Nicola Bossini

Blood volume changes during three different profiles of dialysate sodium variation with similar intradialytic sodium balances in chronic hemodialyzed patients

The aim of this study was to evaluate the effects on blood volume (BV) preservation of three different profiles of dialysate sodium variation with similar intradialytic sodium balances. Ten uremic patients aged 50 +/- 11 years receiving regular bicarbonate hemodialysis for 49 +/- 57 months were studied. Each patient underwent three hemodialysis treatments with different modalities of dialysate sodium profiles: constant sodium hemodialysis (CHD), high-low sodium hemodialysis (H-LHD), and low-high sodium hemodialysis (L-HHD). In CHD, the dialysate sodium concentration was 141 mEq/L and did not change during treatment. In H-LHD and L-HHD, the dialysate sodium concentration at the start of dialysis was 160 mEq/L and 133 mEq/L, respectively, and remained constant for 60 minutes. At this time, a single-step break point of variation of dialysate sodium concentration occurred. The dialysate sodium concentration changed according to a model aimed to keep identical the amount of dialysate sodium exchanged in the three different dialysis procedures. The duration of hemodialysis, the blood flow rate, the dialysate flow rate, and the dialysis membrane were the same for all three different hemodialysis modalities. The ultrafiltration rate was kept constant during treatment. Total dialysate collection and intradialytic sodium balance were calculated for each hemodialysis session. Blood pressure and heart rate were monitored at 10-minute intervals; percent reductions of BV (%R-BV) were continuously monitored by an online optical reflection method (Hemoscan; Hospal-Dasco, Medolla, Italy). The results have shown a lower intradialytic %R-BV with H-LHD compared with L-HHD and CHD. No differences in total ultrafiltration rate, systolic and diastolic blood pressures, and heart rate were observed among the three different dialysis procedures. The total dialysate sodium collected and the intradialytic sodium balances were very similar among the three different dialysis procedures, confirming the accuracy of the precision of the sodium model used. The H-LHD sodium profile may be a useful tool in the prevention of excessive %R-BV and of dialysis intolerance episodes.

Steroid withdrawal five days after renal transplantation allows for the prevention of wound-healing complications associated with sirolimus therapy

Abstract:  Background:  Sirolimus (SRL) can increase the risk of wound complications. In this study, we investigated the impact of steroids when added to SRL, in this side effect.

The number of circulating recent thymic emigrants is severely reduced 1 year after a single dose of alemtuzumab in renal transplant recipients

To better understand the kinetics of the delayed reconstitution of peripheral CD4+ T‐cells after depletion with a single administration of alemtuzumab (AL) for renal transplantation, we evaluated in these patients the percentage and absolute number of recent thymic emigrants (RTEs) CD4+ T cells, together with naive and memory subsets, defined by the analysis of CD31, CD45RA and CCR7 expression, and compared with patients treated with a nondepleting protocol based on basiliximab, and with healthy controls. In AL‐treated patients, the number of circulating CD4+ T cells was greatly reduced 1 year after the infusion (P < 0.01), but the proportions of central memory, effector memory and terminally differentiated effector memory subsets among CD4+ cells were significantly increased. On the contrary, the proportion and the absolute number of naïve CD4+ T cells, although progressively increasing with time, were severely reduced. In particular, the absolute number of RTEs had only very slight increase with time (P = 0.049) and was dramatically low 1 year after the therapy (P < 0.01 vs. healthy controls; P < 0.05 vs. basiliximab‐treated transplant recipients). These data suggest that a prolonged defective thymic output after AL therapy in renal transplant recipients is one of the main causes of the persistent CD4+ T‐cell lymphopenia observed in these patients.

Tacrolimus versus cyclosporine for early steroid withdrawal after renal transplantation.

