The Association of Vitamin D Status and Vitamin D Replacement Therapy with Glycemic Control, Serum Uric Acid Levels, and Microalbuminuria in Patients with Type 2 Diabetes and Chronic Kidney Disease.

OBJECTIVE: To evaluate the relationship of vitamin D status and vitamin D replacement therapy with glycemic control, serum uric acid (SUA) levels, and microalbuminuria (MAU) in patients with type 2 diabetes (T2DM) and chronic kidney disease (CKD). Subjectsand Methods: A total of 1,463 patients with T2DM and CKD (aged 14-88 years), 927 females and 536 males, were included in this study. The serum data of 25-hydroxyvitamin D, i.e., 25(OH)D, level, SUA, hemoglobin (Hb)A1c, creatinine, estimated glomerular filtration rate, and urine albumin-to-creatinine ratio (UACR) were obtained from the medical records. The Mann-Whitney U test, the χ2 test, the Mantel-Haenszel test, and linear regression models were used for data analysis. RESULTS: Vitamin D deficiency and insufficiency were evident in 770 (52.0%) and 357 (24.0%) patients, respectively. Median HbA1c levels (7.3 [IQR 3.9] vs. 6.5 [IQR 2.3]%; p < 0.01) were significantly higher in patients deficient in vitamin D than in those with a normal vitamin D status. A significantly low level of vitamin D was noted with a high UACR (ß -0.01; 95% CI -0.01 to -0.001; p = 0.017) and HbA1c (ß -1.1; 95% CI -1.6 to -0.6; p < 0.001), but with low levels of SUA (ß 1.3; 95% CI 0.5-2.2; p = 0.002). Vitamin D replacement was associated with a significantly low level of HbA1c (7.4 [2.7] vs. 6.7 [1.9]%; p < 0.001]. CONCLUSION: In this study, there was a high prevalence of hypovitaminosis D among T2DM patients with CKD, with a higher UACR, higher HbA1c, and lower SUA being noted as playing a role in predicting a decrease in vitamin D levels and potential benefits of vitamin D replacement therapy on glycemic control in T2DM management.

Novel Masters of Erythropoiesis: Hypoxia Inducible Factors and Recent Advances in Anemia of Renal Disease.

Anemia seen in patients with chronic kidney disease is a particular form of 'anemia of chronic disease'. Although multifactorial in origin, erythropoiesis-stimulating agents (ESAs) and adjuvant iron therapy represent the primary treatment for anemia in chronic kidney disease. Subsequent clinical observations revealed that these ESA hyporesponsive patients often had increased systemic inflammation as a consequence of their comorbidities. Use of high ESA doses to overcome this ESA hyporesponsiveness posed some concerns regarding associated adverse events of therapy and increased mortality in this special patient population. Recognizing the pivotal roles of hypoxia inducible factors (HIFs) in orchestrating elements of erythropoiesis opened new avenues in the management of renal anemia. Several phase 1 and 2 studies confirmed the results of early experimental studies supporting the beneficial role of augmenting HIFs for erythropoiesis. In this review, we describe the physiologic functions of HIF in erythropoiesis with special emphasis on interactions with iron and hepcidin metabolism and inflammation.

Splenic artery embolization with Ankaferd blood stopper in a sheep model.

PURPOSE: Splenic artery embolization is a minimally invasive therapeutic procedure utilized in a number of disorders. Ankaferd blood stopper (ABS) is a novel hemostatic agent with a new mechanism of action independent of clotting factors. We aimed to investigate the safety and efficiency of ABS for splenic artery embolization in a sheep model. METHODS: Seven adult female sheep were included in the study. Selective celiac angiography was performed using a 5F diagnostic catheter and then a 2.7F hydrophilic coating microcatheter was advanced coaxially to the distal part of the main splenic artery. Under fluoroscopic guidance, 6 mL mixture composed of half-and-half ABS and contrast agent was slowly injected. Fluoroscopy was used to observe the deceleration and stagnation of the flow. Control celiac angiograms were obtained immediately after the embolization. After the procedure, the animals were observed for one day and then sacrificed with intravenous sodium thiopental. RESULTS: Technical success rate was 100%. None of the animals died or experienced a major systemic adverse event during the procedure. All of the spleens appeared dark on macroscopic examination due to excessive thrombosis. Microscopically, the majority of the splenic sinusoids (90%-95%) were necrotic. CONCLUSION: In our study, splenic artery embolization by ABS was found to be safe and effective in the short-term. Further studies are needed to better understand the embolizing potential of this novel hemostatic agent.

Effects of Coenzyme Q10 Supplementation on Exercise Performance and Markers of Oxidative Stress in Hemodialysis Patients: A Double-Blind Placebo-Controlled Crossover Trial.

