Kidney transplantation at Necker Hospital: the most recent 5-year period (2004-2009).

The results of our last 5 years activity in kidney transplantation clearly show that it is possible to perform high-risk transplantations with very acceptable results: ECD kidneys, dual transplantation, recipients with DSAs. In depth statistical analysis of these data should allow a clearer definition of the best strategies to use in these situations.

Sirolimus may reduce fertility in male renal transplant recipients.

Assessment of sex hormones in organ transplant recipients suggests that sirolimus may impair testicular function. The aim of this study was to evaluate the frequency and severity of sirolimus-associated alterations in sperm parameters and their impact on fathered pregnancy rate. An observational study was carried out in male patients aged 20-40 years who received a kidney transplant during 1995-2005. Patients were sent a questionnaire by post, and sperm analysis was proposed. The fathered pregnancy rates according to the immunosuppressive regimen were estimated and compared using the Poisson model. Complete information was obtained from 95 out of 116 recipients. Patients treated with sirolimus throughout the post-transplant period had a significantly reduced total sperm count compared to patients who did not receive sirolimus (28.6 +/- 31.2 x 10(6) and 292.2 +/- 271.2 x 10(6), respectively; p = 0.006), and a decreased proportion of motile spermatozoa (22.2 +/- 12.3% and 41.0 +/- 14.5%, p = 0.01). Moreover, the fathered pregnancy rate (pregnancies/1000 patient years) was 5.9 (95% CI, 0.8-42.1) and 92.9 (95% CI, 66.4-130.0) in patients receiving sirolimus-based and sirolimus-free regimens, respectively (p = 0.007). Of six patients in whom sirolimus treatment was interrupted, only three showed a significant improvement in sperm parameters. Sirolimus is associated with impaired spermatogenesis and, as a corollary, may reduce male fertility.

Cyclosporine withdrawal in stable renal transplant recipients after azathioprine-mycophenolate mofetil conversion.

BACKGROUND: Cyclosporine A (CsA) nephrotoxicity is a nonimmunologic factor of chronic allograft dysfunction (CAD) in kidney transplant recipients. Mycophenolate mofetil (MMF) may allow CsA dosage reduction or even complete withdrawal in selected populations with CsA nephrotoxicity or CAD. The aim of the present study was to evaluate the efficacy and safety of CsA withdrawal after azathioprine (AZA)-MMF conversion in a population of stable renal transplant recipients. METHODS: Twenty-eight first cadaver kidney recipients were included. AZA was then discontinued, MMF was introduced and after 4 months CsA was completely withdrawn. All patients underwent inuline clearance measurement and renal biopsy at inclusion and at the end of the follow-up (40 wk). RESULTS: CsA was completely discontinued in 20 patients. No patient lost his graft during the study period, but 1 patient experienced a reversible acute rejection episode. Inuline clearance improved significantly in the whole series. At the end of follow-up, histological worsening was observed in 50% of patients without any specific risk factor. In these patients, inuline clearance did not improve. Systolic blood pressure, the need for anti-hypertensive drugs and HDL cholesterol improved. CONCLUSION: In stable kidney transplant recipients, CsA withdrawal after AZA replacement by MMF switch was safe with regard to acute rejection. It improved blood pressure and the lipid profile, but, in 50% of patients was associated with histologic deterioration.

Plasma kinetics of 125I-labelled amyloid P component in beta 2M amyloidosis: a possible approach to quantitate disease activity.

Dialysis amyloidosis is one of the most incapacitating complications of long-term dialysis treatment. Quantitative assessment of amyloid deposition using radiolabelled tracers has been recently proposed but convincing evidence of its validity in uraemic patients remains to be provided. We studied the plasma kinetics of i.v. administered 125I-labelled serum amyloid P component (125I-SAP) in 20 chronic haemodialysis patients compared with those of nine healthy volunteers and three non-dialysed patients with systemic amyloidosis. Plasma clearance of the tracer was abnormal in 17 of 20 dialysis patients in whom plasma radioactivity declined in a bi-exponential mode, in contrast to the single-exponential slope observed in all healthy controls. 125I-SAP plasma half-life of the second component, probably reflecting metabolic clearance, was significantly prolonged in these dialysis patients compared with the healthy controls (35.3 versus 24.6 h, P < 0.001). Among the long-term haemodialysis patients the calculated extravascular distribution of 125I-SAP was significantly greater in those with severe arthropathy than in asymptomatic patients. These findings demonstrate for the first time that SAP clearance is disturbed in haemodialysis patients due to both failing renal elimination and retention in extravascular sites. The extravascular diffusion is greatly enhanced in patients with clinical evidence of amyloidosis. Therefore the study of plasma 125I-SAP kinetics promises to be a valuable tool to quantitate the extent of amyloidosis.

