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Background: Recurrence of focal segmental glomerulosclerosis (FSGS) or steroid-resistant nephrotic syndrome (SRNS) after kidney transplant leads to significant morbidity and potentially earlier allograft loss. To date however, reported rates, risk factors and treatment outcomes have varied widely. Methods: We applied computational phenotypes to a multicenter aggregation of electronic health records data from 7 large pediatric health systems in the USA, to identify recurrence rates, risk factors, and treatment outcomes. We refined the data collection by chart review. Results: From > 7 million patients, we compared children with primary FSGS/SRNS who received a kidney transplant between 2009 and 2020 and who either developed recurrence (n = 67/165; 40.6%) or did not (n = 98/165). Serum albumin level at time of transplant was significantly lower and recipient HLA DR7 presence was significantly higher in the recurrence group. By 36 months post-transplant, complete remission occurred in 58.2% and partial remission in 17.9%. Through 6 years post-transplant, no remission after recurrence was associated with an increased risk of allograft loss over time (p < 0.0001), but any remission showed similar allograft survival and function decline to those with no recurrence. Since treatments were used in non-random fashion, using spline curves and multivariable non-linear analyses, complete + partial remission chance was significantly higher with greater plasmapheresis sessions, CTLA4-Ig doses or LDL-apheresis sessions. Only treatment with anti-CD20, CTLA4-Ig agents, or LDL-apheresis sessions were associated with complete remission. Excluding 25 patients with mutations did not significantly change our results. Conclusions: Our contemporary high-risk cohort had higher favorable response rates than most prior reports, from combinations of agents. [ABSTRACT FROM AUTHOR]

We report the use of an autosomal-dominant polycystic kidney disease (ADPKD) donor kidney in a paediatric recipient. A 14-year-old boy on haemodialysis for 4 years following loss of a first kidney transplant, highly sensitised, and with limited vascular options for ongoing dialysis access, was offered a deceased brain death donor transplant from a mid-30s donor with known ADPKD but normal kidney function and negligible proteinuria. After extensive discussion with the patient and family, discussing all alternative options and review of available literature, the kidney was accepted and implanted. Graft function was immediate. An early post-transplant creatinine rise was attributed to possible antibody-mediated rejection, treated with plasmapheresis and rituximab. Ten months post-transplant, the patient remains dialysis-free with stable function. Extended criteria kidneys are already considered for highly sensitised or long-waiting dialysis patients. Though the literature is limited, kidneys from patients with ADPKD could be considered within extended criteria offers on a case-by-case basis. [ABSTRACT FROM AUTHOR]

The article focuses on investigating the potential protective role of breastfeeding (BF) in the clinical progression of hemolytic uremic syndrome (HUS) in children with Shiga toxin-producing Escherichia coli (STEC) infection. Topics include a comparison between breastfed and formula-fed groups, the evaluation of clinical outcomes such as the need for dialysis or blood transfusion, and the study's conclusion, which found no significant protective effect of breastfeeding on the course of HUS.