Coenzyme Q10 (CoQ10) supplementation has been shown to decrease oxidative stress in a number of clinical settings. However, there are mixed results regarding the role of CoQ10 supplementation on exercise performance. Chronic kidney disease is recognized as an inflammatory state, and hemodialysis patients have low level of exercise performance. We aimed to evaluate the effect of CoQ10 supplementation on oxidative stress markers and exercise performance measures. This was a prospective, double-blind, placebo-controlled, crossover study in which all patients received placebo and oral CoQ10 200 mg/d. Participants underwent 6-minute walking test and cycle ergometer. Blood samples were drawn to determine malondialdehyde, oxidized low-density lipoprotein, superoxide dismutase, and glutathione peroxidase. Walking distance in 6-minute walking test and estimated maximal oxygen consumption (VO2max) were recorded. Twenty-eight patients were randomized, but 23 patients completed the study protocol. Serum CoQ10 level significantly increased with supplementation compared with basal values (P < 0.05). Neither walking distance nor estimated VO2max was different between the placebo and CoQ10 groups (P > 0.05). Serum malondialdehyde levels significantly increased in both groups compared with baseline values just after the exercise (P < 0.05). There was no difference in markers of oxidative stress and antioxidant system between placebo and CoQ10 supplementation with exercise (P > 0.05). The results of this study showed no significant effect of CoQ10 supplementation on exercise performance measures and oxidative system markers compared with placebo in maintenance hemodialysis patients.

Dietary potassium: a key mediator of the cardiovascular response to dietary sodium chloride.

Potassium and sodium share a yin/yang relationship in the regulation of blood pressure (BP). BP is directly associated with the total body sodium and negatively correlated with the total body potassium. Epidemiologic, experimental, and clinical studies have shown that potassium is a significant regulator of BP and further improves cardiovascular outcomes. Hypertensive cardiovascular damage, stroke, and stroke-related death are accelerated by salt intake but might be curbed by increasing dietary potassium intake. The antihypertensive effect of potassium supplementation appears to occur through several mechanisms that include regulation of vascular sensitivity to catecholamines, promotion of natriuresis, limiting plasma renin activity, and improving endothelial function. In the absence of chronic kidney disease, the combined evidence suggests that a diet rich in potassium content serves a vasculoprotective function, particularly in the setting of salt-sensitive hypertension and prehypertension.

Coenzyme Q10 supplementation and diastolic heart functions in hemodialysis patients: a randomized double-blind placebo-controlled trial.

Coenzyme Q10 (CoQ10) supplementation has been shown to improve diastolic heart function in various patient cohorts. Systolic and diastolic dysfunctions are common in patients with end-stage renal disease. Favorable effects of CoQ10 on cardiac functions are yet to be seen in hemodialysis patients. We aimed to evaluate effect of CoQ10 supplementation on diastolic function in a cohort of maintenance hemodialysis patients. This was a prospective, double-blind, placebo-controlled, crossover study in which all patients received placebo and oral CoQ10 200 mg/d during the 8 weeks in each phase, with a 4-week washout period. Participants underwent conventional and tissue Doppler echocardiography before and after each study phase. Parameters characterizing left ventricle diastolic function and other standard echocardiographic measurements were recorded. Twenty-eight patients were randomized, but 22 patients completed study protocol. Intraventricular septum (IVS) thickness and left ventricle mass were significantly decreased in CoQ10 group (P = 0.03 and P = 0.01, respectively). Myocardial peak systolic and early diastolic velocities derived from IVS were significantly increased (P = 0.048 and P = 0.04, respectively). Isovolumetric relaxation time and E/Em ratio calculated for IVS also significantly reduced in CoQ10 group (p = 0.02 and p = 0.04, respectively). There was no significant difference in any of the studied echocardiographic parameters in placebo group. The results of this study showed that CoQ10 supplementation did not significantly improved diastolic heart functions compared with placebo in maintenance hemodialysis patients.

Short-term effects of Ankaferd hemostat for renal artery embolization: an experimental study.

PURPOSE: Renal artery embolization (RAE) is a minimally invasive therapeutic technique that is utilized in a number of disorders. Ankaferd is a novel hemostatic agent with a new mechanism of action independent of clotting factors. We used Ankaferd for RAE in a sheep model. METHODS: Seven adult female sheep were included in the study. Selective renal arteriogram using 5-F diagnostic catheter was performed to make sure that each kidney was fed by a single renal artery and the animal had normal renal vasculature. Coaxial 2.7-F microcatheter was advanced to the distal main renal artery. Under fluoroscopic guidance, 2 mL of Ankaferd mixed with 2 mL of nonionic iodinated contrast agent was slowly injected. Fluoroscopy was used to observe the deceleration of flow and stagnation. Control renal angiograms were performed just after embolization. After the procedure, the animals were observed for 1 day and then sacrificed with intravenous sodium thiopental. RESULTS: The technical success was observed in seven of the seven animals.. After embolization procedure, none of the animals died or experienced a major systemic adverse event. On macroscopic examination of the embolized kidneys, thrombus at the level of main renal artery formed after Ankaferd embolization was more compact compared with the thrombi that was not Ankaferd-associated, which was observed elsewhere. Microscopically, majority of the renal tubular cells (80-90 %) were necrotic, and there was epithelial cell damage in a small portion of the cells (10-20 %). CONCLUSIONS: RAE was safe and effective in the short-term with Ankaferd in studied animals. Further studies should be conducted to better delineate the embolizing potential of this novel hemostatic agent.

