Evaluation of efficacy and safety of mycophenolate sodium in patients with de novo and maintenance renal transplantation: results of a multicenter, prospective, observational study.

OBJECTIVE: This study evaluates the effect of enteric-coated mycophenolate sodium (EC-MPS) on patient and graft survivals, the incidence of rejection episodes, and graft function among de novo and maintenance renal transplant recipients. PATIENTS AND METHODS: This open label, multicenter, prospective, post-marketing observational study of 470 renal transplantation patients at 23 centers in Turkey includes 331 de novo patients whose mean age was 29.6 ± 13.2 years and 139 maintenance patients of 34.0 ± 13.0 years. The latter subjects had EC-MPS substituted for mycophenolate mofetil or added to the immunosuppressive therapy. Patients were followed for 12 months to evaluate graft function and treatment failure. RESULTS: The most common primary disease requiring transplantation was glomerulonephritis (24.3%). De novo and maintenance groups were similar in terms of overall rejection rates and acute rejection incidence whereas chronic rejection was evident only among the latter cohort (P < 0.001). Time to an acute rejection episode was significantly longer among maintenance rather than de novo patients (220.8 versus 18.7 months; P = 0.015). Overall, 12 and 36 month survival rates were 91.6 ± 1.3% and 86.9% ± 0.3% among subjects experiencing acute rejection versus 99.7 ± 0.2% and 50.3% for those displaying chronic rejection. Among maintenance group no deterioration of renal function was observed after conversion from mycophenolate mofetil to EC-MPS. The incidences of leukopenia, new-onset anemia, or liver dysfunction were similar between de novo and maintenance patients. Gastrointestinal discomfort was more prevalent among the maintenance group, reaching a significant level at the fourth visit (P < 0.05). EC-MPS dose reduction was required in only 16.7% of patients at visit, it was more frequent among the de novo group (17.9 versus 13.8%). CONCLUSION: EC-MPS was an effective adjunctive therapy for de novo as well as maintenance renal transplant recipients in the Turkish population due to a relatively low incidence of dose reductions necessitated by adverse events as well as with an increased likelihood of long-term graft survival.

Can calcium, phosphate, calcium phosphate product and intact parathyroid hormone levels be appropriately controlled in dialysis patients?

OBJECTIVE: To review the target levels of calcium (Ca), phosphate (P), calcium phosphate products (Ca × P) and intact parathyroid hormone (iPTH) levels in patients undergoing hemodialysis (HD) and peritoneal dialysis (PD) and compare them with the Kidney Disease Outcome Quality Initiative (K/DOQI) recommendations. SUBJECTS AND METHODS: Three hundred and fifty-seven patients who had been undergoing dialysis for more than 3 months were included. Patients who had undergone a parathyroidectomy were excluded. The levels of Ca, P, iPTH and Ca × P were monitored for the last 3 months. The Ca and P levels were measured by standard techniques, and iPTH was assessed by the intact molecule assay. RESULTS: Between HD and PD patients, there was no statistically significant difference for age, duration of dialysis or primary disease causing end-stage renal disease. The percentage of patients whose serum Ca, P, Ca × P product and iPTH were within K/DOQI recommended target ranges were 61.2, 66.4, 82.2 and 28.3% in HD patients, and 56.3, 60.6, 85.9 and 22.5% in PD patients, respectively. When all results for each group - HD and PD - were analyzed, 12.8% of patients had all 4 markers within the target range. CONCLUSION: Achieving target ranges of mineral markers is important in dialysis patients, but reaching K/DOQI target levels is difficult. Hence, physicians should be careful in using P binders and vitamin D analogs to achieve the normal ranges.

Outcome of the using older donors for kidney transplantation;Gazi University, Ankara experience.

The extreme organ shortage in Turkey has led to expansion of living and diseased donors. We retrospectively analyzed patient data to determine the outcomes of elderly donors. Among 210 donors, 28 (13.3%) were atleast ≥55 years old. In this group, 17 were from living and 11 from diseased donors. Mean cold ischemia time was 68 ± 21 minutes. The immunosuppressive protocol consisted of induction therapy (simulect 20 mg on days 0 and 4) and immunosuppression with calcineurin inhibitors, mycophenolic acid, and steroids. Nine patients (32.6%) with delayed graft function (DGF) required transient hemodialysis. None of the recipients or their grafts were lost due to surgical complications. We noted 5 acute rejection episodes which were all reversed by pulse steroids. Mean creatinine levels at 1, 3, and 5 years were 1.7, 2.1 and 2.3 mg/dL respectively. Patient and graft survivals at 1, 3, and 5 years were 100%, 96%, and 92% and 100%, 92%, and 92%, respectively. Although 3.6% of recipients displayed DGF, it did not affect graft outcomes. In conclusion, kidney transplantation from older donors should be considered to be an option for kidney transplantation.

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.

