A UFLC-MS/MS Method for the Simultaneous Analysis of Urinary Podocin and Podocalyxin in Patients with Nephrotic Syndrome.

OBJECTIVE: To create an efficient and robust mass spectrometric method for the simultaneous quantitation of podocin and podocalyxin in urine samples and to evaluate urinary podocin and podocalyxin levels in patients with nephrotic syndrome (NS). METHODS: A mass spectrometric method was generated for the measurement of tryptic peptides in urine sediment. Separation of peptides was achieved via liquid chromatography, and mass spectrometric analyses were conducted by electrospray ionization triple-quadrupole mass spectrometry in the multiple reaction monitoring mode. RESULTS: Intra- and interassay precision values were below 12% and accuracies ranged from 87% to 111% for both of peptides. The validated method was successfully applied to detect these peptides in patients with NS. Urine podocin and podocalyxin levels were significantly higher in patients with NS compared to healthy controls. CONCLUSIONS: This proposed mass spectrometric method provides technological evidence that will benefit the clinical field in the early diagnosis and follow-up of NS.

Serum uromodulin levels, MR imaging findings, and their relationship with eGFR-based CKD staging in ADPKD patients.

PURPOSE: Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease that may progress to end-stage renal disease, characterized by increased kidney volume due to cystic formations. In this study, we aimed to investigate the relationship between serum uromodulin levels, total kidney volume and estimated glomerular filtration rate (eGFR) in patients with ADPKD. METHODS: This study included a total of 54 ADPKD patients and 18 healthy volunteers (control group). Total kidney volumes were calculated through magnetic resonance images using ellipsoid method. Serum uromodulin measurements were measured using an ELISA method. RESULTS: Serum uromodulin levels were lower in patients compared with the control group (2.47 ± 0.16 vs 2.6 ± 0.28, p = 0.021). There was no significant difference in uromodulin values among the patients in chronic kidney disease (CKD) stages 1-2, 3 and 4-5. TKV measurements of CKD stage 4-5 patients were significantly higher than the stage 1-2 patients (p = 0.015). A negative correlation was observed between TKV and eGFR (r = - 0.433, p = 0.001). A positive correlation was observed between uromodulin and eGFR (r = 0.274, p = 0.02). When the serum levels of uromodulin and the level of eGFR were evaluated using simple linear regression analysis, R2 value was found to be 0.075, suggesting that 7.5% change in serum uromodulin values corresponds with the change in eGFR value. CONCLUSION: These findings are consistent with previous studies that reported that serum uromodulin may be a good biomarker for demonstrating renal function in the early stages of CKD, before eGFR levels deteriorate. Serum uromodulin level may be useful in demonstrating renal functions in the follow-up of individuals with ADPKD.

A case of cyclic hemoperitoneum in a hemodialysis patient: Encapsulated peritoneal sclerosis complicated by endometriosis and fungal peritonitis.

Encapsulated peritoneal sclerosis (EPS) is a rare, but frequently fatal, long-term complication of peritoneal dialysis. Endometriosis is a common gynecological problem but hemoperitoneum due to endometriosis has been reported to be extremely rare in hemodialysis (HD) patients. A 25-year-old female HD patient was admitted to our clinic with nausea, vomiting, abdominal pain, and weight loss for last 3 months. Candida tropicalis and Candida glabrata were isolated in the fungal cultures from peritoneal fluid. Her abdominal computerized tomography scan has shown irregular peritoneal calcifications, diffuse peritoneal thickening, dilatation of the small bowel loops, and cocoon formation which all were typical for EPS. Hemoperitoneum was reported to recur for four times with intervals suggesting menstrual cycles. Her peritoneal biopsy, along with the signs of EPS, has also revealed the presence of endometriosis. The patient died with symptoms of septic shock in the first year of EPS diagnosis.

Mesalazine induced focal segmental glomerulosclerosis in a patient with ulcerative colitis.

