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Background There is concern about the impact of immunosuppressive agents taken by male kidney transplant (KT) recipients on the risk of foetal malformations. The aim of our survey was to estimate the paternity rate and the outcomes of pregnancies fathered by kidney transplanted males. Methods This survey analysed 1332 male KT recipients older than 18 years, followed in 13 centres in France. A self-reported questionnaire was used to collect data on the patients, treatments at the time of conception and the pregnancy outcomes. Results The study included data on 349 children from 404 pregnancies fathered by 232 male KT recipients. The paternity rate was 17% (95% CI [15–20]). There were 37 (9%, 95% CI [7–12]) spontaneous abortions, 12 (3%, 95% CI [2–5]) therapeutic abortions, 2 (0.5%, 95% CI [0.1–1]) still births, and 13 (4%, 95% CI [2–6]) malformations reported. Compared to the general population, there was no difference in the proportion of congenital malformations nor unwanted outcomes whether the father was exposed or not to immunosuppressive agents. Conclusions This survey does not provide any warning signal that pregnancies fathered by male patients exposed to immunosuppressive agents, notably the debated MMF/MPA, have more complications than pregnancies in the general population.

Hypocomplementemic urticarial vasculitis is a rare systemic vasculitis, affecting small vessels, characterised by chronicle urticaria, hypocomplementemia, and systemic manifestations. Renal involvement, whose prevalence varies between 9% and 60%, is mainly glomerular. We here report the case of a 59 years old woman presenting kidney failure, associated with chronicle urticaria and arthralgias. Laboratory investigation showed haematuria, proteinuria, hypocomplementemia and anti-SSa antibody positivity. A percutaneous kidney biopsy revealed focal and segmental glomerulonephritis associated with an acute interstitial nephritis. Hypocomplementemic urticarial vasculitis diagnosis was established after identifying anti-C1q antibodies. The lack of a dry syndrome, the negativity of a Schirmer test and the lack of sialadenitis on a salivary gland biopsy excluded an associated Gougerot-Sjogren Syndrome. The patient was treated with hydroxychloroquine and low-dose steroids, enabling a clinical and biological recovery. Of the 82 cases in the literature describing hypocomplementemic urticarial vasculitis associated nephropathies, 72 (88%) were a glomerular impairment, most frequently secondary to membranoproliferative glomerulonephritis. Only 6 (7%) tubulo-interstitial nephritis have been reported, 4 of them being associated with a glomerulonephritis. Patients were more likely to be women, aged in their third decade. The most frequent renal manifestations were haematuria (60%), and proteinuria (52%). Kidney failure was rarely observed (22%), with a fairly good renal prognosis. Hypocomplementemic urticarial vasculitis was associated with a systemic disease in 11 (13%) patients. In the absence of recommendations, the treatment strategy remains to be defined.

BACKGROUND Renal cancer accounts for 3% of adult malignancies; renal cell carcinoma (RCC) represents 80% of all renal cancers, and is characterized by late recurrences. Recurrences after kidney transplantation are associated with a high mortality rate. We aimed to determine if recurrences are linked to tumor characteristics and to delays between diagnosis and transplantation. METHODS We retrospectively analyzed data from French kidney-transplanted patients with medical histories of pretransplant renal cancer, focusing on the most common histological subtypes: clear cell and papillary cancers. Characteristics of the tumors, patients, and kidney transplantations were documented, and posttransplant patient survival was analyzed. RESULTS Of 143 patients, 13 experienced cancer recurrence after kidney transplantation. The mean delay in recurrence was 3 ± 2.3 years posttransplantation, and the cumulative incidences of recurrence were 7.7% at 5 years and 14.9% at 10 years. The risk of recurrence was higher in patients with clear cell RCC (13% vs 0%, P = 0.015). There was no correlation between posttransplant recurrence and the interval before transplantation. Factors associated with a higher risk of cancer recurrence were histological clear cell RCC (P = 0.025), tumor stage pT2 (P = 0.002), and Fuhrman grade IV (P < 0.001). Recurrences were associated with a high mortality rate; 76.9% of patients with recurrences had died by the end of the follow-up period. CONCLUSIONS Recurrences of clear cell RCC are not uncommon after kidney transplantation and are associated with very poor prognoses. These results should be considered before listing patients with a history of renal cancer for transplantation.

Resume Plusieurs modalites de traitement de l’insuffisance renale chronique terminale sont aujourd’hui disponibles. La transplantation renale a partir de donneurs vivants est la plus avantageuse pour les receveurs en termes de survie et de qualite de vie, en plus d’etre la plus economiquement viable pour la societe. Cette option souleve la question du devenir des donneurs vivants, sujets sains qui se soumettent a une procedure chirurgicale lourde. Plusieurs travaux ont ete menes comparant le devenir de donneurs de rein a celui de sujets controles. Les criteres d’evaluation etaient les potentielles complications de la nephrectomie a court comme a long termes : survenue d’une insuffisance renale, d’une hypertension arterielle, d’une proteinurie, possibilite de grossesse ulterieure, qualite de vie, survie du patient. Les resultats des premieres etudes ne mettaient pas en evidence de risque lie au don par rapport a celui existant dans la population generale. Mais depuis 2013, des publications ont rapporte l’existence d’un risque plus eleve d’insuffisance renale chronique, voire de mortalite, chez les donneurs de rein compares a des sujets controles selectionnes comme des candidats au don. Le risque lie au don est estime acceptable et minime, aux seules conditions d’une evaluation et d’une selection rigoureuse des candidats et d’un suivi regulier des donneurs indispensable.

Encapsulating peritoneal sclerosis is a rare but devastating complication of long-term peritoneal dialysis with a high mortality rate. The incidence is between 0.5 and 2.5%, decreasing with time. PSE is defined as a clinical syndrome with signs of gastrointestinal obstruction, inflammation parameters, radiological and macroscopic changes. The duration of treatment and the cessation of peritoneal dialysis are the main risks. About 75% occured in patients on hemodialysis or after kidney transplantation. Morphological alterations are disappearance of mesothelial layer, submesothelial fibrosis, interstitial sclerosis and vasculopathy. Ultrafiltration failure, fast transport status of the peritoneal membrane and loss of sodium sieving, the most powerful predictor, are the functional abnormalities. Biomarkers in peritoneal effluent include cancer antigen 125, interleukin-6. The pathophysiology is probably a consequence of a multiple-hit process in which expression of growth factors and cytokines play a central role. Medical strategies (corticosteroids, tamoxifen) in association with parenteral nutrition and/or surgery (enterolysis) are discussed. Prevention is the use of physiological peritoneal dialysis solutions, icodextrine instead of high glucose concentration solutions and peritoneal lavage after peritoneal dialysis stopping.

