Lymphocyte and monocyte vitamin D receptor expression during paricalcitol or calcitriol treatments in patients with stage 5 chronic kidney disease.

PURPOSE: In this study, we aimed to investigate the effect of paricalcitol and calcitriol usage on vitamin D receptor (VDR) contents of CD8+ , CD4+ lymphocytes and monocytes in stage 5d chronic kidney disease (CKD) patients. METHODS: Thirty-six hemodialysis patients older than 18 years of age and 19 healthy controls (group HC) without any known acute or chronic diseases were included in the study. The group of patients undergoing scheduled hemodialysis comprised three subgroups: group CL: patients on calcitriol (n: 10), group PC: patients on paricalcitol (n: 13), and group NT: patients not taking any vitamin D or VDR activating medications (n: 13). CD8+/VDR, CD4+/VDR and MONO/VDR values were representing the ratio of VDR representing cells among related cell group. On the other hand, values of CD8+/MFI, CD4+/MFI and MONO/MFI have shown the total amount of cellular VDR content per cell which has been given as of mean fluorescence intensity in the flow cytometric process. Main CKD mineral bone disorder parameters such as a hemogram, serum BUN, creatinine, albumin, Ca, iP, iPTH, 25(OH)D3 levels were also measured. RESULTS: Average VDR contents in CD8+, CD4+ and monocytes were not different among three patient groups on hemodialysis. But in all hemodialysis subgroups, CD8+/VDR, CD4+/VDR, MONO/VDR, CD8+/MFI, CD4+/MFI and MONO/MFI levels were found to be higher compared with the healthy control subjects (p < 0.001). Among hemodialysis groups, no significant CD8+/VDR, CD4+/VDR, and MONO/VDR content differences were found with regard to the type of VDR activator agent used. There was no difference in serum levels of 25(OH)D3 and CRP among groups participating in the study. CONCLUSION: There was no difference between CD8+/VDR, CD4+/VDR, and MONO/VDR levels in hemodialysis patients using calcitriol or paricalcitol, suggesting that both treatment agents may have a similar effect on VDR contents in lymphocytes and monocytes in that patient population. But in all hemodialysis subgroups, CD8+/VDR, CD4+/VDR, and MONO/VDR levels were found to be higher compared with the healthy control subjects, suggesting an overexpression of VDR through a non CRP and/or 25(OH)D3 dependent mechanism.

Treatment of secondary hyperparathyroidism with paricalcitol in patients with end-stage renal disease undergoing hemodialysis in Turkey: an observational study.

OBJECTIVE: To evaluate monthly percentage changes of intact parathyroid hormone (iPTH) and other major bone marker levels in patients with secondary hyperparathyroidism (SHPT) undergoing hemodialysis (HD) and receiving paricalcitol. METHODS: A total of 493 (F/M 244/249) adult patients with SHPT who were undergoing HD in 22 HD units and receiving paricalcitol treatment, with iPTH > 300 mg/mL, adjusted serum levels of calcium (Ca) < 10.2 mg/dL, and serum levels of inorganic phosphorus (iP) < 6 mg/dL were included in this multi-center, national, prospective, observational study. Data regarding efficacy, safety, and adverse events of paricalcitol treatment were collected during a 12-month follow-up period through monthly visits along with serum iPTH, Ca, iP, alkaline phosphatase (ALP) and other required biochemistry tests as necessary. Mortality data until 6 months after the end of the study were also investigated. RESULTS: The mean age was 58.3 ± 15.8 years and the mean duration of HD was 6.2 ± 5.5 years, respectively. As of 12th month, mean iPTH values decreased from 646 ± 424 pg/mL to 473 ± 387 pg/mL (p < 0.001); no statistically significant changes were observed in Ca levels (p > 0.05). Serum ALP levels also significantly decreased (p = 0.001) and serum phosphorus levels significantly increased (p < 0.001) during the study observation period. Reasons for early terminations were being lost to follow-up (n = 119, 24.1%), hyperphosphatemia (iP > 6 mg/dL, n = 108, 21.9%), low iPTH levels (iPTH < 150 mg/dL, n = 97, 19.7%), and withdrawal of consent (n = 41, 8.3%). In total 32 patients (6.5%) were prematurely terminated the study with hypercalcemia (Ca > 10.2 mg/dL). 46.9% of those hypercalcemic patients had other anomalies with iP and iPTH levels along with hypercalcemia. CONCLUSION: Paricalcitol treatment, resulted in successful iPTH control. In approximately 6.5% of the patients paricalcitol treatment was discontinued since Ca levels reached > 10.2 mg/dL in those patients. No unfavorable effects on serum phosphorus and Ca-phosphorus (Ca × P) product were observed.

