Renal transplantation outcomes in obese patients: a French cohort-based study.

BACKGROUND: Whilst there are a number of publications comparing the relationship between body mass index (BMI) of kidney transplant recipients and graft/patient survival, no study has assessed this for a French patient cohort. METHODS: In this study, cause-specific Cox models were used to study patient and graft survival and several other time-to-event measures. Logistic regressions were performed to study surgical complications at 30 days post-transplantation as well as delayed graft function. RESULTS: Among the 4691 included patients, 747 patients were considered obese with a BMI level greater than 30 kg/m2. We observed a higher mortality for obese recipients (HR = 1.37, p = 0.0086) and higher risks of serious bacterial infections (HR = 1.24, p = 0.0006) and cardiac complications (HR = 1.45, p < 0.0001). We observed a trend towards death censored graft survival (HR = 1.22, p = 0.0666) and no significant increased risk of early surgical complications. CONCLUSIONS: We showed that obesity increased the risk of death and serious bacterial infections and cardiac complications in obese French kidney transplant recipients. Further epidemiologic studies aiming to compare obese recipients versus obese candidates remaining on dialysis are needed to improve the guidelines for obese patient transplant allocation.

Transplant nephrectomy after graft failure: is it so risky? Impact on morbidity, mortality and alloimmunization.

PURPOSE: To determine the impact of transplant nephrectomy on morbidity and mortality and HLA immunization. METHODS: All patients who underwent transplant nephrectomy in our centre between 2000 and 2016 were included in this study. A total of 2822 renal transplantations and 180 transplant nephrectomies were performed during this period. RESULTS: The indications for transplant nephrectomy were graft intolerance syndrome: 47.2%, sepsis: 22.2%, vascular thrombosis: 15.5%, tumour: 8.3% and other 6.8%. Transplant nephrectomies were performed via an intracapsular approach in 61.7% of cases. The blood transfusion rate was 50%, the morbidity rate was 38% and the mortality rate was 3%. Transplant nephrectomies more than 12 months after renal transplant failure were associated with more complications (p = 0.006). Transfusions in the context of transplant nephrectomy had no significant impact on alloimmunization. CONCLUSION: The risk of bleeding, and therefore of transfusion, constitutes the major challenge of this surgery in patients eligible for retransplantation. Even if transfusions in this context of transplant nephrectomy had no significant impact on alloimmunization, this high-risk surgery, whenever possible, must be performed electively in a well-prepared patient.

[Management of adverse effects related to human immunoglobulin therapy: Recommendations for clinical practice]. / Prise en charge des événements indésirables chez les patients sous traitement par immunoglobulines : recommandations pour la pratique clinique.

Both intravenous and subcutaneous immunoglobulins are therapeutic modalities approved in various conditions, including primary and secondary immune deficiencies and autoimmune disorders. To date, immunoglobulins have more often been considered as a safe medication, with minor adverse effects such as hypertension, fever and chills, nausea, myalgia or headache. However, with the wider use of immunoglobulins in the treatment of autoimmune diseases, severe side effects have also been reported to occur in immunoglobulin-treated patients, especially anaphylaxis, aseptic meningitis, acute renal impairment, thrombotic events as well as haematological manifestations. This paper reviews all the potential adverse events related to immunoglobulin therapy and establishes a comprehensive guideline for the management of these events.

Failure of Calcineurin Inhibitor (Tacrolimus) Weaning Randomized Trial in Long-Term Stable Kidney Transplant Recipients.