Focal segmental glomerulosclerosis (FSGS) and other glomerulonephritis due to the use of 5-aminosalicylic acid derivatives have been reported in the literature. A 38-year-old male who had been using mesalazine for four years because of ulcerative colitis applied to doctor due to swelling in the lower extremities. The patient was diagnosed with nephrotic syndrome (NS). Renal biopsy was performed, and FSGS was diagnosed. Antiproteinuric treatments were initiated with steroid therapy. The patient has been followed with the normal renal function of the after treatment. 5-aminosalicylic acid derivatives affect renal functions at different levels and caused in NS.

Sexual Dysfunction Is Associated with Depression and Anxiety in Patients with Predialytic Chronic Kidney Disease.

OBJECTIVE: We aimed to determine the prevalence of sexual dysfunction and clarify the relationship between sexual dysfunction and depressive mood state, drugs, and disease activities in patients with predialytic chronic kidney disease (CKD). MATERIALS AND METHODS: In total, 150 patients with CKD who had an estimated glomerular filtration rate of 15-60 mL/min were included; 65 healthy controls were selected. A detailed medical and sexual medical history was taken from individuals in the control and patient groups by applying the Golombok-Rust Inventory of Sexual Satisfaction and Hospital Anxiety and Depression Scale. RESULTS: Sexual frequency (p=0.027), impotence (p<0.001), and premature ejaculation scores (p<0.001) in male patients and sexual frequency (p=0.004), communication (p=0.004),, satisfaction (p<0.001), avoidance (p=0.008), orgasmic dysfunction (p<0.001), sensuality (p=0.002), and total sexual dysfunction scores (p<0.001) in female patients with CKD were found to be higher compared with the control group. In female patients, the depression scores of patients with stage 3 CKD were found to be higher than those of patients with stage 4 CKD (p=0.028). The avoidance scores of male patients with depression (p=0.006) were high. In contrast, the communication score of female patients with depression was high (p=0.004). It has been detected that the factors that affect the sexual dysfunction score of patients with CKD in males are age (p=0.006), hypertension (p=0.008), anxiety (p=0.003), and depression (p=0.002) and those in female patients are age (p=0.034), anxiety (p<0.001), and depression (p=0.001). CONCLUSION: Patients with predialytic CKD substantially have sexual dysfunction. The most important factors that affect sexual dysfunction are age, hypertension, anxiety, and depression.

High serum soluble CD200 levels in patients with autosomal dominant polycystic kidney disease.

CD200 is a novel immune-effective molecule, existing in a cell membrane-bound form, as well as in a soluble form in serum, which performs to modulate inflammatory and acquired immune responses. Autosomal dominant polycystic kidney disease (ADPKD) is characterized by the development of large renal cysts and progressive loss of renal function. As defects in cell cycle arrest and apoptosis of renal tubular epithelial cells occur in ADPKD, we asked whether serum soluble CD200 might underlie and effect on ADPKD. Serum soluble CD200 levels were measured in 44 patients with ADPKD and 24 healthy volunteers. Concentrations of soluble CD200 in the serum samples were quantified using an ELISA kit. The mean serum soluble CD200 levels were higher in patients with ADPKD than in the control group (71.4±29.2 and 21.4±5.6 pg/mL, p<0.001). Positive correlation was detected between serum soluble CD200 levels and glomerular filtration rate (r=0.772, p<0.001), and serum albumin level (r=0.466, p=0.001). Negative correlation was detected between serum soluble CD200 levels and serum creatinine levels (r=-0.761, p<0.001), and C reactive protein levels (r=-0.364, p=0.015). In the ADPKD patients group, serum soluble CD200 levels were lower in patients with stage 5 chronic kidney disease (CKD) than in patients with stages 1-2 (p<0.001), 3 (p=0.005) and 4 CKD (p=0.006). Serum soluble CD200 levels were similar in patients with stages 1-2, 3, and 4 CKD (p>0.05). Our results show that patients with ADPKD have activated soluble CD200 levels which were related to renal function and inflammation.