Background: Anti-GBM disease is a rare vasculitis mediated by pathogenic antibodies against collagen IV. Anti-GBM disease presents with rapid progressive glomerulonephritis and leads to kidney failure if untreated. KDIGO recommends plasma exchanges (PEX) for antibody elimination and steroids plus cyclophosphamide (CTX) to suppress antibody production. CTX is associated with severe side effects including gonadal toxicity. Rituximab (RTX) and mycophenolate mofetil (MMF) might be a less toxic but equally efficient alternative to CTX. Studies in pediatric anti-GBM disease patients receiving RTX and MMF instead of CTX are lacking.A retrospective survey in 8 tertiary German centers was performed. The clinical data of patients diagnosed between 2014 and 2022 were collected and analyzed.Five adolescent patients treated with PEX and RTX and/or MMF due to anti-GBM disease were analyzed. All patients had anti-GBM antibodies, hematuria, glomerular proteinuria, and pulmonary hemorrhage. eGFR was 124 ml/min/1.73 m2 (range 47–162), and all patients were non-dialysis-dependent but with relevant histological kidney affection (mean crescents on kidney biopsy 77%). Antibody clearance was achieved after 13 PEX cycles (range 6–31). Four out of 5 patients received methylprednisolone pulses. All patients received oral prednisolone and MMF, and four patients received a median of 4 RTX doses (range 2–4). After a mean follow-up of 27 months, 4/5 patients had conserved or improved kidney function, while one patient (20%) developed kidney failure.In this small series of pediatric non-dialysis-dependent anti-GBM disease patients, first-line treatment with RTX and MMF showed a favorable kidney outcome in 4/5 cases and had an acceptable side effect profile.A higher resolution version of the Graphical abstract is available as Supplementary informationA higher resolution version of the Graphical abstract is available as Supplementary informationMethods: Anti-GBM disease is a rare vasculitis mediated by pathogenic antibodies against collagen IV. Anti-GBM disease presents with rapid progressive glomerulonephritis and leads to kidney failure if untreated. KDIGO recommends plasma exchanges (PEX) for antibody elimination and steroids plus cyclophosphamide (CTX) to suppress antibody production. CTX is associated with severe side effects including gonadal toxicity. Rituximab (RTX) and mycophenolate mofetil (MMF) might be a less toxic but equally efficient alternative to CTX. Studies in pediatric anti-GBM disease patients receiving RTX and MMF instead of CTX are lacking.A retrospective survey in 8 tertiary German centers was performed. The clinical data of patients diagnosed between 2014 and 2022 were collected and analyzed.Five adolescent patients treated with PEX and RTX and/or MMF due to anti-GBM disease were analyzed. All patients had anti-GBM antibodies, hematuria, glomerular proteinuria, and pulmonary hemorrhage. eGFR was 124 ml/min/1.73 m2 (range 47–162), and all patients were non-dialysis-dependent but with relevant histological kidney affection (mean crescents on kidney biopsy 77%). Antibody clearance was achieved after 13 PEX cycles (range 6–31). Four out of 5 patients received methylprednisolone pulses. All patients received oral prednisolone and MMF, and four patients received a median of 4 RTX doses (range 2–4). After a mean follow-up of 27 months, 4/5 patients had conserved or improved kidney function, while one patient (20%) developed kidney failure.In this small series of pediatric non-dialysis-dependent anti-GBM disease patients, first-line treatment with RTX and MMF showed a favorable kidney outcome in 4/5 cases and had an acceptable side effect profile.A higher resolution version of the Graphical abstract is available as Supplementary informationA higher resolution version of the Graphical abstract is available as Supplementary informationResults: Anti-GBM disease is a rare vasculitis mediated by pathogenic antibodies against collagen IV. Anti-GBM disease presents with rapid progressive glomerulonephritis and leads to kidney failure if untreated. KDIGO recommends plasma exchanges (PEX) for antibody elimination and steroids plus cyclophosphamide (CTX) to suppress antibody production. CTX is associated with severe side effects including gonadal toxicity. Rituximab (RTX) and mycophenolate mofetil (MMF) might be a less toxic but equally efficient alternative to CTX. Studies in pediatric anti-GBM disease patients receiving RTX and MMF instead of CTX are lacking.A retrospective survey in 8 tertiary German centers was performed. The clinical data of patients diagnosed between 2014 and 2022 were collected and analyzed.Five adolescent patients treated with PEX and RTX and/or MMF due to anti-GBM disease were analyzed. All patients had anti-GBM antibodies, hematuria, glomerular proteinuria, and pulmonary hemorrhage. eGFR was 124 ml/min/1.73 m2 (range 47–162), and all patients were non-dialysis-dependent but with relevant histological kidney affection (mean crescents on kidney biopsy 77%). Antibody clearance was achieved after 13 PEX cycles (range 6–31). Four out of 5 patients received methylprednisolone pulses. All patients received oral prednisolone and MMF, and four patients received a median of 4 RTX doses (range 2–4). After a mean follow-up of 27 months, 4/5 patients had conserved or improved kidney function, while one patient (20%) developed kidney failure.In this small series of pediatric non-dialysis-dependent anti-GBM disease patients, first-line treatment with RTX and MMF showed a favorable kidney outcome in 4/5 cases and had an acceptable side effect profile.A higher resolution version of the Graphical abstract is available as Supplementary informationA higher resolution version of the Graphical abstract is available as Supplementary informationConclusions: Anti-GBM disease is a rare vasculitis mediated by pathogenic antibodies against collagen IV. Anti-GBM disease presents with rapid progressive glomerulonephritis and leads to kidney failure if untreated. KDIGO recommends plasma exchanges (PEX) for antibody elimination and steroids plus cyclophosphamide (CTX) to suppress antibody production. CTX is associated with severe side effects including gonadal toxicity. Rituximab (RTX) and mycophenolate mofetil (MMF) might be a less toxic but equally efficient alternative to CTX. Studies in pediatric anti-GBM disease patients receiving RTX and MMF instead of CTX are lacking.A retrospective survey in 8 tertiary German centers was performed. The clinical data of patients diagnosed between 2014 and 2022 were collected and analyzed.Five adolescent patients treated with PEX and RTX and/or MMF due to anti-GBM disease were analyzed. All patients had anti-GBM antibodies, hematuria, glomerular proteinuria, and pulmonary hemorrhage. eGFR was 124 ml/min/1.73 m2 (range 47–162), and all patients were non-dialysis-dependent but with relevant histological kidney affection (mean crescents on kidney biopsy 77%). Antibody clearance was achieved after 13 PEX cycles (range 6–31). Four out of 5 patients received methylprednisolone pulses. All patients received oral prednisolone and MMF, and four patients received a median of 4 RTX doses (range 2–4). After a mean follow-up of 27 months, 4/5 patients had conserved or improved kidney function, while one patient (20%) developed kidney failure.In this small series of pediatric non-dialysis-dependent anti-GBM disease patients, first-line treatment with RTX and MMF showed a favorable kidney outcome in 4/5 cases and had an acceptable side effect profile.A higher resolution version of the Graphical abstract is available as Supplementary informationA higher resolution version of the Graphical abstract is available as Supplementary informationGraphical abstract: Anti-GBM disease is a rare vasculitis mediated by pathogenic antibodies against collagen IV. Anti-GBM disease presents with rapid progressive glomerulonephritis and leads to kidney failure if untreated. KDIGO recommends plasma exchanges (PEX) for antibody elimination and steroids plus cyclophosphamide (CTX) to suppress antibody production. CTX is associated with severe side effects including gonadal toxicity. Rituximab (RTX) and mycophenolate mofetil (MMF) might be a less toxic but equally efficient alternative to CTX. Studies in pediatric anti-GBM disease patients receiving RTX and MMF instead of CTX are lacking.A retrospective survey in 8 tertiary German centers was performed. The clinical data of patients diagnosed between 2014 and 2022 were collected and analyzed.Five adolescent patients treated with PEX and RTX and/or MMF due to anti-GBM disease were analyzed. All patients had anti-GBM antibodies, hematuria, glomerular proteinuria, and pulmonary hemorrhage. eGFR was 124 ml/min/1.73 m2 (range 47–162), and all patients were non-dialysis-dependent but with relevant histological kidney affection (mean crescents on kidney biopsy 77%). Antibody clearance was achieved after 13 PEX cycles (range 6–31). Four out of 5 patients received methylprednisolone pulses. All patients received oral prednisolone and MMF, and four patients received a median of 4 RTX doses (range 2–4). After a mean follow-up of 27 months, 4/5 patients had conserved or improved kidney function, while one patient (20%) developed kidney failure.In this small series of pediatric non-dialysis-dependent anti-GBM disease patients, first-line treatment with RTX and MMF showed a favorable kidney outcome in 4/5 cases and had an acceptable side effect profile.A higher resolution version of the Graphical abstract is available as Supplementary informationA higher resolution version of the Graphical abstract is available as Supplementary information [ABSTRACT FROM AUTHOR]

The article presents answers to a clinical quiz published within the issue on the case of a previously healthy 8-year-old boy who was referred for further evaluation of macroscopic hematuria.

Background: Steroid-resistant nephrotic syndrome (SRNS), commonly caused by focal segmental glomerulosclerosis (FSGS), is associated with progression to stage 5 chronic kidney disease, requirement for kidney replacement therapy and a risk of disease recurrence post-kidney transplantation. Ofatumumab (OFA) is a fully humanised monoclonal antibody to CD20, with similar mechanisms of action to rituximab (RTX). Methods: We report a case series of seven UK patients (five paediatric, two adult), all of whom developed FSGS recurrence after kidney transplantation and received OFA as part of their therapeutic intervention. All also received concomitant plasmapheresis. The 2-year outcome of these seven patients is reported, describing clinical course, kidney function and proteinuria. Results: Four patients (all paediatric) achieved complete urinary remission with minimal proteinuria 12 months post-treatment. Three of those four also had normal graft function. Two patients showed partial remission—brief improvement to non-nephrotic proteinuria (197 mg/mmol) in one patient, maintained improvement in kidney function (estimated glomerular filtration rate 76 ml/min/1.73 m2) in the other. One patient did not demonstrate any response. Conclusions: OFA may represent a useful addition to therapeutic options in the management of FSGS recurrence post-transplantation, including where RTX has shown no benefit. Concomitant plasmapheresis in all patients prevents any definitive conclusion that OFA was the beneficial intervention. [ABSTRACT FROM AUTHOR]

