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Thrombotic microangiopathy (TMA) is one of the hallmark vascular lesions of antiphospholipid syndrome nephropathy (APSN). These lesions are at high risk of recurrence after kidney transplantation. The complement pathway is thought to be active in this process. We used eculizumab to treat three consecutive kidney transplant recipients with posttransplant TMA due to APSN recurrence that was resistant to plasmapheresis and explored the complement deposition and apoptotic and vascular cell markers on the sequential transplant biopsies. Treatment with eculizumab resulted in a rapid and dramatic improvement of the graft function in all three patients and in improvement of the TMA lesions within the graft. None of these patients had TMA flares after eculizumab was withdrawn. At the time of TMA diagnosis, immunofluorescence studies revealed intense C5b-9 and C4d depositions at the endothelial cell surface of the injured vessels. Moreover, C5b-9 colocalized with vessels exhibiting a high rate of apoptotic cells. Examination of sequential biopsies during eculizumab therapy showed that TMA lesions, C4d and apoptotic markers were rapidly cleared but the C5b-9 deposits persisted for several months as a footprint of the TMA. Finally, we noticed that complement inhibition did not prevent the development of the chronic vascular changes associated with APSN. Eculizumab seems to be an efficient method for treating severe forms of posttransplant TMA due to APSN recurrence. Terminal complement inhibition does not prevent the development of chronic APSN.

Nephrotoxicity of calcineurin inhibitors (CNIs) is an acute, reversible and chronic, irreversible pathology. Histologically, acute nephrotoxicity manifests as hemodynamic modifications caused by vasoconstriction of the essentially afferent arterioles resulting in a drop in the glomerular filtration rate. Chronic nephrotoxicity is characterized by arteriolar hyalinosis resulting in a variety of tubulointerstitial and glomerular lesions with an essentially ischemic mechanism. However, these histological lesions, whether chronic or acute, are not specific of CNI toxicity and can be seen in the course of many pathological circumstances in kidney transplantation. This absence of specificity makes the histological diagnosis of CNI nephrotoxicity difficult. In addition, the individual risk of developing CNI nephrotoxicity, difficult to predict based solely on the pharmacokinetic parameters of systemic CNI exposure, also involves local exposure (CNI concentrations in the graft) modulated by several, notably pharmacogenetic factors. The difficulty of diagnosing CNI nephrotoxicity and the interindividual variability of its risk require development of new diagnostic tools so that the patients at highest risk of developing severe CNI nephrotoxicity lesions, in whom minimization protocols would produce the best risk-benefit ratio, can be identified.

Resume La biopsie renale est un outil precieux utilise pour la surveillance des greffons et la gestion de leur survie. Depuis 1993, grâce aux recherches realisees sur des tissus biopsiques qui ont permis de distinguer les differents types de rejet et de trouver des marqueurs de rejet reversible ou irreversible, une classification des lesions renales a ete mise en place, la classification de Banff, regulierement mise a jour depuis. La derniere en date (2005) definit le rejet chronique medie par anticorps, abandonne le terme de nephropathie d’allogreffe et decrit une nouvelle classe avec la fibrose interstitielle et atrophie tubulaire (FI/AT). Les biopsies systematiques ou de depistage permettent de reveler des lesions de rejet infraclinique avant toute degradation de la fonction renale, de mieux comprendre la physiopathologie de la nephropathie d’allogreffe, de preciser le diagnostic, mais aussi de reveler d’autres lesions plus specifiques pouvant beneficier d’un traitement. Elles ont cependant leurs limites avec les difficultes d’interpretation, les risques qu’elles font encourir au patient et leur cout.

