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Purpose: The aim was to investigate the diagnostic efficacy of urinary protein/creatinine ratio (UPCR) and factors influencing its substitutability of 24-h urine protein (24hUP) in children with proteinuria., Methods: A total of 356 children were recruited, including 149 with non-nephrotic-range proteinuria and 207 with nephrotic-range proteinuria which were further divided into Henoch-Schönlein purpura nephritis (HSPN), lupus nephritis (LN), and primary nephrotic syndrome (PNS). The urine protein and creatinine were measured by routine methods. Bland-Altman analysis was used to test the agreement. Spearman correlation was performed to evaluate the relevance. The receiver operating characteristic curve was used to analyze the diagnostic efficacy of UPCR., Results: Bland-Altman analysis showed there was an excellent agreement between UPCR and 24hUP in each group. Correlations between UPCR and 24hUP were strong in 356 children (r = 0.869) and in the non-nephrotic-range proteinuria group (r = 0.806), but moderate in nephrotic-range proteinuria group (r = 0.586). With the increase of nephrotic-range proteinuria, the correlations between UPCR and 24hUP were decreased further, however, after UPCR was adjusted by 24-h urine creatinine (24hUCr), the correlation coefficient was improved (r = 0.682). In three subgroups with nephrotic-range proteinuria, high correlation coefficient (r = 0.731) was observed in HSPN, but not in LN (r = 0.552) and PNS (r = 0.563). The sensitivity and specificity of UPCR for diagnosing nephrotic-range proteinuria were 89.9 % and 92.2%., Conclusions: UPCR is competent in evaluating proteinuria. The degree of proteinuria, 24hUCr and the underlying pathological types of renal disease may be the important influencing factors in the correlation between UPCR and 24hUP in children with nephrotic-range proteinuria., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: School urinary screening has been performed in Japan., Methods: Ikeda City and Toyono Town introduced, in 2012 and 2013, urinary protein/creatinine (Cr) ratio measurement into the urine-screening protocols designed for students aged between 4 and 15 years. For each student whose urinary protein/Cr ratio was ≥ 0.15 g/gCr (positive case), an appointment was made with a specialist at Ikeda City Hospital. The results of these screening urinalyses conducted through 2018 are summarized., Results: 14,606 junior high and elementary school students aged between 6 and 15 years were included. On average, they underwent 4.16 screening tests. 77 positive cases were detected, and seven students were diagnosed with high-risk chronic kidney disease (CKD). Of these, four underwent renal biopsy, and two, one, and one were diagnosed with IgA nephropathy, MPGN, and FSGS, respectively. In three students, detection of CKD would have been difficult without urinary screening. Incident rates of high-risk CKD and IgA nephropathy are estimated as 11.5 and 3.3 cases/100,000 students/year. 78.0% of positive cases without high-risk CKD showed no urinary abnormality after one year. 2301 kindergarten students aged between 4 and 6 years received an average of 1.74 screening urinalyses; none was positive or high-risk CKD. The estimated cost of detecting one high-risk CKD student whose detection would have been difficult without this screening was 3,156,711 Japanese yen., Conclusion: School urinary screening using the urinary protein/Cr ratio can efficiently refer to a specialist. It detects a few children with high-risk CKD early with spending high cost.

Blood pressure (BP) was measured in 31 renal azotaemic dogs by oscillometric measurement at the posterior tibia artery, and urine and blood samples were collected. Haematology, blood chemistry and urinalysis were performed and urinary protein:creatinine ratio (UPC) and fractional excretions of electrolytes (FE(e)) were calculated. The results showed that only 19% of dogs with renal azotaemia were hypertensive, whereas almost all of them had high urinary protein and electrolyte excretions. There was no association between BP, UPC and FE(e). A positive correlation was found between all pairs of electrolyte fractional excretions. When the severity of renal impairment was observed using plasma creatinine concentration, neither BP nor UPC was correlated. Only the FE( e ) was associated with the degree of azotaemia. The results suggest that dogs with renal azotaemia do not necessarily have hypertension. The fractional urinary excretion of electrolytes may be a good indicator for severity of renal dysfunction in azotaemic dogs.