Long-term renal transplant outcome is limited by side effects of immunosuppressive drugs, particularly calcineurin inhibitor (CNI). We assumed that some patients selected for a "low immunological risk of rejection" could be eligible and benefit from a CNI weaning strategy. We designed a prospective, randomized, multicenter, double-blind placebo-controlled clinical study (Eudract: 2010-019574-33) to analyze the benefit-risk ratio of tacrolimus weaning on highly selected patients (≥4 years of transplantation, normal histology, stable graft function, no anti-HLA immunization). The primary endpoint was improvement of renal function. Fifty-two patients were scheduled in each treatment arm, placebo compared to the CNI maintenance arm. Only 10 patients were eligible and randomized. Five patients were assigned to the placebo arm and five were assigned to the tacrolimus maintenance arm. In the tacrolimus maintenance arm, all patients maintained stable graft function and no immunological events occurred. Contrastingly, in the placebo arm, all five patients had to reintroduce a full dose of tacrolimus since three of them presented an acute rejection episode (one humoral, one mixed, and one borderline) and two displayed anti-HLA antibodies without histological lesion (one donor-specific antibodies [DSA] and one non-DSA). Clearly, tacrolimus withdrawal must be avoided even in long-term highly selective stable kidney recipients.

De novo kidney graft tumors: results from a multicentric retrospective national study.

De novo tumors in renal allografts are rare and their prevalence is underestimated. We therefore analyzed renal cell carcinomas arising in renal allografts through a retrospective French renal transplant cohort. We performed a retrospective, multicentric survey by sending questionnaires to all French kidney transplantation centers. All graft tumors diagnosed after transplantation were considered as de novo tumors. Thirty-two centers participated in this study. Seventy-nine tumors were identified among 41 806 recipients (Incidence 0.19%). Patients were 54 men and 25 women with a mean age of 47 years old at the time of diagnosis. Mean tumor size was 27.8 mm. Seventy-four (93.6%), 53 (67%) and 44 tumors (55.6%) were organ confined (T1-2), low grade (G1-2) and papillary carcinomas, respectively. Four patients died of renal cell carcinomas (5%). The mean time lapse between transplantation and RCC diagnosis was 131.7 months. Thirty-five patients underwent conservative surgery by partial nephrectomy (n = 35, 44.3%) or radiofrequency (n = 5; 6.3%). The estimated 5 years cancer specific survival rate was 94%. Most of these tumors were small and incidental. Most tumors were papillary carcinoma, low stage and low grade carcinomas. Conservative treatment has been preferred each time it was feasible in order to avoid a return to dialysis.

Epidemiology of posttransplant lymphoproliferative disorders in adult kidney and kidney pancreas recipients: report of the French registry and analysis of subgroups of lymphomas.

A registry of posttransplant lymphoproliferative disorders (PTLD) was set up for the entire population of adult kidney transplant recipients in France. Cases of PTLD were prospectively enrolled between January 1, 1998, and December 31, 2007. Ten-year cumulative incidence was analyzed in patients transplanted after January 1, 1989. PTLD risk factors were analyzed in patients transplanted after January 1, 1998 by Cox analysis. Cumulative incidence was 1% after 5 years, 2.1% after 10 years. Multivariate analysis showed that PTLD was significantly associated with: older age of the recipient 47-60 years and >60 years (vs. 33-46 years, adjusted hazard ratio (AHR) = 1.87, CI = 1.22-2.86 and AHR = 2.80, CI = 1.73-4.55, respectively, p < 0.0001), simultaneous kidney-pancreas transplantation (AHR = 2.52, CI = 1.27-5.01 p = 0.008), year of transplant 1998-1999 and 2000-2001 (vs. 2006-2007, AHR = 3.36, CI = 1.64-6.87 and AHR = 3.08, CI = 1.55-6.15, respectively, p = 0.003), EBV mismatch (HR = 5.31, CI = 3.36-8.39, p < 0.001), 5 or 6 HLA mismatches (vs. 0-4, AHR = 1.54, CI = 1.12-2.12, p = 0.008), and induction therapy (AHR = 1.42, CI = 1-2.02, p = 0.05). Analyses of subgroups of PTLD provided new information about PTLD risk factors for early, late, EBV positive and negative, polymorphic, monomorphic, graft and cerebral lymphomas. This nationwide study highlights the increased risk of PTLD as long as 10 years after transplantation and the role of cofactors in modifying PTLD risk, particularly in specific PTLD subgroups.

Sotrastaurin, a novel small molecule inhibiting protein kinase C: first clinical results in renal-transplant recipients.