Massive haematuria successfully managed by intravesical Ankaferd in a haemodialysis patient complicated with disseminated intravascular coagulation.

Massive haematuria is a life-threatening condition, demanding immediate management of bleeding. The mortality is very high in the case of delayed management of bleeding, especially in elderly patients with concomitant comorbidity. The treatment options of haematuria are wide, and depend on underlying conditions. However, therapeutic choices are limited in the presence of massive and intractable haematuria caused by disseminated intravascular coagulation (DIC). Ankaferd blood stopper (ABS) is a novel, commercially available, haemostatic agent, which has been approved by the Ministry of Health for local use in Turkey. Here, for the first time in the literature, we report a case of diffuse intravesical bleeding stopped by intravesical use of ABS in a 72-year-old man, haemodialysis patient complicated with sepsis and DIC.

Safety profiles of total dose infusion of low-molecular-weight iron dextran and high-dose iron sucrose in renal patients.

Iron sucrose and low-molecular-weight iron dextran (LMW-ID), two commonly used iron solutions, have been compared in terms of allergic adverse event profiles to date. However, the safety of total dose infusion of LMW-ID has been investigated by only one study in chronic kidney disease (CKD) (not dialysis) patients. Thus, we aimed to compare adverse event profiles of total and high-dose LMW-ID and iron sucrose infusions in a heterogenous renal patient group comprising CKD, hemodialysis, and peritoneal dialysis. In this retrospective chart review study, we included 110 predialysis CKD, 101 peritoneal dialysis, and 118 hemodialysis patients. We included a total of 329 patients who were administered parenteral iron sucrose or LMW-ID between September 2006 and April 2010. Adverse events were determined both by medical and nursing follow-up notes. Laboratory data and clinical characteristics were collected from patient charts. Adverse event rates were compared between iron sucrose and LMW-ID infusions. In a total of 329 patients, 530 infusions (3470 ampules) were administered. We detected adverse reaction in only 1 patient. This adverse reaction, which manifested as generalized pruritus, occurred in a patient who received 500 mg of iron sucrose infusion. There were neither anaphylactic reactions nor deaths associated with infusion of either preparation. We did not observe any other adverse event related to administration of 500 and 1000 mg of iron sucrose at single infusion. The results of this study showed comparable safety of total dose LMW-ID and high-dose iron sucrose in a heterogenous group of renal patients.

Colchicine treatment in autosomal dominant polycystic kidney disease: many points in common.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common of the inherited renal cystic diseases and constitutes 10% of the end stage kidney disease population. ADPKD is caused by PKD1 and PKD2 gene mutations in 85% and 15% of the cases respectively. Its high prevalence and negative impact on health outcomes fostered efforts to explain pathophysiologic pathways of cyst formation in kidneys. Among these are increased apoptosis, unopposed proliferation of tubule cells, impaired polarization and planar cell polarity, impaired cAMP pathway, cilier dysfunction, activated mTOR pathway, increased tumor necrosis factor-alpha (TNF-alpha) production. Many drugs have been tried in an attempt to halt cystogenesis in some point. Despite success to some extent in experimental studies, none reached clinical armamentarium yet. Colchicine, originally extracted from Colchicum autunale, is an anti-inflammatory drug that has been in continuous use for more than 3000 years. It has been used successfully to prevent attacks of familial mediterranien fever and amyloidosis, to treat gout and pseudogout attacks for a few decades. Colchicine principally is a microtubule inhibitor, thus prevents cell migration, division, and polarization. It also has anti-apoptotic, anti-proliferative and anti-inflammatory effects and down-regulates (TNF-alpha) receptors. As can easily be seen, many of the effects of colchicine have pathophysiologic counterparts in ADPKD. Thus, we hypothesized that colchicine would be beneficial to prevent or at least delay cyst formation in ADPKD patients. Indirect evidence also support our hypothesis, in which taxol and paclitaxel, other two microtubule inhibitors, were shown to delay cyst formation in experimental models of ADPKD. To our opinion, despite its narrow therapeutic index, widespread experience makes colchicine a suitable candidate for prolonged clinical use, should experimental studies show any benefit in ADPKD.