Background: This cross-sectional study was conducted to determine whether a spot urine protein/creatinine ratio (UPr/UCr) provides accurate quantitation of 24-hr urinary protein excretion (24-hr Prot) in out-patients with primary glomerulonephritis (GN) and different renal function levels., Methods: Patients were classified into three groups according to creatinine (Cr) clearance (ml/min) and into five categories according to morning UPr/UCr. Correlation between 24-hr Prot and UPr/UCr was calculated according to the three renal function levels. The Bland and Altman method was used to assess agreement between 24-hr Prot and UPr/UCr. Agreement limits were obtained calculating the mean difference between 24-hr Prot and morning UPr/UCr +/- 2SD. Sensitivity and specificity were determined for different renal function levels and UPr/UCr cut-off values., Results: High correlation coefficients (r=0.91, 0.95 and 0.98) were observed in patients with normal, reduced and severely reduced renal function. Differences and variability between 24-hr Prot and UPr/UCr tended to increase with higher proteinuria levels, and this trend was observed for the three renal function levels. The best UPr/UCrcut-off values to detect abnormal or nephrotic proteinuria were, respectively, 0.3 and 2.6., Conclusions: Correlation and agreement between UPr/UCr and 24-hr Prot was good for all renal function levels, but demonstrated more marked differences as urinary protein excretion increased. Morning UPr/UCr had good sensitivity and specificity for the diagnosis of 24-hr Prot, even in patients with reduced renal function.

Introduction: Kidney biopsy is the reference tool for diagnosing and guiding treatment strategies in inflammatory renal diseases, such as lupus nephritis (LN). We investigated the histopathological findings in first-time kidney biopsies from a large cohort of SLE patients. We focused on the occurrence and type of histopathological findings other than LN, and fulfillment of renal criteria in established SLE classification systems were analyzed., Methods: We retrospectively included SLE patients (n = 139) who underwent a first kidney biopsy between 1995 and 2021, upon clinical suspicion of renal involvement. Based on histology, two groups were defined, LN and non-LN, for which clinical and laboratory features were compared., Results: Findings consistent with LN according to ISN/RPS classification system were present in 123/139 patients (88.5%) and findings not consistent with LN were present in 16 /139 (11.5%). Non-LN patients were older at SLE diagnosis compared to LN patients (M, years 38.0 vs. 30.1, p=0.013) and had longer disease duration (M, years 11.9 vs 0.5) (p=0.027). Among non-LN patients 85.7% met the SLICC criteria item for renal SLE, seen in 94.7% in the LN group (ns). For the ACR/EULAR criteria, 66.7% of the non-LN group fulfilled the criteria compared to 74.8% in LN patients (ns). Proteinuria below the criteria cut-off level (< 0.5 g/24 h) was seen in 20% of patients with class III/IV LN., Conclusion: Our data confirm the importance of kidney biopsy for ruling out the presence of renal pathology other than LN. Patients with low-grade proteinuria may exhibit severe types of LN, which reinforces the need for early biopsies to detect LN. Key Points • Our findings show that histopathology changes other than lupus nephritis may occur in a significant number of patients with clinical and laboratory signs of novel kidney involvement. • Low-grade proteinuria does not exclude findings of active lupus nephritis that require the start of immunosuppressive therapy. • The study stresses the importance of performing kidney biopsies also in the presence of low-grade proteinuria or when signs of kidney function abnormalities occur. • This is crucial as early detection and prompt initiation of therapy may improve outcomes in lupus nephritis., (© 2023. The Author(s).)

