Harun Akar

Renal Behçet's Disease: An Update

OBJECTIVE The aims of this study are (1) to report 33 patients with Behçets disease (BD) having various renal manifestations, and (2) to update current data using our patients and published papers about BD and renal manifestations. METHODS The PubMed database was searched using the terms BD or Behçets syndrome. We found reports of 94 patients (including ours) with BD and specific renal diseases (amyloidosis, 39; glomerulonephritis [GN], 37; renal vascular disease, 19; interstitial nephritis, 1). RESULTS The presentation of renal disease was edema/nephrotic syndrome in 12 patients (36%). Renal disease was incidentally diagnosed by routine urine analysis and measurement of serum creatinine level in 20 patients (61%). Renal failure was present in 23 patients (70%) and 5 of them have had cyclosporine treatment. The frequency of renal disease among BD patients has been reported to vary from less than 1 to 29%. CONCLUSIONS The clinical spectrum of renal BD shows a wide variation. Amyloidosis (AA type), GN, and macroscopic/microscopic vascular disease are the main causes of renal BD. Patients with vascular involvement have a high risk of amyloidosis and amyloidosis is the most common cause of renal failure in BD. Several types of glomerular lesions are seen in BD. Current treatment options for renal BD are not evidence based. Radiological vascular intervention combined with immunosuppressive drugs can be useful in selected cases. Routine urine analysis and measurement of serum creatinine level are needed for early diagnosis of renal BD.

Assessment of volume status and arterial stiffness in chronic kidney disease.

Abstract Aim: There is limited information about arterial stiffness in chronic kidney disease (CKD) which is an independent risk factor for cardiovascular events. Pulse wave velocity (PWV), augmentation index (AIx) are using to determine arterial stiffness. We aimed to study PWV, AIx, volume status in patients with stage 3B-5 CKD and continuous ambulatory peritoneal dialysis (CAPD). Methods: Sixty-six stage 3B-5 CKD patients, 21 CAPD patients, 34 healthy controls were included. Pulse wave velocity, AIx, volume status was evaluated by Mobil-O-Graph®, and bioimpedance spectroscopy, respectively. Results: The Median PWV was 7.5 m/s in CKD, 6.2 m/s in CAPD, 5.9 m/s in healthy controls, and while PWV was found to have increased significantly in CKD patients (p = 0.002), the Alx values were similar in all groups. The median extracellular fluid excess was higher in both the CKD and, CAPD patients when compared with healthy controls (1.26 and 1.21 L, respectively). Overhydration was more prevalent in CKD and CAPD patients (p < 0.001). Age, central systolic blood pressure, body mass index, fat mass, overhydration, CKD, eGFR were the major determinants of PWV. Conclusion: Increased PWV was found in stage 3B-5 CKD patients. Overhydration may contribute this increment.

Effects of atorvastatin on development of peritoneal fibrosis in rats on peritoneal dialysis

Rational: Peritoneal sclerosis is one of the important complications of long-term peritoneal dialysis (PD). In this study, efficacy of atorvastatin on peritoneal histology and functions in non-uremic rats on PD was tested. Objectives: Twenty-two non-uremic Wistar albino rats were randomized into three groups: Sham (intraperitoneal saline), peritoneal dialysis (PD, intraperitoneal 3.86% dextrose containing PD solution), and treatment (TX, intraperitoneal 3.86% dextrose containing PD solution plus atorvastatin added into drinking water). At the end of a 4-week period, 1 h peritoneal equilibration test was performed. Serum lipids and certain cytokines, mediators, markers, and antioxidant enzyme activities in serum and dialysate were studied. Peritoneal thickness was measured and peritoneal inflammation, fibrosis, and vascular proliferation were scored in histological sections. Main findings: In histological examinations, inflammation, fibrosis, and vascular proliferation were significantly more frequent in PD group than Sham group and it seemed to decrease significantly when atorvastatin was used in conjunction with PD. Additionally, peritoneum was significantly thicker in PD group when compared to that of Sham and TX groups. Serum parameters did not significantly differ between groups. On the other hand, dialysate glutathione reductase (GR) activity and TGF-β were significantly lower in TX group than that of the PD group, whereas dialysate IL-6 level was higher in TX group. Principal conclusions: In our study, atorvastatin use appeared to diminish structural changes in peritoneum. Decreased expression of TGF-β in dialysate may be one of the possible underlying mechanisms.

