A randomized controlled pilot trial of anakinra and pioglitazone for protein metabolism in patients on maintenance haemodialysis.

BACKGROUND: Chronic inflammation and insulin resistance are highly prevalent in patients on maintenance haemodialysis (MHD) and are strongly associated with protein energy wasting. We conducted a pilot, randomized, placebo-controlled trial of recombinant human interleukin-1 receptor antagonist (IL-1ra) and pioglitazone to explore the safety, feasibility and efficacy for insulin-mediated protein metabolism in patients undergoing MHD. METHODS: Twenty-four patients were randomized to receive IL-1ra, pioglitazone or placebo for 12 weeks. Changes in serum inflammatory markers and insulin-mediated protein synthesis, breakdown and net balance in the whole-body and skeletal muscle compartments were assessed using hyperinsulinaemic-hyperaminoacidemic clamp technique at baseline and Week 12. RESULTS: Among 24 patients, median (interquartile range) age was 51 (40, 61), 79% were African American and 21% had diabetes mellitus. All patients initiated on intervention completed the study, and no serious adverse events were observed. There was a statistically significant decrease in serum high-sensitivity C-reactive protein in the pioglitazone group compared with placebo, but not in the IL-1ra group. No significant differences in the changes of whole-body or skeletal muscle protein synthesis, breakdown and net balance were found between the groups. CONCLUSIONS: In this pilot study, there were no statistically significant effects of 12 weeks of IL-1ra or pioglitazone on protein metabolism in patients on MHD. CLINICALTRIALS: gov registration: NCT02278562.

Early Diagnostic Markers for Detection of Acute Kidney Injury in Allogeneic Hematopoietic Stem Cell Transplant Recipients.

OBJECTIVES: Acute kidney injury is a relatively frequent complication of allogenic hematopoietic stem cell transplant, resulting in increased risk of morbidity and mortality. Early diagnosis and management of acute kidney injury is of great importance for prevention of poor outcomes in these transplant recipients. MATERIALS AND METHODS: Fifty consecutive patients, hospitalized for allogenic hematopoietic stem cell transplant at the Bone Marrow Transplantation Unit of Gazi University Faculty of Medicine, were included in this prospective study. Serial measurements of serum creatinine and creatinine clearance were obtained before administration of conditioning regimen and at 0, 7, 14, 21, and 28 days after start of conditioning. Blood and urine samples were also obtained for the measurement of serum cystatin C and urine neutrophil gelatinase-associated lipocalin levels before conditioning and 24 hours before each serum creatinine measurement. RESULTS: During the median 25 days of follow-up, acute kidney injury developed in 19 patients: 10 patients had stage 1, 7 had stage 2, and 2 had stage 3 acute kidney injury according to the Acute Kidney Injury Network classification. There were significant positive correlations between serum cystatin C levels and serum creatinine levels and negative correlations with creatinine clearance levels at each time point (P < .001), whereas no statistically significant associations were observed with urinary neutrophil gelatinase-associated lipocalin levels. Both univariate and multivariate Cox regression models showed a statistically significant association between serum cystatin C levels and development of acute kidney injury, whereas urine neutrophil gelatinase-associated lipocalin levels did not show any significant associations. CONCLUSIONS: Serum cystatin C levels might be a useful marker for early detection of acute kidney injury in adult allogenic hematopoietic stem cell transplant recipients. Close monitoring of kidney function by sensitive biomarkers might provide early recognition and timely management of acute kidney injury in high-risk patient populations.

Tissue sodium accumulation and peripheral insulin sensitivity in maintenance hemodialysis patients.

