Capacity for the management of kidney failure in the International Society of Nephrology North America and the Caribbean region: report from the 2023 ISN Global Kidney Health Atlas (ISN-GKHA).

The International Society of Nephrology Global Kidney Health Atlas charts the availability and capacity of kidney care globally. In the North America and the Caribbean region, the Atlas can identify opportunities for kidney care improvement, particularly in Caribbean countries where structures for systematic data collection are lacking. In this third iteration, respondents from 12 of 18 countries from the region reported a 2-fold higher than global median prevalence of dialysis and transplantation, and a 3-fold higher than global median prevalence of dialysis centers. The peritoneal dialysis prevalence was lower than the global median, and transplantation data were missing from 6 of the 10 Caribbean countries. Government-funded payments predominated for dialysis modalities, with greater heterogeneity in transplantation payor mix. Services for chronic kidney disease, such as monitoring of anemia and blood pressure, and diagnostic capability relying on serum creatinine and urinalyses were universally available. Notable exceptions in Caribbean countries included non-calcium-based phosphate binders and kidney biopsy services. Personnel shortages were reported across the region. Kidney failure was identified as a governmental priority more commonly than was chronic kidney disease or acute kidney injury. In this generally affluent region, patients have better access to kidney replacement therapy and chronic kidney disease-related services than in much of the world. Yet clear heterogeneity exists, especially among the Caribbean countries struggling with dialysis and personnel capacity. Important steps to improve kidney care in the region include increased emphasis on preventive care, a focus on home-based modalities and transplantation, and solutions to train and retain specialized allied health professionals.

A Prospective Study on Complement Activation Distinguishes Focal Segmental Glomerulosclerosis from Minimal Change Disease.

Introduction: Minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) are related podocytopathies with distinct kidney outcomes. Surprisingly, elevated urinary activation fragments have been found in FSGS despite little complement deposition on immunofluorescence (IF) staining. Whether complement activation distinguishes FSGS from MCD, participating in the development of segmental lesions, remains unknown. Methods: We performed an observational study in patients with MCD and FSGS, and proteinuria ≥1 g/g of creatinine. We included both primary and secondary or unknown causes. We compared urinary fragments of terminal pathway activation, sC5b9, and C5a expressed as creatinine ratios, between MCD and FSGS. Results: Patients with FSGS (n = 41) had a serum albumin of 31±10 g/l and proteinuria of 5.1 (2.6-9.1) g/g at sampling, whereas those with MCD (n = 15) had a lower serum albumin (22 ± 9 g/l; P = 0.002), and a proteinuria of 3.8 (1.9-7.7) g/g (P = 0.40). Urinary sC5b9 and C5a were 8.7 (1.7-52.3) and 1.26 (0.45-1.84) µg/mmol of creatinine, respectively in patients with FSGS; compared to 0.8 (0.0-1.5) and 0.06 (0.01-0.15) µg/mmol of creatinine in MCD (P < 0.001), respectively. We found no association between urinary complement fragments and age, estimated glomerular filtration rate (eGFR), or chronic kidney lesions. When analyzing samples with proteinuria ≥ 3 g/g, the c-statistics for urinary sC5b9 and C5a were 0.96 and 1.00, respectively, in differentiating FSGS from MCD. Conclusion: We found no urinary complement activation fragments in MCD, in comparison to FSGS, despite similar levels of proteinuria. This suggests a role for complement activation in the pathogenesis of FSGS and provides an additional tool for distinguishing these 2 entities.

IgA nephropathy in children with minimal proteinuria: to biopsy or not to biopsy?