High serum soluble α-Klotho levels in patients with autosomal dominant polycystic kidney disease.

This study aims to determine fibroblast growth factor-23 and soluble α-Klotho levels in patients with autosomal dominant polycystic kidney disease. A total of 76 patients with autosomal dominant polycystic kidney disease and 32 healthy volunteers were included in the study. Serum fibroblast growth factor-23 and soluble α-Klotho levels were measured with ELISA kits. Parathyroid hormone, phosphate, calcium, creatinine, 25-hydroxyvitamin D3 levels, urinary protein to creatinine ratio and estimated glomerular filtration rate were also measured or calculated. Patients with autosomal dominant polycystic kidney disease had significantly higher serum parathyroid hormone (p<0.001), fibroblast growth factor-23 (p<0.001), soluble α-Klotho levels (p=0.001) and lower serum 25-hydroxyvitamin D3 levels (p<0.001) as compared with healthy volunteers. Serum fibroblast growth factor-23, soluble α-Klotho and 25-hydroxyvitamin D3 levels were similar in all five chronic kidney disease stages of autosomal dominant polycystic kidney disease (p>0.05). Fibroblast growth factor-23 (r=-0.251, p=0.034) and soluble α-Klotho levels (r=-0.251, p=0.034) were found to be negatively correlated with estimated glomerular filtration rate. This study shows increased fibroblast growth factor-23 levels in patients with autosomal dominant polycystic kidney disease which is in harmony with the general trend in patients with chronic kidney disease of other aetiologies, but, unlike them, also a significant increase in serum soluble α-Klotho levels in patients with autosomal dominant polycystic kidney disease suggesting an aberrant production or a decreased clearance of α-Klotho molecule. Considering the unique increases in erythropoietin levels due to erythropoietin production in renal cysts, we assume, patients with autosomal dominant polycystic kidney disease may potentially have different soluble α-Klotho production/clearance characteristics than the patients with other parenchymal renal diseases.

Autosomal Dominant Polycystic Disease is Associated with Depressed Levels of Soluble Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is characterized by multiple, large renal cysts and impaired kidney function. Although the reason for the development of kidney cysts is unknown, ADPKD is associated with cell cycle arrest and abundant apoptosis of renal tubular epithelial cells. AIMS: We asked whether serum-soluble TNF-related apoptosis-inducing ligand (sTRAIL) might underlie ADPKD. STUDY DESIGN: Case-control study. METHODS: Serum sTRAIL levels were measured in 44 patients with ADPKD and 18 healthy volunteers. The human soluble TRAIL/Apo2L ELISA kit was used for the in vitro quantitative determination of sTRAIL in serum samples. RESULTS: Mean serum sTRAIL levels were lower in patients with ADPKD as compared to the control group (446.9±103.1 and 875.9±349.6 pg/mL, p<0.001). Serum sTRAIL levels did not differ among stages of renal failure in patients with ADPKD. There was no correlation between serum sTRAIL levels and estimated glomerular filtration rate in patients with ADPKD (p>0.05). CONCLUSION: Our results show that ADPKD patients have depressed sTRAIL levels, indicating apoptosis unrelated to the stage of chronic renal failure.

The effects of dual and triple combinations of trandolapril, telmisartan, and verapamil on overt proteinuria in the patients with diabetic nephropathy.