Introduction Although kidney transplantation carries a survival benefit compared with dialysis, mortality, especially the first year after transplantation, is high in recipients older than 70. The aim of this study was to evaluate early death and graft failure, and to determine the risk factors associated with these events in this specific population. Methods All patients older than 70 years who received a kidney transplant between January 2000 and December 2014 in the North-West of France were included (n = 171). Baseline characteristics and outcomes after transplantation were studied. Kaplan-Meier analysis was performed to assess patient and graft survival, and Cox regression analysis to evaluate risk factors for graft failure and patient death. Results The mean recipient age was 73.3 ± 2.5 years. Death-censored graft survival at 1, 3, and 5 years were 82.6%, 78.7%, and 75.4%, respectively. Patient survival at 1, 3, and 5 years was 90.1%, 82.5%, and 68.1%, respectively. One year after transplantation, 17 patients (9.9%) were dead, mainly from infectious (58.5%) or cardiovascular disease (29.4%). According to the Cox multivariate analysis, the independent risk factors for death or graft failure during the first year were arrhythmia (odds ratio [OR] 2.26; 95% confidence interval [CI] 1.08–4.8), left-ventricular ejection fraction (LVEF) under 56% (OR 2.38; 95% CI 1.18–4.83), human leucocyte antigen (HLA) antibodies (OR 2.1; 95% CI 1.04–4.2), deceased donor from cardiovascular cause (OR 5.18; 95% CI 1.22–6.3), and acute rejection (OR 2.77; 95% CI 1.2–6.3). Conclusion In kidney transplant recipients older than 70 years, cardiac evaluation and immunosuppression optimization seem to be crucial to improve short-term patient and graft survival., Graphical abstract

Background Kidney graft survival in simultaneous pancreas–kidney (SPK) recipients is known to decrease after pancreas graft failure. Methods Sixty-three consecutive SPK recipients were retrospectively reviewed. Kidney graft function and proteinuria were evaluated at three months after the transplantation and at last follow-up. Histopathologic findings of protocol biopsies performed three months and one yr after transplantation were analyzed. Results Twelve patients lost the pancreas graft. Donors' characteristics were similar in patients with or without pancreas failure. After a median follow-up of 36 months, mean eGFR with a functional pancreas was 69.5 mL/min/1.73 m² vs. 56.3 mL/min/1.73 m² (p = 0.01) after pancreas loss. Patients who lost pancreas had a median proteinuria of 0.28 g vs. 0.13 g per 24 h (p = 0.02). Analysis of three-month protocol biopsies revealed more frequent isolated glomerulitis after pancreas failure (p = 0.0001), without peritubular capillaritis or C4d deposition. No donor-specific anti-HLA antibodies were detectable in these patients. Chronic tubulointerstitial changes were more frequent in patients with pancreas loss. There was no evidence of diabetic nephropathy recurrence. Conclusion SPK recipients develop an early kidney graft dysfunction after pancreas failure. Histopathologic findings revealed frequent glomerulitis without antibody-mediated rejection and early chronic changes.

Summary Background: Our objective was to clarify the clinical outcome of renal transplantation based on residual daily urine output (RDUO). Material/Methods: We retrospectively analyzed a prospective database of 276 patients who underwent renal transplantation (Tx) between January 2008 and December 2012. Patients had pre-transplantation daily urine output measurement of 24-h proteinuria and were clinically re-evaluated the day before transplantation. We included patients with no daily urine output and those with residual daily urine output. Real bladder capacity was not measured. We excluded patients with a history of lower urinary tract malformation, those treated by trans-ileal conduit or enterocystoplasty, and those with early graft thrombosis or graft primary non-function. Results: Sex ratio, age at Tx, pre-Tx MHC antibodies levels, donor age, and cold ischemia duration were not significantly different between the 2 groups. Dialysis duration was longer in group I (p

International audience; BACKGROUND: POR*28 is a recently newly described allelic variant of the cytochrome P450 oxydoreductase (POR) which might be associated with an increased metabolic activity of P450 cytochromes (CYP) 3A5 and 3A4. Consequently, carriers of at least one allele of this polymorphism could require increased calcineurin inhibitors doses to reach the target residual concentrations (Co). The objective of this study is to test whether the allelic variant of POR, which is associated with an increased metabolic activity of CYP3A, impacts Tacrolimus (Tac) pharmacokinetics. METHODS: We tested this hypothesis in a population of 229 kidney transplant recipients (KTR) from a large, multicenter, prospective and randomized study. We have analyzed the association between POR*28 genotype and the proportion of individuals reaching the target Tac residual concentration (Tac Co) 10 days after transplantation. We have also measured the association between POR*28 and the Tac Co, and adjusted Tac Co (Tac Co/Tac dose) over time using generalized mixed linear models. RESULTS: Ten days after transplantation, there was no difference of frequencies of KTR within the target range of Tac Co (Co 10-15 ng/ml) according to the POR*28 genotype (p=0.8). The mean Tac Co at day 10 in the POR*1/*1 group was 15.3±9.7 ng/ml compared with 15.7±7.8 ng/ml in the POR*1/*28 group and 14.2 ±6.8 ng/ml, in the POR*28/*28 group, p=0.8. The adjusted Tac Co was not associated with POR*28 genotype over time (random effects model, p=0.9). When restricted to KTR expressing CYP3A5, POR*28 gentoype did not impact the proportion of individuals within the Tac Co target range neither the adjusted Tac Co (random effects model, p=0.1). CONCLUSIONS: POR*28 does not significantly influence Tac pharmacokinetic parameters in a large cohort of KTR. This study does not confirm recent findings indicating that POR*28 carriers require more Tac to reach target Co

Long-term outcomes in renal transplant recipients withdrawn from steroid and submitted to further minimization of immunosuppressive regimen after 1 year are lacking. In this multicenter study, 204 low immunological risk kidney transplant recipients were randomized 14.2 ± 3.7 months post-transplantation to receive either cyclosporine A (CsA) + azathioprine (AZA; n = 53), CsA + mycophenolate mofetil (MMF; n = 53), or CsA monotherapy (n = 98). At 3 years postrandomization, the occurrence of biopsy for graft dysfunction was similar in bitherapy and monotherapy groups (21/106 vs. 26/98; P = 0.25). At 10 years postrandomization, patients' survival was 100%, 94.2%, and 95.8% (P = 0.25), and death-censored graft survival was 94.9%, 94.7%, and 95.2% (P = 0.34) in AZA, MMF, and CsA groups, respectively. Mean estimated glomerular filtration rate was 70.4 ± 31.1, 60.1 ± 22.2, and 60.1 ± 19.0 ml/min/1.73 m(2), respectively (P = 0.16). The incidence of biopsy-proven acute rejection was 1.4%/year in the whole cohort. None of the patients developed polyomavirus-associated nephropathy. The main cause of graft loss (n = 12) was chronic antibody-mediated rejection (n = 6). De novo donor-specific antibodies were detected in 13% of AZA-, 21% of MMF-, and 14% of CsA-treated patients (P = 0.29). CsA monotherapy after 1 year is safe and associated with prolonged graft survival in well-selected renal transplant recipient (ClinicalTrials.gov number: 980654).