Background Proteinuria is a common manifestation of chronic kidney disease (CKD), and there is a high incidence of CDK and its complications following renal transplantation. However, little data are available on the association between proteinuria and graft/patient survival in the paediatric transplant population. The primary aim of this study was to investigate the associations between posttransplant proteinuria and graft/patient survival in children after renal transplantation. Methods In this retrospective study, we screened all 91 children receiving renal allografts at a single institution between 1997 and 2007. The inclusion criteria were a functioning graft at 1 year posttransplant, data availability and no recurrence of focal-segmental glomerulosclerosis. The final cohort included 75 patients. Proteinuria was considered to be pathologic if the urinary protein/creatinine ratio was >30 mg/mmol. Donor and recipient characteristics, data on proteinuria, estimated glomerular filtration rate (eGFR) and rejection episodes were analysed. The most recent of the biopsies performed during the follow-up after 1 year posttransplant were analysed separately in the proteinuric group and the non-proteinuric group. Results Proteinuria at 1-year posttransplant was pathologic in 35 % of patients. The 5-year graft survival rate was significantly lower in the proteinuric group than in the non-proteinuric group (77 vs. 100 %; p < 0.001). Proteinuria at 1 year posttransplant was associated with reduced long-term graft survival independent of other risk factors, including decreased eGFR or episodes of acute corticosensitive and corticoresistant rejection. The most frequent histologic finding in the proteinuric group was chronic rejection. There was no significant difference in the 5-year patient survival rate between the proteinuric group and the non-proteinuric group. Conclusion This study emphasizes the importance of proteinuria as a prognostic factor of renal allograft survival in children., Author(s): Tomas Rosik[sup.1] , Maria Chadimova[sup.2] , Jiri Dusek[sup.1] , Jaromir Hacek[sup.2] , Nadezda Simankova[sup.1] , Karel Vondrak[sup.1] , Jakub Zieg[sup.1] , Tomas Seeman[sup.1] [sup.3] Author Affiliations: (1) Department of [...]

Background Immunoglobulin A vasculitis (IgA-V), formerly known as Henoch-Schonlein purpura (HSP), is the most common small vessel vasculitis in children. In recent years, the role of T cells in the pathogenesis of HSP/IgA-V has become a focus of research. Methods Renal biopsy specimens from 22 pediatric patients diagnosed with Henoch-Schonlein nephritis (patient group) were compared to normal renal tissue in nephrectomy specimens from 20 pediatric patients diagnosed with Wilms tumor (control group). All renal specimens were scored according to International Study of Kidney Disease in Children (ISKDC) and Oxford classification. Immunohistochemical analyses of interferon-gamma (IFN-[gamma]), interleukin (IL)-4, IL-17 and FOXP3 expression were performed. Results All glomeruli and tubules of the HSP/IgA-V patients showed significantly higher IFN-[gamma] and IL-17 expression than those of the control group. Glomerular IFN-[gamma] and IL-17 staining grades correlated with the urinary protein/creatinine ratio (r = 0.62, p = 0.02 and r = 0.507, p = 0.016, respectively). IL-17 expression also correlated with the percentage of crescents (r = 0.518, p = 0.014). IL-4 staining was present in only nine of the 22 patient biopsies and did not correlate with any of the parameters studied. Interstitial areas of patient biopsies had more FOXP3+ cells/[mu]m.sup.2 than those of the control group (p < 0.001), but differences in glomerular and tubular FOXP3+ levels (cells/[mu]m.sup.2) between the two groups were not statistically different. The ISKDC and Oxford scores did not correlate with any parameter studied. However, endocapillary hypercellularity did correlate with IFN-[gamma] expression. Conclusions Based on these results, we conclude that IFN-[gamma] and IL-17 contribute to HSP/IgA-V in children., Author(s): Bora Gülhan[sup.1] , Diclehan Orhan[sup.2] , Gülsev Kale[sup.2] , Nesrin Besbas[sup.1] , Seza Özen[sup.1] Author Affiliations: (1) Department of Pediatric Nephrology, Faculty of Medicine, Hacettepe University, Sihhiye, 06100, Ankara, [...]