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.

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.

The influence of CTLA-4 single nucleotide polymorphisms on acute kidney allograft rejection in Turkish patients.

Cytotoxic T-lymphocyte antigen-4 (CTLA-4) is a cell surface protein, which down-regulates the immune response at CTLA-4/CD28/B7 pathway. We aimed to investigate the influence of the -318 C/T, +49 A/G, -1661 A/G and CT60A/G, and CTLA-4 gene polymorphisms on acute rejection of kidney allograft in Turkish patients. The study design was a case-control study that consists of three groups: Group 1 (n = 34) represented the kidney transplant (Ktx) recipients who experienced acute rejection, Group 2 (n = 47) was randomly assigned Ktx recipients without acute rejection, and Group 3 (n = 50) consisting of healthy volunteers to evaluate the normal genomic distribution. The polymerase chain reaction-restriction fragment length polymorphism technique was used to determine the polymorphisms. Genotype and allele frequencies among three groups denoted similar distributions for +49 A/G, -1661 A/G, and CT60A/G. Conversely, -318 C/T genotype was three times more frequent in the acute rejection group than in the non-rejection group (OR = 3.45; 95%CI = 1.18-10.1, p = 0.015) and two times more frequent than the healthy control group (OR = 2.45; 95% CI = 0.98 - 6.11, p = 0.047). Additionally, having a T allele at -318 position was significantly associated with acute rejection (0.147 vs. 0.043, OR = 3.45; 95% CI = 1.13-10.56, p = 0.02). 318C/T gene polymorphism and T allelic variant were found to be associated with increased acute rejection risk in Turkish kidney allograft recipients.

A short story of Klotho and FGF23: a deuce of dark side or the savior?

Fibroblast growth factor 23 (FGF23) is an osteocyte and osteoblast derived peptide hormone, which requires Klotho as a cofactor for its biologic actions. FGF23 acts as a phosphaturic agent and it is capable of reducing serum inorganic phosphate (Pi) via direct inhibition of renal NaPi-2a transporter in the proximal tubuli, as well as indirectly, via the suppression of calcitriol synthesis. In patients with chronic kidney disease (CKD), circulating FGF23 levels are markedly elevated, while Klotho production is decreased. Experimental observations indicating that lack of activities of both Klotho and FGF23 may cause decreased life span, premature aging and accelerated atherosclerosis and generalized vascular calcifications have raised the question whether FGF23 could be a new risk factor and predictor of cardiovascular (CV) disease in both renal and non-renal patient groups. Clinical studies, however, have yielded conflicting results. Some of these studies have found that serum FGF23 is independently associated with mortality and CV events in CKD patients, while others have failed to show any relationship. Furthermore, some studies have even suggested that FGF23 may have a protective role against vascular calcifications and CV disease. Thus, there is clearly a need for further research in this area, and special interest should be paid to the physiologic consequences of high FGF23/low Klotho state, which is typical for patients with CKD.

Peripheral Treg count and it's determinants in unsensitized and sensitized chronic kidney disease patients.

PURPOSE: Sensitization to HLA antigens resulting in anti-HLA antibodies (panel reactive antibodies; PRA) is a major problem in chronic kidney disease (CKD) patients awaiting transplantation. Induction of anti-HLA antibodies normally occurs through blood transfusion, pregnancy and prior transplantation. However, some patients develop these antibodies for unknown immunological reasons. It is hypothesized that deviations in immune regulation may account for PRA positivity in these patients. We, therefore, investigated whether a quantitative deficiency in peripheral natural regulatory T cells (CD4(+)CD25(high)Foxp3(+); nTreg) plays a role in this phenomenon. METHODS: Peripheral blood mononuclear cells from 14 patients with positive (Class I and Class II; 10-100 %) and 25 patients with negative PRA, who had not previously been sensitized by blood transfusion, pregnancy and prior transplantation and who had not received any immunomodulatory treatment within the last year, were analyzed for absolute lymphocyte and nTreg numbers through flow cytometry. Samples from 10 healthy people were also used as control. RESULTS: Mean absolute nTreg numbers were determined to be severely reduced in CKD patients (12 ± 9; n = 39) compared with healthy individuals (53 ± 17; n = 10) (p = 0.008). However, absolute nTreg numbers were similar between PRA- (12 ± 11) and PRA+ (11 ± 8) groups. Interestingly, there was a moderate correlation between the nTreg numbers and HLADR2 genotype (n = 9, r = 0.508, p < 0.05). CONCLUSION: This is the first study to demonstrate that the quantitative peripheral nTreg deficiency in CKD patients does not show a causal relationship with the presence of anti-HLA antibodies.