Resume Introduction Le fer dextran de bas poids moleculaire peut etre administre en une perfusion unique d’une dose totale correspondante a la carence en fer. L’objectif de cette etude observationnelle etait de determiner si l’administration unique d’une dose totale de fer dextran permettait de corriger la carence martiale du patient en dialyse peritoneale pendant une duree de quatre mois. Patients et methodes Les patients traites par dialyse peritoneale depuis plus de trois mois et ayant une anemie (hemoglobine Resultats Douze des dix-sept patients inclus terminaient l’etude. La dose totale moyenne administree etait de 742 ± 150 mg sans effet indesirable rapporte. Quatre mois apres l’injection on observait une augmentation significative de la moyenne de l’hemoglobinemie (10,1 ± 0,7 g/dL vs 11,4 ± 1,2 g/dL, p Conclusion Chez le patient traite par dialyse peritoneale, le fer dextran de faible poids moleculaire en injection unique d’une dose totale permet de corriger l’anemie ferriprive pendant une duree de quatre mois.

Gueutin V, Ficheux M, Châtelet V, Lecouf A, Henri P, Hurault de Ligny B, Ryckelynck J-P, Lobbedez T. Hydration status of patients with end-stage renal disease after kidney transplantation. Clin Transplant 2011: 25: E656–E663. © 2011 John Wiley & Sons A/S. Abstract: Background: This study was carried out to estimate the modification of hydration status within the first three months of renal transplantation. Subjects and methods: Fifty patients who underwent a first kidney allograft were prospectively followed for three months after renal transplantation to assess hydration status by bioimpedance spectroscopy. Results: Two hours before the transplant procedure, 10/42 (23.8%) patients were overhydrated. Two days after surgery, 32/40 (80.0%) patients were overhydrated and at three months, 14/27 (51.9%) patients remained fluid-overloaded. Peritoneal dialysis (PD) patients had a lower hydration status (−0.60 L) than hemodialysis (HD) patients (0.70 L; p

Lymphomatoid granulomatosis (LYG) in renal transplant recipients is rare multisystemic angiocentric lymphoproliferative disorder with significant malignant potential. Here, we describe LYG in a 70-year-old renal allograft recipient who, 4 years after transplantation, on tacrolimus and mycophenolate mofetil and prednisone maintenance immunosuppression, complained of low-grade fever, persistent headache and gait disturbance. The MRI of the brain revealed diffuse periventricular cerebral and cerebellar contrast-enhanced lesions. The CT scan of the thorax showed multiple pulmonary nodular opacities in both lung fields. The patient was diagnosed LYG based on the cerebral biopsy showing perivascular infiltration of CD20-positive B-lymphocytes with granulomatous lesions and immunofluorescence staining with anti-EBV antibodies. With careful reduction of the immunossuppression combined with the use of rituximab, our patient showed a complete disappearance of LYG, and she is clinically well more than 4 years after the diagnosis, with good kidney function. No recurrence has been observed by radiological imaging until now. This is the first report of a durable (>4 years) complete remission of LYG after treatment with rituximab in renal transplantation.

Post-transplant diabetes mellitus (PTDM) is a well-known complication in renal transplant recipients (RTRs). While a number of risk factors for PTDM have been identified, the potential impact of pre-transplant dialysis modality on subsequent development of PTDM has not yet been explored. We performed a multicenter retrospective study on 2010 consecutive RTRs who did not have a history of diabetes prior to renal transplantation. PTDM was defined as a need for anti-diabetic therapy in an RTR without a history of diabetes prior to transplantation. Analysis of the risk factors for development of PTDM was performed with respect to pre-transplant dialysis modality. A total of 137 (6.8%) patients developed PTDM; 7% in the hemodialysis group and 6.5% in the peritoneal dialysis (PD) group (p = 0.85). In the multivariate analysis, age (p

Summary This study attempted to establish whether a calcineurin inhibitor (CNI)-free immunosuppressant regimen based on sirolimus (SRL) is associated with a preservation of conduit arteries endothelial function in kidney recipients or not. Twenty-nine kidney recipients were randomized to receive since transplantation SRL (n = 15) or cyclosporin A (CsA, n = 14) associated with mycophenolate mofetil (MMF) and steroids (6 months) in a parallel prospective study. Systolic, diastolic blood pressures, glomerular filtration rate (GFR) and radial artery flow-mediated dilatation (FMD) induced by postischaemic hyperaemia were assessed in a blind manner at one (M1) and 7 months (M7) after transplantation. Endothelium-independent dilatation was assessed by glyceryl trinitrate spray. There was no difference between the groups for all vascular parameters at M1. At M7, systolic blood pressure was lower (SRL: 119 ± 3 vs. CsA: 138 ± 4 mmHg, P

Long-term function of kidney allografts depends on multiple variables, one of which may be the compatibility in size between the graft and the recipient. Here, we assessed the long-term consequences of the ratio of the weight of the kidney to the weight of the recipient (KwRw ratio) in a multicenter cohort of 1189 patients who received a transplant between 1995 and 2006. The graft filtration rate increased by a mean of 5.74 ml/min between the third and sixth posttransplantation months among patients with a low KwRw ratio (

