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Journal: American journal of nephrology

26

Background: Studies on benefits of intravenous iron therapy among hemodialysis patients with functional iron deficiency anemia have shown conflicting results. We conducted a meta-analysis to assess the efficacy and safety of intravenous iron in this subset of patients. Methods: We searched MEDLINE (through December 2012), the Cochrane Central Register of Controlled Trials and ClinicalTrials.gov for single-arm studies and randomized controlled trials (RCT) that examined the effect of intravenous iron for functional iron deficiency anemia in hemodialysis patients on anemia parameters and markers of oxidative stress and inflammation. Studies of absolute iron deficiency were excluded. Random-effect model meta-analyses were used to compute changes in outcomes of interest. Results: We identified 34 studies (2,658 patients), representing 24 single-arm studies, and 10 parallel-arm RCT. In the analyses of the study arms, intravenous iron therapy resulted in a significant increase in hemoglobin, serum ferritin, transferrin saturation rate, serum iron, reticulocyte hemoglobin content as well as a significant decrease in the percentage of hypochromic erythrocytes and erythropoietin dose. There were significant increases in plasma malonyldialdehyde level and thiobarbituric acid-reactive substances, and a decrease in neutrophil respiratory burst. The analyses of the RCT revealed less robust net changes in these parameters, and there was no increased risk of adverse events including infections, cardiac events and mortality. Conclusions: Intravenous iron therapy for functional iron deficiency anemia in hemodialysis patients improves anemia parameters but exerts some effects on markers of oxidative stress that are of unclear clinical significance. The long-term safety and efficacy of this treatment strategy requires further study. © 2014 S. Karger AG, Basel.

Concepts: Hemoglobin, Iron, Randomized controlled trial, Anemia, Iron deficiency anemia, Transferrin, Iron deficiency, Serum iron

26

Obesity impacts many inter-related, and sometimes conflicting, considerations for transplant practice. In this article, we describe an approach for applying available data on the importance of body composition to the kidney transplant population that separates implications for candidate selection, risk stratification among selected candidates, and interventions to optimize health of the individual. Transplant recipients with obesity defined by elevated body mass index (BMI) have been shown in many (but not all) studies to experience an array of adverse outcomes more commonly than normal-weight transplant recipients, including wound infections, delayed graft function, graft failure, cardiac disease, and increased costs. However, current studies have not defined limits of body composition that preclude clinical benefit from transplantation compared with long-term dialysis in patients who have passed a transplant evaluation. Formal cost-effectiveness studies are needed to determine if payers and society should be compensating centers for clinical and financial risks of transplanting obese end-stage renal disease patients. Recent studies also demonstrate the limitations of BMI alone as a measure of adiposity, and further research should be pursued to define practical measures of body composition that refine accuracy for outcomes prediction. Regarding individual management, observational registry studies have not found beneficial associations of pretransplant weight loss with patient or graft survival. However, association studies cannot distinguish purposeful from unintentional weight loss as a result of illness and comorbidity. Prospective evaluations of the impact of targeted risk modification efforts in this population including dietary changes, monitored exercise programs, and bariatric surgery are urgently needed.

Concepts: Renal failure, Chronic kidney disease, Kidney, Nephrology, Obesity, Body mass index, Weight loss, Bariatric surgery

6

Cancer immunotherapy, such as anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and anti-programmed death 1 (PD-1), has revolutionized the treatment of malignancies by engaging the patient’s own immune system against the tumor rather than targeting the cancer directly. These therapies have demonstrated a significant benefit in the treatment of melanomas and other cancers.

Concepts: Immune system, Vitamin D, Cancer, Oncology, Chemotherapy, Tumor, Neoplasm

5

The relationship between serum potassium, mortality, and conditions commonly associated with dyskalemias, such as heart failure (HF), chronic kidney disease (CKD), and/or diabetes mellitus (DM) is largely unknown.

Concepts: Chronic kidney disease, Hypertension, Diabetes mellitus

4

We performed a comprehensive literature review to examine evidence on the effects of hydration on the kidney. By reducing vasopressin secretion, increasing water intake may have a beneficial effect on renal function in patients with all forms of chronic kidney disease (CKD) and in those at risk of CKD. This potential benefit may be greater when the kidney is still able to concentrate urine (high fluid intake is contraindicated in dialysis-dependent patients). Increasing water intake is a well-accepted method for preventing renal calculi, and current evidence suggests that recurrent dehydration and heat stress from extreme occupational conditions is the most probable cause of an ongoing CKD epidemic in Mesoamerica. In polycystic kidney disease (PKD), increased water intake has been shown to slow renal cyst growth in animals via direct vasopressin suppression, and pharmacologic blockade of renal vasopressin-V2 receptors has been shown to slow cyst growth in patients. However, larger clinical trials are needed to determine if supplemental water can safely slow the loss of kidney function in PKD patients.

Concepts: Renal failure, Chronic kidney disease, Kidney, Nephrology, Urine, Renal physiology, Electrolyte, Polycystic kidney disease

3

Therapeutic options for the treatment of anemia secondary to chronic kidney disease (CKD) remain limited. Vadadustat (AKB-6548) is an oral hypoxia-inducible factor prolyl-hydroxylase domain (HIF-PHD) inhibitor that is being investigated for the treatment of anemia secondary to CKD.

Concepts: Chronic kidney disease, Kidney, Erythropoietin, Medicine, Epidemiology, Clinical trial, Medical terms, ClinicalTrials.gov

2

The remarkable success of clinical trials in mineralocorticoid receptor (MR) inhibition in heart failure has driven research on the physiological and pathological role(s) of nonepithelial MR expression. MR is widely expressed in the cardiovascular system and is a major determinant of endothelial function, smooth muscle tone, vascular remodeling, fibrosis, and blood pressure. An important new dimension is the appreciation of the role MR plays in immune cells and target organ damage in the heart, kidney and vasculature, and in the development of insulin resistance.

Concepts: Immune system, Blood, Heart, Blood vessel, The Canon of Medicine, Cardiac muscle, Organ, Circulatory system

2

Different studies in the past have shown that the risk of cancer development is increased in chronic dialysis patients. However, data concerning the cancer risk in Asian dialysis patients was scarce. More importantly, there was lack of information about the cancer-specific mortality in dialysis patients.

Concepts: Cohort study, Dialysis, Cohort, Epidemiology, Cancer, Demography, Actuarial science, Life expectancy

2

Autosomal dominant tubulointerstitial kidney disease subtype HNF1B (ADTKD-HNF1B) is caused by a mutation in hepatocyte nuclear factor 1 homeobox beta (HNF1B). Although 50-60% of ADTKD-HNF1B patients develop hypomagnesemia, HNF1B mutations are mainly identified in patients with structural kidney defects or diabetes.

Concepts: DNA, Cancer, Ionizing radiation, Genetic disorder, Mutation, Evaluation methods, Hepatocyte nuclear factors

1

Hyperuricemia is associated with the progression of chronic kidney disease (CKD), but it is not known whether the relationship is causal. We examined the association of hyperuricemia and uric acid lowering therapy (UALT) with progression of CKD in patients with CKD 3 and 4 in the Cleveland Clinic CKD registry.

Concepts: Chronic kidney disease, Uric acid, Hyperuricemia