BACKGROUND: Tubulointerstitial lesions and glomerular inflammation severity have been shown to correlate with proteinuria in children with IgA nephropathy (cIgAN). However, there is a lack of data regarding severity of histopathologic findings in cIgAN in patients with minimal to absent proteinuria since kidney biopsy indications are not well defined in these cases. METHODS: Twenty-eight cIgAN patients with kidney biopsy from 4 different centers in Paris (France) and Montreal (Canada) with a urine protein/creatinine ratio (UPCr) ≤ 0.03 g/mmol and a normal estimated glomerular filtration rate (eGFR > 90 ml/min/1.73 m2) on the day of kidney biopsy prior to treatment were included. RESULTS: Median age was 11.82 (9.32-13.45) years, and median follow-up was 4 years (2.87-6.53). At time of biopsy, median eGFR was 116 (102.3-139.7) ml/min/1.73 m2, and median UPCr was 0.02 (0.011-0.03) g/mmol. Microscopic or macroscopic hematuria was present in 35.7% and 64.3% of cases, respectively. Kidney biopsy microscopy analysis showed mesangial (M1), endocapillary (E1), or extracapillary (C1) hypercellularity in 53.5%, 32.1%, and 7.1% of patients, respectively. Chronic histological lesions were also present: glomerulosclerosis (S1) in 42.8% and tubular atrophy/interstitial fibrosis in 7.1%. Podocytopathic features were detected in 21.4%. An ACE inhibitor or immunosuppressive therapy (IS) was prescribed in 42.8% and 21.4% of these patients respectively. One-third (35.7%) received no treatment. At last follow-up, median eGFR was 111.9 (90.47-136.1) ml/min/1.73 m2, and median UPCr was 0.028 (0.01-0.03) g/mmol. CONCLUSION: cIgAN with minimal proteinuria at time of biopsy might be linked with acute and chronic glomerular lesions.

Obinutuzumab in Frequently Relapsing and Steroid-Dependent Nephrotic Syndrome in Children.

BACKGROUND: B-cell depletion with rituximab induces sustained remission in children with steroid-dependent or frequently relapsing nephrotic syndrome. However, most patients relapse after B-cell recovery, and some patients do not achieve B-cell depletion. Obinutuzumab is a second-generation anti-CD20 antibody designed to overcome such situations in B-cell malignancies and was recently reported to be safe and effective in other autoimmune diseases affecting the kidneys. METHODS: We retrospectively report 41 children with steroid-dependent or frequently relapsing nephrotic syndrome treated with a single low-dose infusion of obinutuzumab at Robert-Debre Hospital between April 2018 and December 2020. Participants were treated because of rituximab resistance or relapse after rituximab and received a single infusion of 300 mg/1.73 m 2 obinutuzumab with cessation of oral immunosuppressors within 2 months. RESULTS: B-cell depletion was achieved in all participants and lasted a median of 8.3 months (interquartile range, 6.4-11.1), a duration exceeding that for last rituximab treatment. At 12 and 24 months, 92% (38/41) and 68% (28/41) of patients, respectively, were in sustained remission. Mild infusion reactions occurred in five participants (12%) and neutropenia in nine (21%). No significant decrease in IgG level was reported during treatment, and whereas IgM levels decreased in 34 patients (83%), they were normal at last follow-up in 32 (78%). CONCLUSIONS: These results identified low-dose obinituzumab as a promising treatment option in children with steroid-dependent or frequently relapsing nephrotic syndrome, including those resistant to rituximab. The tolerance profile of obinutuzumab was similar to that of rituximab, but hemogram and immunoglobulin levels should be monitored.

Specific immune biomarker monitoring in two children with severe IgA nephropathy and successful therapy with immunoadsorption in a rapidly progressive case.

