Hyperuricemia influences chronic cyclosporine nephropathy.

BACKGROUND: The observation that long-standing hyperuricemia is associated with chronic tubulointerstitial disease, afferent arteriolopathy, intrarenal vasoconstriction, and increased vascular resistance raises the hypothesis that hyperuricemia might contribute to chronic cyclosporine (CsA) nephropathy. The aim of the present study was to investigate the effect of hyperuricemia on chronic CsA nephropathy. METHODS: Patients who were treated with CsA-based immunsuppressive regimens and underwent a renal biopsy were enrolled in this case-control study. We retrospectively obtained posttransplant baseline serum creatinine, uric acid (UA), mean serum UA, and creatinine values 3 months prior to biopsy. CsA trough levels, mean blood pressure, diuretic and antihypertensive treatment were recorded. Biopsy specimens showing CsA nephropathy (n = 34) were revaluated by a pathologist to score CsA nephropathy according to recent quantitative criteria for calcineurin inhibitor arteriolopathy as proposed by M.J. Mihatsch. RESULTS: As compared with the non-CsA nephropathy group, recipient and donor ages, donor origin and cold ischemia times were similar for the CsA nephropathy group (P > .05). Mean CsA doses, CsA trough (C(0)), and C(2) levels were not different between the groups (P > .05). Systolic and diastolic blood pressure, glomerular filtration rate, diuretic usage, and antihypertensive treatment were also similar in CsA nephropathy and non-CsA nephropathy groups (P > .05). Mean serum UA level within 3 months prior to biopsy in the CsA nephropathy and non-CsA nephropathy groups were 7.5 +/- 1.4 mg/dL versus 5.7 +/- 1.4 mg/dL, respectively (P < .001). CONCLUSION: Hyperuricemia seems to exacerbate CsA-induced nephropathy.

Do MMP-1 levels of gingival fibroblasts have a role in the gingival overgrowth of cyclosporine-treated patients?

The aim of this study was to compare the matrix metalloproteinase-1 (MMP-1) levels in gingival fibroblast cultures derived from two groups of renal transplant patients receiving cyclosporine (CsA) who exhibit gingival overgrowth and who have healthy periodontium. Gingival fibroblasts obtained from four patients with CsA-induced gingival overgrowth (CsA-GO) and four patients who receive CsA but have healthy periodontium were incubated with increasing concentrations of CsA and cultured for 72 hours. Expression levels of MMP-1 in all the groups were measured four times at 0, 24, 48, and 72 hours by the Rapid Collagenase Assay Kit. No significant difference was seen at baseline. As the CsA concentration and the duration in the cell media increased, the CsA-GO showed that fibroblasts displayed significantly suppressed MMP-1 levels with respect to the baseline, at which fibroblasts from CsA patients with healthy periodontium exhibited the same result as at the highest CsA concentration. Results of this study indicated that CsA therapy did not have a significant effect on MMP-1 levels. Since the overall pathogenesis of drug-induced gingival hyperplasia has been accepted as multifactorial, down-regulation of MMP-1 expression may play a minor role.

Evaluation of telomerase activity in gingival fibroblasts of cyclosporine-treated patients.

Gingival overgrowth (GO) is a common side effect following administration of cyclosporin A (CsA). Various case reports have shown that squamous cell carcinomas could arise in GO induced by CsA and phenytoin. It is also known that human telomerase activated in about 90% of cancers is mainly composed of hTR, hTERT, and TPI. The aim of this study was to investigate the potential role of telomerase activity in the pathogenesis of CsA-induced GO. Included in the study were 9 patients on CsA: 4 with and 5 without GO. Gingival tissues were obtained during gingivectomy or flap procedures; gingival fibroblasts were cultured in Dulbecco's modified Eagle's medium (DMEM) supplemented with 10,000 U/mL penicillin, 10 mg/mL streptomycin, 2 mmol/L l-glutamine, and 10% heat-inactivated fetal bovine serum at 37 degrees C under a humidified 95% air virgule 5% CO(2) atmosphere. Quantitative detection of hTERT mRNA was performed with the commercially available LightCycler Telo TAGGG hTERT Quantification Kit using real-time online PCR. The hTERT mRNA expression was positive in one patient, while hTERT mRNA expression was negative in the others. Because results indicated that there may be a relationship between CsA-induced GO and positive telomerase activity, detailed studies should be performed to confirm the present findings.

