Circadian rhythm of serum phosphate, calcium and parathyroid hormone levels in hemodialysis patients.

BACKGROUND: Serum levels of Phosphate (P), Calcium (Ca) and Parathyroid hormone (PTH) show circadian rhythms in healthy people. The aim of this study is to investigate whether there is also a rhythm in Hemodialysis (HD) patients. METHODS: We studied 15 (11 M, 4 F) HD patients, ages were 26 - 70 (mean 53 +/- 15) years. Two of the patients had history of parathyroidectomy operation. Serum levels of phosphate, calcium, albumin and PTH were evaluated six times at 07.00, 11.00, 15.00, 19.00, 23.00 and 03.00 on the second day after scheduled HD session. RESULTS: The lowest serum phosphate levels were found at 15.00 (5.41 +/- 1.76 mg/dL), the highest levels were 5.97 +/- 1.77 mg/dL at 03.00. The lowest serum Ca levels were 7.90 +/- 1.31 mg/dL at 03.00, the highest levels were 8.39 +/- 1.20 mg/dL at 15.00. Serum levels of PTH increased two times in a day and then decreased. The lowest levels were 330.07 +/- 203.57 pg/mL at 07.00, the highest levels were 418.30 +/- 206.24 pg/mL at 15.00. The results of two patients who had parathyroidectomy history disclosed that the lowest levels of phosphate were 2.87 +/- 0.12 mg/dL at 15.00, the highest levels were 4.37 +/- 1.25 mg/dL at 07.00. Serum Ca levels were as; the lowest levels: 8.29 +/- 3.5 mg/dL at 03.00, the highest levels 9.30 +/- 3.50 mg/dL at 19.00. As expected, serum PTH levels were constantly low during the day disclosing no correlation with other parameters. CONCLUSIONS: These results show that serum P, Ca and PTH levels exhibit a circadian rhythm also in HD patients. The rhythm predominantly depends on endogen factors and intravascular volume.

Predictors of early postoperative hypocalcemia in hemodialysis patients with secondary hyperparathyroidism.

We sought to investigate predictors of early development of postoperative hypocalcemia in secondary hyperparathyroidism. Thirty-six hemodialysis patients (21 men, 15 women; mean age, 39.6 +/- 13.2 years; mean hemodialysis duration, 77.9 +/- 47.1 months) underwent parathyroidectomy. We recorded preoperative adjusted serum calcium (Ca(+2)), phosphate, alkaline phosphatase, intact parathyroid hormone, and hemoglobin levels; mean systolic and diastolic blood pressure levels; parathyroid ultrasonography and scintigraphic data; and number and weight of the resected adenomas. Patients were divided into two groups based on Ca(+2) levels within 24 hours of parathyroidectomy: the hypocalcemia group (serum Ca(+2) levels < or = 8 mg/dL; n = 26 patients) and the normocalcemia group (>8 mg/dL; n = 10 patients). A total parathyroidectomy with autotransplant was performed in 23 patients and a subtotal parathyroidectomy in 13 patients. Age (36.0 +/- 9.7 vs 49.2 +/- 16.6 years; P = .006); levels of preoperative serum Ca(+2) (9.6 +/- 0.7 vs 10.4 +/- 1.1 mg/dL; P = .01), alkaline phosphatase (346.7 +/- 354.7 vs 653.3 +/- 553.7 mg/dL; P = .05), and hemoglobin (10.5 +/- 1.4 vs 12.3 +/- 2.5 g/dL; P = .009); and number (2.0 +/- 1.3 vs 2.9 +/- 0.9; P = .04) and weight (1.9 +/- 2.1 vs 3.2 +/- 1.7; P = .01) of excised parathyroid adenomas were significantly lower among the hypocalcemia than the normocalcemia group. Among hemodialysis patients with secondary hyperparathyroidism, age, levels of preoperative serum Ca(+2) and alkaline phosphatase, and number and weight of adenomas were associated with early development of postoperative hypocalcemia.

Weight gain after living-related renal transplantation affects long-term graft function.

Weight gain is a common problem in renal transplant recipients. This study investigated whether weight gain after living-related renal transplantation affects long-term graft function. The cohort included 93 patients (28 females, 65 males of mean age, 33.78 +/- 9.78 years who were recipients of kidneys from living-related donors. The data set related risk factors to occurrence of chronic allograft nephropathy (CAN): namely, number of HLA mismatches, PRA levels, delayed graft function, acute rejection, suboptimal immunosuppression, hypertension, hyperlipidemia, and size mismatch. Patients with a 10% increase in body mass index sustained throughout at least 2 years posttransplantation were categorized as group 1 (abnormal weight gain; n = 65) and the others were categorized as group 2 (no or normal weight gain; n = 28). Chronic allograft nephropathy was more frequent among group 1 (P < .03). The mean times to CAN diagnosis in groups 1 and 2 were 1053.41 +/- 461.86 days and 1128.57 +/- 416.09 days, respectively (P > .05). Of all the risk factors for CAN, occurrence of acute rejection was the most important (OR = 5.39, 95% CI: 2.07 to 14.03, P < .001). When this factor was excluded, weight gain emerged as the most important risk factor (OR = 3.04, 95% CI: 1.01 to 9.69, P < .04). There were no significant differences between the groups with respect to the frequencies of immunologic and nonimmunologic risk factors (P > .05 for all). The results suggest that excessive weight gain after living-related renal transplantation may be an additional risk factor for development of CAN. Patients should pay attention to diet and control weight gain after transplantation.