Background. Although cyclosporine maintenance therapy reduces the risk of acute rejection and increases short-term graft survival in renal transplant recipients, its associated nephrotoxicity increases the risk of chronic graft dysfunction. The dose that allows an optimal risk-to-benefit ratio has not been established. Methods. This multicentre study enrolled stable renal allograft recipients receiving cyclosporine and mycophenolate mofetil without corticosteroids in their second year post-transplant. Patients were randomized to a cyclosporine dose targeted to a standard area under the concentration–time curve (AUC)0–12 h (usual exposure, n =1 04) or 50% of the study standard AUC0–12 h (low exposure, n = 108) using a three-point pharmacokinetic sampling. The primary endpoint was the percentage of patients with treatment failure at 24 months (graft loss/acute rejection/ nephrotoxicity/>15% serum creatinine level increase). Results. Treatment failure was reported in 37 out of 101 (37%) patients in the usual-exposure and 19 out of 106 (18%) patients in the low-exposure groups (P = 0.003). Mean estimated glomerular filtration rate decreased from baseline to 2 years with usual exposure and increased with low exposure (P < 0.001). Mean systolic and diastolic blood pressures were lower with low exposure (P = 0.03 and P = 0.008, respectively). Conclusion. In renal transplant recipients receiving maintenance therapy without corticosteroids, a minimization strategy using three-point pharmacokinetic sampling to reduce and maintain cyclosporine exposure to 50% of the usual levels is safe and reduces the risk of graft dysfunction.

Background Kidney recipients maintaining a prolonged allograft survival in the absence of immunosuppressive drugs and without evidence of rejection are supposed to be exceptional. The ERA-EDTA-DESCARTES working group together with Nantes University launched a European-wide survey to identify new patients, describe them and estimate their frequency for the first time. Methods Seventeen coordinators distributed a questionnaire in 256 transplant centres and 28 countries in order to report as many operationally tolerant patients (TOL; defined as having a serum creatinine

International audience; We present the results at 8 years of the Spiesser study, a randomized trial comparing de novo sirolimus and cyclosporine in kidney transplant recipients at low immunologic risk. We assessed estimated glomerular filtration (eGFR), graft, patient, and death-censored graft survival (log-rank compared), de novo DSA appearance, risk of malignancy, post-transplant diabetes mellitus (PTDM), and anemia. Intent-to-treat and on-treatment analyses were performed. Graft survival was similar in both groups (sirolimus: 73.3%, cyclosporine: 77.7, P = 0.574). No difference was observed between treatment groups concerning patient survival (P = 0.508) and death-censored graft survival (P = 0.858). In conditional intent-to-treat analysis, mean eGFR was greater in sirolimus than in cyclosporine group (62.5 ± 27.3 ml/min vs. 47.8 ± 17.1 ml/min, P = 0.004), in particular because graft function was excellent in patients maintained under sirolimus (eGFR = 74.0 ml/min). Importantly, no detrimental impact was observed in patients in whom sirolimus has been withdrawn (eGFR = 49.5 ml/min). Overall, 17 patients showed de novo DSAs, with no difference between the two groups (P = 0.520). Malignancy did not differ by treatment. An initial maintenance regimen based on sirolimus provides a long-term improvement in renal function for kidney transplant patients, especially for those maintained on sirolimus.

Background The French healthcare system offers the possibility of increasing the use of peritoneal dialysis (PD) by involving in patient care nurses who work in the private system. Objective This study was conducted to evaluate the impact of a private home-nurse network on one dialysis program. Methods This was a retrospective study of 239 dialysis patients who started dialysis in our center between 1 January 1998 and 31 December 2003. Results Of these 239 patients, 142 were treated with hemodialysis and 97 with PD during the study period. Among the PD patients, 36 of 97 were treated with assisted PD and 61 of 97 with self-care PD. Assisted-PD patients were older (74 ± 10 vs 52 ± 18 years, p < 0.001) and presented more comorbidity (Charlson Comorbidity Index 7 ± 2.5 vs 4.3 ± 2.4, p < 0.05) compared with self-care patients. Continuous ambulatory PD was the modality of choice in the assisted group (32/36). Assisted patients were frequently hospitalized (31/36); actuarial survival free of hospitalization at 6 months was 46%. Patients with nurse assistance had a high risk of peritonitis (actuarial survival free of peritonitis: 52% at 1 year). Technique survival was 85% at 6 months and 58% at 1 year. Actuarial patient survival was 90% at 6 months and 83% at 1 year. Conclusion Assisted PD enables increased use of PD in incident dialysis patients. However, in view of the comorbidities of the assisted-PD patients, the need for frequent hospitalization has to be taken into account in such a program.

Peritonitis is still a frequent complication in peritoneal dialysis patients. Medical guidelines have been established to manage this infection. These guidelines do not provide any information regarding the requirement for hospitalization. The main objective of this study was to evaluate the impact of peritonitis episode on the hospitalization rate and on the hospitalization duration in a centre where peritoneal dialysis patients were hospitalized in case of peritonitis. This was a retrospective study of incident peritoneal patients over a six years period. Among 101 peritoneal dialysis patients 65% were hospitalized. Two hundred and twenty hospital stays were registered. The total duration of hospital stays was 2091 days. The hospitalization rate was 2 per patient and per year, the hospital duration was 19 days per patient per year. Of the 220 hospital stays, 67 (30%) were due to a peritoneal infection. Peritonitis episodes represent 581/2091 (28%) days of hospitalization. The mean duration of hospitalization for peritonitis was 8.7+/-7 days. Among the patients hospitalized for a peritonitis episode, 57% were assisted by a nurse at home to perform their peritoneal dialysis exchanges. Of the 67 peritonitis episodes, 91% were discharged from the hospital without any complication. This study emphases the fact that peritonitis has an important impact on the hospitalization rate and on the hospitalization duration in peritoneal dialysis patients. In an attempt to decrease the rate of hospitalization, educational programs are clearly needed in order to treat more peritonitis without any hospitalization requirement.

Background: Two hundred and forty cadaveric renal transplant recipients given anti-thymocyte globulin (Thymoglobulin®) as induction immunotherapy were followed up prospectively to review safety and efficacy. Methods: The median number of infusions was 10 [2–21] with a cumulative dose of 8.8 mg/kg [2.0–23.2 mg/kg]. During the fortnight following transplantation, 231 patients (96%) received a calcineurin inhibitor; all patients were given steroids and azathioprine or mycophenolate mofetil. At 1 yr, 60% of patients were on tripletherapy, 38% on bitherapy, and 2% on monotherapy; 20% had discontinued steroids. Results: Tolerance was excellent with no cases of anaphylaxis. The commonest adverse event was fever (55%). Eighteen patients developed serum sickness on median day 11 [10–14]. Seven patients had thrombocytopenia; six patients had severe neutropenia. All of these adverse events recovered spontaneously. The overall incidence of delayed graft function was 24%. At 1 yr patient and graft survival were 98 and 95%, respectively, and creatinine was 135 ± 43 μmol/L. Clinically suspected and biopsy-proven acute rejection were observed in 65 patients (27%) and 34 patients (14%), respectively. There were 62 non-cytomegalovirus (CMV) infections (two fatal) and 81 episodes of CMV infections. Eight malignancies were reported; two possibly related to immunosuppression. Conclusions: These results demonstrate that anti-thymocyte globulin has a safety profile with good tolerability and excellent efficacy.

