De novo use of everolimus with elimination or minimization of cyclosporine in renal transplant recipients.

BACKGROUND: The purpose of two similarly designed multicenter, prospective, parallel-group, open-label studies was to evaluate early cyclosporine (CsA) elimination versus minimization from an everolimus-CsA-steroid regimen in de novo renal transplant patients. METHODS: Within 24 hours after transplantation, 170 renal transplant patients received everolimus (trough levels 3-8 ng/mL), CsA, and steroids. Those eligible (n = 114) were randomized (1:1) at 3 months to have CsA elimination by month 4 to 6 (±1 week) with everolimus trough levels maintained at 6 to 12 ng/mL or CsA minimization, until 12 months. The randomized population excluded those who discontinued the study prior to randomization due to adverse events, acute rejection episodes of Banff grade IIb/III, or worsening renal function during the month prior to randomization. RESULTS: At 12 months, the estimated glomerular filtration rate (Nankivell) with CsA elimination was noninferior versus CsA minimization (P < .0001, α-level 0.05; 90% confidence interval 0.6-8.5) by 7 mL/min/1.73 m(2) (noninferiority margin). Composite efficacy failure was comparable with CsA elimination and CsA minimization (18.9% and 17.5%, respectively, P = 1.000) and no graft loss or death was reported after randomization. Cytomegalovirus infections were rare under everolimus treatment, and no pneumonitis episode was reported. CONCLUSION: In our selected randomized study population, immediate initiation of everolimus allowed CsA elimination. Renal function was stable on everolimus-based, CsA-free maintenance regimen without compromising efficacy.

Alemtuzumab induction in kidney transplantation: clinical results and impact on T-regulatory cells.

Alemtuzumab (ALT), a humanized monoclonal anti-CD52 antibody, was introduced in solid organ transplantation as an induction agent. ALT associated with anticalcineurins has provided a low incidence of acute rejection episodes (ARE) and potential tolerogenic properties. We analyzed the clinical outcomes and effects on peripheral Treg of renal transplant recipients treated with ALT. Six-month data on kidney alone or kidney combined with pancreas or liver patients treated with ALT and tacrolimus (TAC) in standard doses were compared with those on renal transplant recipients of similar demography who were not treated with ALT. We evaluated patient and graft survivals, ARE incidence, hematological parameters, renal function, adverse events, and CD4+CD25+FoxP3+ T cells in peripheral blood. Demographics of recipients, donors, and transplants were similar in both groups. Mean HLA mismatch was slightly greater among ALT-treated patients (3.5 vs 2.5). No combined transplantation was performed in the ALT-untreated group. Patient and graft survivals were 100% without rejection or serious infections in both groups. ALT-treated recipients showed anemia and leukopenia in 3 patients as well as severe lymphopenia in 5 recipients, who partially recovered on day 90. Final mean plasma creatinine was 1.4 mg/dL, while calculated creatinine clearance was approximately 65 mL/min in both groups. Mean Treg cell percentage was higher among ALT-treated recipients than the comparative group or healthy controls (P < .05). In conclusion, renal transplantation results obtained using ALT with rigorous immunosuppressive therapy were excellent; serious adverse events and acute rejection were absent. The effect of the increased proportion of Treg cells must be evaluated with longer observation.

Early and late humoral rejection: a clinicopathologic entity in two times.

Humoral rejection is an important cause of early and late graft loss. The late variant is difficult to diagnose and treat. There is a close correlation between sclerosing nephropathy and anti-HLA antibodies. We analyzed 113 renal allograft recipients between August 2004 and April 2007. Acute humoral rejection was defined as acute graft dysfunction in presence of donor-specific antibodies (DSA) detected by flow panel reactive antibodies (PRA) and/or C4d positive pericapilary tubules (PTC) detected histopathologically by immunofluorescent or immunoperoxidase at less than 3 months postransplantation. Late humoral rejection was defined as dysfunction occurring after 3 months postransplantation with histopathologic glomerulopathy or vasculopathy and positive C4d PTC. We included all patients who were diagnosed with early or late graft dysfunction and underwent biopsy, all of which were examined for C4d. Four patients had acute humoral rejection treated with IVIG or plasmapheresis. The patient and graft survivals were 100% and serum creatinine averaged 1.7 mg/dL. Three recipients experienced late humoral rejection at 3 to 10 years posttransplantation All received high-dose IVIG; one also was treated with thymoglobulin. Immunosuppression was switched to tacrolimus, mycophenolate mofetil, and steroids. Only one patient recovered renal function; the others returned to dialysis. Among seven patients only one had an actual PRA (>20%) and three showed 10% to 20%. However, six had a positive historical PRA of 10% to 50%. In conclusion, Recognition of acute humoral rejection has contributed to graft rescue by controlling alloantibody production through new specific immunosuppressive therapies in contrast with the clinical response to acute therapy, treatment of a chronic entity has shown poor outcomes, probably because antibody mediated chronic graft damage is already present when the late diagnosis is established by biopsy.

Clinical graft evolution of lymphocytes, polymorphonuclear cells, and antigen expression in tubular renal cells in the urine sediment of 20 renal allograft recipients.