Diabetic nephropathy (DN) is one of the most important causes of the end-stage renal failure and its prevalence is found to be increasing. The presence of hypertension and progressive proteinuria is among the important findings. In this study, the effects of double and triple combinations of trandolapril, telmisartan, and verapamil on proteinuria were investigated in diabetic patients with nephropathy. Seventy-eight patients (mean age: 56.11 ± 11.26 years; 47 females and 31 males) with overt proteinuria and DN were included in this study. The patients were divided into four groups: Group I (n: 18, trandolapril + telmisartan), Group II (n: 20, trandolapril + verapamil), Group III (n: 20, trandolapril +telmisartan + verapamil), and Group IV (n: 20, telmisartan + verapamil). At the end of a three-month therapy, within and between group comparisons were done about the effects of the use of double or triple drug combinations on proteinuria, glomerular filtration rate (GFR), electrolytes, serum albumin, low-density lipoprotein (LDL)- cholesterol, and HbA1C. There was no significant difference among groups in terms of age, gender, diabetes duration, body mass index, and retinopathy frequency. The decreases in proteinuria and mean arterial blood pressure (MABP) were significant in all groups. The decrease in proteinuria was independent of the decrease in MABP [the reduction rate in proteinuria was 39% (P <0.001) in Group I, 37% (P <0.001) in Group II, 42% (P <0.001) in Group III, and 43% (P <0.001) in Group IV; the reduction rate in MABP was 10.6% (P <0.001) in Group I, 13.7% (P <0.001) in Group II, 17.5% (P <0.001) in Group III, and 15.4% (P <0.001) in Group IV]. Decrease in HbA1C (before and after treatment) was significant in Groups III and IV when com- pared to Groups I and II. Any adverse event, like hyperkalemia, was not observed. There was no significant difference among the groups in terms of GFR, LDL-cholesterol, albumin, and potassium. All the patients tolerated the drugs well. In conclusion, in patients with DN, both double or triple combinations of trandolapril, telmisartan and verapamil resulted in significant decreases in proteinuria and MABP. Triple combinations did not have any superiority over double combinations. Therefore, the suitable drug combinations may be chosen according to the clinical status of a patient.

New-Onset Diabetes Mellitus Associated with Sirolimus Use in Renal Transplant Recipients.

New-onset diabetes after transplantation and impaired glucose tolerance are very common in renal transplant patients. New-onset diabetes after transplantation (NODAT) is associated with increased cardiovascular morbidity and mortality, reduced graft and patient survival. Several risk factors for NODAT have been identified: age, obesity, family history of diabetes mellitus and HCV infection. In addition, steroid and calcineurin inhibitors also contribute to the development of NODAT. Sirolimus causes immunosuppressive effects by inhibiting mammalian target of rapamycin (mTOR), and has well known side effects. The effects of sirolimus on glucose metabolism and contribution to NODAT development are not clearly known. In this report, we presented five RTX patients who developed NODAT under the treatment of sirolimus.

FGF-23, α-Klotho Gene Polymorphism and Their Relationship with the Markers of Bone Metabolism in Chronic Peritoneal Dialysis Patients.

OBJECTIVE: The aim of the present study was to evaluate the variations of some major bone metabolism markers with reference to klotho gene polymorphism (KGP) and bone mineral density (BMD) values in patients on chronic peritoneal dialysis (CPD). MATERIALS AND METHODS: In 51 CPD patients and 40 healthy persons, assays for intact parathormone (iPTH), fibroblast growth factor 23 (FGF-23), osteoprotegerin (OPG), osteocalcin (OC), procollagen type-1 N terminal propeptide (PINP), beta- crosslaps (beta CTx), tartrate resistant acid phosphatase (TRAP5b), bone alkaline phosphatase (BAP), 1,25(OH)D3, and 25(OH)D3 and α-klotho gene mutations were performed. RESULTS: In CPD patients, 1,25(OH)D3 and 25(OH)D3 deficiency rates were 96% and 94% respectively. iPTH (249 pg/mL vs 39 pg/mL) and FGF-23 (1089 RU/mL vs 153 RU/mL), OPG, OC, PINP, beta CTx, TRAP5b levels were significantly higher in patients. iPTH levels and whole-body BMD values were negatively correlated in patients. The rate of KGP was similar in all groups. CONCLUSION: In CPD patients, besides vitamin D deficiency, high levels of OPG, OC, PINP, beta CTx, TRAP5b were evident. Positive correlation between iPTH levels and BAP and PINP levels suggested a diagnostic value for those markers during the management of CKD MBD. On the other hand, high serum TRAP5b concentrations did not seem to be affected by neither calcitriol treatment nor the severity of hyperparathyroidism. iPTH and FGF-23 levels and whole-body BMD values showed a significant negative correlation. We were unable to show any correlation between KGP and any of the CKD-MBD parameters measured in this study.

