Present and Future of IgA Nephropathy and Membranous Nephropathy Immune Monitoring: Insights from Molecular Studies.

IgA Nephropathy (IgAN) and Membranous Nephropathy (MN) are primary immune-mediated glomerular diseases with highly variable prognosis. Current guidelines recommend that greater immunologic activity and worse prognosis should guide towards the best treatment in an individualized approach. Nevertheless, proteinuria and glomerular filtration rate, the current gold standards for prognosis assessment and treatment guidance in primary glomerular diseases, may be altered with chronic damage and nephron scarring, conditions that are not related to immune activity. In recent years, thanks to the development of new molecular technologies, among them genome-wide genotyping, RNA sequencing techniques, and mass spectrometry, we have witnessed an outstanding improvement in understanding the pathogenesis of IgAN and MN. In addition, recent genome-wide association studies have suggested potential targets for immunomodulating agents, stressing the need for the identification of specific biomarkers of immune activity. In this work, we aim to review current evidence and recent progress, including the more recent use of omics techniques, in the identification of potential biomarkers for immune monitoring in IgAN and MN.

Bioimpedance-based rather than weight-based ultrafiltration prescription for children on maintenance hemodialysis
.

The determination of dry weight (DW) in young children on hemodialysis (HD) remains challenging. Bioimpedance analysis (BIA) is a potentially helpful means of estimating the need for ultrafiltration and monitoring body fluids in patients on renal replacement therapy, but its role has not yet been clearly defined. The aim of this paper is to share our experience of prescribing ultrafiltration on the basis of BIA parameters alone. The body weight (BW), resistance (Rx), and reactance (Xc) of a 3-year-old girl on chronic HD were recorded pre- and post-HD over a period of 16 months. The BIA parameter that best correlated with actual ultrafiltration (the difference between pre- and post-HD BW) was identified, and the equivalence between actual ultrafiltration and changes in Xc was derived to obtain the following equation: 1 ohm of Xc = 27.4 g of ultrafiltration. Finally, during 21 consecutive HD sessions, ultrafiltration was exclusively prescribed on the basis of the derived equation (BIA-based prescription) after having defined a target post-HD Xc of 45 ohm. The BIA-based prescription period was compared with 21 consecutive HD sessions in which ultrafiltration was prescribed using the conventional approach based on BW (BW-based prescription). Comparison of BIA-based and BW-based ultrafiltration prescription showed significantly fewer HD sessions complicated by hypotension (19 vs. 50%) or by the need for reinfusion (5 vs. 50%), and a better overall quality of HD sessions (86 vs. 37%). No difference in blood pressure was observed, and no acute fluid overload event was detected in either period. BIA-based ultrafiltration seems to be safe, feasible, and effective. The described approach can be particularly useful in the case of patients with problems in setting or maintaining the correct DW.
.

Plasma-exchange in pediatric patients: a single-center experience.

BACKGROUND: Plasma-exchange (PEX) has been well described in pediatrics, but most of the current indications are derived from adult experience. Aim of the study was to review the PEX treatments in our Unit over a six-year period. METHODS: Three hundred and seventy-seven PEX sessions were performed in 38 patients (median age 12.1 years, range 0.6-20.5). Double-needle and single-needle PEX combined with hemodialysis and PEX combined with ultrafiltration were performed in 9, 1 and 3 patients respectively. The most common indications to PEX were atypical hemolytic uremic syndrome (aHUS, 9 patients), focal segmental glomerulosclerosis (FSGS, 9 cases), antibody mediated rejection (AMR) in renal transplant (rTx) recipients (8 patients) and hyperimmunization in patients waiting for rTx (4 cases). RESULTS: We treated five patients with aHUS on native kidneys with PEX only, with complete remission in 4/6 recurrences; PEX was also successfully used to prevent HUS relapse in three patients undergoing rTx. Only one partial remission was obtained in four patients with FSGS on native kidneys, by means of treatment protocols based on PEX and immunosuppressants; conversely, a partial remission was observed in 6/6 patients with recurrence of FSGS on rTx. Immunosuppressive protocols combined with PEX proved useful in sensitized cadaveric rTx recipients (2/4 successfully transplanted), but failed in 6 patients with chronic AMR. As regards complications, two severe adverse reactions occurred: an anaphylactic shock after the use of albumin and an abdominal hemorrhage. CONCLUSIONS: PEX is a relatively safe procedure in children. Pediatric patients with aHUS, recurrent FSGS and sensitized rTx recipients seem to benefit from treatment strategies including PEX.