Use of peritoneal ultrafiltration in the elderly refractory congestive heart failure patients.

BACKGROUND: Refractory congestive heart failure (RCHF), due to its high mortality and hospitalization rates, is a growing health problem. In this study, as an alternative and/or supportive treatment to conventional medical therapies, we have evaluated the clinical value of peritoneal ultrafiltration, performed as a single daily exchange with icodextrin or conventional dextrose-based peritoneal dialysis solutions, in elderly patients with RCHF. METHODS: This was an observational study of 6 elderly patients with RCHF and non-terminal chronic kidney disease (CKD). Their mean age was 72.8 ± 4.9 years. Four of the six patients had NYHA class 4 and two had NYHA class 3 RCHF and a medical history of 18.6 ± 14.9 days/year hospitalization on average, due to decompensated congestive heart failure (CHF). Their baseline glomerular filtration rate, as calculated by the MDRD formula was 49.4 ± 14.6 mL/min/1.73 m(2). During hospitalization, patients were initially treated with several sessions of continuous veno-venous hemofiltration and, following the achievement of hemodynamic stabilization, peritoneal ultrafiltration was initiated as the maintenance ultrafiltration modality. Patients were followed up monthly in terms of their clinical status, hospitalization rates, weight changes, serum sodium levels, and renal function. Echocardiographic changes were also evaluated every 3 months. RESULTS: All patients tolerated peritoneal ultrafiltration well, their functional status improved by 1 or 2 NYHA classes to reach a mean of NYHA class 2 CHF status. During the follow-up period, with a mean daily ultrafiltration rate of 850 ± 176 mL, no hospitalization for decompensated CHF or acute renal failure was required. The patients' renal function was well preserved, with a mean GFR of 49 ± 14.6 mL/min/1.73 m(2) at baseline and 51.6 ± 22.9 mL/min/1.73 m(2) at the 6th month of the study. Additionally, their mean serum sodium levels increased from 128 ± 5.7 mEq/L to 138 ± 5 mEq/L. Echocardiographic evaluation did not show any significant changes during the observation period. No peritonitis or other non-infectious complication of chronic peritoneal dialysis was seen in any of the patients. CONCLUSIONS: Peritoneal ultrafiltration seems to be an efficient and safe procedure and a treatment of choice in elderly patients with RCHF without non-terminal CKD. Peritoneal ultrafiltration improves the quality of life and the effort capacity, and reduces hospitalization rates due to decompensated heart failure and acute renal failure.

Improving technique survival in peritoneal dialysis: what is modifiable?

The continuous quality improvement approach in peritoneal dialysis practice necessitates definition of the factors and the procedures that may possibly be contributing to the final success of peritoneal dialysis. The philosophy of continuous quality improvement uses the Plan, Do, Check, Act (PDCA) cycle. To improve the procedures used during peritoneal dialysis, the first step is to create a plan, then to carry out the plan, to check it, and after the collection of satisfactory information, to execute the chosen improvement action. Several studies have identified the most frequent causes of transfer from PD to HD as infection, catheter problems, inadequate dialysis, and psychosocial factors, among others. According to training guidelines from the International Society for Peritoneal Dialysis, seven points are of major importance to decrease infection risks: exit-site care, catheter placement, antibiotic prophylaxis for procedures, prevention of bowel-source peritonitis, prevention of fungal peritonitis, and connection methods. On the other hand, other factors such as hypoalbuminemia, depression, and obesity should also be taken into consideration for better technique survival in peritoneal dialysis patients.