Successful therapy with rituximab of refractory acute humoral renal transplant rejection: a case report.

Acute humoral rejection (AHR) is generally less responsive to conventional anti-rejection treatment with consequent allograft losses. Therapeutic options include antilymphocyte antibody (ATG), intravenous immunglobulin (IVIG), plasmapheresis, or immunoadsorption with protein A together with intensification of immunsuppression with a tacrolimus/mycophenolate mofetil combination. This report describes a transplant recipient who responded to rituximab therapy as treatment for steroid-, ATG-, IVIG-, and plasmapheresis-resistant AHR.

A renal transplant recipient with delayed gastric emptying in amyloidosis due to familial Mediterranean fever improved with erythromycin: a case report.

Patients with systemic amyloidosis often have symptoms related to impared gastrointestinal motility due to delayed gastric emptying, which results from autonomic nerve or smooth muscle infiltration with amyloid. There is no current report about gastric delaying secondary to amyloidosis due to familial Mediterranean fever. In this report, we have described a renal transplant recipient with delayed gastric emptying secondary to amyloidosis due to familial Mediterranean fever, which improved with erithromycin treatment.

Outcome of kidney transplantation for renal amyloidosis:a single-center experience.

The aim of this retrospective study was to investigate the results of kidney transplantation in patients with renal amyloidosis. We analyzed the results of renal transplantation in 13 amyloidotic transplant recipients compared with those in a control group of 13 nonamyloidotic patients. While the etiology of amyloidosis was rheumatoid arthritis in one patient, in all of the others it was secondary to familial Mediterranean fever. Acute rejection episodes developed once in six and twice in one patient. The renal function in these patients was improved by antirejection treatment. Chronic rejection did not develop in any patient. However six patients (46%) died due to various complications despite functional grafts. The others are still being followed with well-functioning grafts. Among the control group, acute and chronic rejection were diagnosed in three and two patients, respectively: one patient returned to hemodialysis after 26 months of transplantation, while the others are still alive with functional grafts. There was no death in the control group. The 5- and 10-year actuarial patient survival rates of the amyloidosis and control groups were 52.2%, 26.6%, and 100%, 100%, respectively (P = .002). However, the graft survivals of the amyloidosis versus control groups were 100%, 100%, versus 87.5%, 87.5, respectively (P = .47). In conclusion, we observed a high rate of early mortality among recipients with amyloidosis associated with infectious complications. Moreover, patient survivals were lower among amyloidotic renal recipients.

Sexual dysfunction in male patients on hemodialysis: assessment with the International Index of Erectile Function (IIEF).

In this study we determine the sexual problems and the prevalence of erectile dysfunction (ED) in male hemodialysis patients by means of the International Index of Erectile Function (IIEF). A total of 187 male patients were included in the study. All of the patients who underwent hemodialysis were asked to complete the IIEF questionnaire. The IIEF domain scores were calculated and erectile dysfunction grading was determined on erectile function domain. Patients were also asked to report whether they had disclosed their sexual problems to physicians or not.The mean age was 49.3+/-13.2 y and the duration of hemodialysis was 38.1+/-8.4 months. By means of the IIEF, the prevalence of erectile dysfunction of any degree was 80.7%. The prevalence of any ED for the patients <50 y and >or=50 y was 74.5% and 86.6%, respectively. The prevalence and the severity of ED was significantly higher in patients >or=50 y. The frequency of intercourse attempts during the last four weeks was 1-2 in 130 (69.5%) of patients. Only 1% of patients disclosed their erectile problems and sought medical assistance prior to our study.Erectile dysfunction is highly prevalent in hemodialysis patients. The prevalence and the severity of ED increased with age. Evaluations for ED should be included in routine assessment of hemodialysis patients.