Urine samples can be readily obtained from patients in everyday clinical practice. Therefore, the availability of urine allows physicians to obtain relevant clinical information in a timely manner. Since the measurement of urinary protein levels is essential in diagnosing and treating a host of diseases, the potential detection of urinary proteins by urinary strips in an easy, quick, and cheap way is very attractive. However, to ensure optimal use of urinary strips, one needs to be aware of their characteristics and their limitations. In this review, we discuss the characteristics of the urinary strips available for testing urinary protein levels and for detecting urinary albumin. We then consider their analytical performances in their most widely used clinical applications (e.g., in pregnancy, chronic kidney disease, diabetes, and screening of the general population).

Although recent reports suggest a possible role for an imbalance in Th1 and Th2 proinflammatory cytokines in the development and progression of glomerulonephritis, there is little information on Th1 or Th2 predominance in Henoch-Schönlein purpura nephritis (HSPN). Since T-bet and GATA-3 are transcriptional factors that regulate the differentiation of helper T lymphocytes into Th1 and Th2, we examined the relative mRNA expression of T-bet and GATA-3 in the urinary sediment of children with proteinuric HSPN by real-time quantitative PCR. Eight consecutive patients with proteinuric HSPN (4 with grade IIIa and 4 with grade IIIb according to the International Study of Kidney Disease in Children criteria) and 20 healthy subjects were enrolled in this study. The relative expression level of T-bet was significantly higher in the urinary sediment of patients with HSPN at presentation than in that of the healthy controls (p = 0.021), while the relative expression of GATA-3 was significantly lower in the urinary sediment of patients than in that of controls (p = 0.002). Urinary mRNA expression of T-bet correlated with the urinary protein/creatinine ratio (r = 0.608, p = 0.013), and correlated inversely with serum level of total protein (r = -0.574, p = 0.020). Moreover, a significantly increased intensity of T-bet immunostaining was observed in the glomeruli in the biopsy specimen of all study patients. All patients received immunosuppressive therapy. Repeat measurements of urinary mRNA expression of T-bet and GATA-3 after treatment revealed that the expression of T-bet in patients had significantly decreased relative to the baseline (p = 0.003), while the expression of GATA-3 remained static. In a patient subjected to a post-treatment renal biopsy, the increased intensity of immunostaining of T-bet had clearly diminished following immunosuppressive treatment, in accordance with a significant decrease in urinary mRNA expression of T-bet. These observations suggest that patients with proteinuric HSPN demonstrate increased T-bet and depressed GATA-3 expression in the urinary sediment, indicating a possible shift in Th1/Th2 balance towards Th1 predominance., Author(s): Kazushi Tsuruga [sup.1] , Shojiro Watanabe [sup.1] , Eishin Oki [sup.1] , Tomomi Aizawa-Yashiro [sup.1] , Hidemi Yoshida [sup.2] , Tadaatsu Imaizumi [sup.2] , Etsuro Ito [sup.1] , Hiroshi [...]

Limited and discordant data are available on cyclosporine A (CsA) treatment for proteinuria in Alport syndrome (AS). To address this lack of consistent data, we have studied 15 AS patients (14 males; mean age 15.3 ± 6.0 years) treated with CsA. Patient selection criteria included a urinary protein/creatinine ratio ≥ 1 mg/mg and a creatinine clearance >40 ml/min/1.73 [m.sup.2]. CsA treatment was started at an initial dose of 5 mg/kg/day and subsequently adjusted to reach target C2 levels of 500 ng/ml. Renal function, proteinuria, and blood pressure were monitored. Blood pressure was treated to avoid the administration of angiotensin converting enzyme or angiotensin receptor blockers for the first 2 years of therapy. The average follow-up was 3.5 years. Five patients had chronic renal failure at the beginning of treatment, of whom three and one reached end-stage renal failure within 1 and 3 years, respectively. In the remaining 11 patients, the glomerular filtration rate declined by 11 ± 6% within 6 months, but remained stable thereafter. Proteinuria decreased by 63 ± 21% from baseline, but returned nearly to baseline after 2.5 years of follow-up. Based on these results, we suggest that CsA is effective in reducing proteinuria in patients with Alport syndrome but that this effect is temporary. Our data do not support the use of CsA therapy for proteinuric patients with AS, particularly if they have chronic renal failure. Keywords Alport syndrome * Angiotensin converting enzyme inhibitors * Angiotensin receptor blockers * Cyclosporine A * Hereditary nephritis * Glomerular basement membrane, Introduction Alport syndrome (AS) is a genetic disorder caused by mutations in genes that encode for type IV collagen chains expressed in the glomerular basement membrane (GBM). In most patients, [...]