BACKGROUND: Childhood IgA nephropathy (cIgAN) is one of the most common primary glomerulonephritides with the potential to evolve to kidney failure. IgAN is an autoimmune disease involving 3 key factors: galactose-deficient IgA1 (Gd-IgA1), anti-IgA1 autoantibodies, and soluble (s)CD89 IgA Fc receptor. These molecules and immune complexes have been described recently as potential biomarkers of disease progression in childhood IgAN but their evolution in time under immunosuppressive treatment remains unknown. METHODS: We performed a prospective study of two proliferative cIgAN patients by sequentially biomonitoring immune IgA complexes (sCD89-IgA, IgG-IgA), sCD89, and Gd-IgA1 and correlating them with clinical and histological outcome after treatment. RESULTS: After patient 1's treatment, a decrease in sCD89-IgA, IgG-IgA, and free sCD89 was linked to a decrease in proteinuria whereas eGFR (estimated glomerular filtration rate) and Gd-IgA1 levels remained stable. Patient 1 received tacrolimus and monthly intramuscular steroid injections of Kenacort for 10 months. At the end, a relapse induced an increase in proteinuria consistent with an increase of the 3 biomarkers. Patient 2 displayed rapidly progressive IgAN with crescents in more than 90% of glomeruli and received intense immunosuppression treatment associated with the immunoadsorption (IA) approach. During IA, proteinuria decreased rapidly, as well as levels of CD89-IgA, IgG-IgA, sCD89, and Gd-IgA1 biomarkers. After discontinuation of IA, proteinuria increased as well as IgG-IgA complexes whereas sCD89-IgA and sCD89 remained low. Further re-intensification of IA and addition of cyclophosphamide improved proteinuria again with reduced IgG-IgA. A second biopsy was performed showing a reduction of extracapillary proliferation to 6% of glomeruli and only 9% glomerulsoclerosis. CONCLUSIONS: In conclusion, sequential biomonitoring of Gd-IgA1, IgA-immune complexes, and sCD89 in cIgAN was found to be valuable, by correlating with clinical features and glomerular proliferative lesions in cIgAN. These biomarkers could represent useful tools to evaluate kidney injury without repeat kidney biopsies.

Anti-rituximab antibodies in pediatric steroid-dependent nephrotic syndrome.

BACKGROUND: Rituximab is a chimeric anti-CD20 monoclonal antibody that induces sustained remission in children with steroid-dependent nephrotic syndrome. However, there is no consensus on the optimal regimen and monitoring of rituximab. In other autoimmune diseases, anti-rituximab antibodies (ARA) have been reported in 10-40% of patients, but their clinical relevance remains unclear. In nephrotic syndrome, data are scarce. METHODS: We report a single-center retrospective study with immuno- and pharmacological monitoring of rituximab treatment in children with frequent relapsing (FR) or steroid-dependent nephrotic syndrome (SDNS). We analyzed the monthly monitoring of 24 children, receiving a dose of rituximab (375 mg/m2) between December 2017 and April 2018 at the Pediatric Nephrology Department of Robert-Debré hospital, Paris. RESULTS: ARA were detected in 7/24 patients (29%), sometimes after the first infusion of rituximab. ARA were present at baseline in two patients previously treated with rituximab. Both displayed no B-cell depletion. ARA were also reported in 5/22 patients during follow-up, with antibodies always detected in the first month following B-cell recovery. An incomplete CD19+CD20- B-cell depletion at M1 (5-25/mm3) and low serum rituximab levels was predictive of developing ARA. The development of de novo ARA during follow-up was not associated with shorter B-cell depletion. CONCLUSIONS: This study shows that ARA are frequent in children with FR/SDNS and that close immuno- and pharmacological monitoring may help personalizing rituximab treatment in patients needing repeated injections.

Soluble CD89 is a critical factor for mesangial proliferation in childhood IgA nephropathy.

Childhood IgA nephropathy (IgAN) includes a wide spectrum of clinical presentations, from isolated hematuria to acute nephritis with rapid loss of kidney function. In adults, IgAN is an autoimmune disease and its pathogenesis involves galactose deficient (Gd) IgA1, IgG anti-Gd-IgA1 autoantibodies and the soluble IgA Fc receptor (CD89). However, implication of such factors, notably soluble CD89, in childhood IgAN pathogenesis remains unclear. Here, we studied these biomarkers in a cohort of 67 patients with childhood IgAN and 42 pediatric controls. While Gd-IgA1 was only moderately increased in patient plasma, levels of circulating IgA complexes (soluble CD89-IgA and IgG-IgA) and free soluble CD89 were markedly increased in childhood IgAN. Soluble CD89-IgA1 complexes and free soluble CD89 correlated with proteinuria, as well as histological markers of disease activity: mesangial, endocapillary hypercellularity and cellular crescents. Soluble CD89 was found in patient's urine but not in urine from pediatric controls. Mesangial deposits of soluble CD89 were detected in biopsies from patients with childhood IgAN. Serum chromatographic fractions containing covalently linked soluble CD89-IgA1 complexes or free soluble CD89 from patients induced mesangial cell proliferation in vitro in a soluble CD89-dependent manner. Recombinant soluble CD89 induced mesangial cell proliferation in vitro which was inhibited by free soluble recombinant CD71 (also a mesangial IgA receptor) or mTOR blockers. Interestingly, injection of recombinant soluble CD89 induced marked glomerular proliferation and proteinuria in mice expressing human IgA1. Thus, free and IgA1-complexed soluble CD89 are key players in mesangial proliferation. Hence, our findings suggest that soluble CD89 plays an essential role in childhood IgAN pathogenesis making it a potential biomarker and therapeutic target.