Efficacy and safety of sildenafil for treating erectile dysfunction in patients on dialysis.

OBJECTIVE: To assess the efficacy of sildenafil for erectile dysfunction (ED) in patients on haemodialysis (HD) or peritoneal dialysis (PD), as men with end-stage renal disease (ESRD) often have sexual dysfunction (up to 82% among those on chronic dialysis). PATIENTS AND METHODS: Forty-one patients with ED and in ESRD participated in an open-label prospective study. Thirty patients on HD and 11 on PD were asked to complete the International Index of Erectile Function (IIEF) and Fugl-Meyer life-satisfaction scale before and after sildenafil treatment. A total score in the erectile function domain of < or = 25 was accepted as indicating ED. All patients were started on a 25-mg dose, which was increased to 50 mg if there was no response after two trials. In addition, the overall efficacy question was used to evaluate satisfaction, and patients reported any side-effects during treatment. RESULTS: The erectile function and intercourse satisfaction domains improved significantly in both groups (P < 0.01). After sildenafil treatment, two-thirds of those on HD (20/30) and nine of the 11 on PD recovered their erectile function. The pretreatment scores on the IIEF and four domains (except sexual desire) of those responding were significantly higher than in those not responding (P < 0.05). The satisfaction rate on the overall efficacy question was 80% and 82% for the HD and PD groups, respectively. At least one side-effect was seen in 17 patients (43%); one had severe hypotension in the PD group. Overall, mild headache (seven patients, 18%) and flushing (12, 30%) were reported most often. CONCLUSIONS: Sildenafil is a safe and satisfactory drug for improving erectile function in patients with ESRD. Patients were satisfied whether treated by HD or PD. Pretreatment scores on the IIEF may be useful for predicting the success of treatment.

Comparison of two different Kt/V methods in continuous ambulatory peritoneal dialysis patients.

Dialysis adequacy has gained particular interest for the assessment of the quality of dialysis in patients undergoing hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD). Kt/V is used as a test of dialysis adequacy in HD and CAPD patients. The aim of this study was to compare two different Kt/V methods in CAPD patients. A practical method for the calculation of Kt/V will be suggested at the end of this prospective study. The study group included 28 patients. Each patient received CAPD therapy four times per day. During the study, CAPD dialysate samples for a period of 24 hours were obtained by two different methods. One is a modified method for obtaining samples by the patient at home; the other is the conventional method. For study purposes only, we told the patients using the modified method to bring all the bags to the center (contrary to the aim of the modified method). In the first method (modified method), CAPD patients collected 24-hour dialysate and urine samples at home and brought all of the materials to the hospital. A 10 mm3 dialysate sample was drawn from each CAPD dialysate bag, and then a total of 40 mm3 dialysate was mixed in a beaker. A sample of 10 mm3 of dialysate was taken from the mixture in the beaker, and then this dialysate sample, urine, and 5 mm3 venous blood were sent to the laboratory for urea nitrogen (UN) and creatinine level determinations. In addition to these tests, 24-hour dialysate and urine volumes and the patients' weight and height were measured, and Kt/V values were calculated. In the second method (classic method), all the bags from the 24-hour period were collected and mixed in a big bucket, and then a 10 mm3 sample was taken. The remaining procedures were the same as for the first method. Mean Kt/V values were calculated separately for the two methods and were found to be 2.48 by the modified method and 2.52 by the classic method. The results of the two methods were compared with the Wilcoxon paired t-test, which showed no statistically significant difference (p = 0.5228). In conclusion, two different Kt/V methods can be used in CAPD patients. However, the modified method is easily performed, and CAPD patients can collect and take the dialysate and urine samples at home, and bring these materials to the renal unit without transportation problems.

Hypomagnesemia and mild rhabdomyolysis in living related donor renal transplant recipient treated with cyclosporine A.

