung Water by Ultra-Sound Guided Treatment to Prevent Death and Cardiovascular Complications in High Risk ESRD Patients with Cardiomyopathy Trial, a trial adopting ultrasound B lines as an instrument to guide interventions aimed at mitigating lung congestion in high-risk patients on hemodialysis.

Use of Pregabalin in the Management of Chronic Uremic Pruritus

CONTEXT Uremic pruritus (UP) affects many patients suffering from chronic kidney disease (CKD) and has a negative impact on quality of life and survival. It has become increasingly evident that central transmission and sensitization processes similar to those observed in chronic pain are important mechanisms of pruritus. OBJECTIVES To test the potential role of pregabalin in reducing the intensity of UP in CKD patients. METHODS We prospectively collected data on CKD patients who suffered from severe intractable pruritus. Patients were asked to record the intensity of pruritus on a visual analogue scale. RESULTS Twelve patients were studied. The average pretreatment pruritus score was 9.7 ± 0.9 and decreased to 3.7 ± 2.35, 3.2 ± 1.75, and 3 ± 1.5 after one, four, and 24 weeks of treatment, respectively (P < 0.05). The positive effect of pregabalin was demonstrated during the first week of therapy in six patients. Most patients required 25mg a day. Pregabalin was well tolerated, with somnolence and dizziness developing in two patients. CONCLUSION We demonstrated dramatic improvement of long-standing UP after the initiation of pregabalin. We suggest that pregabalin can be used safely in CKD but careful titration of the dose is required to obtain an optimal response and minimize the possible adverse effects.

Neutrophil Gelatinase-Associated Lipocalin as a Predictor of Complications and Mortality in Patients Undergoing Non-Cardiac Major Surgery

Introduction: We tested the hypothesis that urinary and serum neutrophil gelatinase-associated lipocalins (NGAL) early after non-cardiac major surgery predict postoperative acute kidney injury (AKI), complications and mortality. Methods: We studied 74 patients undergoing orthopedic, vascular and abdominal surgery lasting ≧2 h. NGAL was measured in preoperative, as well as 2- and 6-hour postoperative samples. The primary outcome was AKI. Secondary outcome was postoperative infection and death. Results: 10 patients (13.5%) developed AKI, 19 (26%) reached secondary outcomes, of whom 5 (7%) died. Serum NGAL was significantly higher in patients with diabetes and chronic kidney disease (CKD). No significant correlation was detected between serum or urine NGAL and subsequent development of AKI. Urine NGAL at 6 h and serum NGAL at 2 and 6 h were strongly correlated with postoperative infection and death (p = 0.004, p = 0.013 and p = 0.001, respectively). Conclusions: Our data suggest that in the general surgical population, NGAL could serve as a potent early biomarker for postoperative infection, and that the presence of CKD and diabetes mellitus is associated with higher levels of NGAL and may influence its predictive value.

Enoxaparin dosage adjustment in patients with severe renal failure: antifactor xa concentrations and safety.

Study Objective. To evaluate the safety and efficacy by measuring antifactor Xa levels, of enoxaparin 1 mg/kg subcutaneously once every 24 hours in patients with severe renal failure.

Mild hyponatremia is associated with functional and cognitive decline in chronic hemodialysis patients.

BACKGROUND A high incidence and adverse outcomes of cognitive impairment in dialysis patients have recently become recognized. Classical risk factors, uremia, anemia, metabolic disturbances, and hemodynamic instability during dialysis accelerate vascular cognitive impairment. AIMS To evaluate laboratory factors that influence cognitive function in consecutive chronic hemodialysis (CHD) patients over a 2-year period. METHODS Between June 2010 and June 2011 we conducted a prospective, single-center trial that evaluated cognitive function in adult chronic hemodialysis (HD) patients. A battery of cognitive function tests was used: modified mini mental state (3MS), trailmaking tests A (trails A) and B (trails B). The 15-item geriatric depression scale (GDS) and the activities of daily living (ADL) test were used, respectively, for assessing symptoms of depression and global functional status. All tests were performed twice at yearly intervals in consecutive HD patients. Global cognitive impairment was defined as a 3MS < 80 and impaired executive function as a Trails A performance time > 75 seconds and Trails B > 180 seconds. RESULTS 56 chronic HD patients aged 65.00 ± 17.8 years were studied; 57% of them were males. 86% suffered from hypertension (HTN), 40% were diabetics and ~ 1/3 had ischemic heart disease, congestive heart failure (CHF), and dyslipidemia. Average plasma calcium, phosphorus, and PTH were within the recommended range. No features suggestive of malnutrition, severe anemia, inflammation, or inadequate dialysis were detected. 14 patients (24%) had mild chronic hyponatremia (Na ranges 131 - 135 meq/L). Significant disturbances in global cognitive and executive function were detected in the study patients. In 2010, 50% had 3MS < 80, 71% and 91% had severely impaired trails A and B tests (respectively), 54% had symptoms of depression and 50% suffered from impaired ADL. Retesting of the survivors in 2011 revealed increased prevalence of cognitive and functional declines along with worsening depression scoring. Univariate analysis demonstrated significant correlation between cognitive decline and age, female gender, education, poor executive and functional status, inadequate dialysis dose (Kt/V < 1.2, p = 0.023), high plasma phosphorus levels (p > 6 mg/dL, p = 0.034), and hyponatremia (Na < 135 mEq/L, p = 0.001). Multivariate stepwise logistic regression analysis revealed statistically significant associations between hyponatremia and impaired ADL (p = 0.043) and impaired ADL and mortality (p = 0.002). CONCLUSIONS A high prevalence of global cognitive and executive impairment was detected in our hemodialysis cohort. We found an association between mild chronic hyponatremia and impaired functional status. Whether treatments aimed at modifying hyponatremia could mitigate functional decline or mortality remains to be elucidated.

