Catherine Bresson-Vautrin

CD4 lymphocytopenia as a risk factor for skin cancers in renal transplant recipients

BACKGROUND Renal transplant recipients are at increased risk of developing skin cancer. It remains difficult to establish the actual influence of overimmunosuppression in the development of skin cancers. We investigated whether lymphocyte subset count may predict the risk of developing skin cancer in long-term renal transplant recipients. METHODS One hundred fifty long-term renal transplant recipients were followed for a mean period of 26 months. Each patient was examined at least annually by a dermatologist. Lymphocyte subsets were measured annually. RESULTS Fifteen patients exhibited skin cancers. Patients with and without skin cancer did not differ in age, gender, transplant duration, hemodialysis duration before transplantation, immunosuppressive regimen, and serum creatinine concentration. CD4 cell counts were significantly lower in patients with skin cancers (330+/-179/mm3 vs. 503+/-338/mm3; P<0.01), whereas total lymphocyte and CD8 and CD19 cell counts were similar between the two groups. CONCLUSIONS CD4 cell depletion is associated with skin cancer in long-term renal transplant recipients.

Mycophenolate mofetil in renal transplant recipients with cyclosporine-associated nephrotoxicity: a preliminary report.

BACKGROUND There is a great concern over cyclosporine (CsA) nephrotoxicity in renal transplant recipients, and the effects of conversion from CsA to azathioprine (AZA) remain controversial. Large studies have demonstrated that mycophenolate mofetil (MMF), the morpholinoethyl ester of mycophenolic acid, is superior to AZA as a posttransplant immunosuppressant. METHODS Six patients with isolated biopsy-proven CsA nephrotoxicity were converted from CsA-AZA to MMF. RESULTS Mean follow-up was 12+/-2 months. No patient experienced acute rejection. The mean serum creatinine concentration decreased from 225+/-58 to 159+/-66 micromol/L (P<0.0005). Hyperlipidemia and blood pressure improved after CsA withdrawal. CONCLUSION In a selected transplant population with biopsy-proven CsA nephrotoxicity, CsA withdrawal with a concomitant switch from AZA to MMF seems to be safe and allows a significant improvement of renal function.

Recurrence of hemolytic-uremic syndrome in renal transplant recipients: a meta-analysis.

BACKGROUND Recurrence of hemolytic-uremic syndrome (HUS) in the allograft is associated with a very poor renal prognosis. Meta-analysis of previous trials may allow us to better estimate its real frequency, to identify risk factors for recurrence, and to predict the outcome of patients with definite recurrence. METHODS An exhaustive search was conducted of HUS recurrence in renal transplantation from January 1977 to June 1997 using MEDLINE. RESULTS Ten studies comprising 159 grafts in 127 patients were identified. The rate of recurrence was 27.8%. One-year graft survival was 76.6% in patients without recurrence and 33.3% in patients with recurrence (P<0.001). Older age at onset of HUS (16.96+/-7.6 years vs. 9.95+/-6.55 years; P<0.02), shorter mean interval between HUS and transplantation (2.51+/-2.7 years vs. 6.03+/-6.4 years; P<0.01), shorter mean interval between HUS and end-stage renal disease (0.79+/-0.39 years vs. 2.78+/-2.47 years; P<0.01), living-related donors, and the use of calcineurin inhibitors were associated with recurrence. CONCLUSION Risk factors for HUS recurrence in renal transplantation could be identified through this meta-analysis.

Use of pentoxifylline in membranous nephropathy

Urinary TNF-alpha excretion correlates with proteinuria in patients with membranous nephropathy (MGN). Pentoxifylline suppresses or reduces the production of TNF-alpha. Between April, 1999 and August, 2000, we did a single-centre, prospective, pilot study to assess the effects of pentoxifylline (1200 mg/day) on proteinuria in patients with idiopathic MGN. Ten patients were included and treated for 6 months. Pentoxifylline significantly decreased proteinuria from 11 g/day [range 4.6-27] to 1.8 (0-10.9); p=0.001). Pentoxifylline may be a safe and effective adjunct to steroids and immunosuppressants in patients with MGN.

Lymphocyte subsets and assessment of cancer risk in renal transplant recipients

Abstract Renal transplant recipients have a well‐recognized increased risk of de novo neoplasia. In this study, we investigated whether lymphocyte subset count could predict the risk of developing noncutaneous neoplasia (NCSC) in renal transplant recipients (RTR). Between January 1995 and December 1995, lymphocyte subsets (CD4, CD8, CD19) were measured in 281 RTR. This population was studied until November 1999 for the development of NCSC. The mean follow‐up was 42±9 months. Neoplasm was diagnosed in 22 patients (7.9%). Patients who developed a cancer were significantly older (53.8±6 years vs 38±16 years, P<0.0001), had lower CD4 (234±126/mm3 vs 543±214/mm3, P<0.005) and CD19 (19±9/mm3 vs 51±22/mm3, P<0.0001) levels, and more frequently had past histories of skin cancer (24% vs 4%, P<0.01). Cox regression revealed that high CD4 levels (RR 0.73, 95% CI 0.62–0.89 for each 100/mm3 increase in CD4 cell count) were associated with decreased risk of NCSC, whereas age (RR 2.49, 95% CI 1.12–5.92 for each 10‐year increase in age) was predictive of the subsequent development of NCSC. To conclude, CD4 cell depletion is associated with the development of solid cancers and lymphoma in RTR.