Introduction Le syndrome de Fanconi est defini par l’association de troubles metaboliques en rapport avec une dysfonction tubulaire proximale. Acquis, il est majoritairement d’origine medicamenteuse ou lie a l’accumulation endolysosomale de chaines legere libres, au cours de myelomes de faible masse tumorale ou d’autres gammapathies monoclonales. Observation Une patiente de 39 ans est prise en charge pour une IRC (creatinine a 120 μM soit un DFGe a 44 mL/min/1,73m2), sans proteinurie glomerulaire ni anomalie du sediment. Le contexte est celui d’une gammapathie monoclonale IgG-k, avec exces de chaines legeres dans les urines, sans critere de malignite. L’examen histologique diagnostique une tubulopathie proximale par depots de chaines legeres (TPCL). Elle n’a pas recu de traitement specifique. L’evolution sur 3 ans est marquee par une augmentation de la creatininemie, actuellement a 160 μM (DFGe a 31 mL/min/1,73 m2). La patiente a beneficie d’une exploration des fonctions tubulaires et de la fonction de filtration. Le DFG a ete mesure a 57 mL/min/1,73 m2 (clairance urinaire du 51CrEDTA). Il n’est pas retrouve d’anomalie du transport du phosphate, de l’acide urique, du HCO3−, du glucose, des acides amines, mais l’absence totale de secretion tubulaire de creatinine. Discussion La creatinine est excretee minoritairement par secretion tubulaire proximale. Ceci explique que la clairance urinaire de la creatinine surestime physiologiquement le DFG. L’alteration de la secretion tubulaire de creatinine comme signe de syndrome de Fanconi n’est pas decrite. Ici, elle en constitue le seul signe. Cette atteinte peut expliquer l’importante sous-estimation du DFG par la formule MDRD. En outre, en l’absence d’etude de la secretion tubulaire de creatinine au diagnostic, on ne peut exclure que l’augmentation de creatinine sur 3 ans, soit en partie ou totalement en rapport avec la diminution progressive de la secretion tubulaire de creatinine. Conclusion Il s’agit de la premiere description d’une TPCL se manifestant par une alteration isolee de la secretion tubulaire de creatinine. Des etudes complementaires sont necessaires pour preciser la prevalence de cette atteinte et son risque evolutif sur la fonction renale.

Introduction L’analyse histologique extemporanee pre-implantatoire peut etre un outil d’aide a la decision d’acceptation d’un greffon renal. Sa superiorite par rapport aux seules donnees cliniques et biologiques n’est pas encore clairement demontree. Patients et methodes Il s’agit d’une etude monocentrique portant sur les examens extemporanes realises entre novembre 2005 et decembre 2014. Nous avons compare les donnees clinico-biologiques et histologiques des donneurs a criteres elargis (ECD) entre les greffons acceptes ou refuses. Resultats Au cours de cette periode, 85 examens extemporanes pre-implantatoires ont ete realises sur 1222 transplantations a partir d’un donneur decede (7,0 %). Sur les 614 greffes renales a partir d’ECD, 68 examens extemporanes ont ete realises pour evaluer la qualite du greffon (11 %). Les donneurs ECD avec examen extemporane etaient âges de 73 ± 10 ans, decedes de cause vasculaire pour 79 % avec un antecedent d’hypertension arterielle dans 79 %, de diabete dans 16 % et une creatininemie moyenne au prelevement de 111 ± 59 μmol/L. Apres analyse extemporanee, 46 % ( n = 31) des reins ont ete acceptes, 47 % ( n = 32) ont ete refuses sur les criteres histologiques et 7 % ( n = 5) pour d’autres raisons (cross-match positif ou contre-indication du receveur). L’âge des donneurs (73 ± 11 vs 74 ±9 ans), la creatininemie (111 ± 67 vs 118 ± 52 umol/L), l’existence d’une hypertension arterielle (71 % vs 81 %) ou d’un diabete (7 % vs 25 %) et la cause de deces vasculaire (74 % vs 88 %) ne differaient pas significativement entre les donneurs dont le rein a ete accepte ou recuse, respectivement. En revanche, l’histologie des reins de donneurs recuses retrouvait plus de glomerules sclereux (25 % ± 14 vs 12 % ± 15 ; p p p p = 0,006). Discussion Pour un petit contingent de donneurs de type ECD, l’analyse extemporanee de la biopsie pre-implantatoire a ete un element decisif d’acceptation ou non du greffon. Des elements histologiques pejoratifs etaient determinants pour le refus dans 47 % des cas, alors que les donneurs recuses ou acceptes ne differaient pas par les criteres biocliniques usuels. Conclusion La place definitive du role de l’analyse extemporanee de certains donneurs a criteres elargis reste cependant a etablir.