Posterior reversible encephalopathy syndrome after kidney transplantation in pediatric recipients: Two cases.

PRES is a neuro-clinical and radiological syndrome that can result as a consequence of several different conditions including hypertension, fluid overload, and immunosuppressive treatment. Herein, we report two children who received kidney and combined liver-kidney transplantation as treatment for renal hypodysplasia associated with bilateral vesico-ureteral reflux and methylmalonic acidemia, respectively. Early after surgery (seven and 10 days), both patients presented with hypertension and seizures. The patients' immunosuppressive regimen included steroid and calcineurin inhibitors (tacrolimus and cyclosporine, respectively) and basiliximab and one with anti-IL2 receptor. In both cases, the imaging strongly supported the diagnosis of PRES. In details, the CT scan showed hypodensities in the posterior areas of the brain, and brain MRI demonstrated parieto-occipital alterations indicative of vasogenic edema. Treatment with calcineurin inhibitors was temporally discontinued and restarted at lower dosage; arterial hypertension was treated with Ca-channel blockers. Both children fully recovered without any neurological sequels. In conclusion, in children undergoing solid organ transplantation, who develop neurological symptoms PRES, should be carefully considered in the differential diagnosis and once the diagnosis is ruled in, we recommend strict arterial blood pressure control and adjustment or withholding of calcineurin inhibitor therapy should be considered based upon blood levels.

Epidemiology of haemolytic uremic syndrome in children. Data from the North Italian HUS network.

UNLABELLED: Despite the severity of HUS and the fact that it represents a leading cause of acute kidney injury in children, the general epidemiology of HUS is all but well documented. The present study provides updated, population-based, purely epidemiological information on HUS in childhood from a large and densely populated area of northern Italy (9.6 million inhabitants, 1.6 million children). We systematically reviewed the files concerning patients with STEC-HUS and atypical HUS (aHUS) over a 10-year observation period (January 2003-December 2012). We included all incident cases with a documented first episode of HUS before the age of 18 years. We identified 101 cases of HUS during the 10 years. The overall mean annual incidence was 6.3 cases/million children aged <18 years (range 1.9-11.9), and 15.7/million of age-related population (MARP) among subjects aged <5 years; aHUS accounted for 11.9 % of the cases (mean incidence 0.75/MARP). The overall case fatality rate was 4.0 % (3.4 % STEC-HUS, 8.3 % aHUS). CONCLUSION: Given the public health impact of HUS, this study provides recent, population-based epidemiological data useful for healthcare planning and particularly for estimating the financial burden that healthcare providers might have to face in treating HUS, whose incidence rate seems to increase in Northern Italy. WHAT IS KNOWN: • HUS is a rare disease, but it represents the leading cause of acute kidney injury in children worldwide. • STEC-HUS (also called typical, D + HUS) is more common compared to atypical HUS, but recent, population-based epidemiological data (incidence) are scanty. What is New: • Comprehensive, population-based epidemiological data concerning both typical and atypical HUS based on a long observational period.

Rituximab in Children with Steroid-Dependent Nephrotic Syndrome: A Multicenter, Open-Label, Noninferiority, Randomized Controlled Trial.