Acute Renal Failure in the Elderly Treated by One-Time Peritoneal Dialysis

To determine the factors affecting outcome of acute renal failure (ARF) in the elderly, we retrospectively studied 44 patients over the age of 65 who had undergone acute peritoneal dialysis. Thirteen patients (29%) survived 2 months or longer after dialysis treatment (“survivors”). Thirty‐one patients (71%) died within this period (“nonsurvivors”). The main factor distinguishing survivors was the frequency of sepsis (none of 13 survivors vs 17 of 31 nonsurvivors). Preexisting malignancy and total number of acute insults to renal function were signficantly less frequent, and immediate clinical and biochemical outcome of dialysis significantly better in survivors. The overall complication rate of dialysis was high (31 of 44 patients), but was significantly lower in survivors. Acute peritoneal dialysis is a useful procedure in the management of ARF in the elderly. However, we suggest that elderly patients in whom sepsis is a contributory factor to the development of ARF do not benefit from peritoneal dialysis therapy.

Weighing the evidence: obesity, metabolic syndrome, and the risk of chronic kidney disease

Evaluating effect of obesity per se and the metabolic syndrome as a whole on the risk of developing chronic kidney disease (CKD) is key factor in developing a comprehensive public health approach to reduce morbidity and healthcare resource consumption. While there is considerable evidence to support increased risk of CKD in obese individuals and those with the metabolic syndrome, this relationship may be influenced by several factors. These include confounding variables, anthropometric measures, the end-point studied (e.g. development of early stage CKD, progression to end-stage renal disease or mortality), and the complex interrelationship between the various components of the metabolic syndrome. The study by Cao et al. in the current issue of BMC nephrology examines the impact of obesity on CKD risk in people with and without co-existing metabolic syndrome. The findings of this large, prospective study illustrate a clear correlation between increased body mass index (BMI) and risk of CKD regardless of whether or not there is co-existing metabolic syndrome. While the presence of the metabolic syndrome confers some additional risk of CKD in overweight and obese individuals, its effect is relatively modest and accounts for only 26 % of the risk associated with increased BMI. We discuss the complex epidemiological and methodological context in which these important findings should be understood, and their implications for public health and for individual patients and healthcare practitioners.

Preoperative Hemoglobin and Outcomes in Patients with CKD Undergoing Cardiac Surgery

BACKGROUND AND OBJECTIVES Preoperative anemia adversely affects outcomes of cardiothoracic surgery. However, in patients with CKD, treating anemia to a target of normal hemoglobin has been associated with increased risk of adverse cardiac and cerebrovascular events. We investigated the association between preoperative hemoglobin and outcomes of cardiac surgery in patients with CKD and assessed whether there was a level of preoperative hemoglobin below which the incidence of adverse surgical outcomes increases. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS This prospective observational study included adult patients with CKD stages 3-5 (eGFR<60 ml/min per 1.73 m(2)) undergoing cardiac surgery from February 2000 to January 2010. Patients were classified into four groups stratified by preoperative hemoglobin level: <10, 10-11.9, 12-13.9, and ≥ 14 g/dl. The outcomes were postoperative AKI requiring dialysis, sepsis, cerebrovascular accident, and mortality. RESULTS In total, 788 patients with a mean eGFR of 43.5 ± 3.7 ml/min per 1.73 m(2) were evaluated, of whom 22.5% had preoperative hemoglobin within the normal range (men: 14-18 g/dl; women: 12-16 g/dl). Univariate analysis revealed an inverse relationship between the incidence of all adverse postoperative outcomes and hemoglobin level. Using hemoglobin as a continuous variable, multivariate logistic regression analysis showed a proportionally greater frequency of all adverse postoperative outcomes per 1-g/dl decrement of preoperative hemoglobin (mortality: odds ratio, 1.38; 95% confidence interval, 1.23 to 1.57; P<0.001; sepsis: odds ratio, 1.31; 95% confidence interval, 1.14 to 1.49; P<0.001; cerebrovascular accident: odds ratio, 1.31; 95% confidence interval, 1.00 to 1.67; P=0.03; postoperative hemodialysis: odds ratio, 1.38; 95% confidence interval, 1.11 to 1.75; P<0.01). Moreover, preoperative hemoglobin<12 g/dl was an independent risk factor for postoperative mortality (odds ratio, 2.6; 95% confidence interval, 1.1 to 7.3; P=0.04). CONCLUSIONS Similar to the general population, preoperative anemia is associated with adverse postoperative outcomes in patients with CKD. Whether outcomes could be improved by therapeutically targeting higher preoperative hemoglobin levels before cardiac surgery in patients with underlying CKD remains to be determined.