No acute change of serum erythropoietin in response to hypocalcemia or antihypertensive agents in uremic patients.

Endogenous erythropoietin (EPO) secretion can still be modulated in patients with end-stage renal failure but only in response to strong stimuli. Thus even anephric dialysis patients are able to increase EPO production acutely when exposed to a marked hypoxic stimulus. The present study was designed to test the hypothesis that a decrease of plasma calcium or the administration of various antihypertensive agents might be able to induce acute changes of plasma EPO concentration. Four groups of chronic hemodialysis patients were studied. Eight patients volunteered for the induction of an acute, transient hypocalcemia via a calcium-free dialysate during the initial 60 min of a regular dialysis session of 240 min. Plasma immunoreactive (i) EPO, total calcium, and intact parathyroid hormone (iPTH1-84), as well as blood ionized calcium and blood gases were measured before as well as 30, 60, 120 and 240 min after the start of dialysis. In addition, plasma iEPO was measured 48 h after the session. Patients of group 2 (n = 6), group 3 (n = 6), and group 4 (n = 7) received the day after a hemodialysis session a single dose of either acetazolamide, furosemide, or enalapril, respectively, and their plasma iEPO was determined before and 3, 6 and/or 24 h after drug administration. In group 1, plasma total calcium decreased from 2.39 +/- 0.07 mM (mean +/- SEM) to 1.98 +/- 0.02 and 1.83 +/- 0.03 mM after 30 and 60 min of dialysis, respectively, and blood ionized calcium from 1.28 +/- 0.04 to 1.02 +/- 0.03 and 0.92 +/- 0.04 mM, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Aluminium intoxication in the rat induces partial resistance to the effect of recombinant human erythropoietin.

Anaemia is a major complication of chronic renal failure. It is mainly due to a decrease in the production of erythropoietin and at present it can be corrected by recombinant human erythropoietin (rHuEpo). The question has arisen whether aluminium overload, which is frequently observed in uraemic patients, could exert a resistance to the effect of rHuEpo. To answer this question, we submitted two series of rats with two groups in each to an experimental aluminium intoxication. Group II rats received repeated i.p. injections of aluminium, whereas group I (control) rats were given vehicle solution alone. Subsequently, all rats were treated with identical s.c. doses of rHuEpo (100 IU/kg body-weight twice weekly). In the first series, rats were fed ad libitum whereas in the second, rats were pair-fed and received iron supplementation. In the first series, group I rats had an increase of mean haemoglobin in response to rHuEpo: 15.6 +/- 0.3 vs 19.8 +/- 0.3 g/dl, P less than 0.001. In contrast, group II rats had a decrease: 15.1 +/- 0.2 vs 10.1 +/- 0.8 g/dl, P less than 0.001. However, compared to group I rats, group II rats did not gain body-weight and their plasma iron concentration was less. In the second series, mean haemoglobin concentration of group I rats increased from 15.1 +/- 0.2 to 18.9 +/- 0.3 g/dl (P less than 0.001) in response to rHuEpo.(ABSTRACT TRUNCATED AT 250 WORDS)

Utilization of erythropoietin in the treatment of the anemia due to chronic renal failure.

Administration of recombinant erythropoietin constitutes a revolution in treatment of the anemia of chronic dialysis patients. Such treatment has been anxiously awaited. Its realization has been possible thanks to the spectacular progress allowed by the newly developed techniques of recombinant genetics. Correction of this type of anemia can be obtained rapidly and permanently if treatment is continued without interruption. It is followed by a remarkable transformation of the patient's physical and psychic status. The occurrence of certain side effects (e.g., elevation of blood pressure and an increased tendency toward vascular thrombosis), however, requires increased awareness in the follow-up of patients at risk and adaptation of erythropoietin administration to individual needs.