Steroid-dependent nephrotic syndrome (SDNS) carries a high risk of toxicity from steroids or steroid-sparing agents. This open-label, noninferiority, randomized controlled trial at four sites in Italy tested whether rituximab is noninferior to steroids in maintaining remission in juvenile SDNS. We enrolled children age 1-16 years who had developed SDNS in the previous 6-12 months and were maintained in remission with high prednisone doses (≥0.7 mg/kg per day). We randomly assigned participants to continue prednisone alone for 1 month (control) or to add a single intravenous infusion of rituximab (375 mg/m(2); intervention). Prednisone was tapered in both groups after 1 month. For noninferiority, rituximab had to permit steroid withdrawal and maintain 3-month proteinuria (mg/m(2) per day) within a prespecified noninferiority margin of three times the levels among controls (primary outcome). We followed participants for ≥1 year to compare risk of relapse (secondary outcome). Fifteen children per group (21 boys; mean age, 7 years [range, 2.6-13.5 years]) were enrolled and followed for ≤60 months (median, 22 months). Three-month proteinuria was 42% lower in the rituximab group (geometric mean ratio, 0.58; 95% confidence interval, 0.18 to 1.95 [i.e., within the noninferiority margin of three times the levels in controls]). All but one child in the control group relapsed within 6 months; median time to relapse in the rituximab group was 18 months (95% confidence interval, 9 to 32 months). In the rituximab group, nausea and skin rash during infusion were common; transient acute arthritis occurred in one child. In conclusion, rituximab was noninferior to steroids for the treatment of juvenile SDNS.

Hemoconcentration: a major risk factor for neurological involvement in hemolytic uremic syndrome.

BACKGROUND: Shigatoxin-associated hemolytic uremic syndrome (STEC-HUS) is a common thrombotic microangiopathy (TMA) in which central nervous system (CNS) involvement is responsible for the majority of deaths and for severe long-term sequelae. We have analyzed the role of hemoconcentration in disease severity. METHODS: This was a retrospective review of the records and laboratory data at presentation of all patients with STEC-HUS cases (n = 61) over a 10-year period. The patients were grouped into three severity classes: group A, comprising patients who did not require dialysis; group B, patients who were dialyzed without CNS involvement; group C, patients with CNS involvement. RESULTS: Patients with CNS involvement (group C) had a higher mean hemoglobin level (11.2 ± 2.3 g/dL) than those of group A or B ( 9.4 ± 2.1 and 7.5 ± 1.9 g/dL, respectively; p < 0.0001). We also observed that the higher the initial hemoglobin level, the more severe the long-term renal damage (p < 0.007). CONCLUSIONS: In patients with STEC-HUS, hemoconcentration and hypovolemia may be responsible for more severe ischemic organ damage (both short and long term) at disease onset, and these signs should be regarded as risk factors for CNS damage and for more severe TMA. Therefore, we recommend that hydration status should be actively monitored in HUS patients and that dehydration, when diagnosed, should be promptly corrected.

Discontinuation of eculizumab maintenance treatment for atypical hemolytic uremic syndrome: a report of 10 cases.

Atypical hemolytic uremic syndrome (aHUS) is a life-threatening thrombotic microangiopathy, and as many as 70% of patients with aHUS have mutations in the genes encoding complement regulatory proteins. Eculizumab, a humanized recombinant monoclonal antibody targeting C5, has been used successfully in patients with aHUS since 2009. The standard maintenance treatment requires life-long eculizumab therapy, but the possibility of discontinuation has not yet been tested systematically. We report the safety of discontinuing eculizumab treatment in 10 patients who stopped treatment with the aim of minimizing the risk of adverse reactions, reducing the risk of meningitis, and improving quality of life while also reducing the considerable treatment costs. Disease activity was monitored closely at home by means of urine dipstick testing for hemoglobin. During the cumulative observation period of 95 months, 3 of the 10 patients experienced relapse within 6 weeks of discontinuation, but then immediately resumed treatment and completely recovered. Our experience supports the possibility of discontinuing eculizumab therapy with strict home monitoring for early signs of relapse in patients with aHUS who achieve stable remission.