Background: Genetic defects in podocyte proteins account for up to 30% of steroid-resistant nephrotic syndrome (SRNS) in the paediatric population. Most children with genetic SRNS are resistant to immunosuppression and at high risk of progression to stage 5 chronic kidney disease. Kidney transplantation is often the treatment of choice. The possibility of post-transplantation disease recurrence in genetic SRNS remains controversial, and poses fundamental questions about disease biology. Methods: We critically evaluated the published cases of post-transplantation recurrence in genetic patients, particularly testing 'mutations' against the most recent population variant databases, in order to clarify the diagnoses, and compare the clinical courses and responses to therapy. Results: Biallelic pathogenic variants in NPHS1 leading to a complete absence of nephrin were the most commonly reported and best understood instance of nephrotic syndrome occurring post-transplantation. This is an immune-mediated process driven by antibody production against the novel nephrin protein in the allograft. We also identified a number of plausible reported cases of post-transplantation recurrence involving pathogenic variants in NPHS2 (8 patients, biallelic), one in WT1 (monoallelic) and one in NUP93 (biallelic). However, the mechanism for recurrence in these cases remains unclear. Other instances of recurrence in genetic disease were difficult to interpret due to differing clinical criteria, inclusion of patients without true pathogenic variants or the influence of other factors on renal outcome. Conclusions: Overall, post-transplantation recurrence remains very rare in patients with genetic SRNS. It appears to occur later after transplantation than in other patients and usually responds well to plasmapheresis with a good renal outcome. [ABSTRACT FROM AUTHOR]

Background: The objectives of the study are to describe tandem therapeutic plasma exchange (TPE) and continuous kidney replacement therapy (CKRT) patients' outcomes in a large institution. Methods: We reviewed pediatric patients receiving tandem TPE and CKRT from 2013 to 2016. Over the study period, 63 discrete patients received tandem TPE and CKRT for a total of 378 TPE procedures on 1676 days on CKRT. Results: Patient age ranged from newborn to 19 years old with weights ranging from 2.31 to 112.3 kg (17 patients were < 10 kg and less than 1 year old). All procedures were completed in intensive care units (ICU) as CKRT can only be done in this environment. All treatments completed successfully; majority of patients (90%) developed hypocalcemia though none were symptomatic. Case mortality rate was 40%. Disease severity scores at ICU admission were higher and time to TPE and CKRT start was longer in the deceased group. Conclusions: As a conclusion, though complications including hypocalcemia are common with tandem TPE and CKRT in pediatrics, patients remained asymptomatic. Such treatments have to be carefully planned with interdisciplinary teams to address indications, technicalities, and complications. [ABSTRACT FROM AUTHOR]

Background: Approximately 20% of antibody-mediated rejection (ABMR) episodes in the absence of donor-specific antibodies against human leucocyte antigens (HLA-DSA) in pediatric and adult kidney transplant recipients are associated with, and presumably caused by, antibodies against the angiotensin type 1 receptor (AT1R-Ab). While the role of AT1R-Ab for ABMR and graft failure is increasingly recognized, there is little information available on the management of these patients for re-transplantation over the barrier of persisting AT1R-Ab. Case: We report on a male patient with kidney failure in infancy due to obstructive uropathy who had lost his first kidney transplant due to AT1R-Ab-mediated chronic ABMR. Because this antibody persisted during 4 years of hemodialysis, for the 2nd kidney transplantation (living-related transplantation from his mother), he underwent a desensitization regimen consisting of 15 plasmapheresis sessions, infusions of intravenous immunoglobulin G and thymoglobulin, as well as pharmacological blockade of the Angiotensin II (AT II) pathway by candesartan. This intense desensitization regimen transiently decreased elevated AT1R-Ab titers, resulting in stable short-term kidney allograft function. The subsequent clinical course, however, was complicated by acute cellular rejection and chronic ABMR due to persistent AT1R-Ab and de novo HLA-DSA, which shortened allograft survival to a period of only 4 years. Conclusion: This case highlights the difficulty of persistently decreasing elevated AT1R-Ab titers by a desensitization regimen for re-transplantation and the detrimental effect of the interplay between AT1R-Ab and HLA-DSA on kidney transplant survival. [ABSTRACT FROM AUTHOR]

Background: Therapeutic plasma exchange (TPE) is used in kidney diseases as an adjunct treatment. Little has been described as to its effectiveness in kidney disorders in children. This study aimed to assess the safety, efficacy, and outcomes of patients who underwent TPE for kidney indications. Methods: Retrospective chart review of patients receiving TPE from 2010 to 2018 for kidney indications, such as antibody-mediated rejection, bone marrow transplant–associated thrombotic microangiopathy (TA-TMA), atypical hemolytic uremic syndrome, transplant recurrence of focal segmental glomerulosclerosis, and glomerulonephritis. Outcomes assessed were trends in kidney function, mortality, and progression to stage 5 chronic kidney disease (CKD 5). Significant hypocalcemia was defined as ionized calcium < 1 mmol/L. Results: A total of 641 TPE procedures were performed on 47 patients (25 male). Average age was 12.8 ± 5.9 years. Median glomerular filtration rate (GFR) improved from baseline to end of TPE treatments (pre 44.9 (19.8, 79), end 56.1 (23, 98) [p = 0.02]). Ten out of 47 children developed CKD 5. Seven out of 47 patients died; 5 had TA-TMA. Initial 7 consecutive sessions were reviewed for complications. Among 335 procedures, 41 episodes of significant hypocalcemia were noted (12.2%); only 1 was symptomatic. Of the 26 episodes (7.7%) of allergic reactions, all were associated with the use of FFP; 5 were anaphylactic. No TPE-associated mortality was noted. Conclusions: TPE is a relatively well-tolerated useful adjunct therapy in children with kidney indications. The benefit of TPE has to be balanced with risks such as hypocalcemia and allergic reactions which can occur more frequently with FFP. [ABSTRACT FROM AUTHOR]

Background: Acute kidney injury (AKI) is a common complication of critically ill adult patients with COVID-19. However, currently, no studies investigate kidney impairment in children with COVID-19. We investigated incidence and treatment of AKI in pediatric patients with COVID-19 in Wuhan Children's Hospital during the early stages of the COVID-19 pandemic and discuss possible mechanisms of AKI related to SARS-CoV-2 infection. Methods: By extracting data from electronic medical records, we conducted a retrospective observational study of kidney involvement in confirmed pediatric COVID-19 cases in Wuhan Children's Hospital during the coronavirus outbreak, from January 24 to March 20, 2020. Clinical presentations, clinical courses, laboratory findings, and medical interventions are described below. Results: Among 238 confirmed COVID-19 cases, only three were critically ill and needed intensive care unit (ICU) admission. All three developed AKI, but AKI was not detected in any non-critically ill patients outside the ICU. Two of the three patients with AKI had prodromal gastrointestinal symptoms. Significantly elevated interleukin-6 (IL-6) levels and complement activation were observed in these patients with AKI. The three patients with AKI were treated with plasma exchange (PE) and continuous kidney replacement therapy (CKRT), resulting in one complete recovery, one partial recovery, and one mortality due to critical illness. Conclusions: Critically ill children with COVID-19 may develop AKI, especially following prodromal gastrointestinal symptoms. An inflammatory storm and complement-mediated injury may underlie AKI development in children with COVID-19. Our study supports implantation of PE and CKRT in management of critically ill patients with AKI. [ABSTRACT FROM AUTHOR]