Sotrastaurin, a novel protein-kinase-C inhibitor, blocks early T-cell activation. In this 12-month, Phase II study, de novo renal-transplant patients were randomized to sotrastaurin (200 mg b.i.d.) + standard-exposure tacrolimus (SET) or reduced-exposure tacrolimus (RET) (SET: n = 76; RET: n = 66), or control (SET + mycophenolic acid [MPA, 720 mg b.i.d.]; n = 74). In both sotrastaurin groups, patients were converted from tacrolimus to MPA after Month 3, achieving calcineurin inhibitor-free immunosuppression. The primary endpoint was composite efficacy failure (treated biopsy-proven acute rejection, graft loss, death or loss to follow-up). The key secondary endpoint was glomerular filtration rate (GFR). Composite efficacy failure rates were: 4.1%, 5.4% and 1.5% at Month 3 (preconversion) and 7.8%, 44.8% and 34.1% at study end in the control, sotrastaurin + SET and sotrastaurin + RET groups, respectively; these results led to premature study discontinuation. Median GFR at Month 6 was: 57.0, 53.0 and 60.0 mL/min/1.73 m(2), respectively. Study-drug discontinuations due to adverse events occurred in 16.2%, 18.4% and 12.1%, respectively. Leukopenia and neutropenia occurred more frequently preconversion in control versus sotrastaurin groups: 13.7%, 5.6%, and 4.6%; and 11.1%, 4.3% and 3.1%, respectively. The initial sotrastaurin + tacrolimus regimen was efficacious and well tolerated but the postconversion sotrastaurin + MPA regimen showed inadequate efficacy. Longer-term evaluation of sotrastaurin + tacrolimus is warranted.

Chronic lymphocytic leukemia: a hazardous condition before kidney transplantation.

Long-term survival of patients with chronic lymphocytic leukemia (CLL) is over 10 years, and such patients are thus potential kidney recipients in the case of superimposed end-stage renal disease. However, the renal and patient outcome in this condition is unknown. We report the charts of four patients with CLL who were engrafted in France with a deceased-donor kidney and underwent routine triple immunosuppressive therapy. The results show that these patients developed severe infectious episodes (fatal in one case) and tumoral complications including rapid progression of CLL in two cases. Moreover, the graft may be infiltrated and damaged by monoclonal B cells: one patient lost his graft 14 months after transplantation. Various therapeutic options (modifications of the immunosuppressive regimen, anti-CD20 antibodies, irradiation of the graft) showed little (if any) efficacy. Therefore, we believe that CLL is a too hazardous condition to envisage solid organ transplantation with a routine immunosuppressive regimen, and we propose a more appropriate approach.

New onset diabetes mellitus incidence and risk factors in kidney transplantation: results of the observational cross-sectional study diapason.

BACKGROUND: New-onset diabetes mellitus (NODM) is a frequent complication of kidney transplantation. Data on NODM are mainly available in the United States. A study was implemented in a French population of kidney transplants. The incidence and risk factors of NODM were analysed. Diabetes was defined according to American Diabetes/World Health Organization guidelines. METHODS: Diapason is an observational cross-sectional study of 527 kidney transplant patients from 17 units based on data collected at a single routine visit 6 to 24 months after kidney transplantation. RESULTS: The mean age of the patients was 47.2 years, and 61.1% were men; 49.5% were receiving cyclosporine microemulsion and 50.5% tacrolimus. NODM developed in 7.0% after a median interval of 1.6 months. Univariate analysis identified six pretransplantation risk factors: advanced age, impaired fasting glucose, at least two cardiovascular risk factors, hepatitis C status, maximums lifetime body mass index above 25, and tacrolimus or cyclosporine therapy. Four independent factors were identified by multivariate analysis: body mass index above 25 (OR = 5.1), pretransplantation impaired fasting glucose (OR = 4.7), hepatitis C status (OR = 4.7), and tacrolimus versus cyclosporine treatment (OR = 3.0). CONCLUSIONS: NODM is associated with risk factors present prior to kidney transplantation and with treatment with tacrolimus as opposed to cyclosporine. Therefore, the choice of calcineurin inhibitor should be based on the patient's overall risk profile.