Effect of sodium bicarbonate in an experimental model of radiocontrast nephropathy

Aim: The aim of this study is to investigate the efficacy and mechanism of action of intravenous (IV) bicarbonate in preventing radiocontrast nephropathy (RCN). Materials and methods: Twenty-eight Wistar rats were randomized into four groups including control (group 1), radiocontrast (group 2), bicarbonate (group 3), and radiocontrast plus bicarbonate (group 4). Once blood chemistry and arterial blood gases were examined and 24 h urine samples were collected, all rats were administered furosemide (2 mg/kg subcutaneous) and deprived of water for 24 h. Iothalamate sodium (6 mL/kg) was administered to group 2 and group 4. IV bicarbonate (8.4%) was administered to group 3 and group 4 (3 h before the administration of iothalamate). On the fourth day, 24 h urine was collected, and at the end of the day rats were sacrificed and blood chemistry and arterial blood gases were reexamined. Myeloperoxidase (MPO), nitric oxide (NO), total glutathione, and malondialdehyde were quantified on the renal tissue. H&E slides were examined. Results: Basal creatinine and creatinine clearance were similar between groups. There was no significant difference between creatinine and creatinine clearance by the end of the experiment. Glutathione level in group 2 was lower than in group 4. Histopathologically, there was no injury in the control group (group 1) whereas there was an intermediate-severe injury (71.4%) in the radiocontrast group (group 2). The percentage of intermediate-severe injury was significantly lower (71.4% vs. 28.6%, p = 0.02) in the radiocontrast plus bicarbonate group (group 4). Conclusions: Sodium bicarbonate attenuates the development of radiocontrast-induced tubular necrosis.

MPO-ANCA-Associated Small Vessel Vasculitis Presenting as Fever of Unknown Origin

Microscopic polyangiitis (MPA) is an antineutrophil cytoplasmic antibody (ANCA) associated small vessel vasculitis which can present with various clinical manifestations, for which the mainstay of treatment is systemic corticosteroids and immunosuppressants. We report a case of a 54-year-old female admitted to the hospital because of fever during the last month, leukocytosis and elevated erythrocyte sedimentation rate. Persistence of elevated serum creatinine levels and accompanying hematuria led us to perform a renal biopsy, and MPA was diagnosed on the basis of light and immunofluorescence microscopy. Remission was induced with oral corticosteroids and cyclophosphamide therapy in conjunction with plasmapheresis (PF). The objective of this report was to assess the role of PF in the treatment of MPA and report on its utility in patients with MPA who are not responding to standard therapy or who require unacceptably high doses of steroids or immunosuppressants. In a patient presenting with fever of unknown origin, microscopic polyangiitis should also be considered in the differential diagnosis.

Resistive index measurement of native hemodialysis arteriovenous fistula feeding artery as a predictor for fistula dysfunction.

The aim of the present study was to evaluate resistive index (RI) in the feeding artery of the functioning and dysfunctioning arteriovenous fistulas (AVFs). Measurement of RI in the feeding artery using Doppler ultrasound was performed in 48 patients on hemodialysis. Twenty-seven upper arm AVFs and 21 radiocephalic AVFs were studied. The patients were categorized into three groups according to clinical function: group 1, AVFs with normal function (n = 21); group 2, AVFs with abnormal clinical function (reduced pump flow) (n = 20); and group 3, AVFs with abnormal clinical function (increased venous pressure) (n = 7). Resistive index measurements and morphologic changes were compared between functioning and dysfunctioning AVFs. Increased RI values were detected in the AVFs with reduced pump flow. The average RI values of feeding artery were 0.47 ± 0.07 in group 1, 0.67 ± 0.18 in group 2, and 0.49 ± 0.05 in group 3. Two brachial artery aneurysms, one brachial artery pseudoaneurysm, ten venous stenoses, and six venous thromboses were detected in the AVFs with diminished pump flow (18/20 patients, 90%). Both increased RI values and vascular complications were detected by Doppler ultrasound in the patients with reduced pump flow during dialysis. This study shows that Doppler ultrasound examination of AVF feeding artery may provide useful data on morphologic and functional characteristics of AVF.