Urinary samples from 20 kidney transplant recipients were studied to determine the cellular composition of the sediments using an immunocytological (IC) technique. The expression of HLA class I (A, B, C) and class II (DR, DQ, DP), CD2, CD3, CD4, CD8, and interleukin (IL)-2 receptor (IL-2R) on lymphocytes was assessed using a panel of monoclonal antibodies. The results were correlated with graft function and with the number of episodes of acute renal graft rejection (AR) during a period of 6 months posttransplantation. The cellular infiltration of lymphocytes (LC) and polymorphonuclear cells (PMNC) also was studied using a standard cytology (SC) technique. During this period, 17 of 30 episodes of graft dysfunction due to AR occurred in 12 patients: 8 to acute tubular necrosis (ATN) (n = 8); 4 to cyclosporine (CsA) toxicity (n = 4) and 1 to amphotericin toxicity (n = 1). The diagnosis of AR was made clinically by 3 independent observers, using biopsy in some cases. The immunocytology showed a significantly increased expression of HLA-DR, DO, and DP namely, greater than 20% positivity in 10% of samples on the tubular epithelial cells (TEC) of patients presenting with versus without AR (P < or =.001). In addition, a high correlation was observed between the expression of IL-2R and the presence of AR (p < or =.002). The standard cytology results showed a significantly increased percentage of LC and decreased percentage of PMNCs in samples obtained 2 days prior to the clinical manifestations of patients who developed AR (P =.001). A greater level of expression of antigen determinants was observed prior to AR. These results suggest that immunocytology of urinary sediments, which is a noninvasive technique, has enormous clinical potential for the differential diagnosis of AR, ATN, and CsA toxicity. In our study, the use of HLA class IL-specific monoclonal antibodies (Abs) gave a 100% specificity, 95% sensitivity, and 95% predictability. Although our results also indicate a potential value in the increased IL-2R expression, these findings must be confirmed by further studies. Furthermore, the combination of both immunologic and SC techniques in urinary sediments allows early detection of AR and is cost effective and simple features that could be used routinely for follow-up of renal transplant recipients.

Basiliximab: efficacy and tolerability in adults and children.

UNLABELLED: An open, single arm, prospective clinical trial to assess the efficacy and safety of basiliximab (Simulect) combined with cyclosporine microemulsion (Neoral), steroids, and azathioprine was performed in four centers in Chile, two adult and two pediatric. The 23 patients who were enrolled were followed for 12 months. There were four acute rejection episodes (three adults and one child) and three graft losses (two adults and one child) during the study. Renal function in both adult and pediatric patients at 6 and 12 months was good. Basiliximab was well tolerated. The incidence of infections was low, with only one CMV infection. There were no deaths. CONCLUSIONS: The incidence of acute rejection episodes among renal allograft recipients treated with basiliximab is low, showing that the drug is well tolerated. In particular the number of CMV infections is extremely low.

[Renal transplantation in patients with neurogenic bladder]. / Transplante renal en pacientes con vejiga neurogénica.

BACKGROUND: Renal transplantation can be done in patients with neurogenic bladder and clean intermittent self catheterization maintains renal function AIM: To retrospective assess the results of renal transplantation in patients with neurogenic bladder. PATIENTS AND METHODS: The medical records of seven patients aged 10 to 22 years old (3 female) followed during 7 to 32 months were reviewed. All patients had urinary tract infection, prior to transplantation, were instructed on self catheterization and received tri-associated immunosuppression. RESULTS: Grafts came from alive related donors in 5 patients and from cadavers in two. Prior to transplantation, three patients were subjected to nephrectomy and three to bladder enlargement, leaving a pigtail catheter. After transplantation, one lymphocele was drained, one uretherostomy due to an impacted lithiasis and one nephrectomy plus vesical enlargement due to intravesical pressures over 40 cm H2O, were done. One uretheral stricture was treated with dilatation. Seven episodes of pyelonephritis, 19 urinary tract infections and 77 asymptomatic bacteriurias were documented. Serum creatinine at the end of follow up ranged from 0.7 to 2.1 mg/dl. There were 0.7 acute rejection episodes per patient and all grafts survived. CONCLUSIONS: Renal transplantation in patients with neurogenic bladder is feasible, performing a vesical enlargement. There is however a high frequency of infectious episodes.

[Simultaneous pancreas-kidney transplantation. First cases in Chile]. / Trasplante simultáneo páncreas riñón. Primeros casos en Chile.

We report two insulin dependent diabetic patients with a past history of 21 and 30 years complicated with retinopathy, neuropathy and nephropathy with arterial hypertension and kidney failure. Simultaneous pancreas-kidney transplantation was done 8 and 18 months after starting hemodialysis, performing a double intraperitoneal implant with pancreato-duodeno-vesical anastomosis and contralateral kidney grafting with uretero vesical anastomosis using antireflux techniques. In the second case, a second kidney transplant from the same donor was needed, due to a thrombosis of renal vein. There was one rejection episode in each case but renal or pancreatic function was not impaired. Other observed complications were metabolic acidosis and hyperkalemia due to urine loss of bicarbonate, moderate arterial hypertension and bacterial and fungal infections. There was a graft dysfunction due to the association of vancomycin and cyclosporin. In conclusion, in the two presented patients, simultaneous pancreas-kidney transplantations were successful and they remain free of insulin or dialytic therapy 4 and 9 months after the operation.