BACKGROUND: Recent data suggest that sodium (Na+ ) is stored in the muscle and skin without commensurate water retention in maintenance hemodialysis (MHD) patients. In this study, we hypothesized that excessive Na+ accumulation would be associated with abnormalities in peripheral insulin action. METHODS: Eleven MHD patients and eight controls underwent hyperinsulinemic-euglycemic-euaminoacidemic clamp studies to measure glucose (GDR) and leucine disposal rates (LDR), as well as lower left leg 23 Na magnetic resonance imaging to measure Na+ concentration in the muscle and skin tissue. RESULTS: The median GDR and LDR levels were lower, and the median muscle Na+ concentration was higher in MHD patients compared with controls. No significant difference was found regarding skin Na+ concentration between group comparisons. Linear regression revealed inverse relationships between muscle Na+ concentration and GDR and LDR in MHD patients, whereas no relationship was observed in controls. There was no association between skin Na+ content and GDR or LDR in either MHD patients or controls. CONCLUSIONS: These data suggest that excessive muscle Na+ content might be a determinant of IR in MHD patients, although the causality and mechanisms remain to be proven.

Association between hemoglobin, calcium, and lactate dehydrogenase variability and mortality among metastatic renal cell carcinoma.

PURPOSE: There are no robust data on hemoglobin (Hb), lactate dehydrogenase (LDH), and calcium variability for overall survival (OS) in patients with metastatic renal cell carcinoma (mRCC) treated with vascular endothelial growth factor (VEGF)-targeted therapy. We aim to evaluate prognostic implications of Hb, LDH, and calcium variability and establish a novel risk stratification model in RCC patients receiving targeted therapies. METHODS: We retrospectively studied an unselected cohort of patients with mRCC, who were treated with tyrosine kinase inhibitors. We assessed LDH variability, Ca variability, and Hb variability with various methods using standard deviation and fluctuation across thresholds. Kaplan-Meier and log-rank analyses were employed on OS and multivariate Cox proportional hazard model analyzed clinical parameters for their prognostic relevance. RESULTS: A total of 59 patients intermediate-risk group according to the Memorial Sloan-Kettering Cancer Center with mRCC who had early progressed after first-line therapy with interferon-α were included in this retrospective single-center study conducted between February 2008 and December 2011. The mean Hb was 12.4 g/dl (min-max 9.1-15.2) throughout the study. Multivariable-adjusted Cox regression showed that patients in the consistently low-Hb group and patients in the low-amplitude and high-amplitude groups had a statistically significant increase in risk compared with patients who were consistently on target (HR 4.1; 95 % CI 1.3-12.9 and HR 2.9; 95 % CI 1.05-8.1 and HR 4.4; 95 % CI 1.7-11.1, respectively). On the other hand, the higher mean LDH (LDH more than 1 >upper limit of normal) was associated with OS. LDH variability and Ca variability were not associated with mortality. CONCLUSIONS: In patients with mRCC treated with VEGF-targeted therapy, Hb variability and mean LDH level might be associated with OS. This should be investigated prospectively.

The effects of iron on FGF23-mediated Ca-P metabolism in CKD patients.

BACKGROUND: Fibroblast growth factor 23 (FGF23) is an important counterregulatory hormone for phosphate homeostasis. Since it has been reported that iron administration induces hypophosphatemic osteomalacia by triggering FGF23 synthesis, we hypothesized that iron administration might lead to a further increase in FGF23, resulting in alterations to Ca-P metabolism in a stage 5 CKD population. METHODS: This cross-sectional study was performed in a single center, and involved 73 hemodialysis patients (47.7 ± 15.74 years old, 68.5% men), 29 peritoneal dialysis patients (44.55 ± 15.05 years old, 62.1% men), and 55 healthy (43.57 ± 14.36 years old, 55.6% men) subjects. The dialysis group was subcategorized according to iron therapy administration into users and nonusers. RESULTS: The median iFGF23 level was significantly higher in the dialysis population than in the healthy controls [88.050 (25.2-1038.3) pg/ml versus 46.95 (2.4-356) pg/ml (p < 0.001)]. In the dialysis population, a significantly lower median iFGF23 level was observed in iron therapy users than in nonusers [87.6 (25.2-1038.3) versus 119 (51.6-1031); respectively, p = 0.045]. A significant negative association between iron administration and iFGF23 level was revealed by both univariate (r = -0.237, p = 0.016) and multivariate (ß = -0.221, p = 0.032) analysis. No association was found between iFGF23 and serum ferritin and iron levels. Also, there was no association between iron therapy and serum phosphate level. CONCLUSION: In contrast to what is seen for the general population, this study showed that there was a negative relationship between iron administration and serum iFGF23 level in a dialysis population. We can therefore conclude that if high levels of FGF23 are harmful, iron therapy may have a beneficial effect on bone metabolism by reducing FGF23 levels in a dialysis population.