The effects of single hemodialysis session on arterial stiffness in hemodialysis patients.

Increased arterial stiffness in hemodialysis patients is a strong predictor of cardiovascular morbidity and mortality. Pulse wave velocity (PWV) and augmentation index (AIx), which are markers of arterial stiffness, were used to determine the severity of vascular damage noninvasively. This study aimed to investigate the effects of solute volume removal and hemodynamic changes on PWV and AIx of a single hemodialysis session. Thirty hemodialysis patients were enrolled in the study. Before initiation of hemodialysis, every 15 minutes during hemodialysis, and 30 minutes after the completion of the session, measurements of PWV and AIx@75 (normalized with heart rate 75 bpm) were obtained from each patient. Body composition was analyzed by bioimpedance spectroscopy device before and 30 minutes after completion of the hemodialysis session. During the hemodialysis, no significant change was observed in AIx@75. However, PWV decreased steadily during the session reaching statistically significant level at 135th minute (P = 0.026), with a maximal drop at 210th minute (P < 0.001). At 210th minute, decrease in PWV correlated positively with the decrease in central systolic blood pressure, central diastolic blood pressure, central pulse pressure, augmentation pressure, and AIx@75. Multiple regression analysis showed that decrease in PWV at 210th minute was associated with decrease in central systolic blood pressure and central pulse pressure. Ultrafiltration during hemodialysis had no significant effect on PWV and AIx@75. Delta urea correlated positively with delta PWV at 240th minute. A significant decrease in PWV was observed during hemodialysis and correlated with urea reduction; however, we were unable to document any effect of volume removal on arterial stiffness.

Exogenously administered adenosine attenuates renal damage in streptozotocin-induced diabetic rats.

Abstract Background: Diabetic nephropathy (DNP) is one of the most serious complications of diabetes mellitus (DM). In the present study, we investigated the potential of adenosine as a therapeutic candidate for preventing DNP. Methods: Twenty-one adult male rats were included in the study. Fourteen rats were administered a single dose of 60 mg/kg streptozotocin (STZ) to induce diabetes. Seven rats served as normal control group. Diabetic rats were randomly divided into two groups: one group was treated with 1 mL/kg saline/day (DM + saline) and the other group was treated with 5 mg/kg/day adenosine (DM + adenosine) for 6 weeks. After 6 weeks, biochemical parameters including urea, creatinine, blood urea nitrogen (BUN), kidney injury molecule-1 (KIM-1) and tumor necrosis factor-α (TNF-α) were measured in plasma samples. Also, kidneys were removed for histopathological assessment. Results: Both of plasma KIM-1 and TNF-α levels were significantly higher in DM + saline group compared to controls. However, treatment of diabetic rats with adenosine significantly decreased the plasma KIM-1 and TNF-α levels compared to DM + saline group. Significant histopathological changes were observed in diabetic rats whereas adenosine treatment effectively prevented these changes. Conclusions: The findings of the present study suggest that adenosine may be a useful therapeutic agent for preventing DNP.

Impact of Interdialytic Weight Gain (IDWG) on Nutritional Parameters, Cardiovascular Risk Factors and Quality of Life in Hemodialysis Patients

