Amir Kazory

Anemia: The Point of Convergence or Divergence for Kidney Disease and Heart Failure?

Cardiorenal anemia syndrome refers to the simultaneous presence of anemia, heart failure (HF), and chronic kidney disease (CKD) that forms a pathologic triangle with an adverse impact on morbidity and mortality. The reciprocal relationships among these 3 components have been the subject of a number of trials with inconsistent and sometimes paradoxic results. In this paper, the pathophysiologic concepts underlying interactions among these 3 conditions are discussed. Then, the similarities and dissimilarities of the relationships between anemia and either HF or CKD are considered; explanations are provided for differences in the results of the currently available studies. Erythropoietin-stimulating agent protocols are usually based on the results of studies designed for the CKD population, and upper hemoglobin target levels are chosen to avoid cardiovascular complications. It is not yet clear whether those renal guidelines are optimal for patients with HF, especially because those patients may have reversible components of kidney dysfunction, both HF and renal parameters improving with anemia correction. We review these issues and suggest a pragmatic approach to the care of patients with HF until such time that controlled trials establish definitive anemia treatment goals that are dynamic and disease specific, rather than those that adopt a more simplistic hemoglobin-specific approach.

Contemporary Trends in the Pharmacological and Extracorporeal Management of Heart Failure A Nephrologic Perspective

Heart failure and chronic kidney disease share a number of risk factors and pathophysiological pathways. These 2 pathological processes coexist in large numbers of patients. Whereas the presence of chronic kidney disease in patients with heart failure adversely influences their survival, cardiovascular disease is the major cause of mortality in individuals with chronic kidney disease. The management of heart failure by cardiologists has recently expanded from pharmacological treatment to extracorporeal strategies; the interaction between (and concurrent use of) these approaches traditionally has been part of nephrology care and training. The purpose of this review is to explore these management strategies from a nephrologic standpoint and cover the pathophysiology of diuretic resistance, new pharmaceutical strategies to induce natriuresis or aquaresis, and the physiological basis and theoretical advantages of fluid removal by nontraditional peritoneal or hemofiltration approaches. This review also focuses on the technical features, safety, and potential risks of dedicated ultrafiltration devices that do not require dialysis staff or facilities and that are now readily available to nonnephrologists.

Metabolic syndrome and atherosclerotic events in renal transplant recipients.

Background. Metabolic syndrome (MS) is a known cardiovascular risk factor in the general population. We explored the influence of MS on the occurrence of atherosclerotic events (AEs) after renal transplantation. Methods. Three hundred thirty-seven renal transplant recipients were included in the study. Various parameters (e.g., anthropometric and biological) were measured 1 year after transplant. Results. One year after transplant, 32% of the study population met criteria for MS. Older age, male gender, pretransplant high body mass index, and an increase in body mass index ≥5% in the first year after transplant were predictive factors for development of MS at 1 year after transplant. Forty-two patients (12.4%) experienced AEs during the 8 years of follow-up. The cumulated incidence of AEs was greater in patients with MS compared with others without MS (25% vs. 7%; P<0.001). In multivariate analysis, patients with MS at 1 year after transplant had an increased risk of AE (hazard ratio 3.40, 95% confidence interval 1.58−7.32, P=0.002). Older age, low creatinine clearance, high C-reactive protein level, and a past history of cardiovascular disease were other independent risk factors for AE. Conclusions. Similar to the general population, MS is an independent risk factor for AE after renal transplantation. Relevant preventive measures targeting different aspects of MS would then have a potential impact on prevalence of AE in this population.

Pretransplant Serum Vitamin D Levels and Risk of Cancer After Renal Transplantation

Background. Serum levels of 25-OH-D3 inversely correlate with the incidence of various types of cancers in the general population. Because risk factors and incidence of cancer in renal transplant recipients (RTRs) are different from the general population, this study was designed to determine whether pretransplant 25-OH-D3 levels could be predictive of cancer risk in RTRs. Methods. Pretransplant 25-OH-D3 levels were reviewed in 363 consecutive RTRs. The impact of 25-OH-D3 levels on the development of cancer was then analyzed with respect to other known risk factors. Results. One hundred twenty-four patients (34.2%) showed vitamin D deficiency, 185 (51%) vitamin D insufficiency, and 54 (14.8%) with normal vitamin D levels. Thirty-two cancers (8.8%) occurred in 32 patients. A higher incidence of cancer was observed in patients with vitamin D deficiency (13.7% vs. 7% for patients with vitamin D insufficiency [P=0.068] and 3.7% for those with normal vitamin D levels [P=0.007]). 25-OH-D3 levels were lower in patients who developed cancer after transplantation (13.7±6 vs. 18.3±17.8 ng/mL, P=0.022). Age (hazard ratio, 1.06; 95% confidence interval, 1.02–1.11, for each 1 year increase; P=0.009) and low 25-OH-D3 levels (hazard ratio, 1.12; 95% confidence interval, 1.04–1.23, for every 1 ng/mL decrease; P=0.021) were independent risk factors for development of cancer. Conclusion. Pretransplant level of 25-OH-D3 is an important determinant for subsequent development of cancer after transplantation. Future studies should examine whether 25-OH-D3 supplementation can effectively decrease the incidence of cancer in RTRs.