Background. Hypertension and hyperuricaemia are common side-effects of cyclosporin A (CsA) treatment in renal transplant recipients. While it is well established that the calcium channel blocker amlodipine can control CsA-induced hypertension effectively in this patient population, recent evidence suggests amlodipine might also reduce hyperuricaemia. The present study was designed to compare the effects of the calcium channel blocker amlodipine (5–10 mg/day) and the � adrenoceptor antagonist tertatolol (5–10 mg/day) on CsA-induced hyperuricaemia in post-renal transplant recipients with hypertension. Methods. Forty-eight hypertensive renal transplant recipients on a stable dose of CsA were randomized in a double-blind, parallel-group manner to receive either amlodipine (n ¼ 24) or tertatolol (n ¼ 24) for 60 days. The primary outcome measure was the change from baseline in serum uric acid concentration. Secondary analyses of efficacy were based on changes in renal function and blood pressure. Results. Amlodipine significantly decreased serum uric acid levels from 483 ± 99 to 431 ± 110mmol/l (P < 0.001), while tertatolol significantly increased uric acid from 450 ± 98 to 476 ± 84mmol/l (P ¼ 0.006). Amlodipine also significantly increased glomerular filtration rate (P ¼ 0.0048) and the clearance rate of uric acid (P ¼ 0.023) and it reduced the fractional proximal tubular reabsorption of sodium (P < 0.001), compared with tertatolol. Renal plasma flow and filtered fraction were unaffected by both treatments, as was trough CsA blood concentration. Amlodipine lowered systolic blood pressure to a significantly greater extent than did tertatolol (P ¼ 0.007). The time-dependent profile of diastolic blood pressure did not differ significantly between treatment groups. Both drugs were well tolerated. Conclusions. Amlodipine could be more appropriate than tertatolol for CsA-induced hypertension and hyperuricaemia in renal transplant recipients.

Background. Induction therapy with antithymocyte globulin (ATG) reduces the incidence of acute rejection after transplantation. A study was undertaken to assess the efficacy and safety of ATG induction on tacrolimus-based and cyclosporine A (CsA)-based therapies compared with immediate tacrolimus triple therapy in kidney transplant recipients. Methods. In a 6-month, open-label, randomized, prospective study conducted in 30 European centers, 555 renal transplant patients were randomly assigned to tacrolimus triple therapy (Tac triple, n=185), ATG induction with tacrolimus (ATG-Tac, n= 186), or ATG induction with CsA microemulsion (ATG-CsA, n=184); all were combined with azathioprine, and corticosteroids. The primary endpoint was incidence and time to first acute rejection episode confirmed by biopsy. Results. Patient demographics and clinical parameters at baseline were similar. Patient and graft survival rates were similar in all groups. The incidence of clinically apparent acute rejection was significantly higher (P=0.003) for Tac triple (33.0%) compared with ATG-Tac (22.6%) and the incidence for ATG-Tac was significantly lower (P=0.004) than for ATG-CsA (37.0%). The incidences of acute rejection confirmed by biopsy (primary endpoint) were 25.4%, 15.1%, and 21.2% for Tac triple, ATG-Tac, and ATG-CsA, respectively (Tac triple vs. ATG-Tac, P=0.004). The incidences of corticosteroid-resistant acute rejection were 7.0% (Tac triple), 4.8% (ATG-Tac), and 10.9% (ATG-CsA) (ATG-Tac vs. ATG-CsA, P=0.038). In the ATG groups, the incidences of leukopenia, thrombocytopenia, serum sickness, fever, and cytomegalovirus infection were significantly higher (P

Acute graft rejection remains a major problem in renal transplant recipients, and there is no consensus on the optimal immunosuppressive strategy. Immunoprophylaxis with Thymoglobulin or basiliximab has significantly reduced the incidence of acute rejection episodes and graft loss following kidney transplantation. This open, randomized, multicenter study investigated the efficacy and tolerability of basiliximab (20mg day 0-day 4) plus early cyclosporine from day 0 (n = 50) compared with Thymoglobulin plus delayed cyclosporine (n = 50) in adult kidney transplant patients. In addition, all patients received steroids and mycophenolate mofetil (MMF) at standard doses from day 0. Patient and graft survival rates at 12 months were 98 and 94% in the basiliximab group, respectively, compared with 100 and 96% in the Thymoglobulin' group. The incidences of biopsy-confirmed acute rejection (8.0% in each group) and treatment failure (14% in the basiliximab group vs. 8% in the Thymoglobulin group) were comparable in the two groups. There was a non-significant tendency to more dialysis (14 vs. 6%), and fewer cytomegalovirus (CMV) infections (p = 0.005) in the basiliximab group, but the percentage of clinical CMV was not different between the two groups (6 vs. 12%). Both strategies give excellent results, despite the differences in patterns, in nonhyperimmunized patients receiving their first cadaveric renal allograft.

Severe T-cell immunodeficiency after solid organ or bone marrow transplantation may result in the uncontrolled outgrowth of latently Epstein-Barr virus-infected B cells, leading to B-lymphoproliferative disorder (BLPD). Given the potentially important pathogenic role of IL-6 in BLPD, it was tested whether the in vivo neutralization of IL-6 by a monoclonal anti-IL-6 antibody could contribute to the control of BLPD. Safety and efficacy were assessed in 12 recipients of transplanted organs who had BLPD refractory to the reduction of immunosuppression over 8 days. Five patients received 0.4 mg/kg per day. The next 7 patients received 0.8 mg/kg per day. Treatment was scheduled to last 15 days. It was completed in 10 patients, and in the other 2 patients was discontinued early (days 10 and 13, respectively) because of disease progression. Treatment tolerance was good, and no major side effects were observed. High C-reactive protein levels were found in 9 patients before treatment but were normalized under treatment in all patients, demonstrating efficient IL-6 neutralization. Complete remission (CR) was observed in 5 patients and partial remission (PR) in 3 patients. Relapse was observed in 1 of these 8 patients in whom remission was observed. This relapse was unresponsive to treatment. Disease was stable in 1 patient, but it progressed in 3 patients. Seven patients are alive and well. Two patients died because of disease progression, and 3 patients died while in CR (chronic rejection in 2 patients and BLPD sequelae in 1 patient). These data suggest that the anti-IL-6 antibody is safe and should be further explored in the treatment of BLPD.