Rare Collagenous Heterozygote Variants in Children With IgA Nephropathy.

INTRODUCTION: Childhood IgA nephropathy (cIgAN) is a primary glomerulonephritis clinically characterized by microscopic hematuria and proteinuria, the presence of which may potentially overlap with Alport syndrome. Interestingly, earlier studies suggested that familial IgAN could be linked to the chromosome 2q36 region, also the coding region for collagen type 4 alpha 3/4 (COL4A3/A4). METHODS: To investigate a possible relationship or phenocopy between Alport syndrome and cIgAN, COL4A3, COL4A4, and COL4A5 exons were sequenced in 36 cIgAN patients. Clinical data and treatment were collected retrospectively. COL4A3/A4/A5 variants were classified according to American College of Medical Genetics and the Association for Molecular Pathology (ACMG/AMP) guidelines. RESULTS: Four of 36 cIgAN patients were affected by ACMG class 4/5 COL4A3 heterozygous variants (COL4A3-cIgAN). We found no COL4A4 or COL4A5 variant. Despite having rare and deleterious COL4A3 variants, 3 of 4 COL4A3-cIgAN children developed clinical and biologic features of active IgAN rather than Alport syndrome. Response to intensive immunosuppressive treatment was favorable, leading to a reduction of endocapillary and extracapillary proliferation lesions. High levels of immune immunoglobulin G and A (IgG/IgA) complexes, reduction of proteinuria, and gradual stabilization of estimated glomerular filtration rate (eGFR) argued against Alport syndrome. Nevertheless, COL4A3-cIgAN patients seemed predisposed to a more serious IgAN presentation compared with the non‒COL4A3-cIgAN group, with more glomerulosclerosis and a lower eGFR over time. One of the 4 patients underwent kidney transplant with subsequent IgAN recurrence. CONCLUSIONS: Predisposition factors for developing serious cIgAN flare-up should be considered for cIgAN with COL4A3 pathologic heterozygous variants. COL4A3 variants, usually responsible for Alport syndrome in adults, should not automatically exclude an immunosuppressive regimen in cIgAN. Moreover, evidence of an ACMG class 4/5 COL4A3 variant in early-stage cIgAN could be a helpful tool for stratifying severity of cIgAN beyond the Oxford classification.

Erratum: Spatiotemporal trends and prognosis of end stage renal disease patients with biopsy-proven IgA nephropathy in France, 2010-2014.

[This corrects the article DOI: 10.1093/ckj/sfaa029.][This corrects the article DOI: 10.1093/ckj/sfaa029.].

Spatiotemporal trends and prognosis of end-stage renal disease patients with biopsy-proven immunoglobulin A nephropathy in France from 2010 to 2014.