Blood T-cell repertoire in idiopathic nephrotic syndrome recurrence following kidney transplantation.

Corticosteroid resistant idiopathic nephrotic syndrome (CR-INS) is a glomerulopathy that recurs after kidney transplantation in 30-50% of patients, suggesting the involvement of systemic albuminuric factors, probably produced by activated T cells. We investigated peripheral T-cell selection and expansion before and after transplantation to identify and characterize T-lymphocyte patterns potentially associated with INS recurrence. We used a combined qualitative and quantitative assessment of Vbeta mRNA alterations at the level of the complementary determining region 3-length distribution (CDR3-LD) of the T-cell receptor (TCR). Peripheral blood mononuclear cells (PBMC) were collected from 18 CR-INS patients (8 with recurrence and 10 without recurrence) on the day of transplantation as well as at 1 month, 1 year and 5 years after transplantation, and Vbeta transcriptomes were analyzed. Our data show that blood T cells from patients with INS recurrence display a TCR repertoire that is stable in time and has a similar level of CDR3-LD alterations as the T-cell repertoire of control patients, both before and after transplantation. These results suggest that the process of INS recurrence does not involve TCR activation or specific clonal expansion of T cells. However, these results do not exclude a role for T cells in the production of an albuminuric factor.

[Viruses involved in allograft recipients'cutaneous carcinomas]. / Virus impliqués dans les carcinomes cutanés des greffés rénaux.

BACKGROUND: Cutaneous carcinomas are frequent in renal allograft recipients. Their treatment can be difficult especially in cases of multiple carcinomas. The aim of this study was to determine whether human papillomavirus are more frequent in patients group with multiple cutaneous carcinomas and whether other viruses such as Epstein-Barr virus, cytomegalovirus, and herpes simplex might be associated in this kind of tumour. PATIENTS AND METHODS: Forty-three patients were included. Twenty-two had a single carcinoma (group 1) and 21 had multiple cutaneous carcinomas (group 2). Histologic analysis and in situ hybridization were used to search for Epstein-Barr virus, human papillomavirus, herpes simplex virus and cytomegalovirus latency genes. RESULTS: In both groups, epidermoid carcinomas were more frequent than basal cell carcinomas and delay between graft and first carcinoma was similar (5 years). In situ hybridization was more often positive in group 2 (41/50) than in group 1 (13/22). Human papillomavirus DNA was detected more frequently in the group with multiple carcinomas (26/50) than in the group with a single carcinoma (6/22). Moreover, cytomegalovirus was more frequent in group 2. CONCLUSION: This study shows a higher prevalence of human papillomavirus DNA in the carcinomas of the multiple carcinoma population. Moreover, for the first time, cytomegalovirus DNA was detected in carcinomas of renal allograft recipients with a higher frequency in the patients with multiple carcinomas.

Advances in transplant immunobiology.

The present review briefly addresses the most recent knowledge acquired in the field of transplant immunology. A particular emphasis is placed on articles published during the past 12-18 months that have focused on allorecognition, dendritic cells and tolerance.

Clinical features and contribution of virological findings to the management of Kaposi sarcoma in organ-allograft recipients.