Cyclosporin withdrawal with concomitant conversion from azathioprine to mycophenolate mofetil in renal transplant recipients with chronic allograft nephropathy: a 2‐year follow‐up

Abstract Because recent large studies have demonstrated that mycophenolate mofetil (MMF) is superior to azathioprine (AZA) as a post‐transplant immunosuppressant, it has been speculated that MMF could have a cyclosporin (CsA)‐sparing effect in renal transplant recipients with chronic allograft dysfunction. Between April 1996 and October 1998, 31 patients with chronic allograft dysfunction were assigned to have conversion from AZA to MMF with concomitant CsA withdrawal. Patient and graft outcomes were analysed. Mean follow‐up time after MMF conversion was 27±11 months. Serum creatinine concentration (sCt) significantly decreased after conversion and remained stable at the end of followup (227±31 μmol/1 vs. 185±50 μmol/l; P<0.0005). Mean variation in sCt was −24% after conversion, whereas it was + 20% in the year before conversion (P<0.001). There was a significant inverse relationship between proteinuria at baseline and improvement in renal function (r=‐0.35; P=0.01). Proteinuria increased during follow‐up (0.79±0.6 vs. 1.79±1.08 g/day; P=0.04). Isolated CsA nephropathy was associated with the best outcome. Renal function significantly improved in patients with grade 1 chronic rejection and remained stable in patients with grade 2 chronic rejection. Two patients (6.5%) experienced late acute rejection, respectively 13 and 24 months after CsA withdrawal. Eight patients (29%) experienced systemic infections requiring hospitalization. Blood pressure control and lipid profile improved after conversion. CsA withdrawal with a concomitant switch from AZA to MMF allows a substantial and durable improvement in renal function. Both allograft histology and proteinuria at baseline are predictive of the evolution of renal function after conversion. Physicians should consider the risk of over‐immunosuppression possibly associated with this therapeutic strategy.

Peritoneal Dialysis Reduces the Number of Hospitalization Days in Heart Failure Patients Refractory to Diuretics

♦ Background: Previous small studies have reported favorable results of peritoneal dialysis (PD) in the setting of chronic refractory heart failure (CRHF). We evaluated the impact of PD in a larger cohort of patients with CHRF where end-stage renal disease was excluded. ♦ Methods: All patients who received PD therapy for CRHF between January 1995 and December 2010 in two medical centers in France were included in this retrospective study. Baseline characteristics were compared with clinical parameters during the first year after initiation of PD. Mortality, safety, and sustainability of PD were also analyzed. ♦ Results: The 126 patients included had a mean age of 72 ± 11 years and an estimated glomerular filtration rate of 33.5 ± 15.1 mL/min/1.73 m2. Mean time on PD was 16 ± 16.6 months. During the first year, patients with a left ventricular ejection fraction (LVEF) of 30% or less experienced improvement in cardiac function (30% ± 10% vs 20% ± 6%, p < 0.0001). We observed a significant reduction in the number of days of hospitalization for acute decompensated heart failure after PD initiation (3.3 ± 2.6 days/patient-month vs 0.3 ± 0.5 days/patient-month, p < 0.0001). One-year mortality was 42%. ♦ Conclusions: In CRHF, PD significantly reduces the number of days of hospitalization for acute heart failure. Improved LVEF may have led to the comparatively good 1-year survival in this cohort.

Polycystic kidney size and outcomes on peritoneal dialysis: comparison with haemodialysis

Background For many nephrologists, patients with polycystic kidney disease (PKD) have an increased risk of complications and technique failure on peritoneal dialysis (PD) due to enlarged kidneys. The literature showed that PD can be as good a therapeutic option as haemodialysis (HD) for patients with PKD. However, no study has focused on the impact of polycystic kidney size on outcomes for patients on PD. Methods This is a retrospective monocentric study. Fifty-eight patients with PKD started dialysis between January 2000 and December 2010: 24 on PD and 34 on HD. Kidney size assessed by abdominal computed tomography scans was available for 45 patients (19 on PD and 26 on HD). PD technique survival, specific PKD complications and mechanical and infectious PD complications, as need for pre-transplant nephrectomy and kidney transplantation, were considered. Results The two cohorts were similar in terms of age and body surface area. The median kidney size was not significantly different between PD and HD patients [19.1 cm (12.5–32.5) versus 16.5 cm (11.8–33.8), respectively, P = 0.13]. However, we identified an increased number of PD patients with larger kidneys [(>25 cm) (27.8% on PD versus 7.7% on HD (P = 0.07)]. Neither cystic (infection or haemorrhage) nor mechanical complications (hernias and leaks) were different in PD or HD. Ten patients experienced PD-related peritonitis, mainly due to non-enteric bacterial pathogens. The main reason for stopping PD and HD was transplantation. Six PD patients underwent nephrectomy in order to access the transplant programme. Among them, five were maintained on PD after surgical procedure with good adequacy dialysis criteria. Conclusions We observed no deleterious impact of kidney size on outcomes on PD when compared with HD. A large kidney size in patients with PKD is not a contraindication to PD. Patients for whom a pre-transplant nephrectomy is mandatory can also safely opt for PD as a dialysis method.