Assessment of Long-Term Outcomes in Hbs Ag-Negative Renal Transplant Recipients Transplanted from Hbs Ag-Positive Donors.

BACKGROUND: The aim of this study was to evaluate the long-term outcomes of renal transplantation from Hbs Ag-positive donors to Hbs Ag-negative recipients. MATERIAL AND METHODS: A total of 78 patients who underwent renal transplantation in our clinic between January 2006 and May 2014 were included in the study. Patients were divided into 2 groups: Group 1: Donor Hbs Ag (+) (n=26, Hbs Ab (-), Hbe Ag (-), Hbe Ab (+), Hbc Ig total (+) and HBV DNA (+), male/female (M/F): 16 (61.5%)/10 (38.5%), and Group 2: Donor Hbs Ag (-) (n=52, M/F: 41 (78.8%)/11 (21.2%). Hbs Ab levels were similar in recipients in both groups. Data were collected retrospectively. Analyses were performed by using SPSS 20.0 software, and patient and graft survival were measured by using Kaplan-Meier survival curve and compared by using the log-rank test. RESULTS: Demographic data were similar in the 2 groups. The rate of acute Hepatitis B infection was significantly higher in Group 1 than in Group 2 [n=3 (11.5%) vs. n=0 (0%), respectively, p=0.012]. Acute hepatitis B attacks were detected in vaccinated patients. Graft survival rates (groups 1 and 2, respectively; at 1st, 3rd, 5th and 8th years: 95% vs. 96%, 95% vs. 94%, 85% vs. 88%, 85% vs. 82%, p=0.970) and patient survival rates (p=0.098), acute rejection rates (p=0.725), delayed graft function, chronic allograft dysfunction, new-onset diabetes after transplantation (NODAT), cytomegalovirus infection, and the need for postoperative dialysis and plasmapheresis were similar between groups. CONCLUSIONS: Our study revealed that the risk of developing acute hepatitis B was higher in patients renally transplanted from Hbs Ag (+) donors, but the other clinical outcomes were similar between groups.

The association of serum-free light-chain levels with markers of renal function.

BACKGROUND: The kidney is often affected in plasma cell dyscrasias, usually due to the effects of nephrotoxic monoclonal-free light chains. Renal failure due to a monoclonal gammopathy may be detected by the highly sensitive serum-free light-chain (sFLC) ratio yet missed by electrophoretic assays. The aim of this study was to assess sFLC levels in relation to markers of renal function. METHODS: Five-hundred thirteen patients were included in this study. sFLC levels were measured by Freelite® (The Binding Site Group Ltd, Birmingham, UK) assay using the BNII nephelometer (Siemens Diagnostics, Germany). Kappa/lambda (κ/λ) sFLC ratio was calculated. Serum creatinine levels were analyzed by modified Jaffe method in Cobas 8000 analyser. GFR was estimated by the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation. Patients were assigned to two groups depending on their eGFR values: ≤ 60 mL/min/1.73 m(2) (Group 1, n = 103) and > 60 mL/min/1.73 m(2) (Group 2, n = 410). Data were expressed as median and min-max. All the statistical analyses were done with SPSS version 20.0 and a significance level of 0.05 was considered. RESULTS: Serum κ-FLC median value was 36.4 (5.62-16,000) mg/L, serum λ-FLC was 21.7 (4.91-8770) mg/L, κ/λ sFLC ratio was 1.33 (0.01-3258) and serum creatinine was 1.56 (0.63-7.21) mg/dL in Group 1. Both λ sFLC and κ/λ sFLC ratios were correlated with eGFR (r = -0.318, r = 0.198, p < 0.05, respectively). We did not find any significant correlation between κ/λ sFLC ratio and eGFR in Group 2. CONCLUSIONS: We examined the association between sFLC concentrations and renal function. Our preliminary findings suggest that serum λ-FLC might be considered as a useful marker for predicting renal function. Prospective studies are needed to clarify the usefulness of these parameters for identifying renal failure due to a monoclonal gammopathy.