INTRODUCTION This study compares cyclosporine (CsA) with tacrolimus (Tac) in preventing acute rejection (AR) after steroid withdrawal (SW) 5 days after renal transplantation (Tx). METHODS The data were collected from 2 prospective sequential studies carried out from February 2002 to May 2006. Forty-nine patients received CsA, 56 patients Tac. Rapamycin (Rapa) was added to both calcineurin inhibitors (CNIs). The studies were homogeneous regarding both clinical procedures and patient demographics. RESULTS Three years after SW, Tac was more effective than CsA in reducing the risk both of AR (35% vs. 53%; p<0.06) and mainly of relapses (9% vs. 33%; p<0.007). In addition, Tac enabled more patients to go onto a steroid-free regime (88% vs. 65%; p<0.01). No difference arose concerning the timing of AR, graft function, CNI withdrawal, incidence of side effects or patient and graft survival rates. In both groups, rejection after SW was associated with a worse graft function. CONCLUSIONS Tac was more effective than CsA in preventing AR after early SW, and increased significantly patient probability of maintaining a steroid-free regime. In this setting, Tac and CsA had the same safety profile. However, a follow-up longer than 3 years might be needed to estimate the consequences of the higher rate of AR encountered under CsA therapy.

Patient Mortality After Graft Failure Reduces Kidney Transplant Patient Survival Only in the Long Term: An “Intention to Treat” Analysis

The benefits of kidney transplantation over dialysis on patient survival have been demonstrated without considering the outcomes of patients with graft loss. To determine whether mortality after graft failure reduced the transplantation advantage in patient survival, we retrospectively reviewed the outcomes of 918 first-deceased renal transplant recipients from May 1979 to August 2005. Patient survivals were 88% and 72% at 10 and 20 years; cancer (26%) and cardiovascular disease (25%) were the major causes of death. Graft survivals were 72% and 50% at 10 and 20 years; chronic rejection was the major cause of graft loss (50%). Patient outcomes after return to dialysis were reviewed in 224 of 240 patients. The survivals were 97%, 83%, and 70% at 1, 5, and 10 years, respectively; cardio-cerebrovascular disease (56%), infections (9%), cachexia (9%), and cancer (8%) were the major causes of death. Mortality correlated with patient age at transplantation (P< .001). Re-listed patients (96 of 224) were younger (32+/-10 vs 43+/-11 years; P< .001), had a shorter dialysis period pretransplant (3.2+/-3.1 vs 4.3+/-3.9 years; P< .03), and a better survival at 10 years (98% vs 56%; P< .001). Ten-year mortality for patients who returned to dialysis was 20% higher than for patients with a functioning graft (P< .001). The reduction in overall patient survival was 2.2% at 10 years (P=NS), 5% at 15 years (P=NS), and 14% at 20 years (P< .05). The same results have been demonstrated for patients >50 years at transplantation. In conclusion, the mortality rate after return to dialysis did not influence the long-term benefits of kidney transplantation.

Steroid-free immunosuppression regime reduces both long-term cardiovascular morbidity and patient mortality in renal transplant recipients.

Abstract:  The aim of this retrospective study was to assess the impact of steroid therapy on cardiovascular disease (CVD) and patient mortality, in 486 on‐CsA renal transplant recipients, with a follow‐up of 9.5 ± 4.3 yr. Two hundred and one patients had their steroids permanently withdrawn at sixth month after transplantation (G1); 285 patients did not (G2) as they were unable (acute rejection after suspension) or unsuitable (because of clinical criteria or immunosuppressive protocols). The CVD considered were coronary artery disease diagnosed by angiography and myocardial infarction. G1 and G2 patients were well‐matched regarding CVD risk factors, except for age (G1: 44 ± 14 yr; G2: 40 ± 12 yr; p < 0.003), incidence of male (G1: 62%; G2: 72%, p < 0.02) incidence of acute rejection (G1: 39%; G2: 83%, p < 0.0001). Both CVD and deaths occurring during the first year of transplantation were excluded from the analysis. At 20 yr, the cumulative probability of developing a CVD, was 3.8% in G1; 23.8% in G2 (p < 0.0005). Patient survival rate was 95% in G1; 62% in G2 (p < 0.003). Mortality caused by CVD was higher in G2 (4.2% vs. 0.5%; p < 0.03). The Cox analysis identified in steroid therapy the main independent risk factors for both CVD (hazard ratio 9.56 p < 0.0001) and patient mortality (hazard ratio 5.99, p < 0.0001). At 10th and 15th year after transplantation, the mean‐daily dose of steroids was 4.2 mg.