C4d on erythrocytes (EC4d), C4d peritubular capillary deposition (PTC-C4d) staining and histology were compared in a cross-sectional cohort of 146 renal allograft biopsies (132 patients). EC4d levels paralleled PTC-C4d staining, but were more predictive of peritubular capillaritis (PTC). Donor-specific antibodies (DSA), PTC-C4d, EC4d and PTC were analyzed in an independent longitudinal follow-up cohort (96 biopsies, 76 patients). Seventy-six samples were PTC and EC4d concordant, 11 positive and 65 negative, 7 PTC-EC4d+ and 13 PTC+EC4d-. EC4d levels were related to DSA occurrence. With ABMR defined by PTC and DSA, all apparently discordant patients, EC4d negative, were correctly reassigned comparing EC4d level curves with rejection kinetics, with positive EC4d samples predating biopsy or late biopsies compared with ABMR flare-ups. All EC4d-positive patients without PTC or DSA had permanent high EC4d levels unrelated to rejection. EC4d was more abundant in PTC-positive (mean = 108.5%± 3.4; n = 50) than PTC-negative samples (mean = 88.1%± 1.3; n= 96; p < 0.0001). Sensitivity, specificity, positive predictive value and negative predictive value of PTC-C4d and EC4d for PTC were, respectively, 75%, 79%; 64%, 76% (p < 0.05); 28%, 46% (p < 0.05) and 93%, 94%. Values were similar for DSA. A noninvasive blood test, EC4d, and particularly longitudinally monitoring EC4d levels, may increase surrogate ABMR testing options.

International audience; Screening renal biopsies (RB) may assess early changes of interstitial fibrosis (IF) after transplantation. The aim of this study was to quantify IF by automatic color image analysis on sequential RB. We analyzed RB performed at day (D) 0, month (M) 3 and M12 from 140 renal transplant recipients with a program of color segmentation imaging. The mean IF score was 19 ± 9% at D0, 27 ± 11% at M3 and 32 ± 11% at M12 with a 8% progression during the first 3 months and 5% between M3 and M12. IF at M3 was correlated with estimated glomerular rate (eGFR) at M3, 12 and 24 (p < 0.02) and IF at M12 with eGFR at M12 and 48 (p < 0.05). Furthermore, IF evolution between D0 and M3 (ΔIFM3-D0) was correlated with eGFR at M24, 36 and 48 (p < 0.03). IF at M12 was significantly associated with male donor gender and tacrolimus dose (p = 0.03). ΔIFM3-D0 was significantly associated with male donor gender, acute rejection episodes (p = 0.04) and diabetes mellitus (p = 0.02). Thus, significant IF is already present before transplantation. IF evolution is more important during the first 3 months and has some predictive ability for change in GFR. Intervention to decrease IF should be applied early, i.e. before 3 months, after transplantation.

The results of our last 5 years activity in kidney transplantation clearly show that it is possible to perform high-risk transplantations with very acceptable results: ECD kidneys, dual transplantation, recipients with DSAs. In depth statistical analysis of these data should allow a clearer definition of the best strategies to use in these situations.

Introduction Bien qu’en nette regression dans les pays developpes, le pronostic de la glomerulonephrite aigue post-infectieuse chez l’adulte reste reserve. Patients et methodes Nous avons mene une etude multicentrique retrospective pour faire un etat des lieux de cette maladie glomerulaire en termes epidemiologique, clinique, histologique, microbiologique et pronostique ; et discuter de l’interet d’un traitement immunosuppresseur pour recuperer une fonction renale optimale. Resultats Soixante-dix patients ont ete inclus, 70 % de caucasiens : 50 hommes, 20 femmes. L’âge moyen est de 58,08 ans ; 25,4 % des sujets sont diabetiques, 18,6 % alcooliques chroniques, 5,1 % toxicomanes. Au diagnostic, l’hematurie est quasi constante ; 40 % des patients ont un syndrome nephrotique inaugural avec une proteinurie moyenne de 3,24 g/24 h ; la creatininemie moyenne est de 355 μmol/L (58–1587 μmol/L). Vingt patients ont un taux de C3 bas. Soixante-dix-huit pour cent des patients ont une proliferation endocapillaire pure. Pour les 22 % restants, on note une proliferation extracapillaire associee ou isolee. La porte d’entree infectieuse n’est pas identifiee dans 14,75 % des cas. Les germes les plus frequemment identifies sont le staphylocoque aureus et le streptocoque mais dans la majorite des cas (45,9 %), le micro-organisme pathogene n’est pas identifie. Cinq patients vont beneficier d’epuration extrarenale en phase aigue et 2 de facon chronique. Avec un suivi moyen de 457,5 jours, le taux de creatinine serique est de 166 μmol/L en moyenne avec une proteinurie de l’ordre de 2,2 g/24 h. Discussion et conclusion La glomerulonephrite aigue post-infectieuse reste frequente sur un terrain a risque « immunodeprime », avec un profil clinique, histologique, microbiologique variable. La corticotherapie ne semble pas influer sur le pronostic renal.