Abstract Urinary protein/creatinine ratio (Up/cr) is a simple measurement for evaluation of proteinuria. However, exact effects of body size and gender on urinary excretion of creatinine and Up/cr remain unknown. [...]

Byline: Lisa J. Norman (1,3), Ian A. Macdonald (2), Alan R. Watson (1) Keywords: Chronic renal insufficiency; Disease progression; Dietary restriction; Phosphorus; Sodium; Protein; Calcium Abstract: There is a lack of evidence to support the belief that dietary measures are beneficial in slowing the progression of chronic renal insufficiency (CRI). We prospectively monitored nutrient intakes and progression of CRI over a 2-year period in children aged 2--16 years with differing levels of severity of CRI, as part of their ongoing joint medical/dietetic care. Children were grouped following [[.sup.51]Cr]-labelled EDTA glomerular filtration rate (GFR, ml/min per 1.73 m.sup.2) estimations, into &apos;normal&apos; kidney function [GFR &gt 75, mean 106 (SD 19.5), n =58], providing baseline data only, mild (GFR 51--75, n =25), moderate (GFR 25--50, n =21), and severe (GFR &lt 25, n =19) CRI. Children with CRI were followed for 2 years, with 51 completing the study (19 mild, 19 moderate, 13 severe CRI) and were excluded if they subsequently required dialysis. Regular medical and dietary advice was provided and yearly 3-day semi-quantitative dietary diaries and baseline and 6-monthly measurements of blood pressure and urinary protein/creatinine ratio were obtained. Mean reductions in estimated GFR over 2 years were --9.4, -5.8, and --6.0 ml/min per 1.73 m.sup.2 for mild, moderate, and severe CRI, respectively. Mean systolic blood pressure standard deviation score (SDS) fell significantly in all groups by 0.7 SDS, whereas there was little change in proteinuria. From reported dietary intakes, median sodium intakes increased (+10 mmol/day) and protein intakes decreased (-0.4 g/kg per day). Median phosphate intakes did not change significantly, whereas calcium intakes fell in all groups, with an overall median of --20% reference nutrient intake (RNI) (F =33.3, P &lt 0.001). Of children with moderate CRI, 65% finished with calcium intakes below 80% RNI, and parathyroid hormone (PTH) concentrations significantly increased in this group (F =6.0, P =0.021). Higher phosphate and sodium intakes were associated with greater deterioration in estimated GFR in children with mild CRI (r .sup.2=0.30, P =0.02 r .sup.2=0.31, P =0.02, respectively). There was no such correlation for protein intake or PTH. This study emphasises the need for a joint medical and dietetic approach and indicates a number of interventions other than protein restriction, which could be commenced early in children with CRI in an attempt to delay progression. Author Affiliation: (1) Children and Young People&apos;s Kidney Unit, Nottingham City Hospital, Nottingham, UK (2) School of Biomedical Sciences, Medical School, University of Nottingham, UK (3) Department of Nutrition and Dietetics, Nottingham City PCT, 261 Beechdale Road, Aspley, Nottingham, NG8 3EY, UK Article History: Registration Date: 30/06/2004 Received Date: 24/10/2003 Accepted Date: 27/05/2004 Online Date: 03/09/2004

