C3 nephritic factor can be associated with membranous glomerulonephritis.

BACKGROUND: C3 nephritic factor (C3NeF) has been described in association with membranoproliferative glomerulonephritis and is involved in 80 % of cases of dense deposit disease. C3NeF is an immunoglobulin G (IgG) autoantibody which binds to the complement component 3 (C3) convertase C3bBb, thereby inhibiting its decay and leading to massive C3 cleavage. Commonly associated with C3NeF are low C3 levels, decreased total haemolytic complement (CH50) and normal C4 levels. C3NeF patients often present with proteinuria, haematuria and high blood pressure. Evolution to end-stage renal disease is common. Treatment consists of steroids and/or immunosuppressants, with variable efficiency. Renal transplantation is marked by histological recurrence, leading to higher rates of allograft loss. CASES: We report C3NeF in association with membranous glomerulonephritis type 3-4 in two unrelated children. We also demonstrate that, under adequate immunosuppressive therapy, proteinuria is significantly lowered, blood pressure is kept within normal range and long-term renal function remains normal. CONCLUSIONS: C3NeF can be associated with membranous glomerulonephritis in children. Clinical presentation is mild, and mid-term outcome is favourable under adequate therapy. However, complement anomalies persist for several years.

Prediction of membranous nephropathy recurrence after transplantation by monitoring of anti-PLA2R1 (M-type phospholipase A2 receptor) autoantibodies: a case series of 15 patients.

BACKGROUND: The predictive value of anti-M-type phospholipase A2 receptor (PLA2R1) autoantibodies for membranous nephropathy (MN) recurrence after renal transplantation remains controversial. METHODS: Our aim was to monitor anti-PLA2R1 IgG4 activity using a sensitive enzyme-linked immunosorbent assay in 15 kidney transplant recipients with MN, and to test the correlation between antibody titres and MN recurrence. RESULTS: Five patients never exhibited anti-PLA2R1 antibodies, and one of them relapsed. Ten patients (67%) had IgG4 anti-PLA2R1 antibodies at the time of transplantation and during follow-up. The presence of IgG4 anti-PLA2R1 antibodies at the time of kidney transplantation does not imply MN recurrence (P = 0.600, n = 15). However, a positive IgG4 anti-PLA2R1 activity during follow-up (>Month 6) was a significant risk factor for MN relapse (P = 0.0048, n = 10). Indeed, four patients had persistent IgG4 anti-PLA2R1 activity after transplantation and relapsed. Among them, one was successfully treated with rituximab. Another had persistently high IgG4 anti-PLA2R1 activity and exhibited a histological relapse but no proteinuria while on treatment with renin-angiotensin system inhibitors. In contrast, the six other patients who did not relapse exhibited a decrease of their IgG4 anti-PLA2R1 activity following transplant immunosuppression, including two with proteinuria due to biopsy-proven differential diagnoses. A weak transplant immunosuppressive regimen was also a risk factor of MN recurrence (P = 0.0048, n = 10). Indeed, the six patients who received both an induction therapy and a combined treatment with calcineurin inhibitors/mycophenolate exhibited a decrease of IgG4 anti-PLA2R1 activity and did not relapse, while the four patients who did not receive this strong immunosuppressive treatment association had persistently high IgG4 anti-PLA2R1 activity and relapsed. CONCLUSION: The monitoring of IgG4 anti-PLA2R1 titres during follow-up helps to predict MN recurrence, and a strong immunosuppressive treatment of anti-PLA2R1 positive patients may prevent recurrence.

Diagnosis of Streptococcus pneumoniae-associated hemolytic uremic syndrome.

BACKGROUND: Hemolytic uremic syndrome related to pneumococcal infection (P+HUS) can be difficult to diagnose due to the lack of a specific test and the absence of a consensus for definite diagnostic criteria. METHODS: A retrospective study was conducted on the cases that have been considered as P+HUS in the participating centers during the past 10 years. Diagnostic strategy and criteria used for the diagnosis of P+HUS were evaluated and compared with a review of literature data. RESULTS: A total of 17 children were studied. Tests ruling out other causes of HUS were performed in 94% of cases. Direct confirmatory tests for P+HUS were done in a minority of cases as Thomsen-Friedenreich antigen testing using lectin assay were done in only 2 patients (11%). Retrospectively, the diagnosis of P+HUS was confirmed in 28% to 89% of cases depending on the already published criteria used. A literature review focused on the last 15 years confirmed these diagnostic difficulties due to variable definition criteria and bring a new light on the potential usefulness of tests used to reveal T activation in this setting. CONCLUSION: To date, in a context of suspicion of P+HUS, no precise, practical and consensual strategy exists for T-antigen exposure diagnosis. The T-antigen activation test using peanut lectin might be the most appropriate test for a direct diagnosis of P+HUS. A large prospective study is required to confirm this hypothesis. However, before such data are available, its use could be of help when a suspicion of P+HUS is present given the therapeutic impact of such a diagnosis.

Respiratory chain deficiency presenting as congenital nephrotic syndrome.

Nephrotic syndrome (NS) in infancy includes NS of Finnish type (mutation of the nephrin gene), diffuse mesangial sclerosis (idiopathic or linked to WT1 mutation), idiopathic NS, most often steroid resistant, and NS related to infections during pregnancy (virus, syphilis, toxoplasmosis). Later in life, NS has a large variety of etiologies. It has been described in association with neuromuscular symptoms, deafness, and diabetes in a few children and adults with respiratory chain (RC) disorders. To date, however, NS has never been observed in neonates with RC disorders. Here, we report RC deficiency in one infant with certain congenital NS and two siblings with acute neonatal cardiac and renal disease with probable NS. Although clinical and histopathological presentations were initially close to congenital NS of Finnish type, clinical outcome was atypical and nephrin mutation was excluded. Mitochondrial RC complex II+V deficiency was identified in the three patients. Based on these observations, we suggest that RC disorders should be considered in patients with congenital NS.