Is Klotho F352V Polymorphism the Missing Piece of the Bone Loss Puzzle in Renal Transplant Recipients?

BACKGROUND: Bone disorders are next to cardiovascular problems in frequency in renal transplant (RT) recipients. Reduction in 1,25-dihydroxycholecalciferol (1,25D) levels is among the reasons causing bone loss in these patients. Klotho (KL) serves as a co-receptor for fibroblast growth factor 23 (FGF23), and functions in vitamin D metabolism. KL polymorphisms have been identified in several studies, and phenylalanine to valine substitution at amino acid position 352 seemed to be important to KL function. We investigated KL F352V polymorphism and its relation with 1,25D levels in RT recipients. METHODS: The study included 25 RT recipients (8 female, 17 male) and 26 (14 female, 12 male) healthy control subjects who were wild (FF) phenotypes in terms of KL F352V polymorphism. RT recipients with (FV, n = 11) and without (FF, n = 14) a heterozygote polymorphism were determined with high resolution DNA melting analysis of KL F352V polymorphism. Serum 1,25D levels were measured using the RIA method. RESULTS: RT recipients with FV phenotype had significantly lower 1,25D levels (17.58 ± 18.38 pg/ml) compared to recipients with FF phenotype (44.91 ± 24.68 pg/ml) and control subjects (28.24 ± 12.13 pg/ml). 1,25D levels in RT recipients with FF phenotype were significantly higher than control subjects. CONCLUSIONS: KL F352V polymorphism may increase the expression of FGF23 co-receptor, KL protein and thus may decrease renal expression of 1α-hydroxylase, and/or stimulate 24-hydroxylase in RT recipients. The resultant decrease 1,25D levels may participate in bone loss in these patients.

Significant Association between Serum Levels of Von Willebrand Factor (vWF) Antigen with Stages of Cirrhosis.

OBJECTIVE: Von Willebrand factor (vWF) is a mediator that increases endotoxemic medium like in cirrhosis. In this study we evaluated the association of serum VWF antigen (Ag) level with the stage of cirrhosis (according to Child-Pugh classification). MATERIALS AND METHODS: We included 82 cirrhotic patients (Female/Male (F/M): 26/56) and 86 healthy subjects (F/M: 44/42) in the study. Ages of the both groups of patients were not different (P= 0.095). We excluded possible other reasons that may cause VWF level increase. Diagnosis of cirrhosis was made on the basis of biopsy in 7 patients and with clinical and laboratory parameters in 75 patients. VWF Ag level was determined by immunoturbidimetric test. The stage of cirrhosis was defined with Child-Pugh classification. Data were analysed by using Statistical Package for the Social Sciences (SPSS) 10.0 software program. RESULTS: VWF Ag level was significantly higher in cirrhotic patients compared to control group (220±90 and 87±38, P<0.001, respectively). We observed significant increase of VWF Ag level with the increasing stages of cirrhosis according to Child-Pugh score (VWF Ag level for Child A-B-C 156.4±54/215±45/284.8±93, respectively; P values for Child A-B/A-C/B-C; <0.001/<0.001/0.006, respectively). CONCLUSION: Serum VWF Ag level increases in cirrhotic patients and this is more pronounced with higher stages of cirrhosis.

Erythrocyte folate status and serum iron levels in patients undergoing hemodialysis.