The purpose of this review is to describe Streptococcus pneumoniae–associated hemolytic uremic syndrome (P-HUS) with emphasis on new insights into the pathophysiology and management over the past 10 years. Even though awareness of this clinico-pathological entity has increased, it likely remains under-recognized. Recent observations indicate that although neuraminidase activity and exposure of the T-antigen are necessary for development of P-HUS, they are not sufficient; activation of the alternate pathway of complement may also contribute. It is unclear, however, whether or not eculizumab and/or plasmapheresis are of value. [ABSTRACT FROM AUTHOR]

Background: Transplantation is the preferred modality for renal replacement therapy in children. With increasing rates of re-transplantation within the paediatric population, there are more sensitised children on waiting lists. One issue with developing strategies to treat these children is the number of different definitions of sensitisation. and we would therefore recommend an immunological risk stratification approach.Methods: We discuss methods of sensitisation prevention, assessment and management, including paired exchange programmes and desensitisation protocols.Results: There are limited published evidence-based data for desensitisation in adults and none in children; thus, we present information on the available therapies currently in use.Discussion: Further research is required to investigate strategies which prevent sensitisation in children, including the healthcare utility of incorporating epitope-based matching into organ allocation algorithms. Controlled studies are also needed to establish the most appropriate desensitisation regimen(s). [ABSTRACT FROM AUTHOR]

Background: Data on renal allograft outcome in sensitized children are scarce. We report the clinical courses of four children who received desensitization therapy prior to renal transplantation in our institution. Methods: Between 2009 and 2011, four pediatric patients with stage 5 chronic kidney disease received desensitization therapy due to: (1) positive donor-specific antibodies (DSA) and/or crossmatches with potential living donors, (2) more than three positive crossmatches with deceased donors or (3) high calculated panel-reactive antibody of >80 %. Desensitization with rituximab, intravenous immunoglobulin and bortezomib was performed in all patients. Induction therapy included combinations of plasmapheresis and/or alemtuzumab or anti-thymocyte globulin. Standard post-transplant medications included tacrolimus, mycophenolate mofetil and prednisolone. Results: Post-transplant screening revealed DSA in three patients. Biopsy showed no evidence of rejection at 1 month in two patients, one of whom developed chronic active antibody-mediated rejection 4.5 years later. One patient developed borderline acute cellular rejection at 1 month, but the serum creatinine level was stable and DSA disappeared without treatment 1 month later, with stable long-term allograft function at 3 years. Estimated or measured glomerular filtration rate of the patients ranged between 30 and 75 ml/min/1.73 m after 1 to 4.5 years. Conclusions: The four sensitized patients reported here who received desensitization therapy had successful renal transplants with a low risk of immediate post-transplant rejection. Overall, long-term allograft functions and complications from immunosuppression were encouraging. [ABSTRACT FROM AUTHOR]

Plasma exchange, or plasmapheresis, is a treatment method that developed over a period of two decades and involves the removal and replacement of a patient's circulating plasma. The aim of treatment is to remove disease-associated molecules and therefore interrupt disease progression. This article summarizes the developmental history of this treatment and then looks in more detail at data on the use of plasma exchange in treating antineutrophil antibody (ANCA)-associated vasculitis. The eight randomized trials and the Cochrane Systematic Review on treating renal vasculitis are summarized to show that plasma exchange may be effective in this disease, specifically in reducing the development of end-stage kidney disease (ESKD) by approximately 40 %. The plasma exchange and glucocorticoid dosing in the treatment of anti-neutrophil cytoplasm antibody associated vasculitis (PEXIVAS) study is a currently enrolling study aiming to answer some of the outstanding questions relating to the use of this treatment in ANCA-associated vasculitis. [ABSTRACT FROM AUTHOR]

Focal segmental glomerulosclerosis (FSGS) is an important cause of glomerular disease in children and adolescents and nearly 50 % of affected patients will progress to end-stage kidney disease over a 5 to 10-year period. Unfortunately, there is no established treatment for disease in the native kidney. Moreover, up to 55 % of patients develop recurrent disease after receiving a kidney transplant, with a substantially higher risk in patients who have already experienced recurrent disease in a prior transplant. A number of clinical and laboratory factors have been identified as risk factors for this complication. In addition, new investigations into podocyte biology and circulating permeability factors have shed light on the cause of recurrent the disease. While a number of novel therapeutic agents have been applied in the management of this problem, there still is no proven treatment. In this review, we summarize recent advances in the epidemiology, pathophysiology, and treatment of recurrent FSGS in pediatric patients who have received a kidney transplant. [ABSTRACT FROM AUTHOR]

Background: Atypical hemolytic uremic syndrome (aHUS) is a form of thrombotic microangiopathy characterized by uncontrolled activation of the alternative complement pathway with consecutive generation of the terminal complement complex. Mortality is increased, particularly in the first year of the disease. Therapeutic options include plasma therapy and terminal complement blockade using the anti-C5 monoclonal antibody eculizumab. Eculizumab prevents activation of the terminal sequence of the complement cascade and formation of the potentially lytic terminal complement complex (C5b-9). Case-diagnosis/treatment: We report a 3-year-old boy with aHUS due to a novel heterozygous truncating complement Factor H mutation in combination with other changes known to be associated with an increased risk for aHUS. Despite eculizumab treatment and maximal suppression of the classical and alternative complement pathways, C3d and sC5b-9 remained consistently elevated and the patient showed repeated relapses. Conclusions: Not every patient with aHUS and uncontrolled complement activation shows optimal therapeutic response to eculizumab with the recommended or even increased dosing regimen. Reliable outcome measures to determine the efficacy of treatment have to be defined. [ABSTRACT FROM AUTHOR]

Background: Kidney transplantation is the treatment of choice for end-stage renal disease. However, since pediatric patients have long projected life-years, it is also optimal for them to get well-matched transplants to minimize long-term sensitization. In North America, pediatric kidney transplantation is largely dependent upon the use of deceased donor organs, making it challenging to identify timely, well-matched transplants. Pediatric recipients may have willing living donors who are either HLA- or ABO-incompatible (ABOi); therefore, one solution is to utilize ABOi transplants and paired exchange programs to enhance HLA matching and living donation. Case-diagnosis/treatment: We adopted this approach for a highly sensitized patient with cPRA 90 %, who received a successful ABOi paired exchange transplant. The recipient received pre-transplant immunomodulation until an acceptable isohemagglutinin titer <1:8 was reached before transplantation. The patient was induced with anti-thymocyte globulin and maintained on steroid-based triple immunosuppression. Eighteen-month allograft function is excellent with an estimated glomerular filtration rate (eGFR) of 83.53 ml/min/1.73 m. The patient did not develop de novo donor-specific HLA antibodies or have any episodes of acute rejection Conclusions: This case highlights the safety and efficacy of using paired exchange in combination with ABOi transplants in pediatric kidney transplantation to optimize HLA matching, minimize wait times, and enhance allograft survival. [ABSTRACT FROM AUTHOR]