OBJECTIVES: To describe the clinical features of Kaposi sarcoma (KS) in organ-allograft recipients and to determine the contribution of human herpesvirus 8 (HHV-8) investigations to the management of KS. DESIGN, SETTING, AND PATIENTS: We examined 20 organ-allograft recipients with KS at Pitié-Salpêtrière Hospital, Paris, France, between November 1, 1991, and May 31, 1999. METHODS: We detected HHV-8 antibodies using an indirect immunofluorescence assay and the HHV-8 DNA genome using nonnested polymerase chain reaction with KS-associated herpesvirus 330(233) primers in peripheral blood mononuclear cells collected at transplantation and KS diagnosis. We detected the HHV-8 genome in involved and uninvolved tissue specimens and in 10 patients' serum samples collected 1 month before the first manifestation of KS. We determined the HHV-8 double-strand DNA sequence and subtypes of open reading frame 26. INTERVENTION: Management of KS consisted of progressively tapering immunosuppressive therapy regardless of KS dissemination. Associated infections were treated when possible. Chemotherapy was prescribed only when a functional disability persisted, and polychemotherapy was prescribed for life-threatening disease. MAIN OUTCOME MEASURES: Percentage of recipients with KS remission and stabilization, organ-graft survival, and death rates. RESULTS: Remission of KS was obtained in 9 (45%) of the 20 patients independently of disease dissemination, with a mean follow-up of 35 months. The kidney graft survived in 12 (67%) of the 18 patients. Only 1 patient (5%) died of KS progression. All allograft recipients had anti-HHV-8 antibodies before transplantation. We detected HHV-8 DNA in all involved tissue samples but not in serum samples 1 month before KS onset. The most prevalent subtype was HHV-8 C (9 [53%] of 17 patients) and was not associated with extradermatological extension of KS compared with subtypes A and B'. CONCLUSIONS: Virological investigations of HHV-8 contribute poorly to KS management. Prospective studies are needed to determine the role of HHV-8 virological investigations and to identify associated cofactors so as to prevent KS in organ-allograft recipients.

Effect of plasma fractions from patients with focal and segmental glomerulosclerosis on rat proteinuria.

BACKGROUND: Patients suffering from focal and segmental glomerulosclerosis (FSGS) and in whom this disease recurs after transplantation are likely to have an active form of the disease and to have a factor(s) (such as, albuminuric factor) present in their blood that alters glomerular permeability for albumin. METHODS: We used a sequential 50 and 70% ammonium sulfate (AS) precipitation of plasma from patients with relapsing FSGS and non-FSGS nephrotic syndrome (NS), in addition to plasma from healthy individuals, to obtain both an immunoglobulin (Ig)-rich fraction (50% AS precipitate) and a non-Ig fraction (70% AS supernatant). These fractions were injected intra-arterially or intravenously/intraperitoneally into Sprague-Dawley rats, and proteinuria (g protein/mmol creatinine) was measured for 24 hours. Ig fractions eluted from immunoadsorption onto protein A were also tested. A biochemical characterization was then carried out on the 70% AS supernatants by ultrafiltration on 30 and 50 kD cut-off membranes and by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Differentially stained bands were sequenced. RESULTS: The 70% AS supernatants from FSGS patients induced proteinuria when injected intra-arterially into normal rats. This effect was significantly different (P < 0.05) from that observed when similar fractions were prepared from the plasma of patients suffering from non-FSGS NS, but was not different from that observed with fractions from healthy individuals and even with an injection of saline solution. Injections of other plasma fractions did not induce a significant proteinuria in the FSGS group versus the non-FSGS NS group. SDS-PAGE of 70% AS supernatants revealed a protein of 23 kD that was more concentrated in AS supernatants from FSGS plasma than the other plasma samples and that was identified by microsequencing as apolipoprotein A1. After sequential ultrafiltration of 70% AS supernatants on 30 and 50 kD cut-off membranes, a second band of 43 kD was found at a much higher concentration in the FSGS samples than in non-FSGS NS and healthy individuals samples. This band is likely to correspond to a candidate albuminuric factor recently reported by another group [1], and was identified by microsequencing as alpha1 acid glycoprotein or orosomucoid. Consequently, purified orosomucoid from the plasma of FSGS, non-FSGS NS patients, or healthy individuals was injected intra-arterially into rats. No differences were found between the proteinuria induced in each group. CONCLUSIONS: These data strongly suggest that in vivo injection of material into the rat is not a reliable model for testing plasma fraction activity and that the 43 kD orosomucoid is not likely to be the albuminuric factor.

Prevention of acute rejection with antithymocyte globulin, avoiding corticosteroids, and delaying cyclosporin after renal transplantation.