The present study was aimed to evaluate erythrocyte folate and the iron levels in diabetes and hypertension patients treated with/without hemodialysis. The effects of erythropoietin and iron treatment as well as vitamin supplementation on measured parameters were considered. The 67 controls consisted of healthy subjects (n = 22), hypertensive subjects (n = 22), and diabetic subjects (n = 23) without any renal disorder. According to primary renal disorders, the patients undergoing hemodialysis (n = 68) were classified into four groups as diabetic nephropathy, hypertensive nephropathy, reflux nephropathy or interstitial nephritis, and renal insufficiency depending on other causative factors. The mean value of erythrocyte folate levels of all patients undergoing hemodialysis was higher than the healthy control group (P < 0.05). Erythrocyte folate levels in hypertensive and diabetic nephropathy patients were higher than their own hypertensive or diabetic controls and also healthy controls (both, P < 0.05). Serum iron levels of all subgroups in hemodialysis patients were found to be similar with healthy controls (all, P > 0.05). The only significance observed within the subgroups was between diabetic controls and diabetic nephropathy patients (P < 0.05). None of the treatment or supplementation of erythropoietin, iron and vitamin affected erythrocyte folate levels (all, P > 0.05). The increase in erythrocyte folate status of patients with end stage renal diseases might be the result of sum or individual effects of causative factors such as renal pathology, compensation mechanism against renal anemia, or routine folate supplementation.

Effects of ivabradine on 6-minute walk test and quality of life in patients with previously implanted CRT-D.

BACKGROUND: We aimed to evaluate clinical effects of additional heart rate control by ivabradine on life quality score and 6-minute walking test in patients with previously implanted biventricular cardiac resynchronization therapy defibrillator (CRT-D) with ischemic heart failure under regular treatment. METHODS: Fifteen men and 14 women with a median age of 63 years (range, 48-79 years) were studied. Twenty-one patients were in New York Heart Association class II (8 patients were in class III), CRT-D implanted previously, and with resting heart rates greater than 70 beats per minute with sinus rhythm despite conventional medication. Patients were given 2.5- to 7.5-mg ivabradine orally twice a day, and drug dosage was titrated to decrease the patients' average heart rate to 70 beats per minute. Before and 3 months after ivabradine treatment, all patients underwent extensive clinical, echocardiographic, and laboratory evaluation. RESULTS: Ivabradine treatment produced dose-dependent reductions in heart rate at rest and at peak exercise (91.9 ± 6.3 to 71.7 ± 4.8 and 114.4 ± 7.6 to 96.8 ± 4.8; P = 0.001 and P = 0.001, respectively). There were also significant improvements in life quality score (52.4 ± 9.5 to 37.9±7.8; P = 0.001) and 6-minute walking distance (278.7 ± 85.8 to 373.3 ± 94.0; P = 0.001) of patients. All patients with New York Heart Association class III became class II after 3 months of ivabradine treatment. CONCLUSION: Heart rate reduction in a short-term period by ivabradine produced significant improvements in exercise capacity and life quality in patients with CRT-D and conventional therapy.

Clinical course and side effects of anti-IgE monoclonal antibody in patients with severe persistent asthma.

BACKGROUND: Omalizumab, a recombinant humanized monoclonal antibody to IgE, is recommended as a new option for the treatment of severe persistent allergic asthma. The purpose of this study is to assess the effects omalizumab treatment on life quality and its side effects in severe persistent asthma patients. METHODS: In this study, we evaluated 19 severe persistent asthma patients who received therapy with omalizumab for 8 months. Omalizumab was administered every 2 weeks at doses between 150 to 375 mg. Symptoms and severity of allergic reactions were recorded before and after being on omalizumab. IgE levels, mean platelet volume (MPV), platelet levels, pulmonary function test, and asthma control test were evaluated in all patients before and 8 months after the treatment. Local and systemic side effects of omalizumab were evaluated. Stool parasites were examined in the 4th and 8th month after initiation of treatment to investigate any parasitosis. RESULTS: The patients had severe persistent asthma for periods ranging from 3 to 8 years, and they were diagnosed with allergic asthma for 7 - 28 years. Thrombocytopenia developed in a male patient after the 22nd dose of the drug was given. When the platelet count fell down to 55000, the omalizumab treatment was suspended. During the therapy period, one patient had parasitosis (giardiasis), one patient had severe side effects, one patient had dyspnea two hours after the injection, and one patient had a dyspnea attack 2 hours after the injection. The changes in MPV levels were not statistically significant. There was also a significant decrease in IgE levels after the treatment. CONCLUSIONS: Monitoring of complete blood cell count is very important when using this drug. Though we did not see anaphylaxis in any patients, we believe that the patients should be monitored at least for 3 hours after the omalizumab injection.