Acute antibody-mediated rejection is a diagnostic challenge in renal transplantation medicine. However, it is an important diagnosis to make, since chronic antibody-mediated rejection (CAMR) is the main cause of long-term graft loss. Antibody-mediated rejection is diagnosed by detecting donor-specific antibodies (DSAs) in the blood in combination with observing typical histomorphological signs in kidney biopsy, as described in the Banff classification. Therapy is based on the removal of DSAs by administering intravenous immunoglobulins (IVIGs), plasmapheresis, or immunoadsorption. Reoccurrence of antibodies is diminished by the use of rituximab, increased immunosuppression, and in some cases additional experimental substances. A combination of these techniques has been shown to be successful in the majority of cases of acute and chronic antibody-mediated rejection. Routine DSA monitoring is warranted for early detection of antibody-mediated rejection. [ABSTRACT FROM AUTHOR]

Background: Minimal Change Disease (MCD) in relapse is associated with increased podocyte CD80 expression and elevated urinary CD80 excretion, whereas focal segmental glomerulosclerosis (FSGS) has mild or absent CD80 podocyte expression and normal urinary CD80 excretion. Methods: One patient with MCD, one patient with primary FSGS and three patients with recurrent FSGS after transplantation received CD80 blocking antibodies (abatacept or belatacept). Urinary CD80 and CTLA-4 levels were measured by ELISA. Glomeruli were stained for CD80. Results: After abatacept therapy, urinary CD80 became undetectable with a concomitant transient resolution of proteinuria in the MCD patient. In contrast, proteinuria remained unchanged after abatacept or belatacept therapy in the one patient with primary FSGS and in two of the three patients with recurrent FSGS despite the presence of mild CD80 glomerular expression but normal urinary CD80 excretion. The third patient with recurrent FSGS after transplantation had elevated urinary CD80 excretion immediately after surgery which fell spontaneously before the initiation of abatacept therapy; after abatacept therapy, his proteinuria remained unchanged for 5 days despite normal urinary CD80 excretion. Conclusion: These observations are consistent with a role of podocyte CD80 in the development of proteinuria in MCD. In contrast, CD80 may not play a role in recurrent FSGS since the urinary CD80 of our three patients with recurrent FSGS was only increased transiently after surgery and normalization of urinary CD80 did not result in resolution of proteinuria. [ABSTRACT FROM AUTHOR]

Background: Treatment of systemic lupus erythematosus (SLE) with severe diffuse proliferative nephritis is often challenging, particularly in small children in whom a genetic conditioning is likely to play a role. The effectiveness of standard therapy based on glucocorticoid and immunosuppressive drugs is often unsatisfactory. Case: A 4 year-old girl, whose parents were first-grade cousins of Moroccan ancestry, developed SLE that progressed to severe renal involvement despite standard therapy. She had persistently undetectable serum C4 levels and very low C3 levels (<30 mg/dl), and extremely high anti-DNA titers (>1:640) that remained unmodified during 2 years of follow-up. No mutations of genes encoding for complement inhibitors were detected. Despite aggressive therapy based on prednisone, plasma exchanges, and cyclosporine, the child worsened and eventually developed features of atypical hemolytic uremic syndrome (aHUS). Treatment with eculizumab provided prompt remission of vasculitis, proteinuria, and hematuria, with normalization of renal function. Two attempts to withdraw eculizumab were followed by severe relapses and rescued by reinstating treatment. The child has been treated with eculizumab for > 17 months without relevant side effects. Conclusion: C5 inhibition by eculizumab completely reversed clinical symptoms and laboratory renal signs of severe lupus nephritis. Blocking complement-system activation with the use of targeted drugs may be a new and exciting strategy to treat SLE patients unresponsive to conventional therapy. [ABSTRACT FROM AUTHOR]

The combination of hemodialysis and plasma exchange as one tandem procedure was first described in 1999 by Siami et al. (ASAIO J 45:229-233), but larger pediatric case series were not described until 2012. Even in adults, there are only limited case series. If performed in sequence, up to 8 h of treatment time may be required. With the use of the tandem procedure in stable patients, the same procedures can be completed during the same time as a routine hemodialysis, which is more convenient for patients and may reduce healthcare costs. Little is known about the utilization of the combination of hemodialysis and plasma exchange in children. The purpose of this review is to summarize the adult and scarce pediatric experience. The results of a survey carried out by the authors using the Internet listserver 'PedNeph' to obtain an overview of the current practice patterns of pediatric nephrologists are also presented. [ABSTRACT FROM AUTHOR]

Background: In 2009, the European Paediatric Study Group for Haemolytic Uraemic Syndrome (HUS) published a clinical practice guideline for the investigation and initial therapy of diarrhea-negative HUS (now more widely referred to as atypical HUS, aHUS). The therapeutic component of the guideline (comprising early, high-volume plasmapheresis) was derived from anecdotal evidence and expert consensus, and the authors committed to auditing outcome. Methods: Questionnaires were distributed to pediatric nephrologists across Europe, North America, and the Middle East, who were asked to complete one questionnaire per patient episode of aHUS between July 1, 2009 and December 31, 2010. Comprehensive, anonymous demographic and clinical data were collected. Results: Seventy-one children were reported with an episode of aHUS during the audit period. Six cases occurred on a background of influenza A H1N1 infection. Of 71 patients, 59 (83 %) received plasma therapy within the first 33 days, of whom ten received plasma infusion only. Complications of central venous catheters occurred in 16 out of 51 patients with a catheter in-situ (31 %). Median time to enter hematological remission was 11.5 days, and eight of 71 (11 %) patients did not enter hematological remission by day 33. Twelve patients (17 %) remained dialysis dependent at day 33. Conclusions: This audit provides a snapshot of the early outcome of a group of children with aHUS in the months prior to more widespread use of eculizumab. [ABSTRACT FROM AUTHOR]

Background: Atypical hemolytic uremic syndrome (aHUS) is a form of thrombotic microangiopathy (TMA) caused by dysregulation of the complement system. Outcomes of kidney transplantation are poor owing to aHUS recurrence and loss of graft. Patients carrying CFH mutations or CFH/CFHR1 hybrid genes present a very high risk of recurrence despite preventive plasmapheresis. Evaluation of recent data suggests that prophylactic eculizumab pretransplant might be the preferred therapy if available. Case-diagnosis/treatment: We report 3-year follow-up data in a 9-year-old boy with aHUS and successful renal transplant treated with prophylactic eculizumab without recurrence. He presented with aHUS at age 3, irreversible renal failure and uncontrolled severe hypertension with concentric left ventricular hypertrophy, recurrent acute pulmonary edema, and congestive heart failure despite five hypotensive agents and bilateral nephrectomy. Complement analysis demonstrated the presence of a CFH/CFHR1 hybrid gene inherited from his mother and a SNP risk CFH haplotype inherited from his father. Kidney transplant was performed with prophylactic eculizumab and subsequent fortnightly administration. Three years post-transplant, graft function remains stable (serum creatinine 0.9 mg/dl), hypertension is controlled, no left ventricular hypertrophy, no opportunistic infections, and negative clinical chemistry parameters for hemolysis. Conclusion: Eculizumab is a safe and effective therapy for preventing TMA recurrence and provides long-term graft function in aHUS with the CFH/CFHR1 hybrid gene. [ABSTRACT FROM AUTHOR]

