Serhan Piskinpasa

Major Barriers against Renin–Angiotensin–Aldosterone System Blocker Use in Chronic Kidney Disease Stages 3–5 in Clinical Practice: A Safety Concern?

Renin–angiotensin–aldosterone system (RAAS) blockers are underutilized in patients with chronic kidney disease (CKD). We aimed to determine barriers against the use of RAAS blockers in these patients. Patients with stage 3–5 CKD referred to Hacettepe University Hospital Nephrology Unit during a 1 year period were evaluated for RAAS blocker use. Two hundred and seventy-nine patients (166 male, 113 female) were analyzed. The mean age of the patients was 56.7 ± 15.2 years, mean serum creatinine was 2.45 ± 1.44 mg/dL, and mean glomerular filtration rate was 33.3 ± 15.1 mL/min. The mean follow-up time was 22.0 ± 21.9 months and the clinical visit number was 4.0 ± 3.5. Angiotensin-converting-enzyme inhibitors or angiotensin receptor blockers were used by 68.8% of all patients and 67.7% of diabetic patients at the time of analysis. In 82.1% of patients, RAAS blockers had either been used earlier or were being used. Hyperkalemia was the principal reason for both not starting and also discontinuing these drugs in patients with CKD. In 37.4% of patients, reasons for not starting RAAS blockers were unclear. This study showed that hyperkalemia is the major barrier against the use of RAAS blockers in patients with CKD. There was, however, a subset of patients who did not receive RAAS blockers even without clear contraindications.

Use of Mesenchymal Stem Cells and Darbepoetin Improve Ischemia-Induced Acute Kidney Injury Outcomes

Background: Interest has recently been focused on the possible role of bone marrow-originating stem cells and the therapeutic role of erythropoietin in the recovery of ischemia-induced acute kidney injury (AKI). The aim of the present study was to compare treatment with mesenchymal stem cells (MSCs) to treatment with darbepoetin-α (DPO) or both concomitantly in a rat model of ischemia/reperfusion (I/R) AKI. Methods: Forty male Sprague-Dawley rats were included, and 28 of them were randomly assigned to controls (treated with serum physiologic) or one of the three treatment groups treated with either DPO, MSCs, or both (MSCs and DPO concomitantly) after the induction of I/R injury. Hematocrit, serum creatinine, and BUN levels were obtained at 0, 24, 48, and 72 h of surgery, and renal tissue was obtained at 72 h after nephrectomy for histological analysis. Tissue injury was quantified by standardized histological scoring systems, using light and electron microscopes. Results: Treatment with MSCs or DPO improved renal function compared with controls. However, the improvement observed in renal function in the MSC/DPO group was better than that in the other groups. Histological analysis demonstrated that tissue injury was significantly decreased in rats in the MSC or DPO groups compared to that of the controls; however the best recovery was observed in rats treated with MSCs and DPO concomitantly. Conclusion: These results suggest that concomitant application of DPO and MSCs may be a potential novel renoprotective therapy for patients after having sustained an ischemic renal insult.

High frequency of aspirin resistance in patients with nephrotic syndrome

BACKGROUND Aspirin has a beneficial role in prevention of cardiovascular and thromboembolic events. Patients may experience thromboembolic events despite aspirin treatment, a phenomenon called aspirin resistance. We evaluated the frequency of aspirin resistance and its correlation with clinical and biochemical parameters among patients with nephrotic syndrome (NS). METHODS A total of 83 patients (50 males, 33 females, age range 18-79 years) with NS using aspirin 100 mg/day were included in the study. Demographic information and aetiology of NS based on the histology of a renal biopsy were recorded for each patient. Blood samples were drawn to investigate the association of aspirin resistance with inflammation and thrombotic risk factors. Aspirin resistance was defined as a normal collagen/epinephrine closure time<159 s using a platelet function analyzer (PFA-100). RESULTS Aspirin resistance was determined in 51 patients (61.4%). The number of patients exposed to azathioprine therapy was significantly higher in the aspirin-sensitive group (P=0.043), whereas patients exposed to cyclosporine therapy were significantly higher in the aspirin-resistant group (P=0.017). More patients in the aspirin-resistant group were on angiotensin-converting enzyme inhibitor therapy compared with the aspirin-sensitive group (P=0.024). The aspirin-resistant group showed significantly higher serum low-density lipoprotein cholesterol (LDL-C) (151±47 versus 104±21 mg/dL; P<0.001), triglyceride levels (192±116 versus 134±82 mg/dL; P=0.015) and glomerular filtration rates (91.8±43.0 versus 74.0±35.6 mL/min/1.73 m2; P=0.044) compared with the aspirin-sensitive group. In multivariate analysis, LDL-C was the only parameter associated independently with aspirin resistance [odds ratio (OR) 1.04, 95% confidence interval (CI) 1.02-1.06; P=0.004]. CONCLUSIONS A significant number of patients with NS are resistant to aspirin therapy. Serum LDL-C level is closely associated with aspirin resistance in NS.