Serum prolactin and macroprolactin levels in diabetic nephropathy.

OBJECTIVE: Three molecular forms of prolactin with molecular weights of 23 (monomeric), 50 - 60 and > 100 kDA (macroprolactin) have been defined. Prolactin levels have been shown to be reduced in especially poorly controlled diabetes mellitus and the prevalence of macroprolactinemia in diabetic patients has been higher than the non-diabetic population. PATIENTS AND METHODS: A total 234 Type 2 diabetic patients with different nephropathy stage was included in the study. Serum prolactin levels were analyzed by the Electrochemiluminescense method. Following polyethylene glycol (PEG) precipitation, recovery less than or equal to 40% was taken as evidence that a significant level of macroprolactin was present in the serum. RESULTS: Hyperprolactinemia and macroprolactinemia were detected in 40 (17%) and 13 (5.5%) patients, respectively. Macroprolactinemia was detected 13 of 40 patients with hyperprolactinemia (32.5%). Increased prolactin and macroprolactin levels in patients with moderate and severe renal failure (Stage 3, 4, and 5) according to the U.S. NKF-DOQI classification (p < 0.001). Prolactin and macroprolactin levels were not increased in patients with normoalbuminuria, microalbuminuria and macroalbuminuria (p > 0.05). Serum creatinine levels correleted positively with both prolactin (r = 0.51, p < 0.001) and macroprolactin levels (r = 0.43, p < 0.001). On the other hand, glomerular filtration rate correlated negatively with both prolactin (r = -0.54, p < 0.001) and macroprolactin levels (r = -0.44, p < 0.001). Albuminuria significantly related with neither prolactin nor macroprolactin levels (p > 0.05). CONCLUSION: In the present study, we found that not only serum prolactin but also serum macroprolactin levels increased especially in moderate to severe renal failure which was due to decreased glomerular filtration and renal parenchymal function resulting in an increased amount of monomeric prolactin and macroprolactin in the circulation in patients with Type 2 diabetes mellitus.

Demographic and clinical characteristics of patients with autosomal dominant polycystic kidney disease: a multicenter experience.

AIM: Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease. It accounts for 5-10% of patients with end-stage renal disease (ESRD). The aim of this multicenter study was to investigate the demographic and clinical characteristics of patients with ADPKD. METHODS: 1,139 patients with ADPKD who were followed up at 12 different centers were recruited for this study. The investigated demographic and clinical characteristics were gender, age, smoking history, educational status, the existence of hypertension, hematuria, urinary tract infection, urinary tract stones and renal replacement therapy. Patients were considered as hypertensive if they were taking antihypertensive medications or if they had blood pressure (BP) of 140/90 mm Hg or greater. If the patients were currently on antihypertensive drugs, the classes of these agents were noted. RESULTS: 548 male and 591 female patients were included and the mean age at initial diagnosis was 37.1 ± 16.3 years. 20.3% were current smokers whereas 15% were ex-smokers. The mean systolic and diastolic BPs were 136.1 ± 29.8 and 84.9 ± 17.8 mm Hg, respectively. 63.7% used antihypertensive drugs and 73.1% of those used renin-angiotensin system blockers. 11.8% had ESRD, of which 75.8% were treated with hemodialysis. CONCLUSION: This study showed that hypertension is the most common (72.6%) clinical finding in ADPKD patients in Turkey and renin-angiotensin system blockers are widely used.