Background: Focal segmental glomerulosclerosis (FSGS) recurs in 20-40 % of allografts. Plasmapheresis (TPE) has been one of the mainstays of treatment with variable results. Rituximab (RTX), a monoclonal antibody to the protein CD20, is being used for treatment of recurrent FSGS (recFSGS) but pediatric experience is limited. Methods: We conducted a retrospective review of eight patients with recFSGS, treated with RTX (1-4 doses) after having minimal response to TPE. Complete response was defined as a decrease in urine protein creatinine ratio (Up/c) to less than 0.2 and partial response was a decrease in Up/c ratio by 50 % of baseline and in the sub-nephrotic range (U p/c <2). Results: Complete response was seen in two of eight patients, and partial response was seen in four of eight patients. Two patients had no response. At last follow-up, all the partial responders had sub-nephrotic range proteinuria (Up/c ratios ranging from 0.29 to 1.6). Delayed response, up to 9 months post-RTX, was also seen in some of the patients. Significant complications such as rituximab-associated lung injury (RALI), acute tubular necrosis, and central nervous system(CNS) malignancy were also observed in our case series. Conclusions: Rituximab can be used with caution as a treatment for recFSGS. Efficacy is variable from none to complete response. Even partial reduction in proteinuria is of benefit in prolonging the life of the allograft. Long-term, multicenter studies are needed to prove its sustained efficacy in those who respond and to monitor for serious adverse effects. [ABSTRACT FROM AUTHOR]

The MYH9 gene encodes a non-muscle myosin IIA heavy chain (NMMHC-IIA) expressed in podocytes. Heterozygous MYH9 mutations cause a set of overlapping syndromes characterized by variable degrees of deafness, morphologic abnormalities of platelets and focal segmental glomerulosclerosis (FSGS) with progressive renal dysfunction. Similar glomerular lesions are seen in a variety of nephropathies, including an idiopathic form of FSGS in children which recurs in renal allografts, implying a circulating factor that affects glomerular podocyte biology. It is unknown whether NMMHC-IIA is perturbed in the idiopathic form of FSGS. We describe a pediatric patient with typical idiopathic FSGS, in whom proteinuria recurred within hours of deceased donor renal transplantation but who responded to plasmapheresis. We demonstrate in vitro that plasmapheresis effluent from our patient rapidly decreased cultured podocyte levels of the phosphorylated myosin light chain (MLC) that mediates NMMHC-IIA binding to actin and induced dispersion of NMMHC-IIA from its usual position along actin stress fibers. FSGS plasma also caused dispersion of slit diaphragm proteins (nephrin and podocin) and vinculin-positive focal adhesion complexes. Our observations suggest that the putative circulating factor in idiopathic FSGS disrupts normal NMMHC-IIA function in podocytes and might contribute to the pathogenesis of recurrent FSGS in other children. [ABSTRACT FROM AUTHOR]

ute antibody-mediated rejections (aAMR) after renal transplantation are defined by rapidly deteriorating graft function, detection of donor-specific antibodies (DSA) and characteristic histological features. In adults, anti-rejection strategies comprise intravenous immunoglobulin (IVIG), steroid pulses, plasmapheresis and rituximab. Data of children with aAMR are scarce. We report four episodes of aAMR in three children (aged 10, 10 and 11 years respectively) occurring early after renal transplantation. Pre-transplant complement-dependent cytotoxicity crossmatches were negative; in the case of re-transplantation repeated antigens were excluded. Basic immunosuppression comprised cyclosporine A, MMF and steroids. All four rejection episodes were histologically proven and associated with acute renal failure. De novo DSAs were detected in two aAMRs; one patient was additionally tested positive for AT1-receptor antibodies. All aAMRs were treated with steroid pulses, tacrolimus, MMF, IVIG, plasmapheresis and one single dose of rituximab. Despite therapy one graft was lost; in the remaining three cases kidney function re-established within 1-8 weeks. At follow-up, 14, 15 and 22 months' post-rejection their GFRs were 65, 88 and 105 ml/min/1.73 m respectively. A combined therapy of steroid pulses, IVIG, plasmapheresis and rituximab is potentially effective in the treatment of aAMR in children. [ABSTRACT FROM AUTHOR]

15-year-old male patient developed atypical hemolytic uremic syndrome (aHUS) at 16 months of age leading to end-stage renal disease. The family history was suggestive of autosomal dominant aHUS, and he was more recently found to have a C3 heterozygous gene mutation ( 1835C>T mutation in exon 14, which determines the amino-acidic substitution R570W) with no other complement abnormalities. He had two renal transplants, the first at 2.5 years, and the second at 8 years of age, but allograft dysfunction developed in both transplants leading to graft failure due to recurrent HUS at 5 years and 18 months post-transplantation respectively. At 15 years of age he received a third transplant from a deceased donor with pre-emptive plasmapheresis. He had immediate graft function and nadir serum creatinine was 1.3-1.4 mg/dl. Severe allograft dysfunction and hypertension developed 2 months after transplantation following influenza infection. Renal allograft biopsy showed thrombotic microangiopathy. He received plasmapheresis followed by eculizumab therapy. Allograft function returned to baseline 3 weeks after starting therapy, and post-treatment allograft biopsies showed improvement in thrombotic microangiopathy. He continues to receive eculizumab every 2 weeks with stable graft function 13 months after transplantation. [ABSTRACT FROM AUTHOR]