Renal interstitial expansion is now considered a useful marker of progression of several nephropathies. This study describes a multicenter, prospective, double-blind, pla- cebo-controlled, randomized trial of the effects of Perindopril (4 mg/d) on kidney structure and function over 2 yr in 26 type 2 diabetic patients with proteinuria ranging from 70 to 4210 mg/d and relatively preserved GFR (creatinine clearance .60 ml/min). All patients underwent baseline renal biopsy, but four (15%) were not randomized because of the presence of non- diabetic nephropathy. The remaining 22 were randomized (11 to Perindopril (PE), 11 to placebo (PO)), and 19 (9 PE, 10 PO) underwent follow-up biopsy at 2 yr. BP was controlled equally in both groups throughout. Proteinuria increased in PO patients (11562 mg/d) but declined in PE patients (2156 mg/d) (P , 0.05). Morphometric analysis was performed by light micros- copy using a Biocom computer. Over the 2 yr, mean cortical interstitial fractional volume identical at baseline increased significantly in PO patients (31.7 6 5.3 versus 40.2 6 11.1%; P 5 0.001) but was unchanged in PE patients (33.8 6 4.9 versus 34.7 6 6.6%; P 5 0.50). It is concluded that: (1) nondiabetic nephropathy is present in approximately 15% of albuminuric type 2 diabetic patients; and (2) Perindopril pre- vents interstitial expansion in hypertensive patients with biopsy-proven diabetic glomerulopathy. These results support a role of angiotensin II in the progression of interstitial changes in type 2 diabetic patients with nephropathy.

Summary In this ancillary study of the CONCEPT trial, we studied the role of CsA withdrawal at 3 months (3M) post-transplant on the intensity of epithelial phenotypic changes (EPC, an early marker for kidney fibrogenesis) on the 12M surveillance biopsy. Although conversion from CsA to sirolimus (SRL) at 3M was reported to have improved mean graft function at 12M, it did not reduce the score of EPC (1.73 ± 1.15 in the SRL group vs. 1.87 ± 1 in the CsA group, P = 0.61). Acute rejection, which had occurred twice more frequently in SRL-converted patients included here, was associated with 12M EPC. Interestingly, we observed that the patients durably exposed to CsA and who developed 12M EPC had a significant progression of blood pulse pressure (pp) from 1 to 6M post-transplantation (Δpp = +12.3 mmHg, P = 0.0035). Pulse pressure at 4, 6, and 9M and pp progression from 1 to 6M were significantly associated with the development of EPC at 12M in renal grafts. Logistic regression analysis revealed that a high 6M pp (≥60 mmHg) was an independent risk factor for 12M EPC with an odds ratio of 2.25 per additional 10 mmHg pp (95%CI: 1.14–4.4, P = 0.02) after adjustment with recipient's and donor's age, acute rejection incidence and immunosuppressive regimen. A post hoc analysis of the data collected in the whole population CONCEPT study revealed that pp was significantly higher at 6 months in patients maintained on CsA and that at this time point pp correlated negatively with GFR at 1 year.

Purpose Post-transplantation lymphoproliferative disorder (PTLD) is associated with significant mortality in kidney transplant recipients. We conducted a prospective survey of the occurrence of PTLD in a French nationwide population of adult kidney recipients over 10 years. Patients and Methods A French registry was established to cover a nationwide population of transplant recipients and prospectively enroll all adult kidney recipients who developed PTLD between January 1, 1998, and December 31, 2007. Five hundred patient cases of PTLD were referred to the French registry. The prognostic factors for PTLD were investigated using Kaplan-Meier and Cox analyses. Results Patients with PTLD had a 5-year survival rate of 53% and 10-year survival rate of 45%. Multivariable analyses revealed that age > 55 years, serum creatinine level > 133 μmol/L, elevated lactate dehydrogenase levels, disseminated lymphoma, brain localization, invasion of serous membranes, monomorphic PTLD, and T-cell PTLD were independent prognostic indicators of poor survival. Considering five variables at diagnosis (age, serum creatinine, lactate dehydrogenase, PTLD localization, and histology), we constructed a prognostic score that classified patients with PTLD as being at low, moderate, high, or very high risk for death. The 10-year survival rate was 85% for low-, 80% for moderate-, 56% for high-, and 0% for very high–risk recipients. Conclusion This nationwide study highlights the prognostic factors for PTLD and enables the development of a new prognostic score. After validation in an independent cohort, the use of this score should allow treatment strategies to be better tailored to individual patients in the future.

Among patients with the idiopathic nephrotic syndrome who have focal and segmental glomerulosclerosis and undergo renal transplantation, 15 to 55 percent have recurrent nephrotic syndrome. The recurrence may be caused by a plasma factor or factors that increase glomerular permeability, because plasma exchange transiently decreases or abolishes proteinuria in some patients. We studied the effect on proteinuria of the removal of protein (mostly immunoglobulins) by adsorption onto protein A from the plasma of patients with recurrent nephrotic syndrome.Eight patients were treated with one to three cycles of two to seven 1-day sessions of protein adsorption, and the patients' urinary protein excretion was measured repeatedly. Their immunosuppressive regimens were not changed during the treatment. The adsorbed proteins were eluted from the protein A and injected into rats, and the urinary albumin excretion of the rats was measured.The protein-adsorption treatment consistently decreased urinary protein excretion by an average of 82 percent at the end of a cycle (P0.001). In one patient proteinuria disappeared, and in another urinary protein excretion remained below 2.5 g per day with repeated cycles of protein adsorption. In all but one patient the effect of adsorption was limited in time, with a return to the preadsorption level of protein excretion within a maximum of two months. The administration to rats of material eluted from the protein A increased urinary albumin excretion 2.9- to 4.6-fold (P0.001 and P = 0.005, respectively). Although protein A primarily binds immunoglobulins, the active fraction of the eluted proteins had a molecular weight below 100,000, indicating that immunoglobulin was not directly involved.Adsorption of plasma protein decreases urinary protein excretion in patients with recurrence of the nephrotic syndrome after renal transplantation. Studies of the adsorbed proteins should provide information about the mechanism of this disease.