24‐Hour Blood Pressure Monitoring in the Evaluation of Supine Hypertension and Orthostatic Hypotension

The presence of orthostatic hypotension has been shown to be a significant, independent predictor of all‐cause mortality. Systolic and diastolic orthostatic hypotension, reversal of the circadian pattern, and postprandial hypotension are some of the hemodynamic factors that may contribute to the increased mortality seen in patients with orthostatic hypotension. The high variability of blood pressure in orthostatic hypotension cannot usually be adequately assessed by a one‐time measurement. In this group of patients, 24‐hour ambulatory blood pressure monitoring may be more useful.

Acquired hypercoagulable state in renal transplant recipients.

Stable renal transplant recipients manifest a chronic hypercoagulable state with an increased risk of thromboembolic complications, which appears to be multifactorial. While this group of patients could present the known risk factors for thromboembolism in the general population (e.g. diabetes, cancer, pregnancy), they may also suffer from other situations which are mostly related to transplantation and are consequently specific to them. Here, we review briefly the clinical aspects and controversies of the most important of these factors including immunosuppressive agents, antiphospholipid antibodies, hyper-homocysteinemia, pre-transplant dialysis modality, and post-transplant erythrocytosis. In addition, other more recent topics including hypercysteinemia, recurrent proteinuria, and acute CMV infection are discussed.

Synthetic marijuana and acute kidney injury: an unforeseen association

Synthetic cannabinoids (SCs) have emerged as drugs of abuse with increasing popularity among young adults. The potential renal complication related to the abuse of SC was not recognized until recently. Here, we present a case of severe acute kidney injury (AKI) that developed after inhalation of SC in an otherwise healthy young patient. A kidney biopsy revealed severe acute tubular necrosis, and supportive management resulted in the recovery of the kidney function. Herein, we briefly summarize the only two previous reports (a total of 21 cases) on the association between SC abuse and renal dysfunction and identify the common aspects in all observations.

Peritoneal Dialysis Reduces the Number of Hospitalization Days in Heart Failure Patients Refractory to Diuretics

♦ Background: Previous small studies have reported favorable results of peritoneal dialysis (PD) in the setting of chronic refractory heart failure (CRHF). We evaluated the impact of PD in a larger cohort of patients with CHRF where end-stage renal disease was excluded. ♦ Methods: All patients who received PD therapy for CRHF between January 1995 and December 2010 in two medical centers in France were included in this retrospective study. Baseline characteristics were compared with clinical parameters during the first year after initiation of PD. Mortality, safety, and sustainability of PD were also analyzed. ♦ Results: The 126 patients included had a mean age of 72 ± 11 years and an estimated glomerular filtration rate of 33.5 ± 15.1 mL/min/1.73 m2. Mean time on PD was 16 ± 16.6 months. During the first year, patients with a left ventricular ejection fraction (LVEF) of 30% or less experienced improvement in cardiac function (30% ± 10% vs 20% ± 6%, p < 0.0001). We observed a significant reduction in the number of days of hospitalization for acute decompensated heart failure after PD initiation (3.3 ± 2.6 days/patient-month vs 0.3 ± 0.5 days/patient-month, p < 0.0001). One-year mortality was 42%. ♦ Conclusions: In CRHF, PD significantly reduces the number of days of hospitalization for acute heart failure. Improved LVEF may have led to the comparatively good 1-year survival in this cohort.

Ultrafiltration for decompensated heart failure: renal implications

The negative prognostic impact of worsening renal function in patients with decompensated heart failure has been widely recognised. As diuretics are thought to contribute to deterioration of kidney function in this setting, attempts have been made to either spare or suppress the diuretic-related pathophysiological mechanisms involved in this phenomenon. In this regard, extracorporeal ultrafiltration represents a novel therapy for patients with heart failure, lacking the adverse impacts of diuretics on kidney function (eg, activation of tubuloglomerular feedback). Consequently, besides its other positive clinical outcomes, there has been much hope for ultrafiltration therapy to play a protective role against negative effects of diuretics in patients with decompensated heart failure. However, the potential biological advantage has not been confirmed by clinical studies; currently available data from recent clinical trials have so far failed to demonstrate such expected positive results possibly due to counterbalance of the potential negative effects and other not well-known mechanisms. This paper briefly reviews the relevant pathophysiological mechanisms as well as existing evidence in this area and emphasises on the need for further studies specifically designed to explore the impact of ultrafiltration on kidney function in patients with decompensated heart failure.

Cardiorenal Syndrome: Ultrafiltration Therapy for Heart Failure—Trials and Tribulations

Heart failure remains the leading cause of hospitalization in older patients and is considered a growing public health problem with a significant financial burden on the health care system. The suboptimal efficacy and safety profile of diuretic-based therapeutic regimens coupled with unsatisfactory results of the studies on novel pharmacologic agents have positioned ultrafiltration on the forefront as an appealing therapeutic option for patients with acute decompensated heart failure (ADHF). In recent years, substantial interest in the use of ultrafiltration has been generated due to the advent of dedicated portable devices and promising results of trials focusing both on mechanistic and clinical aspects of this therapeutic modality. This article briefly reviews the proposed benefits of ultrafiltration therapy in the setting of ADHF and summarizes the major findings of the currently available studies in this field. The results of more recent trials on cardiorenal syndrome that present a counterpoint to previous observations and highlight certain limitations of ultrafiltration therapy are then discussed, followed by identification of major challenges and unanswered questions that could potentially hinder its more widespread use. Future studies are warranted to shed light on less well characterized aspects of ultrafiltration therapy and to further define its role in ADHF and cardiorenal syndrome.