Nephrotoxicity of calcineurin inhibitors (CNIs) is an acute, reversible and chronic, irreversible pathology. Histologically, acute nephrotoxicity manifests as hemodynamic modifications caused by vasoconstriction of the essentially afferent arterioles resulting in a drop in the glomerular filtration rate. Chronic nephrotoxicity is characterized by arteriolar hyalinosis resulting in a variety of tubulointerstitial and glomerular lesions with an essentially ischemic mechanism. However, these histological lesions, whether chronic or acute, are not specific of CNI toxicity and can be seen in the course of many pathological circumstances in kidney transplantation. This absence of specificity makes the histological diagnosis of CNI nephrotoxicity difficult. In addition, the individual risk of developing CNI nephrotoxicity, difficult to predict based solely on the pharmacokinetic parameters of systemic CNI exposure, also involves local exposure (CNI concentrations in the graft) modulated by several, notably pharmacogenetic factors. The difficulty of diagnosing CNI nephrotoxicity and the interindividual variability of its risk require development of new diagnostic tools so that the patients at highest risk of developing severe CNI nephrotoxicity lesions, in whom minimization protocols would produce the best risk-benefit ratio, can be identified.

Hemolytic uremic syndrome (HUS) associated with anti-Factor H (anti-FH) autoantibodies is a recently described pathophysiological entity. Monitoring of anti-FH IgG titer may be a sensitive marker of disease activity and guide treatment to eliminate circulating anti-FH antibodies. We report here a case of atypical HUS (aHUS) in which anti-FH autoantibodies were detected during the course of a fifth kidney transplant, 30 years after the first flare of aHUS. This exceptional case suggests that early, specific management based on immunosuppressive therapy and plasma exchanges monitored by anti-FH IgG titer may result in long-term graft survival.

No treatment has consistently induced long-term remission of proteinuria in adult patients with focal segmental glomerulosclerosis (FSGS) recurrence after kidney transplantation. We undertook an open-label, nonrandomized pilot trial of intensive and prolonged treatment of FSGS recurrence. Over an 18-month period, 10 adult kidney transplant recipients with FSGS recurrence received concomitantly high-dose steroids, intravenous cyclosporine for 14 days followed by oral cyclosporine therapy, and an intensive and prolonged course of plasma exchanges (PE). We compared this treatment with those of a control group of 19 patients with a FSGS recurrence transplanted between 1997 and 2005. Complete, rapid (mean 23 +/- 7 days) and sustained remission was obtained in 9/10 patients (90%) as opposed to 27% in the control group. At month 3 and month 12, proteinuria was 0.16 g/day (range 0.05-0.3 g/day) and 0.19 g/day (range 0.05-1 g/day) respectively. Only one patient remained in partial remission at month 12 but he had already lost two previous grafts due to FSGS recurrence. PEs were stopped at month 9 in all patients except for the patient with a partial remission who remains PE-dependent. This small pilot study provides very encouraging results demonstrating that this treatment rapidly achieves complete and sustained remission in a high proportion of patients.

Renal biopsy is an invaluable tool used for the monitoring of grafts and the management of their survival. Since 1993, thanks to research on biopsy tissues that enabled to distinguish the different types of rejection and to find markers of reversible or irreversible rejection, a classification of renal lesions has been established to achieve the regularly updated Banff classification. The last in date (2005) has defined the antibody-mediated chronic rejection, forsaken the term "chronic allograft nephropathy" and described a new class with interstitial fibrosis and tubular atrophy (IF/TA). Systematic or screening biopsies allow revealing infraclinical rejection lesions before any renal function degradation, better understanding of allograft nephropathy pathophysiology, confirming the diagnostic, but also displaying other more specific lesions that could benefit from a treatment. However, the interest of biopsies is limited by interpretation problems and risks for the patient.

The effects of posttransplant prophylactic intravenous immunoglobulin (IVIg) were investigated in renal transplant recipients at high immunological risk. Thirty-eight deceased-donor kidney transplant recipients with previous positive complement-dependent cytotoxicity crossmatch (n=30), and/or donor-specific anti-HLA antibodies (n=14) were recruited. IVIg (2 g/kg) was administrated on days 0, 21, 42 and 63 with quadruple immunosuppression. Biopsy-proven acute cellular and humoral rejection rates at month 12 were 18% and 10%, respectively. Glomerulitis was observed in 31% and 60% of patients at months 3 and 12, respectively, while allograft glomerulopathy rose from 3% at month 3 to 28% at 12 months. Interstitial fibrosis/tubular atrophy increased from 18% at day 0 to 51% and 72% at months 3 and 12 (p0.0001). GFR was 50 +/- 17 mL/min/1.73 m(2) and 48 +/- 17 mL/min/1.73 m(2) at 3 and 12 months. PRA decreased significantly after IVIg (class I: from 18 +/- 27% to 5 +/- 12%, p0.01; class II: from 25 +/- 30% to 7 +/- 16%, p0.001). Patient and graft survival were 97% and 95%, respectively and no graft was lost due to rejection (mean follow-up 25 months). In conclusion, prophylactic IVIg in high-immunological risk patients is associated with good one-year outcomes, with adequate GFR and a profound decrease in PRA level, but a significant increase in allograft nephropathy.