Transplantation Outcome in Patients on PD and HD

In the past, peritoneal dialysis (PD) has been considered a second choice dialysis modality for many aspects and that negative attitude has been extended also to possible negative effects on renal transplantation. In the last years, many papers have faced the question whether PD could attain similar results in renal transplantation as hemodialysis and there is sufficient evidence to answer that question. On the short time after transplantation, patients coming PD have lower prevalence of delayed graft function than hemodialysis patients, but higher prevalence of renal vascular thrombosis, above all in children. Incidence of acute graft rejection is not different between the two dialysis modalities. The long-term outcome of renal transplantation is similar in patients coming from either PD or hemodialysis.

Early (fifth day) vs. late (sixth month) steroid withdrawal in renal transplant recipients treated with Neoral® plus Rapamune®: four-yr results of a randomized monocenter study

Sandrini S, Setti G, Bossini N, Chiappini R, Valerio F, Mazzola G, Maffeis R, Nodari F, Cancarini G. Early (fifth day) vs. late (sixth month) steroid withdrawal in renal transplant recipients treated with Neoral® plus Rapamune®: four‐yr results of a randomized monocenter study. 
Clin Transplant 2009 DOI: 10.1111/j.1399‐0012.2009.01171.x.
© 2009 John Wiley & Sons A/S.

Early histopathologic changes predicting long-term kidney transplant survival

IN THE CYCLOSPORINE era, short-term results of renal transplantation have dramatically improved; however, the rate of graft loss in the long-term has only marginally improved. Progressive and irreversible decline in renal function suggests a continuous immunologic mechanism leading to chronic rejection (CR) or the participation of nonimmunologic events in the pathogenesis of allograft function deterioration. The risk factors predisposing to CR are not completely known. Clinical variables including donor age, gender, HLA matching, immunosuppressive schedule, and frequency and intensity of acute rejection episodes have been extensively investigated. Morphologic findings have been extensively studied as the most valuable indicators in the diagnosis of acute renal dysfunction such as acute rejection or nephrotoxicity. On the other hand, most authors showed high prevalence of pathologic changes on graft biopsies taken from stable patients. Their value in predicting long-term graft outcome has not completely been established. The knowledge of prognostic value of histologic lesions could facilitate therapeutic decisions and thereby improve the outcome of allograft. We explored the relationship between graft loss for CR and morphologic lesions observed early in well-functioning renal allografts. This study was done at a single centre in a cohort of transplant recipients with long-term follow-up.

Kidney transplantation in HIV‐positive patients treated with a steroid‐free immunosuppressive regimen

One of the main concerns associated with renal transplantation in HIV‐infected patients is the high risk of acute rejection, which makes physicians reluctant to use steroid‐free immunosuppressive therapy in this subset of patients. However, steroid therapy increases cardiovascular morbidity and mortality. The aim of this study was to define the efficacy of a steroid‐sparing regimen in HIV‐infected renal transplant recipients. Thirteen HIV‐infected patients were consecutively transplanted. The induction therapy consisted of basiliximab and methylprednisolone for 5 days followed by a calcineurin inhibitor plus mycophenolate acid. The mean follow‐up was 50 ± 22 months. Eight patients (61.5%) experienced acute rejection, and 75% of the first episodes occurred within 2 months after transplantation. The probability of first acute rejection was 58% after 1 year and 69% after 4 years. Seven of eight patients recovered or maintained their kidney function after antirejection therapy and steroid resumption. At the last follow‐up, seven of 13 patients (54%) had resumed steroid therapy. The 4‐year patient and graft survivals were 100% and 88.9%, respectively. The benefits of this steroid‐free regimen in HIV‐infected renal recipients must be reconsidered because of the high rate of acute rejection. New immunosuppressive steroid‐free strategies should be identi‐fied in this set of patients.