BACKGROUND: Although end-stage renal disease (ESRD) is frequently used as an outcome marker for primary immunoglobulin A nephropathy (IgAN), the clinical course after reaching ESRD is not well documented. This study examined patients' characteristics and survival in ESRD-related biopsy-proven IgAN in France. METHODS: French Renal Epidemiology and Information Network Registry data from 2010 to 2014 were used to analyse patients' survival and outcome in incident ESRD patients >16 years of age with biopsy-proven primary IgAN, in comparison with other primary and secondary glomerulonephritis (GN), adult polycystic kidney disease (ADPKD) or diabetes. Multivariable survival analysis was adjusted for age, sex, time on dialysis and comorbidities. RESULTS: Among 17 138 incident dialysis patients with ESRD, IgAN (242.8/10 000 dialysis initiation) represents the most common GN related to ESRD during 2010. IgAN patients were the youngest, and had the fewest comorbidities and the highest use of peritoneal dialysis (PD) (17%). In comparison with the haemodialysis group, hazard ratios for death were not different in the preemptive transplantation group [0.46, 95% confidence interval (CI) 0.17-1.28] and in the PD group (0.77, 95% CI 0.44-1.33). Mortality rates in IgAN patients with preemptive transplantation and in those receiving dialysis waiting for transplantation were 2.9% (95% CI 0.0-5.6) and 6.7% (95% CI 0.9-12.3). Mortality rates of ADPKD patients receiving dialysis waiting for transplantation were higher (18%, 95% CI 3.1-30.6). CONCLUSION: IgAN has the best prognosis among primary and secondary GN. IgAN patients receiving dialysis waiting transplantation seem to have a more favourable prognosis than ADPKD patients, who usually comprise the reference population. The underlying reasons for the difference in access treatment modalities should be investigated to improve survival with respect to renal disease.

New therapeutic perspectives for IgA nephropathy in children.

Childhood IgA nephropathy (cIgAN) differs from the adult by having an abrupt clinical onset, often presenting as an acute attack that can progress to a chronic phase. No treatment guidelines have been established for the treatment of cIgAN. Given the severity of acute attack in children, and the number of life-years at stake, pediatricians prescribe immunosuppression in addition to renin-angiotensin system blockade. Non-specific immunosuppressors, such as corticosteroids, have systemic toxic effects, and given recent therapeutic advances in adult glomerulonephritis, new tailored strategies should be expected for children. The mucosal immune system has been highlighted as a key player in IgAN pathogenesis, and several biomarkers have been identified with a direct role in pathogenesis. In this review, we discuss current studies of conventional and novel therapeutic approaches for cIgAN.

Updating the International IgA Nephropathy Prediction Tool for use in children.

Although IgA nephropathy (IgAN) is a common cause of glomerulonephritis in children, the absence of a method to predict disease progression limits personalized risk-based treatment decisions. The adult International IgAN Prediction Tool comprises two validated Cox survival models that predict a 50% decline in estimated glomerular filtration rate (eGFR) or end stage kidney disease (ESKD) using clinical risk factors and Oxford MEST histology scores. Here, we updated the Prediction Tool for use in children using a multiethnic international cohort of 1,060 children with IgAN followed into adulthood. The updated pediatric Prediction Tool had better model fit than the original adult tool with lower Akaike Information Criterion, higher R2D and similar C-statistics. However, calibration showed very poor agreement between predicted and observed risks likely due to the observed disease trajectory in children. Therefore, the Tool was updated using a secondary outcome of a 30% reduction in eGFR or ESKD, resulting in better R2D (30.3%/22.2%) and similar C-statistics (0.74/0.68) compared to the adult tool but with good calibration. The trajectory of eGFR over time in children differed from adults being highly non-linear with an increase until 18 years old followed by a linear decline similar to that of adults. A higher predicted risk was associated with a smaller increase in eGFR followed by a more rapid decline, suggesting that children at risk of a 30% decrease in eGFR will eventually experience a larger 50% decrease in eGFR when followed into adulthood. As such, these two outcomes are analogous between pediatric and adult Prediction Tools. Thus, our pediatric Prediction Tool can accurately predict the risk of a 30% decline in eGFR or ESKD in children with IgAN.

Clinical and histological differences between adults and children in new onset IgA nephropathy.

