No abstract

No abstract

Introduction Recurrence of atypical hemolytic uremic syndrome (aHUS) in renal allografts is common, leading to dialysis and graft failure. Pretransplant versus posttransplant initiation of eculizumab treatment in patients with aHUS has not been rigorously investigated. We hypothesized eculizumab pretransplant would reduce dialysis incidence posttransplant. Methods Of patients enrolled in the Global aHUS Registry ( n = 1549), 344 had ≥1 kidney transplant. Of these, 188 had received eculizumab. Eighty-eight patients (47%) were diagnosed with aHUS and received eculizumab before, and during, their most recent transplant (group 1). A total of 100 patients (53%; group 2) initiated eculizumab posttransplantation. This second group was subdivided into those diagnosed with aHUS before ( n = 52; group 2a) or after ( n = 48; group 2b) their most recent transplant. Results Within 5 years of transplantation, 47 patients required dialysis; the risk of dialysis after transplantation was significantly increased in group 2b (hazard ratio [HR] 4.6; confidence interval [CI] 1.7–12.4) but not 2a (HR 2.3; CI 0.9–6.2). Graft function within 6 months of transplantation was significantly better in group 1 (median estimated glomerular filtration rate of 60.6 ml/min per 1.73 m 2 ) compared with 31.5 and 9.6 ml/min per 1.73 m 2 in groups 2a ( P = 0.004) and 2b ( P = 0.0001), respectively. One meningococcal infection (resolved with treatment) and 3 deaths (deemed unrelated to eculizumab) were reported. Conclusions Outcomes for transplant patients with aHUS treated with eculizumab were improved compared with previous reports of patients with aHUS not treated with eculizumab. Our findings suggest delayed aHUS diagnosis and therefore treatment is associated with an increased risk of dialysis posttransplantation and reduced allograft function.

Compared with outright use of NGS, our tiered genetic testing strategy was considerably more rapid and marginally less expensive. Apart from a high aetiological fraction of NPHS2 and WT1 genes, our study has identified an unexpectedly high frequency of a limited set of presumably ancestral causative mutations in NUP93. The results may aid in tailoring testing strategies in Central European populations.

No abstract

Autosomal recessive steroid-resistant nephrotic syndrome (NS) is a rare, genetically determined nephropathy caused mainly by a mutation in the NPHS2 gene. This type of NS is usually resistant to other immunosuppressive therapy as well, but a few cases of cyclosporine A-induced partial remission of inherited NS have been reported. We present a boy that developed NS at the age of 18 months. There was no decrease of proteinuria on standard prednisolone therapy, and a diagnosis of steroid-resistant NS was established. However, the proteinuria decreased significantly following the initiation of cyclosporine A therapy (from 1280 to 380 mg/m(2) per day) without any negative effects on renal function (stable glomerular filtration rate 130-150 ml/min per 1.73 m(2)). The molecular genetic test revealed a homozygous R138Q mutation in the NPHS2 gene. Our case demonstrates that cyclosporine A can induce partial remission in patients with genetic forms of NS without influencing the glomerular filtration rate. However, its long-term effect and safety in children with hereditary forms of nephrotic syndrome have yet to be investigated.

I n 2013 recessive mutations in DGKE, which encodes diacylglycerol kinase epsilon (DGKE), were first reported to cause atypical hemolytic uremic syndrome (aHUS) 1 and nephrotic syndrome, with glomerular microangiopathy said to resemble membranoproliferative (mesangiocapillary) glomerulonephritis (MPGN) 2 (Online Mendelian Inheritance in Man #615008), though the pathophysiological mechanisms remain poorly understood. aHUS is characterized by a clinical presentation with thrombocytopenia, microangiopathic hemolytic anemia, and organ injury. 3 aHUS is a broad term that has been used to refer to cases of thrombotic microangiopathy (TMA), in

Atypical hemolytic uremic syndrome (aHUS) is a thrombotic microangiopathy with severe clinical manifestation, frequent recurrence, and poor long-term prognosis. It is usually caused by abnormalities in complement regulation. We report 2 cases of children affected by a catastrophic extrarenal complication. A 4-year-old Indian girl developed gangrene of the finger tips 2 days after initial presentation of aHUS. Factor H autoantibodies were identified. Renal function continued to decline despite daily plasma exchanges, and she was started on peritoneal dialysis 5 days after admission. The distal tips of the left hand remained gangrenous with a line of demarcation. Three weeks later, she did not return for follow-up and died at home because of dialysis-related complications. An Arabic girl developed end-stage renal disease due to aHUS in the fourth month after birth. A de novo activating C3 mutation was found. At age 9 months, she suddenly developed ischemic changes in fingers of both hands and several toes. The lesions progressed, and several finger tips became gangrenous despite intense plasma exchange therapy. The decision was made to administer complement blocking therapy with the C5 antibody eculizumab. All nonnecrotic digits rapidly regained perfusion. The 3 already gangrenous fingers healed with loss of the end phalanges. During maintenance, eculizumab aHUS activity subsided completely and some late recovery of renal function was observed. aHUS may present by thrombotic macroangiopathy of small peripheral arteries. Eculizumab appears effective in preserving tissue viability if administered before gangrene occurs and should be considered as first-line rescue therapy in such cases.