Relationship between carotid artery intima-media thickness and brachial artery flow-mediated dilation in peritoneal dialysis patients.

BACKGROUND AND AIM: Carotid artery intima-media thickness (CIMT) and brachial artery flow-mediated dilation percentage (FMD%) are two commonly used parameters for detecting subclinical atherosclerosis. However, studies investigating the relationship between CIMT and brachial artery FMD% in different populations have produced conflicting results. The aim of this study was to determine the relationship between CIMT and brachial artery FMD% in patients on peritoneal dialysis (PD) METHODS: Fifty-two PD patients without known cardiovascular disease and 30 age-gender matched controls were included in the study. Endothelial function was determined using ultrasonography (US) to measure the FMD of the brachial artery, and this parameter was expressed as the percentage change from the baseline diameter of the brachial artery (FMD%). We also measured CIMT by US and analysed the relationship between CIMT and brachial FMD%. RESULTS: The CIMT was significantly higher in patients than in the control group (0.84 +/- 0.08 vs. 0.75 +/- 0.06 mm, P < 0.01), whereas brachial artery FMD% was lower in patients than in the controls (8.2 +/- 5.0 vs. 11.7 +/- 5.5%, P < 0.01). There was no significant correlation between CIMT and FMD% (r = -0.004, P = 0.94). CONCLUSION: Although PD patients are known to be characterized by an impaired flow-mediated vasodilatation of brachial artery and increased in CIMT, we did not find a significant correlation between FMD% and CIMT in our PD patient cohort. One possible explanation for our results is that each method measures a different aspect and stage of atherosclerosis.

Advanced oxidative protein products are independently associated with endothelial function in peritoneal dialysis patients.

AIM: Oxidative stress (OS) and asymmetric dimethylarginine (ADMA) are accepted as non-classical cardiovascular risk factors in end-stage renal disease patients. To clarify the role of these factors in the atherosclerotic process, we investigated if OS and ADMA are associated with endothelial function (EF) in peritoneal dialysis (PD) patients. METHODS: Fifty-two non-diabetic PD patients without known atherosclerotic disease as well as 30 age- and sex-matched healthy individuals were included. We measured serum thiobarbituric acid-reactive substances (TBARS), malondialdehyde (MDA), advanced glycation end-product (AGE), pentosidine, advanced oxidation protein products (AOPP), ADMA and EF as described by Celermejer et al. in all subjects. RESULTS: TBARS, MDA, AOPP, AGE, pentosidine and ADMA levels were significantly higher in PD patients than in controls (P < 0.001). Flow-mediated dilatation (FMD)% and nitrate mediated dilatation (NMD)% in PD patients were lower than in the control group (7.7 +/- 4.0% vs 11.70 +/- 5.50%, P < 0.01 and 17.6 +/- 8.3% vs 26.4 +/- 4.6%, P < 0.01). Additionally, it was found that AOPP are independently correlated with FMD% and NMD% in PD patients (beta = -463, P < 0.01 and beta = -420, P < 0.05). CONCLUSION: This study shows that PD patients without known atherosclerotic disease can also be characterized by endothelial dysfunction and AOPP levels independently predict endothelial function level in PD patients.

Phosphorus control in peritoneal dialysis patients.