BACKGROUND: Previous reports suggest initial presentation of IgA nephropathy (IgAN) in children is different from adults. No systematic comparison of clinical, biological, and histological childhood- and adult-onset IgAN is currently available. METHODS: We compared pediatric and adult clinical and histological characteristics at IgAN diagnosis. Data on 211 consecutive patients from two different centers in Paris (82 children, 129 adults) were reviewed. Kidney biopsies were scored for Oxford classification and podocytopathic (P1) features. RESULTS: We report higher eGFR at diagnosis in children compared to adults (89.5 vs. 64 ml/min/1.73 m2; p = 0.0001) but no difference in proteinuria. Histological analysis of kidney biopsy found higher proportions of mesangial (M1) and endocapillary (E1) hypercellularity in children compared with adults (M1 [80.7% vs. 27.9%, p = 0.0001]; E1 [71.3% vs. 30%, p = 0.0001]). Focal glomerulosclerosis (S1), tubular atrophy/interstitial fibrosis ≥ 25% (T1), and P1 were more frequent in adults (S1 [81.5% vs. 61.3%, p = 0.0012], T1 [49.5% vs. 1.35%, p = 0.0001], P1 [33.8% vs. 16.4%, p = 0.008). Proteinuria associated with M1, E1, and C1 in children (M1, p = 0.0001; E1, p = 0.0005; C1, p = 0.0014) but S1, P1, and T1 in adults (S1, p = 0.0001; P1, p = 0.0001; T1, p = 0.001). After steroid treatment (41 children and 28 adults), proteinuria decreased in children (p < 0.001, follow-up 38 months) and adults (p < 0.001, follow-up 76.9 months), whereas eGFR remained stable in adults but increased significantly in children (90.6 to 110 ml/min/1.73m2). CONCLUSION: Proteinuria in children with IgAN is a marker of glomerular proliferative lesions whereas its presence in adults often reflects the presence of chronic lesions. This suggests the need for histological assessment.

Steroid therapy in children with IgA nephropathy.

IgA nephropathy (IgAN) is one the most common primary glomerulonephritis in children and adolescents worldwide, with 20% of children developing end-stage kidney disease (ESKD) within 20 years of diagnosis. There is a need for treatment guidelines, especially for steroids in children with primary IgAN, since the STOP-IgA trial casts doubts on the use of steroids in adults with intermediate risk. Pediatricians are prone to prescribe steroids in addition to renin-angiotensin system blockade (RASB) when proteinuria is > 0.5 g/l, eGFR deteriorates < 70 ml/min/1.73 m2, or when a biopsy sample shows glomerular inflammation. Lack of randomized controlled trials (RCTs) in children with IgAN has led to an absence of consensus on the use of immunosuppressive agents in the treatment of progressive IgAN. This literature review evaluates the available evidence on steroid treatment in children with IgAN.

Human C-terminal CUBN variants associate with chronic proteinuria and normal renal function.

BACKGROUNDProteinuria is considered an unfavorable clinical condition that accelerates renal and cardiovascular disease. However, it is not clear whether all forms of proteinuria are damaging. Mutations in CUBN cause Imerslund-Gräsbeck syndrome (IGS), which is characterized by intestinal malabsorption of vitamin B12 and in some cases proteinuria. CUBN encodes for cubilin, an intestinal and proximal tubular uptake receptor containing 27 CUB domains for ligand binding.METHODSWe used next-generation sequencing for renal disease genes to genotype cohorts of patients with suspected hereditary renal disease and chronic proteinuria. CUBN variants were analyzed using bioinformatics, structural modeling, and epidemiological methods.RESULTSWe identified 39 patients, in whom biallelic pathogenic variants in the CUBN gene were associated with chronic isolated proteinuria and early childhood onset. Since the proteinuria in these patients had a high proportion of albuminuria, glomerular diseases such as steroid-resistant nephrotic syndrome or Alport syndrome were often the primary clinical diagnosis, motivating renal biopsies and the use of proteinuria-lowering treatments. However, renal function was normal in all cases. By contrast, we did not found any biallelic CUBN variants in proteinuric patients with reduced renal function or focal segmental glomerulosclerosis. Unlike the more N-terminal IGS mutations, 37 of the 41 proteinuria-associated CUBN variants led to modifications or truncations after the vitamin B12-binding domain. Finally, we show that 4 C-terminal CUBN variants are associated with albuminuria and slightly increased GFR in meta-analyses of large population-based cohorts.CONCLUSIONCollectively, our data suggest an important role for the C-terminal half of cubilin in renal albumin reabsorption. Albuminuria due to reduced cubilin function could be an unexpectedly common benign condition in humans that may not require any proteinuria-lowering treatment or renal biopsy.FUNDINGATIP-Avenir program, Fondation Bettencourt-Schueller (Liliane Bettencourt Chair of Developmental Biology), Agence Nationale de la Recherche (ANR) Investissements d'avenir program (ANR-10-IAHU-01) and NEPHROFLY (ANR-14-ACHN-0013, to MS), Steno Collaborative Grant 2018 (NNF18OC0052457, to TSA and MS), Heisenberg Professorship of the German Research Foundation (KO 3598/5-1, to AK), Deutsche Forschungsgemeinschaft (DFG) Collaborative Research Centre (SFB) KIDGEM 1140 (project 246781735, to CB), and Federal Ministry of Education and Research (BMB) (01GM1515C, to CB).