Three-yr safety and efficacy of everolimus and low-dose cyclosporine in de novo pediatric kidney transplant patients.

The three yr results of a multicenter trial in de novo pediatric KT treated with a proliferative signal inhibitor and low dose CNI are presented. Thirty-seven children (9.1 ± 5 yr old) received basiliximab, cyclosporine A (CyA C2:1400 ng/mL), (MMF C0:1.5-3 µg/mL), and prednisone. Three wk later everolimus was started (C0:5-10 ng/mL), CyA was reduced (C2:600 ng/mL after 90 days 300 ng/mL), and MMF discontinued. During the three-yr period patient and graft survivals were 96%. One patient died for causes unrelated to the immunosuppression. Cumulative acute rejection rate including protocol and indication biopsies was 21.9%. None of the patients had signs of chronic humoral rejection. Incidence of dnDSA was 5%, 11%, and 22% at one, two, and three yr post-transplant, respectively. Mean glomerular filtration rate measured at one yr and three yr post-transplant was 105.5 ± 31 and 110.7 ± 27 mL/min/1.73 m(2), respectively. A growth velocity of 7.7 ± 6.7 cm/yr was achieved with positive catch-up growth. No malignancy or post-transplant lymphoproliferative diseases were diagnosed. In conclusion, the treatment based on basiliximab induction, everolimus, low-dose cyclosporine, and low-dose prednisone leads to good long-term efficacy in de novo pediatric KT recipients.

Rituximab is a safe and effective long-term treatment for children with steroid and calcineurin inhibitor-dependent idiopathic nephrotic syndrome.

In children with idiopathic nephrotic syndrome, rituximab can maintain short-term remission with withdrawal of prednisone and calcineurin inhibitors. Long-term effects including the number of repeated infusions to maintain remission are unknown. To test this, we treated 46 consecutive children with idiopathic nephrotic syndrome lasting for at least 1 year (mean 6.3 years), maintained in remission with oral prednisone and calcineurin inhibitors. They received 1-5 rituximab courses during a median follow-up of 3 years. Oral agents were tapered after each infusion, and completely withdrawn within 45 days. Rituximab was well tolerated. Six-month probabilities of remission were 48% after the first infusion and 37% after subsequent infusions. One- and 2-year-remission probabilities were, respectively, 20 and 10%. Median time intervals between complete oral-agent withdrawal and relapse were 5.6 and 8.5 months, respectively, following the first and subsequent courses. The time to reconstitution of CD20 cells correlated with the duration of remission, but was not associated with variation in FcyR, CD20, or SMPDL-3B polymorphisms. Podocyte Src phosphorylation was normal. Thus, rituximab can be safely and repeatedly used as a prednisone and calcineurin inhibitor-sparing therapy in a considerable proportion of children with dependent forms of idiopathic nephrotic syndrome. Further study is needed to identify patients who will benefit most from rituximab therapy.

Impact of graft loss among kidney diseases with a high risk of post-transplant recurrence in the paediatric population.