Hyperphosphatemia is independently associated with an increased risk of death among dialysis patients. In this study, we have assessed the status of phosphate control and its clinical and laboratory associations in a large international group of patients on chronic peritoneal dialysis (PD) treatment. This cross-sectional multicenter study was carried out in 24 centers in three different countries (Canada, Greece, and Turkey) among 530 PD patients (235 women, 295 men) with a mean+/-s.d. age of 55+/-16 years and mean duration of PD of 33+/-25 months. Serum calcium (Ca(2+)), ionized Ca(2+), phosphate, intact parathyroid hormone (iPTH), 25-hydroxy vitamin D(3), 1,25-dihydroxy vitamin D(3), total alkaline phosphatase, and bone alkaline phosphatase concentrations were investigated, along with adequacy parameters such as Kt/V, weekly creatinine clearance, and daily urine output. Mean Kt/V was 2.3+/-0.65, weekly creatinine clearance 78.5+/-76.6 l, and daily urine output 550+/-603 ml day(-1). Fifty-five percent of patients had a urine volume of <400 ml day(-1). Mean serum phosphorus level was 4.9+/-1.3 mg per 100 ml, serum Ca(2+) 9.4+/-1.07 mg per 100 ml, iPTH 267+/-356 pg ml(-1), ionized Ca(2+) 1.08+/-0.32 mg per 100 ml, calcium phosphorus (Ca x P) product 39+/-19 mg(2)dl(-2), 25(OH)D(3) 8.3+/-9.3 ng ml(-1), 1,25(OH)(2)D(3) 9.7+/-6.7 pg ml(-1), total alkaline phosphatase 170+/-178 U l(-1), and bone alkaline phosphatase 71+/-108 U l(-1). While 14% of patients were hypophosphatemic, with a serum phosphorus level lower than 3.5 mg per 100 ml, most patients (307 patients, 58%) had a serum phosphate level between 3.5 and 5.5 mg per 100 ml. Serum phosphorus level was 5.5 mg per 100 ml or greater in 28% (149) of patients. Serum Ca(2+) level was > or =9.5 mg per 100 ml in 250 patients (49%), between 8.5 and 9.5 mg per 100 ml in 214 patients (40%), and lower than 8.5 mg per 100 ml in 66 patients (12%). Ca x P product was >55 mg(2)dl(-2) in 136 patients (26%) and lower than 55 mg(2)dl(-2) in 394 patients (74%). Serum phosphorus levels were positively correlated with serum albumin (P<0.027) and iPTH (P=0.001), and negatively correlated with age (P<0.033). Serum phosphorus was also statistically different (P = 0.013) in the older age group (>65 years) compared to younger patients; mean levels were 5.1+/-1.4 and 4.5+/-1.1 mg per 100 ml, respectively, in the two groups. In our study, among 530 PD patients, accepted uremic-normal limits of serum phosphorus control was achieved in 58%, Ca x P in 73%, serum Ca(2+) in 53%, and iPTH levels in 24% of subjects. Our results show that chronic PD, when combined with dietary measures and use of phosphate binders, is associated with satisfactory serum phosphorus control in the majority of patients.

Oxidative stress and asymmetric dimethylarginine is independently associated with carotid intima media thickness in peritoneal dialysis patients.

BACKGROUND: Oxidative stress (OS) and asymmetric dimethylarginine (ADMA) are accepted as nonclassical cardiovascular risk factors in end-stage renal disease patients. To clarify the role of these factors in the atherosclerotic process, we investigated if OS and ADMA are associated with common carotid artery intima media thickness (CIMT) in peritoneal dialysis (PD) patients. METHODS: Thirty PD patients without known atherosclerotic disease and classical cardiovascular risk factors as well as age- and gender-matched 30 healthy individuals were included. We measured serum thiobarbituric acid-reactive substances (TBARS), malondialdehyde (MDA), advanced glycation end product (AGE), pentosidine, advanced oxidation protein products (AOPP), ADMA and CIMT in each subjects. RESULTS: TBARS, MDA, AOPP, AGE, pentosidine and ADMA levels were significantly higher in PD patients than in controls (p < 0.001). CIMT in patients was higher than in the control group (0.83 +/- 0.09 vs. 0.77 +/- 0.06 mm; p < 0.01). CIMT was independently correlated with TBARS (beta = 0.33, p < 0.01), MDA (beta = 0.27, p < 0.01), AOPP (beta = 0.22, p < 0.02), AGE (beta = 0.45, p < 0.01), pentosidine (beta = 0.56, p < 0.01) and ADMA (beta = 0.54, p < 0.01). CONCLUSIONS: OS markers and serum ADMA levels independently predict the CIMT level in PD patients.

Mutations of chronic granulomatous disease in Turkish families.