Abstract Introduction. The amount of interdialytic weight gain (IDWG) considering body weight is of great importance in hemodialysis patients. In general practice, patients are asked to get standard weight between two hemodialysis sessions. However, it should be individualized considering patient’s weight. We aimed to determine the association between the IDWG and the nutritional parameters, cardiovascular risk factors, and quality of life. Methods. Thrity-two patients receiving hemodialysis at least for one year were enrolled into the study. Patients were monitored for 12 consecutive hemodialysis sessions; and the arithmetic mean of IDWG was calculated. IDWG% was calculated in accordance with patients’ dry weight. Data of patients with IDWG<3% (Group I) and IDWG≥3 (Group II) were compared. Sociodemographic variables, laboratory, anthropometric measurements, blood pressure, left ventricular mass index, Subjective Global Assessment Scale and SF-36 Quality of Life Scale were applied to evaluate the patients. Results. 59.4% (n=19) and 40.6% (n=13) of patients were included in Group I and Group II, respectively. In Group II, albumin (p=0.02), potassium (p=0.02), phosphorus (p=0.04), nPCR (p=0.03), physical function (p=0.04), role limitations caused by physical problems (p=0.04), general health (p=0.03), physical quality of life (p=0.04) scores were significantly higher. A significant correlation was detected between IDWG and physical and mental quality of life, total score SF-36, albumin, total protein and the potassium values. Conclusions. Patients with an IDWG ≥ 3% have better nutritional parameters and quality of life scales. The limiting of IDWG to 1-2 kg, ingoring patient weight may give rise to malnutrition and a reduced quality of life.

Efficacy and Tolerability of Amifostine in Elderly Cancer Patients

BACKGROUND Amifostine is a cytoprotective agent used to prevent cisplatin nephrotoxicity. It is associated with dose-limiting acute toxicities of emetic symptoms (nausea and vomiting) and transient hypotension. OBJECTIVE The aim of this study was to analyze the efficacy and tolerability of amifostine in elderly cancer patients. METHODS This 18-month, prospective, comparative study was conducted at the Department of Internal Medicine, Adnan Menderes University Hospital (Aydin, Turkey). Adult (aged 40-<85 years) hospitalized patients with advanced-stage cancer without comorbid diseases were enrolled. Patients were divided into 2 groups: age <70 years (group 1) and ≥70 years (group 2). All patients were treated with amifostine + cisplatin-based chemotherapy (CT). Amifostine 910 mg/m(2) (maximum, 1500 mg) was administered as a 15-minute IV infusion. Clinical systolic and diastolic blood pressures (SBP and DBP, respectively) were measured at 0 minute (baseline), at 8 and 15 minutes of amifostine infusion, and at 30 minutes after the start of amifostine infusion. In addition to physical examination, chest radiography, electrocardiography, blood chemistry (including serum electrolytes and renal function tests), complete blood count, and complete urinalyses were performed before each CT administration and at the post-CT day of toxicity assessment. RESULTS Thirty-five consecutive patients were enrolled (22 men, 13 women; mean [SD] age, 61 [12] years; group 1, n = 22; group 2, n = 13). Patients received a total of 153 CT cycles (median, 4 cycles/patient; group 1, 96 cycles; group 2, 57 cycles). Amifostine caused significant SBP and DBP reductions at 8 minutes of infusion compared with baseline in groups 1 (both P < 0.001) and 2 (P = 0.002 and P = 0.006, respectively). Overall, 20 patients (57.1%) experienced ≥ 1 symptomatic hypotensive episode; these rates were not significantly different between groups 1 (11 cases, 50.0%) and 2 (9 cases, 69.2%). Amifostine infusion was interrupted a similar number of times (6 times in group 1 and 4 times in group 2 [6.3% and 7.0% of administrations, respectively]) due to hypotension, but could be restarted in all. At 15 minutes, mean SBP and DBP values were not significantly different from baseline in either group. The mean baseline SBP values were similar between groups at baseline, and, overall, the differences in mean SBP and DBP values were not significant between groups at any time point. All other toxicities were comparable, and serum creatinine concentrations did not change significantly from baseline with CT in either group. CONCLUSIONS In this study of the efficacy and tolerability of amifostine in elderly patients with advanced-stage cancer without comorbid diseases, amifostine was effective in reducing cisplatin-induced nephrotoxicity, with transient systolic and diastolic hypotension being the most prominent adverse effect. All other toxicities were either low grade or preventable. No significant differences in amifostine tolerability or toxicities were observed between the study groups.