BACKGROUND: Some kidney diseases tend to recur in the renal allograft after transplantation. We studied the risk of graft loss among primary renal diseases known for their high risk of recurrence and compared it with that of patients with hypoplasia and/or dysplasia. METHODS: Within the European Society of Paediatric Nephrology and European Renal Association and European Dialysis and Transplant Association (ESPN/ERA-EDTA) registry, we studied children from 33 countries who received a kidney transplant before the age of 20 between 1990 and 2009. Patients were censored after 5 years of follow-up and cumulative incidence competing risk analysis was used to calculate survival curves. RESULTS: Patients with focal and segmental glomerulosclerosis (FSGS), haemolytic uraemic syndrome (HUS), membranoproliferative glomerulonephritis Type I or II (MPGN), IgA nephropathy or Henoch Schönlein Purpura (HSP/IgA) or systemic lupus erythomatosus (SLE) underwent pre-emptive transplantation significantly less often than patients with hypoplasia and/or dysplasia. The rate of living donation was lower among patients with FSGS and SLE than in patients with hypoplasia and/or dysplasia. In comparison with hypoplasia and/or dysplasia patients with a risk of 14.4%, the 5-year risk of graft loss was significantly increased in patients with FSGS (25.7%) and MPGN (32.4%) while it was not significantly increased in children with HUS (18.9%), HSP/IgA (16.3%) or SLE (20.3%). One-year graft survival strongly improved among HUS patients from 17.1% in 1995-1999 to 3.6% in 2005-2009 and was not accompanied by a decrease in the number of transplantations. CONCLUSION: The risk of graft loss is increased among specific causes of renal failure with a high risk of post-transplant recurrence. It seems likely that, due to anticipation of such risk, physicians perform less pre-emptive transplantation and provide fewer grafts from living related donors in patients with these conditions. Improved risk stratification by physicians, resulting in the identification of patients with HUS at higher or lower risk of recurrence, might explain the much improved graft survival rates.

A review on JC virus infection in kidney transplant recipients.

The polyomavirus (PyV), JC virus (JCV), is a small nonenveloped DNA virus that asymptomatically infects about 80% of healthy adults and establishes latency in the kidney tissue. In case of immunodeficient hosts, JCV can lytically infect the oligodendrocytes, causing a fatal demyelinating disease, known as progressive multifocal leukoencephalopathy (PML). Although the reactivation of another human PyV, BK virus (BKV), is relatively common and its association with the polyomavirus associated nephropathy (PyVAN) following renal transplantation is proven, JCV replication and its impact on graft function and survival are less well studied. Here we describe the biology of JCV and its pathological features and we review the literature regarding the JCV infection analyzed in the setting of transplantations.

Allogeneic mesenchymal stem cell infusion for the stabilization of focal segmental glomerulosclerosis.

Focal segmental glomerulosclerosis (FSGS) is the most frequent acquired renal condition resulting in end stage kidney disease in children. We describe a cell therapy treatment with human allogeneic bone marrow mesenchymal stem cells (MSC) in a 13-year-old patient developing recurrent FSGS after renal transplantation, which was not responding to conventional therapy. This treatment relied on the following measurements:clinical and laboratory evaluation of renal function, proteome array, biopsy, short tandem repeat assay. Before MSC treatment, the patient needed weekly plasmapheresis to achieve proteinuria-to-creatininuria ratio below 5. After three MSC infusions without adverse events, the patient has a stable renal function and the proteinuria target was reached without plasmapheresis. In addition, some circulating inflammatory factors decreased and their levels were still low after one year. This is the first report of an MSC treatment in an FSGS patient. Even though different factors may have contributed to the clinical results, after MSC infusion a stable reduction in the serum level of several inflammatory factors has been registered and the patient does not need anymore plasmapheresis to keep proteinuria under control. In addition, this encouraging single case let us identify some putative efficacy biomarkers that could be of clinical interest in chronic kidney diseases.

Rituximab in children with resistant idiopathic nephrotic syndrome.

Idiopathic nephrotic syndrome resistant to standard treatments remains a therapeutic dilemma in pediatric nephrology. To test whether the anti-CD20 monoclonal antibody rituximab may benefit these patients, we conducted an open-label, randomized, controlled trial in 31 children with idiopathic nephrotic syndrome unresponsive to the combination of calcineurin inhibitors and prednisone. All children continued prednisone and calcineurin inhibitors at the doses prescribed before enrollment, and one treatment group received two doses of rituximab (375 mg/m(2) intravenously) as add-on therapy. The mean age was 8 years (range, 2-16 years). Rituximab did not reduce proteinuria at 3 months (change, -12% [95% confidence interval, -73% to 110%]; P=0.77 in analysis of covariance model adjusted for baseline proteinuria). Additional adjustment for previous remission and interaction terms (treatment by baseline proteinuria and treatment by previous remission) did not change the results. In conclusion, these data do not support the addition of rituximab to prednisone and calcineurin inhibitors in children with resistant idiopathic nephrotic syndrome.