Regional citrate anticoagulation (RCA) has been considered to be a standard component of pediatric apheresis therapy for more than a decade. However, data on dosing recommendations and evaluations of the effectiveness and safety of anticoagulation are rarely found in published reports. The aim of this retrospective analysis was to present our single-center experience with RCA in pediatric apheresis therapy with the aim of developing an operating procedure. Five children aged 7-14 years underwent a total of 72 (range 3-44) therapeutic apheresis sessions with RCA in the form of immunoadsorption therapy (2 patients), low-density lipoprotein (LDL)-apheresis (1 patient), and plasmapheresis (two patients). A 3% citrate solution was used. Citrate flow was started at 4.0% of the blood flow velocity and was adapted to match post-filter ionized calcium levels ≤0.30 mmol/l. Once the patient's ionized calcium fell to <1.05 mmol/l, an intravenous 10% calcium gluconate solution was administered. Twenty pediatric apheresis patients who received standard heparinization, matched for age, body surface area, processed plasma volume, and blood flow velocity, were enrolled in the study as a comparison group. No side effects were experienced in 72 apheresis session. The 3% citrate solution had to be reduced gradually during the apheresis session and was infused at a mean of 2.8-3.8% of the blood flow rate. Serum bicarbonate levels before and after the apheresis session with RCA [23.9 (range 18.9-30.1) vs. 26.3 (20.2-33.0) mmol/l, respectively] were significantly different ( p = 0.013). All patients required intravenous calcium substitution to maintain serum calcium levels within the physiological range. Due to the administration of the 3% citrate solution and calcium, all patients significantly gained weight during the procedure, with a median weight gain of 2.5% ( p < 0.001). The extra fluid load caused problems in patients with kidney failure. Our regimen with RCA is safe, feasible, and effective in pediatric therapeutic apheresis therapy. For RCA in apheresis, we recommend (1) a citrate (3%) flow of 3.3% of the blood flow, (2) prophylactic intravenous calcium substitution from the beginning, and (3) a more highly concentrated citrate solution in the case of oliguric patients. [ABSTRACT FROM AUTHOR]

ntibody-mediated rejection (AMR) is a unique, significant, and often severe form of allograft rejection that is not amenable to treatment with standard immunosuppressive medications. Significant advances have occurred in our ability to predict patients at risk for, and to diagnose, AMR. These advances include the development of newer anti-human leukocyte antigen (HLA)-antibody detection techniques and assays for non-HLA antibodies associated with AMR. The pathophysiology of AMR suggests a prime role for antibodies, B cells and plasma cells, but other effector molecules, especially the complement system, point to potential targets that could modify the AMR process. An emerging and potentially larger problem is the development of chronic AMR (CAMR) resulting from de novo donor-specific anti-HLA antibodies (DSA) that emerge more than 100 days posttransplantation. Therapeutic options include: (1) High-dose intravenously administered immunoglobulin (IVIG), which has many potential benefits. (2) The use of IVIG + rituximab (anti-CD20, anti-B cell). (3) The combination of plasmapheresis (PP) + low-dose IVIG with or without rituximab. Data support the efficacy of all of the above approaches. Newer approaches to treating AMR include using the proteosome inhibitor (bortezomib), which induces apoptosis in plasma cells, and eculizumab (anti-C5, anticomplement monoclonal antibody). [ABSTRACT FROM AUTHOR]

Mycoplasma pneumoniae-associated nephritis has been reported in children with various pathological findings. It nevertheless remains an uncommon disease and, within this clinical context, endo-and extracapillary glomerulonephritis in a child has never been described. We report here a case of a 3-year-old girl diagnosed with severe crescentic glomerulonephritis associated with M. pneumoniae infection who presented with nephrotic syndrome and impaired renal function. The serum C3 complement level was initially low but returned to normal after 1 month. Two courses of three methylprednisolone pulses were administered in association with plasmapheresis and, secondarily, mycophenolate mophetil. This treatment regimen led to disease remission and a favorable renal outcome at the 6-month follow-up. However, the treatment guidelines in this situation remain debatable. [ABSTRACT FROM AUTHOR]

Recurrence of focal segmental glomerulosclerosis (FSGS) after renal transplantation can limit graft survival. Despite new immunosuppressive agents, the incidence of recurrence remains relatively high. To identify risk factors for recurrence and efficacy of treatment, we reviewed the outcome of 23 grafts in 16 children with FSGS who had undergone transplantation between 1985 and 2007 at La Paz Children’s Hospital. Recurrence was 56.3% after the first transplantation. We did not find significant differences in age at diagnosis, age at transplantation, age at end-stage renal disease (ESRD), progression to ESRD, bilateral nephrectomy of native kidneys prior to transplantation, use of induction therapy or of different immunosuppressive regimens between patients with and without recurrence. Plasmapheresis (PP) was carried out in seven of nine patients who had suffered recurrence, achieving remission in six of them. One patient received high doses of cyclosporin (CsA) and plasmapheresis, attaining remission. Graft survival was lower ( P = 0.043) in patients with FSGS than in those with other ESRD etiologies (first year 75% vs 91%; fifth year 44% vs 78%). Recurrence of FSGS limited graft survival (first year 66% vs 85%; third year 20% vs 68%) ( P = 0.07). In our experience, PP can be effective in treating FSGS recurrence, although its effect on long-term graft survival seems more limited. [ABSTRACT FROM AUTHOR]

The article discusses an atypical case of acute kidney injury. Topics discussed include Hemolytic uremic syndrome (HUS) as an acute kidney injury associated with irreversible renal and central nervous system (CNS) complications, HUS caused by regulation, of defective complement alternative pathway (CAP) and investigating Coombs test and low C3 complement level as diagnostic criteria for HUS.

Thrombotic thrombocytopenic purpura (TTP) is a rare disease among pediatric patients, in whom it may be mistaken for hemolytic uremic syndrome (HUS) and idiopathic thrombocytopenic purpura (ITP). Familial forms are caused by mutations in the ADAMTS13 gene, whereas acquired forms may result from an inhibitory antibody directed against ADAMTS13, a metalloprotease that cleaves very large multimers of Von Willebrand factor (VWF), thereby preventing platelet aggregation in blood vessels. We report two cases of TTP. The first was a 15-year-old girl with her first episode of TTP that failed to respond after 10 days of plasmapheresis and was treated with rituximab; she has remained in remission at 12 months of follow-up. The second was a 6-year-old boy with acquired relapsing TTP previously managed with plasmapheresis and prednisolone, who presented with a third relapse that was treated with plasmapheresis and rituximab; he remains in remission 17 months after treatment. Rituximab has been used by pediatricians for treating B cell malignancy, autoimmune diseases and antibody-mediated diseases, such as the Factor VIII inhibitors in hemophilia A, and may also have a promising role in children with acute refractory or chronic relapsing TTP. [ABSTRACT FROM AUTHOR]

Fibrillary glomerulonephritis (FGN) is a rare immune-mediated glomerulopathy characterized by randomly arranged immunoglobulin (Ig) deposits on electron microscopy. Only seven pediatric cases have been reported, and the incidence in adults is about 1.5%. A 12-year-old boy presented with systemic lupus erythematosus (SLE) with World Health Organization Class IV lupus nephritis. A repeat biopsy carried out due to a poor response to standard immunosuppressive therapy and worsening renal functions revealed diffuse proliferative glomerulonephritis with fibrillary deposits. Despite aggressive immunosuppression with plasmapheresis and rituximab, the patient developed end stage renal disease. This is an atypical pediatric case characterized by SLE-associated FGN and a poor prognosis. [ABSTRACT FROM AUTHOR]