The importance of A3 allele in response to hepatitis B vaccine in end-stage renal disease patients.

BACKGROUND: Hemodialysis (HD) patients are at high risk for hepatitis B virus (HBV) infection due to intravenous interventions and therapies: Our aim was to examine how genetic factors affect the response to HBV vaccination in HD patients. METHODS: The frequencies of HLA class I and II alleles were investigated in responders and nonresponders. Response to vaccination was defined as anti-HBsAg > 10 SI U/L (group I). Nonresponders (anti-HBsAg < 10 SI U/L) were defined as group II. The study included HD patients who were negative for antibodies to hepatitis B surface antigen during pretransplantation evaluation. RESULTS: Group I consisting of 166 patients and group II, of 90 patients showed a significantly higher frequency of the HLA A3 allele in group I (n = 20) than group II (n = 3) (P = .02). There were no statistical differences between the two groups regarding age and gender distribution (P > .05). Graft outcome was not different between responders and nonresponders (P > .05). CONCLUSIONS: This preliminary study shows that HLA alleles may have immunomodulatory effects in end-stage renal failure patients. The response to hepatitis B vaccination is affected in multifactorially fashion; HLA A3 may be a genetic predictor for responders, but further studies in larger series are required.

Depression levels before and after renal transplantation.

Depression is a frequent problem among end-stage renal disease patients and is closely associated with their physical well-being. We sought to compare the depression levels and confounding parameters in renal patients. The 88 patients (62 men, 26 women) included: renal transplant recipients (n = 27); renal transplant waiting list patients (n = 30); and chronic allograft rejection patients on dialysis therapy (n = 31). Their mean age was 31.05 +/- 11.78 years. Age, gender, marital status, presence of chronic rejection, duration of functional graft, and hemodialysis were retrieved from patient records. Depression levels were evaluated by the Beck Depression Inventory. The depression stage of the renal transplant recipients was significantly lower than that of hemodialysis patients with chronic allograft rejection (P =.003). The presence of depression was not related to age or gender. Married patients showed a lower percentage of depression (P <.03). There was an inverse correlation between depression and functional graft duration among patients with transplant failure (r = -.370, P =.04). In conclusion, the return to hemodialysis, especially after a short duration of graft function, is associated with depression. The lower depression percentage among married patients may be due to the psychosocial support of the spouses. Therefore, single persons and transplant failure patients who return to dialysis therapy need greater social and psychologic support. Placing greater numbers of patients on transplant waiting lists decreases depression and may provide a higher quality of life with a better outcome during dialysis therapy.

The renin-angiotensin system and endothelial nitric oxide synthase gene polymorphisms and cyclosporine toxicity in renal transplant patients.

Although cyclosporine has improved graft survival, the toxicity of the drug frequently causes problem for renal transplant patients. Cyclosporine displays deleterious effects due to direct toxicity to the nephrons and vasoconstriction of afferent arterioles, effects that may be due to increased angiotensin II and decreased nitric oxide activity. We sought to examine the relation between cyclosporine toxicity and the RAS (angiotensin-converting enzyme, angiotesinogen, angiotensin 1 and 2 receptors, and ecNOS) gene polymorphisms in 111 renal transplant patients. Retrospectively, we correlated the results of graft biopsies from these 111 patients, with the cumulative drug doses (mg), mean blood levels (mg/mL), mean daily doses (mg), and mean doses (mg/kg/d) of cyclosporine. Overall 125 patients (38 women, 87 men) were enrolled in the study. Their mean age was 34.47 +/- 11.04 years. Twenty patients displayed cyclosporine toxicity on graft biopsy; 91 showed no evidence of the disorder. We could not find any relation between cyclosporine toxicity and gene polymorphisms (P >.05), although the mean mg/kg/d dose was significantly high among cyclosporine toxicity group (P =.028, RR = 1.42). In recent studies angiotensin II and nitric oxide have been suggested to be related to cyclosporine toxicity; however, our results failed to reveal an association between cyclosporine toxicity and angiotensin II or nitric oxide-related gene polymorphisms.

Angiotensin-converting enzyme gene polymorphism significantly affects renal posttransplantation erythrocytosis.

Posttransplantation erythrocytosis (PE) is a frequent problem in renal transplant patients. The pathogenesis and mechanisms of both the problem and therapy strategy are unknown. Since ACE and angiotensin 2 receptor inhibitors have been used to successfully manage PE, we speculated a relation between gene polymorphisms and this complication. Ninety-six ( 30 women, 66 men, age 34.4 +/- 11.0 years) renal transplant patients evaluated retrospectively, for gene polymorphisms of ACE, angiotensinogen, angiotensin 1 and 2 receptors (ATR1 and ATR2), as well as endothelial nitric oxide synthase (ecNOS). They were divided into two groups; patients with versus without PE, which was defined as >15 g/dL hemoglobin levels during the first year after renal transplantation. PE was found to be significantly more prevalent among D/D than I/I gene polymorphism of ACE genes (P <.04). The distribution of D/D, I/D, and I/I polymorphisms were 39.1%, 45.9%, and 7.6%, respectively. There was no difference between D/D and I/D polymorphisms. Comparing the I/D and I/I polymorphisms showed PE to be statistically more prevalent in the I/D polymorphism (P <.01). Logistic regression analysis revealed that D/D and I/D polymorphisms were significant risk factors for PE (P <.05, RR = 7.714 and P <.03, RR = 10.199, respectively). While previous studies revealed a relation between angiotensin II and PE, our study discovered the contribution of ACE gene polymorphism.