Since cyclosporine A (CsA) had been used in renal transplant recipients, important improvements in short-term and long-term graft survivals have been detected. In spite of these improvements CsA seems to have several adverse effects. First, CsA leads to nephrotoxicity. Moreover, CsA affects the other organs and systems (skin, liver, nervous system, etc.) and causes, increased risks of infections and malignancies. Hypomagnesemia is one of the side effects of CsA therapy, but it is a rare condition in living related donor renal transplant recipients. It may also cause multi-system dysfunction, especially hypocalcemia and hypokalemia, which cannot be corrected without magnesium therapy. In addition, rhabdomyolysis was detected in animals, but it has not been reported in living related donor renal transplant recipients. In this case report, a living related donor renal transplant recipient who suffered from hypomagnesemia and mild rhabdomyolysis due to CsA therapy will be described and discussed.

Lipid peroxidation and antioxidant activity in chronic haemodialysis patients treated with recombinant human erythropoietin.

In anaemia of chronic renal failure, the most important factor in the shortened erythrocyte survival may be lipid peroxidation of the cell membrane. Defective antioxidant activity may increase this damage. Although recombinant human erythropoietin (r-HuEPO) can effectively correct anaemia in chronic haemodialysis patients, its actions on lipid peroxidation and antioxidant activity are not clear. These actions were investigated in 13 patients undergoing chronic haemodialysis. Antioxidant activity, including red blood cell superoxide dismutase and total glutathione peroxidase levels and the lipid peroxidation product malondialdehyde, were measured before and 3 months after initiation of r-HuEPO treatment, using heparinized venous whole blood for cell and plasma determinations. Age-matched healthy volunteers were controls. Significantly higher levels of superoxide dismutase and total glutathione peroxidase were found in the patients than in the controls (p < 0.01). Plasma malondialdehyde levels were not affected by r-HuEPO. The results are explained by erythropoiesis and cellular haemoglobin synthesis due to r-HuEPO, followed by increase of circulating young red cells. The membranes of these young cells contain more antioxidant enzymes than the others. Despite r-HuEPO treatment, plasma malondialdehyde levels in haemodialysis patients may be higher than normal because of the uraemic milieu and the chronic haemodialysis.

Non-infectious complications of continuous ambulatory peritoneal dialysis: evaluation with peritoneal computed tomography.

The purpose of the study was to evaluate the non-infectious complications of continuous ambulatory peritoneal dialysis (CAPD) using peritoneal computed tomography (PCT). Twenty symptomatic patients were included in the study. Initially 2000 ml of dialysate fluid was infused into the peritoneal cavity and standard peritoneal computed tomography (SPCT) serial scans with 10 mm thickness were performed from the mid-thoracic region to the genital organs. Afterwards, 100 ml of non-ionic contrast material containing 300 mg/ml iodine was injected through the catheter and was distributed homogeneously in the intra-abdominal dialysate fluid by changing the positions of the patients; after waiting 2-4 h, the CT scan was released as peritoneal contrast computed tomography (PCCT). In patients (n = 20) both SPCT and PCCT revealed 90% (n = 18) pathological findings. But PCCT showed 60% (n = 12) additional pathological findings. We believe that PCT is beneficial for evaluation of non-infectious complications of CAPD. But PCCT is superior to SPCT in evaluating non-infectious complications encountered in patients on CAPD treatment.

Behçet's disease with pulmonary involvement, superior vena cava syndrome, chyloptysis and chylous ascites.

Behçet's disease is a chronic multisystem vasculitis of unknown aetiology. This case report describes a patient who applied to the hospital because of dyspnoea, ascites, oedema of lower extremities and recurrent episodes of haemoptysis. For the last 12 yr, he had superior vena cava syndrome (SVCS) and cardiac and pulmonary involvement of Behçet's disease, and biochemical examination of ascite fluid yielded a chylous effusion containing triglyceride 421 mg dl-1 and cholesterol 49 mg dl-1. Chyloptysis was also detected by Sudan III stain. The patient died from cardiac tamponade in spite of cardiac fenestration. To the authors' knowledge, this is the first reported case of Behçet's disease with chylous ascites and chyloptysis in the English literature.