Renal failure develops in approximately 45% of patients with multiple myeloma (MM). In nephrology departments treating patients with the most severe renal involvement, myeloma cast nephropathy (MCN) represents 63–87% of cases assessed by renal biopsy1. In the autopsy series studied by Ivanyi, MCN was found in 32% (18 of 57), renal amyloidosis in 11 % (six) and kappa light chain deposits (LCD) in 5% (three)2. Thus, MCN is the most frequent lesion in myeloma patients and is the major cause of renal failure. However, cast nephropathy is not specifiic to myeloma since it can be observed, albeit very rarely, in non-myeloma patients (see ref. 1). In recent decades MM and renal failure are discovered simultaneously more and more frequently. Nephrologists should therefore be aware of the diagnosis of MM, and the management of these patients requires close collaboration between hematologists and nephrologists.

Vasculitic lesions are defined by necrosis of the vascular wall with perivascular inflammatory infiltrates. Secondary forms of vasculitis are observed in some systemic diseases, after infections, secondary to drugs or to malignancies. Usually, these secondary forms are characterised by the presence of immunoglobulin and complement deposits and thus probably caused by immune complex deposits. Conversely, necrotizing vasculitis occurring without known causal factor are named primary vasculitis, are not associated with immune deposits. Wegener's granulomatosis, microscopic polyangitis, Churg and Strauss syndrome and the isolated form of necrotizing and crescent glomerulonephritis are closely associated with the anti-neutrophil cytoplasm auto-antibodies (ANCA). The two main auto-antigen targets recognised by ANCA are lysosomal enzymes, proteinase 3 and myeloperoxidase, both contained in azurophilic granules of polymorphonuclear neutrophils and in primary lysosomes of monocytes. It has been demonstrated that ANCA antigens are expressed at the neutrophil (and monocyte) membrane after preactivation and are accessible to antibodies. Thus, ANCA may amplify neutrophils and monocyte activation. However, the causal or induced nature of anti-neutrophil auto-immunity in vasculitis remains unknown.

Introduction Le concept de MGRS (monoclonal gammapathy of renal significance) a ete introduit pour distinguer les gammapathies monoclonales responsables d’une atteinte renale. Parmi les MGRS, les glomerulonephrites a IgA monotypiques (GNIgAm) sont peu etudiees. Patients et methodes Seize cas de GNIgAm sont identifies retrospectivement, via le centre national de reference des amyloses AL, et un questionnaire national. Resultats Ratio homme/femme 9/7, âge median 63 ans, suivi moyen 4 ans. La presentation initiale montre : HTA (85 %), proteinurie > 3 g/g (80 %), hematurie (100 %), fonction renale generalement alteree (DFGe Discussion et conclusion Les GNIgAm sont un sous-groupe rare de MGRS. Meme si un composant monoclonal circulant n’est pas systematiquement identifie, un traitement anti-plasmocytaire semble efficace sur les manifestations renales.

These antibodies are specific for antigens in the cytoplasm of neutrophils. The main antigenic targets are proteinase 3(PR3) and myeloperoxydase (MPO) but other targets have been described without determinant conclusions for clinical practice. Staining patterns can be distinguished by an indirect immunofluorescence test (IFI), in which ethanol fixed neutrophils from healthy donors are incubated with patient's sera. Two patterns are distinguished: cytoplasmic pattern (c-ANCA) and perinuclear pattern (p-ANCA). When ANCA are detected by IFI, from a practical point of view, anti -MPO and anti-PR3 antibodies are tested. ANCA have been strongly associated with a spectrum of necrotizing small vessel vasculitides that includes Wegener's granulomatosis, microscopic polyangiitis, Churg and Strauss syndrome, pauci-immune focal necrotizing and crescentic glomerulonephritis. ANCA are a diagnosic marker and useful for the follow-up of the patients. ANCA can be observed in other pathologies: rhumatismal autoimmune diseases, inflammatory gut diseases, after drugs (hydralazine, minocycline, propylthiouracil), after silical exposition, infections (cystic fibrosis, endocarditis, HIV infection). The specificity is different and rarely anti-MPO. The ANCA role for the development of vasculitis is not completely elucidated. Some arguments are against a primary role of ANCA in the development of vasculitis. Certainly, amplification role for neutrophil activation is demonstrated but the primary event responsible of neutrophil activation is not yet defined.