Byline: Willem Proesmans (1), Maria Van Dyck (1) Keywords: Alport syndrome; Angiotensin-converting enzyme inhibitors; Enalapril; Renoprotection Abstract: Ten pediatric patients with Alport syndrome received enalapril for 5 years. There were nine boys. Eight patients have the X-linked form of the disease and two the autosomal recessive form. The median age at the start of treatment was 10.25 years. Only one patient was hypertensive. The starting dose of enalapril was 0.05 mg/kg the target dose was 0.5 mg/kg per day. The median dose given effectively was 0.24, 0.37, 0.45, 0.43, and 0.49 mg/kg per day at years of study 1, 2, 3, 4, and 5, respectively. The median urinary protein/creatinine ratio was 1.58 g/g (range 0.49--4.60) before treatment. This decreased to 0.98, 1.09, 1.35, 1.11, and 1.38 g/g after 1, 2, 3, 4, and 5 years, respectively. The median creatinine clearance at baseline was 100 ml/min per 1.73 m.sup.2 (range 82--133) and after 5 years 92 ml/min per 1.73 m.sup.2 (range 22--115). Three patients did not reach the target dose of enalapril because of orthostatic hypotension. One of them was the only patient to develop chronic renal failure within 5 years. The present study indicates that enalapril reduces urinary protein excretion and preserves glomerular filtration in Alport patients as a group. However, there was individual variation, as in most studies of patients with proteinuric nephropathies given inhibitors of the angiotensin-converting enzyme. Author Affiliation: (1) Renal Unit, Department of Pediatrics, University Hospital Gasthuisberg, Herestraat 49, 3000 Leuven, Belgium Article History: Registration Date: 23/10/2003 Received Date: 04/08/2003 Accepted Date: 09/10/2003 Online Date: 24/01/2004

Byline: Hyun Soo Kim (1), Hae Won Cheon (1), Jeong-Hoon Choe (1), K. H. Yoo (1), Young Sook Hong (1), Joo Won Lee (1), Soon Kyum Kim (1) Keywords: KeywordsaProteinuria; Osmolality; Ratio; Children Abstract: A prospective study was conducted to determine the correlation of early morning urinary protein/osmolality ratio (mg/l/mosmol/kg) with 24-h urinary protein excretion (mg/m.sup.2/day). Study patients consisted of 53 children (aged 1 month to 15 years). Early morning urine samples and 24-h urine samples were collected and analyzed. In group 1 (children without proteinuria), early morning urinary protein/creatinine ratio (Uprot/Ucr, mg/mg) was 0.061+-0.011 and the protein/osmolality ratio (Uprot/Uosm, mg/l/mosmol/kg) was 0.073+-0.014. Twenty-four hour urinary protein excretion in group 1 had no significant correlation with Uprot/Ucr or Uprot/Uosm. In group II (children with proteinuria), Uprot/Ucr was 5.78+-1.10 and Uprot/Uosm was 4.42+-1.34. Twenty- four hour urinary protein excretion in group 2 was 1483.6+-303.7 mg/m.sup.2/day and its correlation with both Uprot/Uosm and Uprot/Ucr was highly significant (r= 0.87, P&lt 0.001 and r=0.88, P&lt 0.001, respectively). The accepted nephrotic level of proteinuria of 40 mg/m.sup.2/h coincides with a Uprot/Uosm ratio of 1.9. In conclusion, early morning urinary Uprot/Uosm is a simple and potentially useful test for 24-h urinary protein excretion, and possibly could be used safely for the assessment of the degree of proteinuria in children. Author Affiliation: (1) Department of Pediatrics, Korea University, Guro Hospital, 80 Guro-Dong, Guro-Gu, Seoul 152-703, Korea e-mail: guroped@chollian.net Tel.: +82-2-8186128, Fax: +82-2-8589396, KR Article note: Received: 13 April 1999 / Revised: 23 February 2000 / Accepted: 15 August 2000