A Successful Renal Transplant in a Pediatric Patient With Glanzmann Thrombasthenia and Hyperimmunization.

We report the case of a patient with type 2 Glanzmann thrombasthenia who underwent successful kidney transplant with his mother's kidney. He started dialysis at 13 months. The patient had been diagnosed with Glanzmann thrombasthenia at 9 years old, after hemorrhagic shock, during which multiple transfusions were required and hyperimmunization had developed. At 12 years old, he received a kidney transplant. Before transplant, ABO- and HLA-compatible platelet donors were identified and convened to donate forthe surgery and in case of emergency. Bleeding was prevented withprophylacticHLA-matched platelet transfusion and tranexamic acid. After transplant, diuresis started immediately with excellent graft function and no severe bleeding. However, after week 5, several episodes of macroscopic hematuria occurred, with obstruction and anuria. The double J ureteric stent was replaced 4 times in 2 months. Finally, the ureteric stent was removed 9 months later. At 22 months after kidney transplant, the patient has a normal graft function and no further bleeding has occurred, underlying the importance of multidisciplinary management.

Immunosuppressive Treatment in Children With IgA Nephropathy and the Clinical Value of Podocytopathic Features.

INTRODUCTION: There is a need for treatment guidelines and prognostic factor identification in children with primary IgA nephropathy. We analyzed the causative effect of steroids and the applicability of the Oxford classification. METHODS: A total of 82 consecutive children (mean 10.6 years; median follow-up 3.3 years) were reviewed; 21 patients (25.6%) presented with acute kidney injury, and 6 (7.3%) with nephrotic syndrome. Renal biopsies were scored for Oxford classification and podocytopathic features in 2 groups: a group treated with steroid therapy (some in association with cyclophosphamide) and supportive care (renin angiotensin system blockade) and a group treated by supportive care alone. RESULTS: The 2 groups were not comparable because baseline clinical data were different. Estimated glomerular filtration rate (eGFR) in immunosupressive group significantly improved between M0 (at onset) and M6 (6 months after treatment) from 89.9 [61.2-114.5] to 110.5 [93.7-120] ml/min per 1.73 m2, P < 0.001. Proteinuria also significantly decreased from (1.6 [1-4.3] to 0.3 [0.2-0.7] g/g, P < 0.001). In the supportive care group, eGFR and proteinuria remained stable. Podocytopathic features were predictive of renal function decline by univariable (-4.9 ± 14.9 ml/min per 1.73 m2, P = 0.0079) and multivariable analysis and of poor renal prognosis to a combined event (renal function impairment more than 10% of the eGFR baseline or chronic kidney disease stage 3 at 6 months) in univariable analysis. MEST-C score failed to prove its prognostic value. CONCLUSION: Immunosuppressive treatment, especially steroid therapy, seems beneficial in children with glomerular inflammation and proliferation. The Oxford classification does not appear to be entirely appropriate in predicting long-term renal prognosis for children, whereas the characteristics of podocytopathy are strongly predictive of renal prognosis.