Short-Term Hemostatic Safety of Strontium Ranelate Treatment in Elderly Women with Osteoporosis

Background: Strontium ranelate offers significant clinical benefits in terms of efficacy, tolerability, and ease of administration in the treatment of postmenopausal osteoporosis. However, there are some data revealing an association between strontium ranelate treatment and increased incidence of venous thromboembolism (VTE), suggesting possible adverse prothrombotic effects of the drug. Objective: To assess the effect of strontium ranelate treatment on primary hemostasis, secondary hemostasis, and the natural anticoagulant defense system, together with prothrombotic markers, in elderly women with osteoporosis. Methods: This study was designed in a prospective manner. Thirty-five elderly women diagnosed with osteoporosis were included. During a 2 month treatment period, participants received strontium ranelate 2 g. Platelet Function Analyzer-100 (PFA-100) in vitro bleeding time was performed to depict primary hemostasis. Secondary hemostatic parameters including prothrombin time, international normalized ratio, activated partial thromboplastin time, anti-cardiolipine immunoglobulin (Ig) M and IgG, antiphospholipid IgM and IgG, protein C, protein S, anti-thrombin III, lupus anticoagulant, fibrinogen, thrombin, activated protein C resistance, and plasma levels of d-dimer were assessed. These parameters were tested before and after 2 month treatment with strontium ranelate. Results: Mean ± SD age of the patients was 72.82 ± 5.69 years. After 60 days of treatment, there was no statistically significant prolongation in PFA-100 in vitro bleeding time and no statistically significant change in the critical hemostatic parameters in patients receiving strontium ranelate that led to discontinuation of the treatment. None of the subjects developed clinical VTE during the 2 month period of strontium ranelate treatment. Conclusions: The hemostatic safety of strontium ranelate in the elderly population with osteoporosis was shown over 2 months of treatment; however, its long-term hemostatic safety should be evaluated further.

An Uninvestigated Risk Factor for Contrast-Induced Nephropathy in Chronic Kidney Disease: Proteinuria

Background: Contrast-induced nephropathy (CIN) is one of the most frequent causes of acute renal failure in hospitalized patients with the incremental use of contrast media. We aimed to investigate whether proteinuria may act as a risk factor for CIN in patients with chronic kidney disease. Methods: Seventy hospitalized patients (37 men, 33 women) with chronic kidney disease, proteinuria, and/or estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73 m2, who were exposed to contrast media were investigated prospectively. Thirty patients were diabetic. All patients received prophylaxis against CIN with acetylcysteine and 0.9% intravenous saline. CIN is defined as either a 25% higher increase in serum creatinine (sCr) from the baseline levels or a 0.5 mg/dL increase in sCr at 72 h after contrast media exposure. Results: CIN was detected in 26 (37.1%) patients. Advanced age, diabetes, heart failure, anemia, baseline sCr of >1.5 mg/dL, baseline eGFR of <60 mL/min/1.73 m2, proteinuria of ≥1 g/day, hypoalbuminemia, and the volume of contrast media of ≥100 mL correlated significantly with CIN. The frequency of CIN was significantly higher in patients with proteinuria of ≥1 g/day compared to patients with proteinuria of <1 g/day (p = 0.009). Conclusion: Proteinuria may be a new risk factor for the development of CIN in patients with chronic kidney disease.