Author(s): Ester Conversano [sup.1] , Hanna Debiec [sup.2] , Manuela Colucci [sup.3] , Francesco Emma [sup.1] , Pierre Ronco [sup.2] , Marina Vivarelli [sup.1] [sup.3] Author Affiliations: (1) https://ror.org/02sy42d13, grid.414125.7, [...], Background Membranous nephropathy is a glomerular disease characterized by the presence of immune-complexes deposited in the subepithelial space of the glomerular basement membrane. It is the main cause of nephrotic syndrome in adults, while in children it is very infrequent. Anti-CD20 monoclonal antibodies, mainly rituximab, represent a specific treatment for this disease. Case report We report the case of a child presenting at 2 years of age with steroid-resistant nephrotic syndrome diagnosed upon kidney biopsy as semaphorin 3B (SEMA3B)-associated primary membranous nephropathy. The patient responded to treatment with cyclosporine, but invariably relapsed upon tapering of this agent. Therefore, at age 9, he was successfully treated with rituximab to overcome cyclosporine dependence. However, after the second rituximab infusion, a rapid reconstitution of CD19 + B cells and a relapse of proteinuria occurred, requiring reintroduction of cyclosporine. Obinutuzumab, a type II anti-CD20 monoclonal antibody, was then infused inducing prolonged CD19 + B cell depletion and remission of proteinuria despite discontinuation of cyclosporine. A greater reduction in circulating anti-SEMA3B antibodies assessed by Western blot was observed after obinutuzumab compared with rituximab infusion. Discussion Obinutuzumab was safe and well-tolerated, and may therefore represent an effective therapeutic alternative in children with primary MN and rituximab resistance.

Author(s): Elia Balestra [sup.1] , Egidio Barbi [sup.1] [sup.2] , Viola Ceconi [sup.1] , Vittorio Di Maso [sup.3] , Ester Conversano [sup.2] , Marco Pennesi [sup.2] Author Affiliations: (1) https://ror.org/02n742c10, [...], Background C3-glomerulopathy (C3G) is a rare pediatric kidney disease characterised by dysregulation of the alternative complement pathway, with glomerular deposition of C3. C3G may often present as a steroid-resistant nephrotic syndrome (SRNS), and there is no established effective therapy: the usual treatment involves corticosteroids and immunosuppressive drugs. Pioglitazone, a PPAR-[gamma] agonist with a protective action on podocytes, was reported in a few cases as helpful in reducing proteinuria when combined with steroids. Case-Diagnosis/Treatment We report the case of a 13-year-old girl with silent past medical history who presented with SRNS. A kidney biopsy showed findings indicative of C3G. A low sodium diet and angiotensin-converting enzyme inhibitor were started; immunosuppressive treatment with mycophenolate mofetil (MMF) was administered due to the cortico-resistance. Because of poor response to the immunosuppressant, a trial with eculizumab was attempted without significant response and persistence of proteinuria in the nephrotic range. A further therapeutic trial was performed with tacrolimus with no disease remission. Due to a severe deterioration in her condition, the girl was hospitalized and treated with high-dose steroid bolus. A daily dose of oral prednisone and MMF were re-started without benefit with persistent levels of nephrotic range proteinuria. The administration of pioglitazone consistently lowered proteinuria levels for the first time since the onset of the disease, with a maintenance of the effect and normalization (< 0.15 g/24 h) at the 10-month follow-up. Conclusions In this patient affected by C3G, pioglitazone proved effective in reducing proteinuria levels.

Background C3 glomerulonephritis (C3GN) is a subtype of C3 glomerulopathy (C3G), characterized by dysregulation of the alternative pathway of complement and by dominant C3 by immunofluorescence on the kidney biopsy. There is no approved treatment for patients with C3G. Immunosuppressive drugs as well as biologics have been used with limited success. In recent decades, substantial advances in the understanding of the complement system have led to the development of new complement inhibitors. Avacopan (CCX168) is an orally administered small-molecule C5aR antagonist that blocks the effects of C5a, one of the most potent pro-inflammatory mediators of the complement system. Case report We describe a child with biopsy-proven C3GN treated with avacopan. She was enrolled in the ACCOLADE double-blind placebo-controlled Phase 2 study (NCT03301467), where during the first 26 weeks she was randomized to receive an avacopan-matching placebo orally twice daily, while in the following 26 weeks, the study was open-label and she received avacopan. After a wash-out period, she was restarted on avacopan through an expanded access program. Conclusions In this case, use of avacopan in a pediatric patient with C3GN was safe and well tolerated. On avacopan, the patient was able to discontinue mycophenolate mofetil (MMF) while maintaining remission., Author(s): Federica Zotta [sup.1] , Francesca Diomedi-Camassei [sup.2] , Antonio Gargiulo [sup.1] , Andrea Cappoli [sup.1] , Francesco Emma [sup.1] , Marina Vivarelli [sup.1] Author Affiliations: (1) grid.414125.7, 0000 0001 [...]