Cyclosporine A (CsA) nephrotoxicity is a nonimmunologic factor of chronic allograft dysfunction (CAD) in kidney transplant recipients. Mycophenolate mofetil (MMF) may allow CsA dosage reduction or even complete withdrawal in selected populations with CsA nephrotoxicity or CAD. The aim of the present study was to evaluate the efficacy and safety of CsA withdrawal after azathioprine (AZA)-MMF conversion in a population of stable renal transplant recipients.Twenty-eight first cadaver kidney recipients were included. AZA was then discontinued, MMF was introduced and after 4 months CsA was completely withdrawn. All patients underwent inuline clearance measurement and renal biopsy at inclusion and at the end of the follow-up (40 wk).CsA was completely discontinued in 20 patients. No patient lost his graft during the study period, but 1 patient experienced a reversible acute rejection episode. Inuline clearance improved significantly in the whole series. At the end of follow-up, histological worsening was observed in 50% of patients without any specific risk factor. In these patients, inuline clearance did not improve. Systolic blood pressure, the need for anti-hypertensive drugs and HDL cholesterol improved.In stable kidney transplant recipients, CsA withdrawal after AZA replacement by MMF switch was safe with regard to acute rejection. It improved blood pressure and the lipid profile, but, in 50% of patients was associated with histologic deterioration.

Rheumatoid purpura or Henoch-Schönlein syndrome is an IgA vasculitis affecting small vessels. The acute disease progresses by successive flare-ups of limited duration. Long-term prognosis depends mainly on the degree of initial renal damage. A review of the literature shows that renal involvement occurs in about 33% of children and 63% of adults with rheumatoid purpura. The most typical manifestation is segmentary focal glomerulonephritis, always associated with granulous IgA deposits in the mesangium. When renal signs are severe enough to warrant renal biopsy (generally at urine protein1 g/d and/or organic renal failure) the risk of developing chronic renal failure is 18% in children and 28% in adults. The best prognostic features are histological. The percentage of crescents, the presence of interstitial fibrosis and the presence of dense sub-epithelial deposits are correlated with risk of chronic renal failure. This risk is high (47%) in children with crescents in more than half the glomeruli. In adults, the percentage of crescents associated with unfavorable course appears to be lower than 50%. Predictions are only valid if no further renal flare-up occurs. In addition, histology cannot precisely predict the course of persistent renal sequelae. The severity of sequelae determines the risk and the rapidity of developing chronic renal failure. It is thus recommended to follow patients with Henoch-Schönlein nephritis for long periods.

Focal and segmental glomerulosclerosis (FSGS) is one of the most common and non-specific patterns of glomerular injury encountered in human renal biopsies. The primary form can be considered when there is a nephrotic syndrome without other causes. The majority of authors agree that podocytes play a role in the development of segmental glomerulosclerosis. The lesion begins with cell hypertrophy, foot process effacement, cell body attenuation, pseudocyst formation, cytoplasmic overload with reabsorption droplets and finally detachment of the glomerular basement membrane (GBM). When the GBM is denuded, it comes into contact with the parietal epithelium and parietal epithelial cells will attach to the GBM, leading to a synechia and, finally, sclerosis. Along this zone, parietal epithelial cells rest on hyalin material. Occlusion and collapse of a group of capillaries is observed, with inclusion of foam cells and hyalin deposits. The origin of primary FSGS has not yet been elucidated. Genetic, racial and developmental factors, macrophages, viral factors and circulating factors are being explored and give encouraging results.

Background. The aim of the present study was to describe the histologic features disclosed by protocol kidney transplant biopsies in patients who experienced neither acute rejection nor acute renal failure during the 2 years after transplantation. Methods. We studied 10 recipients of HLA-identical kidneys from living-related donors and 31 recipients of cadaveric kidneys. They were selected because, during the 2 years after transplantation, they did not experience clinical acute or chronic rejection, their renal function was normal and stable, and they underwent a protocol kidney biopsy at 3 months and at 2 years after transplantation. Results. Histologic chronic allograft nephropathy was present in 25% of patients at 3 months and in 50% at 2 years, but was absent in the recipients of HLA-identical kidneys. Histologic worsening was associated with increased donor age, the presence of asymptomatic grade I acute rejection at 3 months, and an increased cyclosporine trough level. Conclusions. Protocol biopsies contribute important information that could be used to improve the prophylaxis of chronic allograft nephropathy.

