Early and late outcome in both patients was good . Billing et al. major components (lead to typical CNS but also to NS manifesting later in life. Podocin is an intracellular linker protein that interacts with nephrin and serves a scaffolding function for the SD. More than 60 pathogenic mutations described can lead to steroid-resistant nephrotic syndrome (SRNS) presenting from birth to adulthood . The R138Q mutation is associated with early onset NS. The histological presentation is usually one of focal segmental glomerulosclerosis (FSGS). and mutations account for about 75?% of the primary CNS cases . They both cause isolated CNS without major extrarenal manifestations. Other important etiologies (Table?1) are phospholipase C epsilon-1 (and co-enzyme Q2 4-hydroxybenzoate polyprenyltransferase mutation cause muscular symptoms of mitochondriopathies [15, 16]. Genetic defects in that encodes Rho guanosine diphosphate dissociation inhibitor- have recently been shown to cause CNS and neurological handicap [17, 18]. Table 1 Some important podocyte genes, mutations of which can lead to congenital nephrotic syndrome (CNS) (11C18) slit Tirasemtiv (CK-2017357) diaphragm, Syndrome, steroid-resistant nephrotic syndrome, focal segmental glomerulosclerosis, diffuse mesangial sclerosis Renal transplantation in infants with CNS Reports from most registries and larger centers show that graft and patient survival after RTx in infants is at least as good as in older children . A recent Canadian study showed that the greatest risk for graft failure was in Tirasemtiv (CK-2017357) young adultsnot in infants . One Scandinavian study showed results as good in infants as in older patients . Cultural and socioeconomic differences do, however, exist, and results are hard to compare [22, 23]. Today it is clear that early RTx is indicated in CNS patients, as most long-term acquired problems develop during the nephrotic or uremic stage. Perioperative problems in infants are comparable to those in older children and adults. An adult graft, however, can be placed extraperitoneally only after the child weighs about 10?kg. Before that, an intraperitoneal placement of the graft can be considered. Postoperatively, excessive fluids are needed to adequately perfuse the kidney graft . Long-term graft function in infants is similar to that in older children. A recent finding has also shown that growth is good, in fact catch up growth in infants is better , puberty is normal, and final height is acceptable in patients transplanted as infants . Neurocognitive function in children without co-morbidities or complications before RTx is satisfactory and family coping is excellent in developed societies with social support . Proteinuria after RTx After RTx, mild proteinuria is not rare. The most common causes are chronic allograft injury, de novo glomerulopathy and drug toxicity. In this context, a special problem is nongenetic FSGS; this is a major cause of SRNS and in children accounts for 11?% of end-stage renal disease . Heavy proteinuria recurs in 20-40?% of the patients, often within days after RTx . A circulating plasma factor has been suggested as being responsible, and recent research has suggested that circulating soluble urokinase receptor (suPAR), increased TNF- activity, or additional factors are involved [30, 31]. Recurrent proteinuria in NPHS1 patients In 1992, Laine et al. reported on 28 CNF patients, of whom six (24?%) developed severe proteinuria and NS 1-33?months after RTx . Histology showed endothelial swelling and mesangial cell proliferation. All patients were treated with methylprednisolone (MP) and five with additional cyclophosphamide (CP). Only two patients went into remission, and four grafts were lost. One patient showed proteinuria Rabbit Polyclonal to DDX3Y again in the second graft 14?months after re-transplantation. Three additional CNF patients reported to have proteinuria after transplantation had responded, two to steroids and one to steroids and cyclophosphamide [33C35]. This indicates that a risk for proteinuria in CNF seems to exist after early RTx, with some patients responding to therapy. In 2000, Patrakka et al. described 45 CNF (NPHS1) patients receiving 51 kidneys . In this Finnish cohort, 15 episodes of recurrent proteinuria occurred in 13 grafts (25?%). All nine patients with recurrence were homozygous for the Fin-major mutation, which leads to an early stop-codon and total absence of nephrin in the native kidney. Rescue therapy with CP was successful in seven episodes, Tirasemtiv (CK-2017357) but six kidneys were lost. Tirasemtiv (CK-2017357) Antibodies reacting against the glomerulus were found in eight of the nine patients, and high serum anti-nephrin antibody levels were detected by an ELISA Tirasemtiv (CK-2017357) method in four. Thus, it seems that circulating.