Real-time ultrasound guided placement of temporary internal jugular vein catheters: Assessment of technical success and complication rates in nephrology practice

Aim:  Internal jugular vein (IJV) catheterization is often required to gain access for haemodialysis. Use of ultrasound guidance has reduced the complication rates of this procedure. We hypothesized that nephrologists may perform IJV cannulation with a high technical success and low immediate complication rates under real‐time ultrasound guidance.

Relation between serum cathepsin D levels and endothelial dysfunction in patients with chronic kidney disease.

We aimed to investigate the role of cathepsin D, an inflammatory and atherosclerotic mediator, in endothelial dysfunction in chronic kidney disease. The study included 65 patients with stage 2–4 chronic kidney disease (35 females, 30 males; mean age, 55.8±15.6 years). Serum creatinine and cathepsin D levels and glomerular filtration rates (GFRs) were determined, and brachial flow-mediated dilation (FMD) percentage was measured by two-dimensional gray scale and color flow Doppler and vascular imaging. FMD ≤6% was considered to indicate endothelial dysfunction. Mean GFR, median creatinine levels, and median cathepsin D levels were 40.2±11.2mL/min/1.73m2, 1.7mg/dL, and 819.75ng/mL, respectively. Endothelial dysfunction was present in 30 of the 65 patients (46.2%). There was a significant difference between groups with and without endothelial dysfunction in terms of cathepsin D (p=0.001) and creatinine (p=0.03) levels, and negative and significant correlations were found between brachial artery FMD% and cathepsin D (r=−0.359, p=0.003) and creatinine (r=−0.304, p=0.014) levels. Cathepsin D, which is known to be associated with atherosclerosis, may play a role in the process of endothelial dysfunction. Further studies are essential to determine the exact function of cathepsin D in endothelial dysfunction in chronic kidney disease and to determine its value as a tool for early diagnosis and target for treatment of cardiovascular diseases in patients with chronic kidney disease.

Impact of Low- or High-Flux Haemodialysis and Online Haemodiafiltration on Inflammatory Markers and Lipid Profile in Chronic Haemodialysis Patients

Background/Aims: We aimed to evaluate the impact of low- or high-flux haemodialysis (HD) and online haemodiafiltration (OL-HDF) on inflammation and the lipid profile in HD patients. Methods: 50 HD patients were assigned to two groups for HD with low-flux (n = 25) or high-flux (n = 25) polysulphone dialysers for 6 weeks. Subsequently, all patients were haemodialysed with a low-flux polysulphone dialyser for 6 weeks, then transferred to OL-HDF for another 6 weeks. Blood samples for lipids and inflammatory markers (IL-6, IL-8, TNF-α, hs-CRP) were obtained at baseline and every 6 weeks. Results: Changes in inflammatory markers and lipids from baseline to the 6-week dialysis period did not differ between low- and high-flux groups. When patients were transferred from low-flux HD to OL-HDF, IL-6, IL-8, and TNF-α levels significantly decreased whereas HDL and LDL cholesterol significantly increased. Conclusion: Low- and high-flux polysulphone membranes had similar effects on lipids and inflammatory markers, whereas OL-HDF potently reduced pro-inflammatory cytokines.

Acute Thrombotic Thrombocytopenic Purpura Following Orthopedic Surgery: Case Report and Review of the Literature

Thrombotic thrombocytopenic purpura (TTP) is an uncommon cause of hematological and renal abnormalities in the postoperative period. An association between TTP and orthopedic surgery, a rare entity, has been reported in the literature. It has the strong possibility of being fatal and therefore should be treated immediately, mostly by plasmapheresis. We report a 15-year-old girl of TTP following a high tibial valgus osteotomy (HTO).

Evaluation of the mean platelet volume in secondary amyloidosis due to familial Mediterranean fever

Familial Mediterranean fever (FMF) is an inflammatory disorder that is leading cause of secondary amyloidosis (AA). This study was designed to investigate the level of mean platelet volume (MPV) in AA. Seventy-four FMF, 29 AA patients and 180 healthy controls, were included. There was no significant difference between the cases in terms of sex and age. MPV levels were measured in all groups. In the FMF group, MPV level was significantly higher when compared to the control group. MPV level was significantly lower in AA group in comparison with the FMF and healthy control groups. In summary, our present study showed low MPV values in AA due to FMF.