A spontaneous spinal epidural hematoma in a hemodialysis patient: a rare entity.

Hemodialysis patients are at an increased risk of bleeding due to the platelet dysfunction caused by uremia and the use of anticoagulants during dialysis. Spontaneous spinal hematoma is a rare disorder as a complication in hemodialysis patients. Also it includes the hematoma secondary to coagulopathy, vascular malformation and hemorrhagic tumors. Here, we report the case of 77-year-old woman who presented with spinal cord compression due to spontaneous spinal epidural hematoma associated with hemodialysis. When an end-stage renal disease patient suffers from back pain and neurological deficits, the clinician should be alerted for the spontaneous spinal epidural hematoma as well as cerebrovascular events.

Renal cell carcinoma associated immunosuppressive therapy: a case report with Wegener's granulomatosis.

Development of uroepithelial tumors after cyclophosphamide and azathioprine therapy in Wegener's granulomatosis (WG) have been reported in the literature but renal cell carcinoma (RCC), rarely. RCC associated with WG has been previously reported in a few cases. Most of them have simultaneous diseases. Here, we report a case, which developed RCC 8 years after initiation of WG. Long-term immunosuppressive treatment is a risk factor for the development of malignancies; it should be suggested that RCC in our patient might be due to immunosuppressive therapy.

Wegener's granulomatosis with massive gastrointestinal hemorrhage due to jejunal and colonic involvement: report of a case.

Wegener's granulomatosis (WG) is a systemic necrotizing vasculitis of unknown etiology characterized mainly by the involvement of the upper airways, lungs, and kidneys. Although most organ systems can be involved, gastrointestinal involvement in WG is notably uncommon. We herein present the case of a WG patient who developed two massive gastrointestinal hemorrhages treated respectively by surgery and angiographic embolization of the bleeding artery. The present case indicates that gastrointestinal manifestations might thus be considered in the natural history of WG.

Influence of H pylori on plasma ghrelin in patients without atrophic gastritis.

AIM: To determine the association between H pylori infection and serum ghrelin levels in patients without atrophic gastritis. METHODS: Fifty consecutive patients (24 males and 26 females) with either H pylori-positive gastritis (n = 34) or H pylori-negative gastritis (n = 16) with normal gastric acid secretion determined by 24-h pHmetry and without atrophic gastritis in histopathology were enrolled in this study. Thirty-four H pylori-infected patients were treated with triple therapy consisting of a daily regimen of 30 mg lansoprazole bid, 1 g amoxicillin bid and 500 mg clarithromycin bid for 14 d, followed by an additional 4 wk of 30 mg lansoprazol treatment. H pylori infection was eradicated in 23 of 34 (67.6%) patients. H pylori-positive patients were given eradication therapy. Gastric acidity was determined via intragastric pH catheters. Serum ghrelin was measured by radioimmunoassay (RIA). RESULTS: There was no significant difference in plasma ghrelin levels between H pylori-positive and H pylori-negative groups (81.10 +/- 162.66 ng/L vs 76.51 +/- 122.94 ng/L). In addition, there was no significant difference in plasma ghrelin levels and gastric acidity levels measured before and 3 mo after the eradication therapy. CONCLUSION: H pylori infection does not influence ghrelin secretion in patients with chronic gastritis without atrophic gastritis.