Successful solid organ transplantation from septicemic cadaveric donors: case report.

Systemic donor infections especially with gram-negative organisms are regarded as an absolute contraindication to cadaveric organ donation for transplantation. This is largely due to fear of transmitting the pathogenic organisms to the immunosuppressed recipient. However, due to the current shortage of organs available for transplantation, clinicians are faced with the option to use organs from infected donors. Between 1996 to January 2006, we collected 44 solid organs. Two out of nine donors had microorganisms from blood cultured. Case 1 was of 23-year old woman whose cause of brain death was intracerebral bleeding due to a traffic accident. The donor had stayed 9 days in the intensive care unit prior to brain death. Two kidneys, two livers (split), and or heart were used. Klebsiella was the organism on blood culture. Case 2 was of 35-year-old man; cause of brain death was cerebral hematoma due to traffic accident. The donor had stayed 6 days prior to brain death onset. The liver and two kidneys were used. Acinetobacter baumannii was yielded upon blood culture. All donors were treated with appropriate antibiotics for at least 48 hours prior to organ procurement with consequent negative blood cultures, while the recipients received the same culture-specific antibiotics for 10 days following transplantation. One donor (case 1) heart and both donor corneas were not used due to infection. All patients are alive with excellent graft function at a median of 90 days following transplantation. In conclusion, our results suggested that bacteremic donors with severe sepsis under proper treatment can be considered for transplantation.

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.

The effects of rofecoxib on 24-h ambulatory blood pressure and heart rate monitoring in patients with hypertension and osteoarthritis.

The aim of the study was to investigate the effects of the cylooxygenase (COX)-2 specific inhibitor rofecoxib, on blood pressure (BP) and heart rate (HR) in patients with well-controlled hypertension and osteoarthritis via 24-h ambulatory monitoring. Thirty patients with well controlled hypertension were included. Fifteen patients had osteoarthritis and were recommended by their rheumatologists to take rofecoxib 12.5 mg/day (rofecoxib group). The control group consisted of 15 patients who had hypertension but no clinical osteoarthritis and did not receive any anti-inflammatory drugs. Twenty-four-hour ambulatory monitoring of BP and HR were performed on the day before initiation of rofecoxib therapy and on days 3 and 14 of COX-2 therapy. The control group underwent 24-h monitoring three times at similar intervals. Antihypertensive medications were continued. On day 3 of rofecoxib therapy, mean HR for both daytime and nighttime were lower than those at baseline. On day 14, the changes in mean HR did not differ from baseline values. Similarly, diastolic BP (daytime and nighttime) on day 3 appeared to be lower than at baseline. However this difference was not observed on day 14, and mean daytime and nighttime diastolic BP returned to baseline values. There was no statistically significant difference in the mean arterial pressure or systolic BP recordings on days 3 or 14 than at baseline. Rofecoxib 12.5 mg/day did not significantly increase BP during 24-h ambulatory BP monitoring in patients with well-controlled hypertension and osteoarthritis.

Localized Castleman's disease and nephrotic syndrome not responsive to resection plus colchicine therapy.

We describe one patient with localized Castleman's disease (CD) of the mixed hyaline vascular and plasma cell type located at the mesentery of the small bowel, associated with systemic amyloidosis and nephrotic syndrome. A true nephrotic syndrome has rarely been reported in patients with CD. In the literature, it has been suggested that clinical and laboratory manifestations generally improved after surgical resection of the tumor. However, in our case, clinical and laboratory findings did not regress after operation followed by colchicine therapy.

Cyclosporine-A induced neurotoxicity after renal transplantation.

Cyclosporine-A is a highly potent immunosuppressive agent for solid organ transplantation, but has many side effects including nephrotoxicity, hypertension, gum hyperplasia, hepatotoxicity, and neurotoxicity. Neurotoxicity is a less known toxic effect. The pathogenesis of this effect is unclear. However, it has been postulated that hypomagnesemia, hypocholesterolemia, corticosteroids, and/or neurotoxic substances can induce this syndrome. Also, it has been suggested that the endothelial damage caused by Cyclosporine-A may contribute to neuropeptide-mediated ischemia in the brain and lead to the development of neurological symptoms. In this report, we present a case with reversible neurologic deficits whose symptoms returned to normal after the cessation of cyclosporine-A.

Improvement of thyroid hormone profile and thyrotrophin (TSH) surge alterations in hemodialysis patients on erythropoietin treatment.