This guideline for the investigation and initial treatment of atypical hemolytic uremic syndrome (HUS) is intended to offer an approach based on opinion, as evidence is lacking. It builds on the current ability to identify the etiology of specific diagnostic sub-groups of HUS. HUS in children is mostly due to infection, enterohemorrhagic Escherichia coli (EHEC), Shigella dysenteriae type 1 in some geographic regions, and invasive Streptococcus pneumoniae. These sub-groups are relatively straightforward to diagnose. Their management, which is outside the remit of this guideline, is related to control of infection where that is necessary and supportive measures for the anemia and acute renal failure. A thorough investigation of the remainder of childhood HUS cases, commonly referred to as “atypical” HUS, will reveal a risk factor for the syndrome in approximately 60% of cases. Disorders of complement regulation are, numerically, the most important. The outcome for children with atypical HUS is poor, and, because of the rarity of these disorders, clinical experience is scanty. Some cases of complement dysfunction appear to respond to plasma therapy. The therapeutic part of this guideline is the consensus of the contributing authors and is based on limited information from uncontrolled studies. The guideline proposes urgent and empirical plasmapheresis replacement with whole plasma fraction for the first month after diagnosis. This should only be undertaken in specialized pediatric nephrology centers where appropriate medical and nursing skills are available. The guideline includes defined terminology and audit points so that the early clinical effectiveness of the strategy can be evaluated. [ABSTRACT FROM AUTHOR]

We present the cases of two children with steroid-resistant nephrotic syndrome (SRNS) who were treated with rituximab (anti-CD20 monoclonal antibody). Both were resistant to conventional therapy, and renal biopsy showed focal segmental glomerulosclerosis (FSGS). Combination therapy with methylprednisolone pulse therapy and plasmapheresis was the only way to decrease proteinuria. However, the patients suffered severe reactions to steroid treatment. We therefore treated them with rituximab in a single dose of 375 mg/m2, which resulted in the rapid clearing of circulating CD19-positive B cells. One month after rituximab treatment, both achieved partial remission; one patient has maintained complete remission for 8 months, and the other relapsed 8 months after the first rituximab treatment with the recovery of peripheral B-cell counts and received a second rituximab treatment. She achieved complete remission 5 months after the second course and has maintained the remission for 2 months. We conclude that rituximab may be an effective treatment for refractory SRNS with FSGS. [ABSTRACT FROM AUTHOR]

Crescentic glomerulonephritis (CsGN) is an uncommon entity in children. This prospective study was conducted to evaluate the aetiology, clinical spectrum and outcome in children with crescentic glomerulonephritis. The single-centre prospective study comprised of 22 children with biopsy proven CsGN who had been referred to our institute over the period January 2000 to December 2005. These patients were subjected to detailed clinical and biochemical examinations. The diagnosis of underlying renal disease was based on various criteria, including the clinical picture, serology and histopathology. The patients received intravenous methyl prednisolone, oral steroid treatment, and oral cyclophosphamide with or without plasmapheresis. All patients received supportive care, including control of hypertension and oedema and supportive management of renal insufficiency. During this 5-year period, CsGN accounted for 5.1% of all biopsies done in children. The mean age was 12.27 years (range 4 years to 18 years). There were eight girls and 14 boys. The mean duration of symptoms prior to referral was 2.47 months (range 5 days to 21 months). Aetiology was immune complex in 19 cases, anti-glomerular basement membrane (anti-GBM) antibody disease in two cases and pauci-immune (Wegener’s granulomatosis) in one case. The percentage of crescents ranged from 50% to 100% (mean 70.6%). Twenty-one out of 22 (95.5%) children in our series had hypertension at presentation that required treatment with antihypertensive medications. The serum creatinine level at presentation ranged from 1.5 mg/dl to 11.4 mg/dl (mean 5.5 mg/dl). Of the 22 children, two were lost to follow-up, while the mean follow-up period of the rest of the 20 children was 8.13 months (range 1 month to 43 months). At the last follow-up of the 22 children, ten had stage 5 chronic kidney disease (CKD) and three had stage 4 CKD, while seven children had a calculated glomerular filtration rate (GFR) of >60 ml/min per 1.73 m2 body surface area. Persistent proteinuria was seen on follow-up in the majority [13/20 (65%)] of patients. The outcome of CsGN in children continues to be poor, in our experience, due to delayed referral and delayed diagnosis. This was correlated histologically by the presence of fibrocellular crescents in the majority of our patient. Thus CsGN should be treated as a renal emergency. A greater awareness of this disease needs to be created amongst the referring paediatricians in developing countries to facilitate early diagnosis and prompt treatment. [ABSTRACT FROM AUTHOR]

We describe a child presenting with oligoclonal plasma IgM (1.2 g%) and nephrotic syndrome with focal segmental glomerulosclerosis. Oligoclonality was demonstrated by the analysis of the complementary determining region 3 (CDR 3) on immunoglobulin heavy chains and by two dimensional electrophoresis and Western blot analysis that showed the bulk of isoforms having a cationic μU chain compared with the normal homologue (pI 7.5 vs 6.5). Urinary light chains were absent, and bone marrow aspirate was normal. Usual therapies for nephrotic syndrome with steroids and cyclosporin were useless. At the age of 9 years the patient was treated with plasmapheresis plus cyclophosphamide (2 mg/kg per day for 60 days), which temporarily reduced plasma IgM, and proteinuria was normal for 3 years. After this period, due to new recurrence of nephrotic syndrome, the patient received a cycle with anti-CD20 antibodies (500 mg/m2 every week for a month) associated with a cycle of plasmapheresis that normalized proteinuria again, and, after 3 years, the proteinuria is still in remission. This is the first case of nephrotic syndrome associated with oligoclonal plasma IgM and mesangial IgM deposits. Both cyclophosphamide and anti-CD20 antibodies associated with plasmapheresis induced, at different stages, stable and protracted remission of proteinuria without evident side effects. Long term efficacy and safety of the association are still to be determined. [ABSTRACT FROM AUTHOR]

Hypocalcaemic tetany is a known complication of plasmapheresis. It has two causes. Intravenously administered 4.5% human albumin solution (HAS) has no calcium or magnesium, so the replacement of plasma with this fluid depletes these ions. The citrate in fresh frozen plasma (FFP) chelates divalent cations, so the exchange with this at the end reduces the proportion of calcium and magnesium that is ionised. We studied the effect of supplementing HAS with 2 mmol/l calcium chloride and 0.8 mmol/l magnesium sulphate on the changes in ionised and total calcium and magnesium concentrations throughout plasmapheresis. The supplements prevented the falls in these concentrations that is otherwise seen during the HAS infusion, and, thus, the transient fall in ionised calcium concentration induced by the citrate in the FFP was not so profound, reaching 0.92 instead of 0.78 mmol/l ( P = 0.002). Supplementation with calcium and magnesium during HAS maintains their balance and prevents tetany during the FFP infusion. [ABSTRACT FROM AUTHOR]