BACKGROUND: Chronic granulomatous disease (CGD) is an inherited disorder of the innate immune system characterized by impairment of intracellular microbicidal activity of phagocytes. Mutations in one of four known NADPH-oxidase components preclude generation of superoxide and related antimicrobial oxidants, leading to the phenotype of CGD. Defects in gp91-phox, encoded by CYBB, lead to X-linked CGD and have been reported to be responsible for approximately 70% of all CGD cases. The aim of this study was to identify the CGD mutations in a group of Turkish CGD patients and to evaluate the predominance of CGD mutations as X-linked or autosomal recessive (AR) within the Turkish CGD families with known mutations. MATERIALS AND METHODS: Two Turkish CGD families were included in the study, and mutations were identified by sequence analysis of DNA and RNA from peripheral blood in the patients. Before mutation analysis, subgroup analysis of patients was made by flow cytometry with antibodies against NADPH oxidase components and with DHR-123 oxidase activity assay. For comparison, we included previously reported results from four other Turkish CGD families. RESULTS: Two different mutations were identified, one of them a novel mutation g.700G>T located in exon 7 of CYBB, and the other a hot-spot mutation located in exon 2 of the NCF1 gene. These mutations were detected in three patients from two Turkish families. CONCLUSIONS: Until now, we have altogether identified mutations in six Turkish CGD families. In this limited number of families our results show AR-CGD in two-thirds of the Turkish families investigated, in contrast to previous reports in the literature. This is probably due to the high rate of consanguineous marriages in Turkey. Consanguineous parents were found in 75% of the families with AR-CGD patients, which favours homozygous deficiencies.

Osteoporosis in the elderly with chronic kidney disease.

Considering the aging dialysis population of today, increasing our knowledge about the nature, diagnosis and the treatment of bone mineral density (BMD) problems in end-stage renal disease (ESRD) patients deserves more attention. Osteoporosis is basicly defined as a decrease in bone mass. Large epidemiological studies in general population have identified several risk factors for osteoporosis including advancing age, female gender, white race, decreased calcium intake, gastric acid suppression therapy, sedentary lifestyle, premature loss of gonadal function, decreased estrogen secretion, thin body habitus, decreased physical activity, cigarette smoking, alcohol abuse, excess glucocorticoid exposure, and possibly some genetic factors. Osteoporosis in ESRD patients is only a part of a wider spectrum of metabolic bone problems, namely uremic osteodystrophy. Therefore, its diagnosis, management and follow-up may differ from the general population and an individualization of diagnosis and definition for dialysis population may be necessary. However, standard diagnostic tools such as dual energy X-ray absorptiometry (DEXA) have been widely used for the assessment of bone mineral deficiency status in ESRD patients. Regardless of the methods, most of the studies are in concordance with a reduced BMD in HD and PD patients. Dialysis patients are known to be at increased risk for low-trauma fractures. Thinning of cortical bone, which is responsible for the largest contribution toward reduced bone mineral content in chronic renal failure results in increased fracture risk. In either normal population and dialysis patients, fracture risk is increased with age. But in dialysis patients, besides age, several other factors may also affect the degree of bone mineral deficiency, and age-BMD relationship may be blunted. Female sex, in hemodialysis patients is negatively associated with total hip BMD. While several studies have been unable to demonstrate any association between BMD and PTH levels, larger body size has been shown to have a significant positive effect on BMD in both hemodialysis and peritoneal dialysis patients. Although they have been used in small groups of chronic kidney disease (CKD) and ESRD patients, because of their potential nephrotoxicity and hypocalcemic effects, use of biphosphonates in renal patients is questionable. Currently, bone biopsy, in order to exclude adynamic bone disease is recommended before beginning treatment with bisphosphonates in chronic kidney disease and dialysis patients.

Severe vitamin D deficiency in chronic renal failure patients on peritoneal dialysis.

UNLABELLED: The aim of this study was to evaluate the prevalence of vitamin D deficiency in chronic renal failure (CRF) patients on peritoneal dialysis (PD) and to correlate the findings with various demographic and renal osteodystrophy markers. METHOD: This cross-sectional, multicenter study was carried out in 273 PD patients with a mean age of 61.7 +/- 10.9 years and mean duration of PD 3.3 +/- 2.2 years. It included 123 female and 150 male patients from 20 centers in Greece and Turkey, countries that are on the same latitude, namely, 36-42 degrees north. We measured 25(OH)D3 and 1.25(OH)2D3 levels and some other clinical and laboratory indices of bone mineral metabolism. RESULTS: Of these 273 patients 92% (251 patients) had vitamin D deficiency i.e. serum 25(OH)D3 levels less than 15 ng/ml, 119 (43.6%) had severe vitamin D deficiency i.e., serum 25(OH)D3 levels, less than 5 ng/ml, 132 (48.4%) had moderate vitamin D deficiency i.e., serum 25(OH)D3 levels, 5-15 ng/ml, 12 (4.4%) vitamin D insufficiency i.e., serum 25(OH)D3 levels 15 - 30 ng/ml and only 10 (3.6%) had adequate vitamin D stores. We found no correlation between 25(OH)D3 levels and PTH, serum albumin, bone alkaline phosphatase, P, and Ca x P. In multiple regression analyses, the independent predictors of 25(OH)D3 were age, presence of diabetes (DM-CRF), levels of serum calcium and serum 1.25(OH)2D3. CONCLUSION: We found a high prevalence (92%) of vitamin D deficiency in these 273 PD patients, nearly one half of whom had severe vitamin D deficiency. Vitamin D deficiency is more common in DM-CRF patients than in non-DM-CRF patients. Our findings suggest that these patients should be considered for vitamin D supplementation.

