Laure Hélène Noël

C3 glomerulopathy: consensus report

C3 glomerulopathy is a recently introduced pathological entity whose original definition was glomerular pathology characterized by C3 accumulation with absent or scanty immunoglobulin deposition. In August 2012, an invited group of experts (comprising the authors of this document) in renal pathology, nephrology, complement biology, and complement therapeutics met to discuss C3 glomerulopathy in the first C3 Glomerulopathy Meeting. The objectives were to reach a consensus on: the definition of C3 glomerulopathy, appropriate complement investigations that should be performed in these patients, and how complement therapeutics should be explored in the condition. This meeting report represents the current consensus view of the group.

C3 glomerulopathy: a new classification.

Several distinct pathological patterns of glomerular inflammation are associated with abnormal regulation of the complement system, specifically, with dysregulation of the alternative pathway of the complement system. However, these conditions share the pathological finding of complement C3 (C3) deposited within the glomerulus in the absence of substantial immunoglobulin. This finding has alerted us and others to the possible presence of genetic and acquired complement dysregulation in individual patients. This article summarizes our current understanding of the relationship between dysregulation of the complement system and glomerular inflammation. Here, we suggest that glomerular pathologies that are characterized by the isolated deposition of C3 could usefully be classified by the term C3 glomerulopathy. In our view, this classification would alert the pathologist and nephrologist to the importance of screening for acquired and genetic abnormalities in complement regulation. In the future, it could help to identify individuals who might benefit from therapeutic inhibition of the complement system.

Atypical hemolytic uremic syndrome and C3 glomerulopathy: conclusions from a “Kidney Disease: Improving Global Outcomes” (KDIGO) Controversies Conference

In both atypical hemolytic uremic syndrome (aHUS) and C3 glomerulopathy (C3G) complement plays a primary role in disease pathogenesis. Herein we report the outcome of a 2015 Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference where key issues in the management of these 2 diseases were considered by a global panel of experts. Areas addressed included renal pathology, clinical phenotype and assessment, genetic drivers of disease, acquired drivers of disease, and treatment strategies. In order to help guide clinicians who are caring for such patients, recommendations for best treatment strategies were discussed at length, providing the evidence base underpinning current treatment options. Knowledge gaps were identified and a prioritized research agenda was proposed to resolve outstanding controversial issues.

Vitamin D Status and Outcomes After Renal Transplantation

Kidney transplant recipients usually have low vitamin D levels, especially in the early posttransplantation period, but the association between vitamin D status with renal outcomes is not well described in this population. Here, we studied a prospective cohort of 634 kidney recipients who underwent transplantation at a single institution between January 2005 and June 2010. In this cohort, low 25-hydroxyvitamin D concentrations 3 months after transplantation did not predict early death or graft loss but were independently associated with lower measured GFR at 12 months (P=0.001) and higher risk for interstitial fibrosis and tubular atrophy (P=0.01). In contrast, levels of calcium, phosphorus, calcitriol, parathyroid hormone, or fibroblast growth factor-23 were not consistently associated with any of the studied outcomes. In conclusion, low 25-hydroxyvitamin D concentration measured 3 months after transplantation is an independent risk factor for interstitial fibrosis progression and is associated with a lower GFR 1 year after transplantation.

Cyclosporine withdrawal in stable renal transplant recipients after azathioprine‐mycophenolate mofetil conversion

Background: Cyclosporine A (CsA) nephrotoxicity is a non‐immunologic 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. 
Methods: 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). 
Results: 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. 
Conclusion: 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.

Histologic recurrence of Henoch-Schonlein Purpura nephropathy after renal transplantation on routine allograft biopsy.

Background. Henoch-Schonlein Purpura nephropathy (HSPN) recurrence in renal transplant recipients (RTRs) has been reported in 35% of patients, leading in 11% of these patients to graft loss at 5 years. However, its true incidence is unknown. The aim of this study was to investigate this recurrence incidence using routine allograft biopsies (RBs). Methods. All RTRs with biopsy-proven HSP initial nephropathy were included (13 RTRs and 18 renal transplantations). At transplantation, the median age was 34 years, and 85% of RTRs were men. Overall, we analyzed 66 RBs that were routinely performed at 3 and 12 months after RT and when clinically indicated. Histologic recurrence was defined as the presence of IgA deposits within the mesangium and along the glomerular capillary walls. Results. After a median follow-up of 83 months (range, 13–232 months; interquartile range, 26–235 months), histologic recurrence was detected in 69% of patients and in 61% of grafts after a mean period of 24 months (range, 1–156 months). Clinical or biological signs were absent in all but one. Patient survival was 92.8%. Graft loss occurred in five cases, never were related to recurrence. At the last follow-up, the mean glomerular filtration rate was 48±14.2 mL/min/1.73 m2; in patients with and without recurrence, the mean rates were 52.1±17.5 and 42.4±5.3 mL/min/1.73 m2, respectively (P=0.27). Conclusion. Histologic recurrence of HSPN after RT is frequently observed on routine RBs but is not associated with clinical consequences. The short-term prognosis of recurrence is good, but its long-term prognosis remains to be determined.

The Effects of Ciclosporin in Twelve Patients with Severe Systemic Lupus

The treatment of severe forms of systemic lupus resistant to steroid therapy is still unsatisfactory. The risks of the life-threatening manifestations of the disease are not abrogated and chronically administered high doses of corticosteroids generate major side effects. The efficacy of other immunosuppressive drugs (azathioprine, cyclophosphamide) is not clearly established.

Anticorps anti-cytoplasme des polynucléaires (ANCA) et embolies multiples de cholestérol

Cholesterol embolism presents as a systemic vasculitis that is related to a clear-cut primary event — ie embolization of cholesterol crystals from atheromatous plaques. To test the hypothesis that ANCA could be a secondary phenomenon, we analysed sera of 9 patients and found only 1 positive serum for perinuclear ANCA with undefined specificity.

Persistance des anticorps anticytoplasme des polynucléaires neutrophiles (ANCA) chez des patients asymptomatiques atteints de périartérite noueuse et de syndrome de Churg et Strauss. Suivi de 54 patients

ANCA have been described in association with Wegeners granulomatosis, and other systemic vasculitis. Methods to detect the ANCA are indirect immunofluorescence (IFA) and ELISA. We report a retrospective study of 54 patients with proven polyarteritis nodosa (PAN) or Churg-Strauss syndrome (CSS) and concentrate on 5 patients with persistence of ANCA after remission of the disease and establish the significance of ANCA in long term follow-up of PAN and CSS.