BACKGROUND, MATERIAL AND METHODS: This study was performed in 20 patients with end-stage chronic renal failure (CRF) and 10 healthy volunteers. All of the patients were on regular hemodialysis treatment (RHD), 10 of whom were on recombinant human erythropoietin (rHuEPO) therapy. Hematocrit levels of the patients with CRF on rHuEPO were between 0.30 to 0.33 and not on rHuEPO were below 0.24. Baseline serum T3, T4, fT3, fT4 and TSH levels were measured and TRH stimulation test was performed in patients and control subjects. Serum TSH levels were measured hourly during the afternoon (2 to 5 p.m.) and at night (10 p.m. to 2 a.m.) to determine the nocturnal rhythm of TSH. RESULTS: The mean T3 in rHuEPO, not rHuEPO and control groups were 98.01 +/- 5.54, 70.55 +/- 7.09, 98.29 +/- 4.2 ng/dl; T4 6.47 +/- 0.68, 6.39 +/- 0.59, 8.35 +/- 0.46 ng/dl; fT3 2.24 +/- 0.19, 1.52 +/- 0.24, 2.29 +/- 0.17 pg/ml and fT4 0.88 +/- 0. 14, 0.75 +/- 0.14, 0.97 +/- 0.10 ng/dl, respectively. These values were significantly lower in patients not on rHuEPO compared to controls (p < 0.05). In patients on rHuEPO only T4 values were lower than in the controls (p < 0.05). In patients not on rHuEPO the T3, and fT3 were significantly lower than the values of patients on rHuEPO treatment (p < 0.05). Normal in 8 (80%), blunted in 1 (10%), no TSH response in 1 (10%) to TRH stimulation were obtained in rHuEPO group. TSH response was normal in 1 (10%), and delayed in 9 (90%) patients not on rHuEPO. The circadian nocturnal rhythm of TSH was abnormal in 8 (80%) patients not on rHuEPO, in 2 (20%) patients on rHuEPO. As a result, CRF and RHD distorts the circadian TSH rhythm and substantially change the thyroid hormone profile probably by affecting hypothalamic-pituitary-thyroid axis. Distortion of the circadian rhythm of TSH and TSH response to TRH points to a defect at the level of hypothalamus and pituitary gland. CONCLUSION: rHuEPO treatment has some beneficial effects on hypothalamo-pituitary-thyroid axis in the patients on RHD.

Pattern of human leukocyte antigens in Turkish children with celiac disease.

BACKGROUND: Regional variations in the human leukocyte antigen (HLA) distribution patterns of celiac disease (CD) have been reported. The aim of the present study was to assess the distribution of HLA class I and class II in Turkish children with CD and to compare the findings with a control group. METHODS: Human leukocyte antigen typing was performed in 33 children with CD and in 77 healthy individuals, who served as controls, by using standard National Institutes of Health lymphocytotoxicity techniques. RESULTS: A positive association was found between HLA A2 (42 vs 19% for sick subjects compared with healthy controls, respectively), B8 (39 vs. 9% for sick subjects compared with healthy controls, respectively), CW7 (45 vs. 25% for sick subjects compared with healthy controls, respectively), DR3 (70 vs. 17% for sick subjects compared with healthy controls, respectively), DR7 (30 vs. 13% for sick subjects compared with healthy controls, respectively) and DQ2 (52 vs. 34% for sick subjects compared with healthy controls, respectively). The combinations of DR3-DQ2 (30 vs. 12% for sick subjects compared with healthy controls, respectively), DR3-DR4 (21 vs. 1% for sick subjects compared with healthy controls, respectively) and DR7-DQ2 (21 vs. 6% for sick subjects compared with healthy controls, respectively) were also found to be significantly important in children with CD. The highest relative risk (RR) was for HLA B8 in class I (RR 6.50), for DR3 (RR 11.30) in class II and for combination of DR3-DR4 (RR 20.46). The highest etiologic fraction (EF) was for the DR3 antigen (EF 0.55). CONCLUSIONS: The present study emphasizes that HLA genotypes are an important background to CD development, but some additional susceptibility factors remain to be identified.

Nonrelated living-donor kidney transplantation: medical and ethical aspects.

Several patients with end-stage renal disease went to Bombay for renal transplantation from nonrelated living donors and then returned to Turkey for posttransplantation follow-up. The aims of this study are to evaluate the long-term results of renal transplantation from nonrelated living donors in Turkish patients with end-stage renal disease and to discuss the ethical and social aspects of nonrelated kidney donation. One hundred and twenty-seven patients (89 males, 38 females; mean age 38.1, range 17-63 years) were investigated retrospectively. None of the patients went to Bombay on our advice. All transplantations were performed between 1991 and 1995. The mean follow-up period after transplantation was 34.2 (range 1-68) months. Graft survival rates were 85, 83, and 57% after 3 months and 1 and 5 years, respectively. Patient survival rates were 94, 93, and 92% after 3 months and 1 and 5 years, respectively. Seven patients died within the first 3 months after the transplantation. Surgical problems, infections, acute rejection, ciclosporin nephrotoxicity, and hepatic problems were common complications. We conclude that medical and surgical complications occur frequently in paid kidney transplantation, but most of these complications can be prevented by adequate preoperative management, and precautionary measures should be taken to prevent commercialization of renal transplantation before the spread of emotionally related living kidney donation.