Serological cardiovascular and mortality risk predictors in dialysis patients receiving sevelamer: a prospective study.

BACKGROUND: Cardiovascular morbidity and mortality are massively increased in patients with chronic kidney disease (CKD). Sevelamer hydrochloride has been shown to attenuate cardiovascular calcifications in CKD and end-stage renal disease (ESRD) patients. We assessed how sevelamer hydrochloride influences the evolution of serum fetuin-A and other serological factors predicting cardiovascular outcome and survival in haemodialysis patients. METHODS: Fifty-seven prevalent haemodialysis patients were included in a three-phase prospective interventional trial (A-B-A design; 8 weeks per phase). Sevelamer was only administered in the middle phase of the study. Within the other two phases, >or=90% of the patients received calcium acetate for phosphate binding. Detailed time courses of serum biochemistries were analysed in order to obtain detailed insight into the influence of sevelamer upon CKD-mineral and bone disorder (MBD) parameters as well as serum fetuin-A, fibroblast growth factor 23 (FGF23) and uraemic toxin levels [uric acid, indoxyl sulphate, hippuric acid, indole acetic acid, p-cresol and 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid (CMPF)]. RESULTS: Forty-one patients finished the three prospective study phases (intention-to-treat analysis). After treatment with sevelamer, serum fetuin-A significantly increased (+21%), showing a delayed increase outlasting the third (non-sevelamer) study period. Total and low-density lipoprotein (LDL) cholesterol levels, as well as serum calcium, decreased significantly. The opposite occurred with albumin, C-reactive protein and intact parathyroid hormone (iPTH). FGF23, uric acid, indoxyl sulphate, hippuric acid, indole acetic acid, CMPF and serum phosphate did not change significantly during sevelamer treatment. In contrast, in parallel to sevelamer treatment, there was a significant rise in serum P-cresol. CONCLUSIONS: In haemodialysis patients, treatment with sevelamer over 8 weeks was associated with a delayed yet long-lasting increase in serum fetuin-A levels. Increasing the serum level of fetuin-A, a negative acute-phase protein and systemic calcification inhibitor, might be one of the potential anti-calcification mechanisms of sevelamer. Since we failed to detect a decrease in systemic inflammation and uraemic toxins, the exact mechanisms by which sevelamer treatment affects serum fetuin-A remain to be determined.

Genotoxicity and cytotoxicity of cisplatin treatment combined with anaesthetics on EAT cells in vivo.

In this study, DNA damage in tumour cells, as well as irreversible cell damage leading to apoptosis induced in vivo by the combined application of cisplatin and inhalation anaesthetics, was investigated. The genotoxicity of anaesthetics on Ehrlich ascites tumour (EAT) cells of mice, alone or in combined application with cisplatin, was estimated by using the alkaline comet assay. The percentage of EAT cell apoptosis was quantified by flow cytometry. Groups of EAT-bearing mice were (i) treated intraperitoneally with cisplatin, (ii) exposed to repeated anaesthesia with inhalation anaesthetic, and (iii) subjected to combined treatment of exposure to anaesthetics after cisplatin for 3 days. Sevoflurane, halothane and isoflurane caused strong genotoxic effects on tumour cells in vivo. The tested anaesthetics alone showed no direct effect on programmed cell death although sevoflurane and especially halothane decreased the number of living EAT cells in peritoneal cavity lavage. Repeated anaesthesia with isoflurane had stimulatory effects on EAT cell proliferation and inhibited tumour cell apoptosis (6.11%), compared to the control group (10.26%). Cisplatin caused massive apoptosis of EAT cells (41.14%) and decreased the number of living EAT cells in the peritoneal cavity. Combined cisplatin and isoflurane treatment additionally increased EAT cell apoptosis to 51.32%. Combined treatment of mice with cisplatin and all anaesthetics increased the number of living tumour cells in the peritoneal cavity compared to cisplatin treatment of mice alone. These results suggest that the inhalation of anaesthetics may protect tumour cells from the cisplatin-induced genotoxic and cytotoxic effects.

Management of Fournier's gangrene--report of 7 cases and review of the literature.

Fournier's gangrene is a rare infection characterized with fast-progressing myonecrosis, that affect regions of perineum, genitalia and perianal area. This retrospective study presents authors' experiences and their principles in early diagnosis and treatment of Fournier's gangrene. The goal of this paper is to point out numerous diagnostically and therapeutic difficulties that lead to a high mortality if not recognized in time. We here describe seven male patients with myonecrosis and necrotising fasciitis in scrotal, perianal and perineal regions. Average age was 61 years (form 57 to 66 years of age), and average length of treatment was 25.8 days (from 14 to 36 days), with lethality of 14% (one case). We have recognised diabetes mellitus as risk factor, together with urethrostenosis, and other diseases of the perianal region (hemorrhoids, anal fissure, abscesses). Our hypothesis is that the key of the successful treatment is to treat as soon as symptoms onset, early and aggressive necrectomy under broad antibiotic protection. We also emphasize the possibility of recurrence of this disease even several years after treatment.