Skewing of X-chromosome inactivation in three generations of carriers with X-linked chronic granulomatous disease within one family.

BACKGROUND: Chronic granulomatous disease (CGD) is an inherited disorder of the innate immune system characterized by impairment of intracellular microbicidal activity of phagocytes. Mutations in one of the four known NADPH-oxidase components preclude generation of superoxide and related antimicrobial oxidants, leading to the phenotype of CGD. Defects in gp91-phox, encoded by CYBB, lead to X-linked CGD, responsible for approximately 70% of all CGD cases. The aim of the study was to evaluate the hypothesis that age-related skewing of X-chromosome inactivation, as described in several CGD families, is caused by preferential survival of bone marrow clones with an inactive NADPH oxidase. MATERIALS AND METHODS: We studied the neutrophils from three patients and four carriers in three generations of a Turkish family with X-linked CGD. Carrier detection was carried out by the dihydrorhodamine (DHR)-1,2,3 assay, which measures on a per-cell basis the NADPH oxidase-dependent oxidation of DHR by phagocytes. The X-chromosome inactivation pattern was determined with the HUMARA assay in DNA from leucocytes as well as in DNA from a buccal smear of the four carriers. RESULTS: The three patients were identified by a negative DHR test, and the mutation in their CYBB gene was characterized by DNA sequencing. Moreover, we found an age-related degree of skewing of X-chromosome inactivation in the leucocytes of the four X-CGD carriers, both at the protein level (NADPH oxidase activity) and at the DNA level (HUMARA assay). However, similar skewing of X-chromosome inactivation was found in the buccal DNA from these women. CONCLUSIONS: These novel findings indicate that the age-related degree of skewing was probably a chance finding, not related to preferential survival of NADPH oxidase-deficient precursor cells, because this enzyme is not expressed in (buccal) epithelial cells.

Assessment and comparison of endothelial function between dialysis and kidney transplant patients.

Dialysis and kidney transplant patients display endothelial dysfunction. Previous studies concerning comparisons of endothelial function in dialysis and kidney transplant patients included subjects with cardiovascular risk factor(s) that alone may lead to endothelial dysfunction. In this study, we compared endothelial function between dialysis and transplant patients who did not show known cardiovascular risk factors that lead to endothelial dysfunction. We studied age- and gender-matched cohorts: 30 hemodialysis (HD), 30 peritoneal dialysis (PD), and 30 kidney transplant patients. We also included 20 age- and gender-matched healthy controls. We assessed the endothelial function of patients and controls by a noninvasive technique. Serum biochemistry profiles of patients were also similar to controls in terms of lipid profile and fasting blood glucose level. Although mean FMD% levels of HD and PD patients were similar (6.6% +/- 3.1% vs 6.8% +/- 3.0%, P > .05), the mean percent of flow-mediated endothelium-dependent dilatation (FMD%) level in transplant patients was higher than those in HD or PD patients (10.50% +/- 3.0% vs 6.6% +/- 3.1% and 6.8% +/- 3.0%, respectively; P < .01). In addition, the mean FMD% level in healthy controls was higher than those in HD, PD, and transplant patients (14.0% +/- 2.3% vs 6.6% +/- 3.1%, 6.8% +/- 3.0% and 10.50% +/- 3.0%; P < .01, respectively). In conclusion, endothelial functions in transplant patients were better than those in dialysis patients.