BACKGROUND: Despite their well-known side-effects, corticosteroids (Cs) are currently used after kidney transplantation. Avoidance of Cs may improve patient quality of life and eventual long-term survival. We report on a regimen using antithymocyte globulin (ATG) and mycophenolate mofetil (MMF) for induction, and cyclosporin (CsA) plus MMF for maintenance treatment of recipients of primary kidney transplantation. METHODS: We studied 11 consecutive, non-sensitized renal transplant patients (nine cadaver and two living donors). Initial immunosuppression consisted of ATG (1.5 mg/kg/day, i.v.) given for 10 days and MMF (1.0 g/b.i.d.). CsA (8 mg/kg, in two divided doses) was started on post-operative day 11. Cs were only allowed in the case of MMF discontinuation, for the treatment of acute rejection, and in the event of recurrence of the primary glomerulonephritis. RESULTS: All patients completed the entire 10-day ATG course. Main side-effects included fever (>38 degrees C) and serum sickness, observed in 73 and 27% of the patients respectively. The incidence of acute rejection was 27% (three of 11 patients). In two patients with acute rejection, serum sickness was concomitantly diagnosed and renal histology was partially compatible with immune-complex disease. The remaining patient had two episodes of low-grade rejection. All rejection episodes were rapidly reversed. Two patients (18%) were treated with ganciclovir for cytomegalovirus (CMV) infection. Two patients (18%) are currently receiving Cs for recurrence of the native glomerulonephritis and two rejection episodes respectively. All patients are currently alive with functioning kidneys (average follow-up of 8.4 months; average creatinine level of 128 micromol/l). CONCLUSION: This pilot study suggests that ATG induction in combination with MMF and delayed introduction of CsA, in the absence of Cs, is not well tolerated in recipients of kidney transplants. An earlier introduction of calcineurin inhibitors and/or a shorter course of ATG may reduce the incidence of fever and serum sickness secondary to ATG.

Low incidence of kidney rejection after simultaneous kidney-pancreas transplantation after antithymocyte globulin induction and in the absence of corticosteroids: results of a prospective pilot study in 28 consecutive cases.

BACKGROUND: Recipients of simultaneous kidney-pancreas transplantation receive a combination of polyclonal antithymocyte globulin (ATG), cyclosporin or tacrolimus, mycophenolate mofetil (MMF) and corticosteroids (Cs). To avoid the side effects and adverse events associated with Cs, we investigated a new immunosuppressive regimen without Cs after simultaneous kidney-pancreas transplantation. METHODS: A total of 28 consecutive patients who underwent simultaneous kidney-pancreas transplantation were included in this study. All patients received ATG, cyclosporin, and MMF. RESULTS: All patients but one tolerated the ATG course well. MMF was definitively discontinued in three patients because of leukopenia. Cytomegalovirus infection was diagnosed in eight patients (28.5%). Only two patients (7%) required an antirejection treatment. Patient, kidney, and pancreas survival is currently 96.4, 96.4, and 75%, respectively. CONCLUSIONS: The combination of ATG, cyclosporin, and MMF, without Cs, was well tolerated. The unexpectedly low (7%) incidence of acute kidney rejection observed suggests that Cs may partially interfere with the immunosuppressive effect of ATG.

Interaction of anti-HLA antibodies with pig xenoantigens.

BACKGROUND: Many patients with renal failure are condemned to long-term dialysis with little prospect of transplantation because they are highly sensitized with immunoglobulin G (IgG) directed against class I human leukocyte antigens (HLA) of virtually all donors. Xenotransplantation could represent an attractive solution providing their alloantibodies (alloAb) do not recognize porcine motifs. Hitherto there has been no in vivo demonstration of any cross-reactivity and the objective of this work was to investigate this problem using a technique of extracorporeal pig kidney perfusion as a model of clinical xenografting. METHODS: Pig kidneys were perfused ex vivo with plasma from both a group of highly sensitized patients and healthy individuals. Sequential plasma samples were analyzed for the titer of anti-Galalpha1-3Gal antibody (Ab) (major natural xenoreactive Ab) by enzyme-linked immunosorbent assay and anti-HLA class I Ab against a cell panel. At the end of perfusion, kidneys were perfused with a citric acid buffer to elute bound Ab. RESULTS: Galalpha1-3Gal Ab were shown to decrease rapidly in the plasma (in less than 10 min) and then reached a plateau. A fractional decrease in anti-HLA Ab was also found in some of the perfused plasma samples. Anti-Gal Ab were readily detected in all citric acid perfusates and anti-HLA Ab in 8 of 10. The HLA specificities of eluted Ab were mainly concordant with the originally designated specificities for each patient. CONCLUSION: Anti-HLA class I Ab presumably cross-react with pig class I homologues. However, some plasma samples did not cross-react, suggesting that negatively cross-matched pig kidneys could be identified in the pig population for xenotransplantation in these patients. Further studies are required to precisely describe these cross-reactivities and to understand their functional significance in xenotransplantation.