Determining early surrogate markers of long-term graft outcome is important for optimal medical management. In order to identify such markers, we used clinical information from a cross-validated French database (Donnees Informatisees et VAlidees en Transplantation) of 2169 kidney transplant recipients to construct a composite score 1 year after transplantation. This Kidney Transplant Failure Score took into account a series of eight accepted pre- and post-transplant risk factors of graft loss, and was subsequently evaluated for its ability to predict graft failure at 8 years. This algorithm outperformed the traditional surrogates of serum creatinine and the estimated graft filtration rate, with an area under the receiver–operator characteristic curve of 0.78. Validation on an independent database of 317 graft recipients had the same predictive capacity. Our algorithm was also able to stratify patients into two groups according to their risk: a high-risk group of 81 patients with 25% graft failure and a low-risk group of 236 patients with an 8% failure rate. Thus, although this clinical composite score predicts long-term graft survival, it needs validation in different patient groups throughout the world.

Peritoneal dialysis is commonly used in patients awaiting renal transplantation. The occurrence of delayed graft function is lower in CAPD patients than in hemodialysis patients. This could be explain

Tonsillar abnormalities have previously been evidenced in IgA nephropathy (IgAN). We report the results of a systematic quantitative analysis of 303 tonsils obtained in 70 IgAN patients and 142 controls. IgG- and IgA-producing plasma cells, stained by immunofluorescence, were enumerated on serial sections of all samples. Both the percentage and number of IgA+ cells were significantly increased in IgAN patients. This anomaly was also observed in age- or sex-matched subgroups of patients. Performed on a large series of individuals this study confirms the dysregulation of IgA production the upper respiratory tract of IgAN patients.

Starting dialysis in an unplanned manner is a frequent situation in a dialysis centre even for patients with a regular nephrology follow-up. For no clear reason, chronic haemodialysis (HD) is more frequently used than peritoneal dialysis for unplanned dialysis patients.The purpose of this study was to evaluate the results of a dialysis policy dedicated to unplanned dialysis patients. The aim of this policy was to increase the use of peritoneal dialysis (PD) in an attempt to reduce the need for tunnelled catheter.One hundred seventy-one patients from a single centre, who started dialysis between 1 January 2004 and 31 December 2006, were prospectively followed until 31 December 2006. Unplanned dialysis patients were defined as patients entering in dialysis with no vascular access or peritoneal dialysis catheter. PD was presented as a modality of choice for renal replacement therapy to avoid the need for a tunnelled HD catheter.There were 60 unplanned dialysis patients during the study period. Among these patients, 34 agreed to be treated by PD. Compared with unplanned peritoneal dialysis patients, unplanned haemodialysis patients had a greater modified Charlson's comorbidity index (5.9 +/- 2.4 versus 4.4 +/- 1.9, P0.05). The mean duration of the temporary catheter period was 32 +/- 29 days (median: 24 days) for haemodialysis patients compared with 26 +/- 21 days (median: 25 days) for peritoneal dialysis patients (P = NS). The initial hospitalization duration was similar in haemodialysis patients and peritoneal dialysis patients (24 +/- 28 versus 30 +/- 33 days; median value: 17 versus 20 days, P = NS). PD was started 8.6 +/- 10 days (median: 4 days) after catheter insertion. A tunnelled catheter was used only in three patients until peritoneal dialysis was initiated. Acute automated peritoneal dialysis was used in 19 patients. Among 26 haemodialysis patients, 23 were dialyzed through a tunnelled catheter. Of these 23 patients, 15 were successfully converted to fistula. Median time for fistula creation was 2.6 months after dialysis initiation; median time for fistula utilization was 4.4 months. Actuarial patients survival at 1 year was 79% on haemodialysis compared with 83% on peritoneal dialysis (P = NS). After adjustment of the initial modified Charlson's comorbidity index, dialysis modality had no impact on patient's survival. There was no significant difference between haemodialysis patients and peritoneal dialysis patients regarding survival free of re-hospitalization. Actuarial survival free of peritonitis was 73% at 6 months and 58% at 1 year.Peritoneal dialysis is a safe and efficient alternative to haemodialysis for unplanned dialysis patients. Peritoneal dialysis offers the advantage of reducing the need for tunnelled catheter in unplanned dialysis patients.

Early loss of renal grafts is generally caused by vascular or immunologic complications. We describe two patients who received a kidney transplant from the same donor and lost their grafts during the first posttransplant week. Both cases presented necrotizing graft vasculopathy without inflammatory element. The donor was a 21-year-old woman who regularly used "ecstasy" over a 2-year period. After an extensive work-up to investigate the potential causes of graft loss, we considered the possibility of ecstasy being the cause of these two renal-graft losses.

The effect of nephronic mass reduction of kidney transplants has not been analyzed specifically in a large cohort. Transplant injuries in cadaver kidney graft may have led to an underestimation of the magnitude of this factor. The aim of this study was to analyze the consequences of kidney mass reduction on transplantation outcome. The weights of 1142 kidney grafts were collected prospectively immediately before grafting. Donors and recipients15 yr of age, simultaneous kidney/pancreas grafts, and technical failures before day 7 were excluded from the analysis. The analysis was performed on Cockroft-calculated creatinine clearance and proteinuria in 964 patients for whom all of the necessary information was available. This study reports that the smallest kidneys transplanted into the largest recipients (donor kidney weight/recipient body weight [DKW/RBW]2 g/kg, n = 88) increased their clearance by 2.38 ml/min every month for 6 mo (P0.0001) and by 0.27 ml/min thereafter (P0.0001). Conversely, creatinine clearance did not change for the largest kidneys transplanted into the smallest recipients (DKW/RBW ratios/=4 g/kg). Next, using a Cox model analysis, it was shown that the risk of having a proteinuria0.5 g/kg was significantly increased for the low DKW/RBW ratios2 g/kg with 50% of patients having a proteinuria, compared with DKW/RBW ratios/=4 g/kg (P0.001). In cadaver transplant recipients, graft mass has a rapid impact on graft filtration rate and proteinuria. Avoiding major kidney/recipient inadequacy should have a significant influence on long-term transplant function.