Investigation of polyomaviruses replication in pediatric patients with nephropathy receiving rituximab.

Rituximab is a chimeric monoclonal antibody reacting with the CD20 antigen on B cells. It has been proposed as treatment for the idiopathic nephrotic syndrome, recurrent idiopathic nephropathy, and focal segmental glomerulosclerosis refractory to steroids. Rituximab influences T-cell immunity and may predispose the patients to opportunistic infections, such as progressive multifocal leukoencephalopathy caused by the polyomavirus JC (JCV). The risk of latent viruses infections/reactivations in pediatric patients receiving monoclonal antibodies is not well known yet. In this longitudinal 6-month study, the effects of rituximab on JCV and BK virus (BKV) replication have been investigated. Blood, serum, and urine samples have been collected monthly from 11 pediatric patients (mean age: 11 years) with the idiopathic nephrotic syndrome and recurrent idiopathic nephropathy, under rituximab therapy. JCV and BKV real-time PCRs and sequencing of the viral protein 1 and the non-coding control region have been conducted. The same investigations have been undertaken on samples collected from eight pediatric patients (controls, mean age: 6 years), with idiopathic nephrotic syndrome or focal segmental glomerulosclerosis, treated with conventional chemotherapy. JCV was detected in the urine of one patient (9%), and one control (12.5%); BKV was found in the urine of 7/11 patients (63.6%) and 2/8 controls (25%) and in blood samples from four patients. No significant difference was found in the mean viral loads and in the viral molecular characterizations between the two groups. The polyomaviruses replication was not associated with rituximab therapy in children.

Association between CYP3A5 polymorphisms and blood pressure in kidney transplant recipients receiving calcineurin inhibitors.

Abstract Renal cytochrome P450 3A5 (CYP3A5) has been associated with blood pressure (BP) control in humans. We investigated whether CYP3A5 polymorphisms are associated with post- transplant hypertension in a selected population of kidney recipients receiving calcineurin inhibitors. Ninety-two kidney transplant recipients receiving cyclosporine (CyA) or tacrolimus (Tac) were genotyped for CYP3A5 polymorphisms, and the association between the CYP3A5 alleles (*1,*3) and hypertension on post-operative day (POD) 6 and POD 180 was verified, with multiple regression being used to identify the putative co-variates that may predict the extent and severity of hypertension in transplant recipients at different post-transplant times. The CYP3A5*1 carriers had higher systolic (SBP) and diastolic blood pressure (DBP) in both the immediate and delayed post-transplant period when adjusted for anti-hypertensive medication (POD 6: SBP = 161 ± 23 vs. 140 ± 23 mmHg; DBP = 120 ± 15 vs. 87 ± 14 mmHg, p < 0.05. POD 180: SBP = 136 ± 16 vs. 129 ± 14 mmHg; DBP = 89 ± 15 vs. 80 ± 15 mmHg, p < 0.05). The severity of hypertension between the CYP3A5*1 carriers and noncarriers on POD 6 was documented by the significantly different distribution of hypertension classes, but this was not confirmed on POD 180. The CYP3A5 genotype was the only independent variable affecting mean arterial pressure. The results of this study show that CYP3A5 polymorphisms are associated with the severity and degree of hypertension in kidney transplant recipients receiving calcineurin inhibitors regardless of the time of recording. However, the role of concomitant medications such as steroids with strong CYP3A5 inducing activity, should be taken into account.

[Kidney transplant from living donors in children?]. / Trapianto di rene da donatore vivente in pediatria?