Randomized comparison of triple therapy and antithymocyte globulin induction treatment after simultaneous pancreas-kidney transplantation.

BACKGROUND: The incidence of acute rejection is considered to be higher after simultaneous pancreas-kidney (SPK) transplantation as compared to renal transplant alone. Therefore, the majority of SPK transplant recipients commonly receive a combination of cyclosporine (CsA) or tracolimus, and azathioprine or mycophenolic mofetyl, corticosteroids and/or antilymphocyte preparations. This study was designed to compare two immunosuppressive protocols for the prevention of acute rejection in patients undergoing SPK transplantation. The primary end-point was the incidence of acute rejection during the first 12 months after transplantation METHODS: Fifty patients with type-I insulin-dependent diabetes and chronic renal failure were randomized to receive a triple drug immunosuppressive regimen including CsA, azathioprine and corticosteroids (N = 25), or the quadruple sequential combination of rabbit antithymocyte globulin (ATG) given for 10 days, azathioprine, corticosteroids and delayed CsA (N = 25). Maintenance immunosuppression (CsA and azathioprine, without corticosteroids) was similar in both arms. RESULTS: The average follow-up was 36 months in both groups (range 9 to 60 months). No patient was excluded from the study. Although the percentage of patients with adverse events was higher in the ATG group (80 vs. 40%, P < 0.01), none of them resulted in premature discontinuation of the drug. Patients receiving ATG experienced a lower incidence (36% vs. 76%, P < 0.01) and number (13 vs. 29, P < 0.05) of acute renal rejection episodes. However, no difference was observed in patient, pancreas and kidney survival rates between groups. No case of isolated pancreas rejection was observed. CONCLUSIONS: The quadruple sequential combination ATG, azathioprine, corticosteroid and CsA significantly reduced the one year incidence of acute renal rejection after SPK transplantation, compared to a triple immunosuppressive regimen.

Antihuman immunoglobulin affinity immunoadsorption strongly decreases proteinuria in patients with relapsing nephrotic syndrome.

Approximately 20 to 30% of patients with idiopathic nephrotic syndrome and focal glomerulosclerosis experience a relapse of their nephrotic syndrome after transplantation. Previously, it has been shown that ex vivo immunoadsorption on protein A strongly (although transiently) reduces proteinuria in relapsing patients. To investigate whether the factor(s) that give rise to albuminuria are bound directly to protein A in the immunoadsorption procedure or are part of a complex with Ig, four patients with relapse of focal glomerulosclerosis presenting as nephrotic syndrome after transplantation were treated, sequentially, using a (non-protein A) anti-Ig affinity column and a protein A column. This study reports that the effect on proteinuria of immunoadsorption using an anti-Ig immunoaffinity column is comparable in its magnitude and kinetics to that of immunoadsorption on protein A. The two procedures were also equally effective in depleting the relapsing patients' plasma of a factor capable of altering the albumin permselectivity of isolated glomeruli in vitro. This study demonstrates for the first time that immunoglobulins have a role in the nephrotic syndrome. In addition, the fact that the two different immunoadsorption procedures both resulted in the removal of the same putative albuminuric factor in these patients and that no autoreactivity of eluted immunoglobulins was observed on human tissues strongly suggests that the factor or factors that may be responsible for immediate nephrotic syndrome after transplantation are bound to an immunoglobulin. However, no firm evidence can be yet provided against a direct role of immunoglobulins.