Background. Non-Hodgkin’s lymphoma is the second most frequent neoplasia following solid-organ transplantation. The objective of this study is to describe the clinical, histologic, and radiologic features of primary posttransplantation brain lymphomas (PTBL) in addition to their outcome. Methods. Twenty-five kidney transplant patients with histologically proven PTBL from 11 French centers were retrospectively investigated. Results. Immunosuppressive regimen included induction with antithymocyte globulins (ATG) in 20 patients. Median overall delay between transplantation and lymphoma was 18 months (4–264). Six of 10 patients with late posttransplantation brain lymphomas (PTBL) occurrence (>3 years) had been recently switched from azathioprine to mycophenolate mofetil (median switch lymphoma delay 14 months). Cerebral computed tomography (CT) scans and magnetic resonance imaging (MRI) revealed multifocal lesions (n=18), with a ring contrast enhancement (n=20) similar to cerebral abscesses, as observed in HIV-related brain lymphomas. Histology showed large B-cell non-Hodgkin’s lymphoma in 87.5% of cases; Epstein-Barr virus (EBV) was detected in 95%. After lymphoma diagnosis, immunosuppressive treatment was reduced in all patients, and all but one received complementary treatment by surgery (n=2), anti-CD21 antibodies (n=2), chemotherapy including high-dose intravenous methotrexate (n=7), encephalic radiotherapy (n=5), or chemotherapy plus radiotherapy (n=8). Median overall survival was 26 months. Patients with a radiotherapy-based regimen seemed to have a longer survival (36 vs. 7 months, P Conclusions. Our study showed that PTBL are EBV-induced large B-cell lymphomas, which mimic cerebral abscesses on imaging and whose occurrence may be influenced by immunosuppression modifications. Treatment by radiotherapy is associated with better survival.

The impact of renin-angiotensin system (RAS) gene polymorphism on the prognosis of IgA nephropathy (IgAN) is still debated. A longitudinal study of renal prognosis in patients with IgAN was conducted to search retrospectively for a genotype-phenotype association between RAS polymorphisms and end-stage renal failure (ESRF). A classification based on serum creatinine (S(cr)) and 24-h proteinuria (24-P) measured at the time of renal biopsy was used to estimate the risk of ESRF in IgAN: stage 1 (S(cr)/= 150 micromol/L and 24-P1 g), stage 2 (S(cr)150 micromol/L and 24-P1 g or S(cr)or = 150 micromol/L and 24-Por = 1 g), stage 3 (S(cr)150 micromol/L and 24-Por = 1 g). Deletion/insertion polymorphism (D/I) of the angiotensin I converting enzyme gene, M235T polymorphism (T/M) of the angiotensinogen gene and A1166C polymorphism (C/A) of the angiotensin II type 1 receptor gene were determined in 274 Caucasian men with biopsy-proven IgAN (n = 86, 112, and 76 in stages 1, 2, and 3, respectively). Mean global follow-up was 6 +/- 5 yr after renal biopsy. For stages 1, 2, and 3, ESRF developed in 7 (8. 1%), 39 (34.8%), and 49 (64.4%) cases (P:0.0001), 11.7 +/- 4, 5.4 +/- 4, and 2 +/- 2 yr, respectively, after renal biopsy (P:0.001). The distributions of the three genotypes into the three stages were similar. Different distributions were observed when patients were grouped by stage and genotype: ID+DD: 72% in stage 1 versus 84.6% in stages 2 + 3 (P: = 0.02; kappa = 0.14); MT+TT: 66.2% in stages 1 + 2 versus 78.9% in stage 3 (P: = 0.04; kappa = 0.09); and AA+AC: 89.9% in stages 1 + 2 versus 97.4% in stage 3 (P: = 0.04; kappa = -0.1). However, with the use of the Cox proportional hazard model, none of the three genotypes was found to have predictive value for renal survival. Compared with S(cr) and 24-P, genotypes DD, TT, and AA are unlikely to serve as clinically useful predictors of ESRF in IgAN.

The pharmacokinetics of fluconazole given orally (100 mg) or intraperitoneally (50 and 150 mg) were determined in 15 patients with chronic renal failure who were undergoing continuous ambulatory peritoneal dialysis. The half-life (72 to 85 hours) was intermediate between values obtained in healthy volunteers and in patients with renal insufficiency studied during an interhaemodialysis period. The peritoneal clearance, 0.26 to 0.33 L/h, led to an 18% recovery of administered drug in the dialysates after 48 hours. The peritoneal absorption was slow (time to peak plasma concentration 7 hours) but the peritoneal bioavailability was excellent at 87 +/- 5%. The mean concentrations of fluconazole up to 24 hours were 770 and 1900 micrograms/L after single intraperitoneal doses of 50 and 150 mg, respectively. The volume of distribution (40 to 60 L) did not differ from that determined in patients with normal renal function. In the case of fungal peritonitis essentially attributed to Candida spp., a 6-hour intraperitoneal infusion of fluconazole 150 mg every 2 days appears to be a good regimen to rapidly exceed minimum inhibitory concentrations and treat infection without risk of systemic dissemination of fungi or toxicity.

Recurrence of crescentic necrotizing glomerulonephritis after renal transplantation is rare. Successful renal transplantation in patients with antineutrophil cytoplasmic autoantibody (ANCA) glomerulonephritis has been reported. The presence of ANCA at transplantation does not appear to increase the rate of relapse after kidney allografting. Therapy with cyclophosphamide and corticoids usually is effective. We report a case of recurrent perinuclear ANCA crescentic necrotizing glomerulonephritis immediately after renal transplantation that was treated successfully by cyclophosphamide, plasma exchange, and intravenous polyvalent immunoglobulin.

The incidence of mesangial IgA nephropathy (mIgAN) was investigated in a series of patients with alcoholic liver cirrhosis (ALC). Biologic parameters classically reported in IgAN were assessed in 98 patients, namely hematuria, proteinuria, and serum IgA. An immunohistologic study of the liver and kidney was performed in 33 patients who died during the study. Renal data were compared with those obtained in a matched necropsic series of controls. This study confirmed a global elevation of serum IgA levels in ALC. A possible hepatic origin of these immunoglobulins was supported by the observation of plasma cells in portal spaces in 68% of the patients. Biologic signs of renal disease consistent with mIgAN were observed in 16% of the patients; IgAN was diagnosed in 18% of patients with ALC and 10% of the controls. These data suggest that the incidence of mIgAN in ALC is not different than in the general population.

Recent publications have reported a frequent association between IgA nephropathy and episcleritis. In this article, the authors report on the immunohistologic study of an episcleral biopsy obtained in a female patient with Berger's disease and frequent episodes of episcleritis. Numerous dimeric-IgA-secreting cells were demonstrated in the episcleral inflammatory infiltrate. It also should be mentioned that microhematuria often occurred within a few days after the beginning of episcleritis in this patient. These results suggest the participation of ocular mucosal immunity in some cases of IgA nephropathy.