Renal granulomas are a relatively infrequent finding in the kidney biopsy. They have been described in a number of syndromes such as Wegener's granulomatosis, anti-GBM glomerulonephritis, and sarcoidosis, and are commonly believed to be indicative of a fulminant clinical course. In leading textbooks, diverse definitions of renal granulomas are presented, which has led to controversies in identifying them. This, in combination with their rare occurrence, makes it difficult for the general pathologist to identify them. We present the clinical data of 16 patients with renal granulomas, from a total group of 157 patients with systemic vasculitis. Their renal functioning was not significantly different from the other 141 patients in whose renal biopsies renal granulomas were present. Furthermore, we present two practical definitions for the recognition of renal granulomas in the kidney biopsy, and we show a number of examples of their various histopathological shapes.

Antiglomerular basement membrane (anti-GBM) glomerulonephritis (GN) is rare and is characterized by rapidly progressive GN with IgG linear deposits along the GBM in immunofluorescence study and circulating anti-GBM antibodies. This form of GN usually occurs without previous renal disease, but some cases of membranous GN have been reported with secondary development of antiGBM disease [1,2]. Administration of drugs such as D-penicillamine, which are useful for the treatment of rhumatoid arthritis, can be complicated by glomerular disease, more Fig. 2. Linear diffuse IgG deposits on the residual GBM precisely membranous GN, but also minimal-change (Immunofluorescence, ×1000). GN, and crescentic GN [3–5]. Mechanisms for the

Les autoanticorps “anti-cytoplasme des polynucleaires” ou ANCA reconnaissent des antigenes presents dans les granules azurophiles des polynucleaires neutrophiles. Les principaux antigenes cibles sont la proteinase 3 (PR3) et la myeloperoxydase (MPO) mais d’autres cibles ont ete decrites n’ayant pas montre leur importance.

Repeat renal biopsies and serial serum creatinine measurements were done in 36 adults who were treated for steroid-dependent or -resistant idiopathic nephrotic syndrome with 5.54 +/- 0.81 mg/kg/day of cyclosporin A (CsA). Pre-CsA renal biopsy (RB1) had been carried out 11.6 +/- 12.2 months prior to CsA treatment. It showed minimal glomerular changes (MCD) in 22, and 1 to 16 glomeruli with lesions of focal segmental glomerulosclerosis (FSGS) per biopsy in 14. Pretreatment serum creatinine levels were (mumol/liter) 97.6 +/- 39.4 and were higher in FSGS (117.1 +/- 48.3) than in MCD (85.2 +/- 26.9; P0.04). Repeat biopsy (RB2) was done after 19.6 +/- 15.2 months (6 to 78) of CsA treatment. At this time, in 15 patients the minimal glomerular lesions observed on RB1 were unchanged, whereas in 7 patients lesions of FSGS were now visible. In patients with FSGS on RB1 and RB2, serum creatinine at the end of CsA treatment was 130.6 +/- 60.1 mumol/liter, significantly greater (P = 0.022) than the corresponding levels in the subset with MCD (87.3 +/- 24.8). The contrast between the remarkable stability of renal function in the patients with MCD and the worsening of renal function in the subgroup with FSGS was explained in the latter by an aggravation of renal histologic lesions, with a greater number of glomeruli with FSGS, of obsolescent glomeruli, and of interstitial fibrosis/infiltrates. This aggravation of the primary renal disease was observed in some cases where CsA had obtained partial or even complete remission. Few of the tubular lesions and of vascular changes were typical of CsA toxicity but rather suggested development of the primary renal disease. In contrast, although some increase in the degree of tubulointerstitial lesions was observed on RB2, the rating of such lesions was much less severe in patients whose renal biopsy showed persistently normal glomeruli after exposure to CsA. Overall, the most severe interstitial/vascular lesions were observed in patients treated with the highest CsA dosages, and the "cut-off" of dosage safety appeared to be 5.5 mg/kg/day. Two patients died during the study period. Long-term surveillance of the extant 34 patients showed that 8, all of whom had FSGS, evolved to end-stage renal failure due to progression of their primary renal disease after ending CsA treatment. Four patients were failures of CsA and returned to conventional therapy. CsA treatment was continued for 12 to 60 months in fourteen patients who achieved remission.(ABSTRACT TRUNCATED AT 400 WORDS)