A living-donor kidney transplant offers a child at the terminal stages of renal disease better functional recovery and quality of life than an organ from a deceased donor. Before starting the procedure for a living-donor transplant, however, it is necessary to establish if it is really safe. There are diseases, such as focal segmental glomerulosclerosis, atypical HUS and membranoproliferative glomerulonephritis with dense deposits, for which living donation is not recommended given the high incidence of recurrence of the disease but also the frequent loss of the graft. Regarding the selection of the donor, an increased risk of acute rejection has been reported for donors older than 60-65 years and a worsening of the renal outcome if the donor's weight is equal to or less than the recipient's. Finally, it is necessary to take into consideration that complications may arise in the donor both in the perioperative period and in the long term. In conclusion, kidney transplant from a living donor is a natural choice within the pediatric setting. The parents, usually young and highly motivated to donate, are the ideal donors. However, although the risks associated with donation are minimal, they are not totally absent, and consequently it is mandatory to follow standardized procedures according to the guidelines issued by the Centro Nazionale Trapianti.

Urinary mRNA Expression of Glomerular Podocyte Markers in Glomerular Disease and Renal Transplant.

The research of novel markers in urinary samples, for the description of renal damage, is of high interest, and several works demonstrated the value of urinary mRNA quantification for the search of events related to renal disease or affecting the outcome of transplant kidneys. In the present pilot study, a comparison of the urine mRNA expression of specific podocyte markers among patients who had undergone clinical indication to renal transplanted (RTx, n = 20) and native (N, n = 18) renal biopsy was performed. The aim of this work was to identify genes involved in podocytes signaling and cytoskeletal regulation (NPHS1, NPHS2, SYNPO, WT1, TRPC6, GRM1, and NEUROD) in respect to glomerular pathology. We considered some genes relevant for podocytes signaling and for the function of the glomerular filter applying an alternative normalization approach. Our results demonstrate the WT1 urinary mRNA increases in both groups and it is helpful for podocyte normalization. Furthermore, an increase in the expression of TRPC6 after all kinds of normalizations was observed. According to our data, WT1 normalization might be considered an alternative approach to correct the expression of urinary mRNA. In addition, our study underlines the importance of slit diaphragm proteins involved in calcium disequilibrium, such as TRPC6.

Kidney transplant in patients with atypical hemolytic uremic syndrome in the anti-C5 era: single-center experience with tailored Eculizumab.

RATIONALE AND OBJECTIVE: Patients with atypical hemolytic uremic syndrome (aHUS) have long been considered ineligible for kidney transplantation (KTx) in several centers due to the high risk of disease recurrence, graft loss and life-threatening complications. The availability of Eculizumab (ECU) has now overcome this problem. However, the best approach towards timing, maintenance schedule, the possibility of discontinuation and patient monitoring has not yet been clearly established. STUDY DESIGN: This is a single center case series presenting our experience with KTx in aHUS. SETTING AND PARTICIPANTS: This study included 26 patients (16 females) with a diagnosis of aHUS, who spent a median of 5.5 years on kidney replacement therapy before undergoing KTx. We compared the aHUS relapse rate in three groups of patients who underwent KTx: patients who received no prophylaxis, patients who underwent plasma exchange, those who received Eculizumab prophylaxis. Complement factor H-related disease was by far the most frequent etiology (n = 19 patients). RESULTS: Untreated patients and patients undergoing pre-KTx plasma exchange prophylaxis had a relapse rate of 0.81 (CI 0.30-1.76) and 3.1 (CI 0.64-9.16) events per 10 years cumulative observation, respectively, as opposed to 0 events among patients receiving Eculizumab prophylaxis. The time between Eculizumab doses was tailored based on classic complement pathway activity (target to < 30%). Using this strategy, 12 patients are currently receiving  Eculizumab every 28 days, 5 every 24-25 days, and 3 every 21 days. CONCLUSION: Our experience supports the prophylactic use of Eculizumab in patients with a previous history of aHUS undergoing KTx, especially when complement dysregulation is well documented by molecular biology.