Early rapid loss followed by long-term consolidation characterizes the development of lumbar bone mineral density after kidney transplantation.

BACKGROUND: Bone mineral density (BMD) decreases significantly early after renal transplantation. This prospective study was designed to evaluate the long-term lumbar BMD development. METHODS: Sixty-three renal-transplant recipients (mean age 44 +/- 12 years, 37 [59%] male) underwent serial yearly posttransplant laboratory parameter and BMD measurements of the lumbar spine (dual energy x-ray absorptiometry). Combined maintenance immunosuppression included prednisolone in 95% of patients. The minimum number of consecutive scans was three; the maximum number seven (n = 15). Examinations were performed between 3 +/- 2 and 68 +/- 4 months posttransplant. RESULTS: BMD was significantly lower compared with healthy controls at all times after transplantation. t scores were below -1. BMD development revealed a biphasic pattern: between 3 +/- 2 and 10 +/- 2 months, a significant BMD decrease of -0.016 +/- 0.055 g/cm2 (-1.6%, P = 0.024) occurred. Later, a moderate increase resulting in BMD stability until the sixth year posttransplant was detected. Within the first year, posttransplant osteocalcin (from 19 +/- 15 to 32 +/- 23 microg/L) and calcitriol (from 24 +/- 15 to 43 +/- 24 ng/L) displayed a significant increase. Compared with patients with a pronounced decrease, patients with a substantial increase in early posttransplant BMD had a lower baseline BMD (0.989 +/- 0.131 vs. 1.149 +/- 0.202 g/cm2 [P = 0.0122]) and lower creatinine levels (105 +/- 23 vs. 141 +/- 53 mmol/L [P = 0.0227]). CONCLUSION: Our study confirms a significant decrease of lumbar BMD early after renal transplantation. Bone loss was less pronounced than previously described. The longitudinal follow-up verifies a previously assumed biphasic lumbar BMD development: after the first year, no further significant bone loss occurred, and bone density remained relatively stable at significantly lower levels compared with healthy controls.

Development of lumbar bone mineral density in the late course after kidney transplantation.

BACKGROUND: Rapid bone loss is a frequent finding early after kidney transplantation. Only limited data are available on the bone mineral density (BMD) in long-term kidney transplant recipients. METHODS: In 26 kidney transplant recipients (13 men and 13 women, age 45.3 +/- 12.3 years), serum biochemical markers of bone metabolism and BMD at the lumbar vertebrae L2-4 were evaluated prospectively in three serial examinations (E1, E2, E3; method: dual-energy X-ray absorptiometry). Examinations were performed at 47 +/- 2 months, 59 +/- 2 months, and 71 +/- 2 months after transplantation. All patients received standard dual or triple immunosuppression including prednisolone. RESULTS: The mean BMD was significantly lower (P < 0.001) than in sex-matched young controls: T-score was -1.43 +/- 1.49 (E1), -1.39 +/- 1.40 (E2), and -1.44 +/- 1.30 (E3). The BMD did not change significantly (Delta BMD, -0.5 +/- 5.9%) from E1 to E3. Regression analysis did not show significant associations between Delta BMD and biochemical parameters or prednisolone dosage. No clinically apparent new lumbar vertebral fracture occurred. The mean intact parathyroid hormone was 110.1 +/- 97.5 pg/mL (E1), 121 +/- 102.7 pg/mL (E2), and 134.5 +/- 128.6 pg/mL (E3). Serum creatinine was 1.44 +/- 0.45 (128 +/- 40) mg/dL (micromol/L) (E1), 1.44 +/- 0.47 (127 +/- 42) mg/dL (micromol/L) (E2), and 1.45 +/- 0.70 (128 +/- 62) mg/dL (micromol/L) (E3). Ten patients (38.5%) showed an increase of BMD (+5.7 +/- 3.2%) and 15 patients (57.7%) showed a decrease of -4.7 +/- 3.2% (P < 0.0001). Both groups were different in T-scores at E1 (-2.29 +/- 1 versus -0.88 +/- 1.5); intact parathyroid hormone, creatinine, vitamin D levels, and prednisolone dosage were not significantly different. CONCLUSION: This study shows that lumbar BMD is reduced in long-term kidney transplant recipients. During our 24-month observation period, overall lumbar BMD remained stable.