The kidney is affected in a variety of vasculitic syndrome. Vasculitis represent an heterogeneous group of inflammatory disease concerning vessels. They can be considered as secondary in systemic lupus erythematosus, cryoglobulinemia, rheumatoid polyarthritis but also in infectious diseases (Streptococci, hepatitis B) in malignant disease and after drugs. However, in many circumstances, no causes are found. The discovery of autoantibodies directed against components of neutrophil cytoplasm (ANCA) represent a great progress in the understanding of vasculitis. ANCA are autoantibodies directed against neutrophil lysosomial enzymes, preferentially myeloperoxidase and proteinase 3. They are frequently found in patients with idiopathic necrotizing vasculitis, systemic or localized to the kidney (Wegener granulomatosis, microscopic periarteritis, pauci-immune necrotizing glomerulonephritis, Churg and Strauss syndrome and polyarteritis nodosa). Diagnostic and prognostic values are sure, although their presence is unconstant with variable percentage in relation with the type of vasculitis. The increase of ANCA level is not always related with disease relapse. Conversely, a permanent low level means a quiescent disease. At the present time, it is not known if ANCA play a pathogenetic role or if they constitute a marker of the disease.

From 1987 to 1991, 2500 sera were tested for presence of anti-neutrophil cytoplasmic antibodies (ANCA) by standard indirect immunofluorescence (IIF) and specific proteinase 3 (PR3) and myeloperoxydase (MPO) ELISA. Clinical and histological data leading to precise diagnosis were retrospectively obtained in 98 patients with ANCA positivity by IIF and then a comparative study based on ANCA specificity was performed. Vasculitis was present in all cases. Among patients with anti-PR3 (n = 38), 19 had Wegener's granulomatosis (WG), 15 microscopic polyarteritis (mPA), 2 idiopathic necrotizing and crescentic glomerulonephritis (NCGN) and 2 relapsing polychondritis (RP). Among patients with anti-MPO (n = 45), 26 had mPA, 3 classical polyarteritis nodosa (PAN), 5 WG, 8 NCGN, 2 systemic lupus erythematosus (SLE) and one Churg-Strauss syndrome (CSS). Negative MPO and PR3 specific ELISA despite positive IIF were observed in 15 patients (13 WG, 1 mPA, 1 PAN). In the PR3 group, males predominated (66%) and the mean age was 49 years (range 13-85); in the MPO group, females predominated (62%) and the mean age was 57 years (range 13-85). These differences were statistically significant (p0.05). Renal involvement was present in 92% of patients and renal biopsy showed pauci-immune necrotizing and crescentic glomerulonephritis in nearly all cases. PR3 specificity was associated with frequent eye involvement (32%) and presence of granulomas (45%), but was not associated with other autoantibodies. MPO specificity was associated with a higher prevalence of pulmonary hemorrhage (40%) and various autoimmune disorders, especially antinuclear antibodies. Cholestasis was observed in 50% of WG with negative MPO and PR3 ELISA. Renal and patient survival at the 75th percentile was 15 months with MPO-ANCA and 16 months with PR3, and was similar for patients with WG and mPA. Relapses occurred in 20% of patients with anti-MPO and 36% of patients with anti-PR3. Serological follow-up was obtained in 44 patients. With immunosuppressive treatment, ANCA disappeared in 66% of cases and this disappearance was always associated with absence of disease activity.1. This study confirms that the presence of ANCA is a good marker of vasculitis. 2. Despite some clinical differences, MPO and PR3-associated vasculitis have a similar prognosis. 3. The titer of ANCA determined by ELISA is not correlated with the severity of vasculitis but disappearance of ANCA is always associated with absence of disease activity.

Clinical and histological data leading to precise diagnosis were retrospectively obtained in 98 patients with antineutrophil cytoplasmic antibodies (ANCA) detected by indirect immunofluorescence (IIF). Specificity was determined by myeloperoxidase (MPO) and proteinase 3 (PR3) specific ELISA in all and a comparative study based on ANCA specificity was performed. Vasculitis was present in all cases. PR3-ANCA occurred predominantly in males (25/38) with WG (19/38). MPO-ANCA occurred predominantly in older women and were often associated with various autoimmune disorders. There was a high prevalence of lung hemorrhage (18/45) and mPA (26/45) in this group. Patients with negative MPO and PR3 specific ELISA despite positive IIF (n = 15) were almost exclusively WG (13/15) and were characterized by a high prevalence of hepatic and digestive manifestations. Renal and patient survival at the 75th percentile was 15 months with MPO-ANCA and 16 months with PR3, and was similar for patients with WG and mPA. With immunosuppressive treatment, ANCA disappeared in 66% of cases and this disappearance was always associated with absence of disease activity.