Background The best treatment for IgAN is still debated. The trials NEFIGAN and NEFIGARD have demonstrated that TRF-budesonide (Nefecon) efficiently and safely reduced proteinuria in adults, leading to FDA approval of Nefecon for adult IgAN. In pediatric IgAN, an etiological treatment does not yet exist, and the main therapies remain RAAS inhibitors and oral steroids. To our knowledge, this is one of the few pediatric reports of TRF-budesonide therapy. Case report-diagnosis/treatment A 13-year-old boy underwent a kidney biopsy for recurrent macrohematuria and proteinuria, resulting in an IgAN diagnosis (MEST-C score M1-E1-S0-T0-C1). At admission, serum creatinine and UPCR were slightly increased. Three methylprednisolone pulses were performed, followed by prednisone and RAAS inhibitors therapy. However, after 10 months, macrohematuria became constant, and UPCR increased. A new kidney biopsy was performed, showing an increase in sclerotic lesions. Prednisone was discontinued, and a trial with IBD TRF-budesonide 9 mg/day started. One month later, macrohematuria episodes disappeared and UPCR decreased, with a stable kidney function. After 5 months, due to a reduction in morning cortisol levels and difficulty in drug provisioning, we started to wean TRF-budesonide by 3 mg every 3 months, with complete withdrawal after 1 year. During this period, episodes of macrohematuria dramatically decreased, and UPCR and kidney function were maintained stable. Conclusion Our case demonstrates that TRF-budesonide could be considered an effective second-line treatment in pediatric IgAN, particularly when a long course of steroids is necessary to control active inflammation. However, pediatric clinical trials to identify the correct dosage and tolerability of TRF-budesonide are urgently needed., Author(s): Luca Antonucci [sup.1] [sup.2] , Manuela Colucci [sup.3] , Francesco Emma [sup.1] , Marina Vivarelli [sup.1] [sup.3] Author Affiliations: (1) https://ror.org/02sy42d13, grid.414125.7, 0000 0001 0727 6809, Division of Nephrology, [...]

Background The current study tested the hypothesis that urinary angiotensinogen (UAGT) and urinary monocyte chemoattractant protein-1 (UMCP-1) levels provide a specific index of intrarenal renin-angiotensin system (RAS) status and the degree of infiltration of macrophages associated with RAS blockade and immunosuppressant treatment in pediatric patients with chronic glomerulonephritis. Methods We measured baseline UAGT and UMCP-1 levels to examine the correlation between glomerular injury in 48 pediatric chronic glomerulonephritis patients before treatment. Furthermore, we performed immunohistochemical analysis of angiotensinogen (AGT) and CD68 in 27 pediatric chronic glomerulonephritis patients treated with RAS blockades and immunosuppressants for 2 years. Finally, we examined the effects of angiotensin II (Ang II) on monocyte chemoattractant protein-1 (MCP-1) expression in cultured human mesangial cells (MCs). Results Baseline UAGT and UMCP-1 levels positively correlated with urinary protein levels, scores for mesangial hypercellularity, rate of crescentic formation, and expression levels of AGT and CD68 in renal tissues (p < 0.05). UAGT and UMCP-1 levels were significantly decreased after RAS blockade and immunosuppressant treatment (p < 0.01), which was accompanied by AGT and CD68 (p < 0.01), as well as the magnitude of glomerular injury. Cultured human MCs showed increased MCP-1 messenger ribonucleic acid and protein levels after Ang II treatment (p < 0.01). Conclusions The data indicates that UAGT and UMCP-1 are useful biomarkers of the degree of glomerular injury during RAS blockade and immunosuppressant treatment in pediatric patients with chronic glomerulonephritis., Author(s): Tomoki Hattori [sup.1] [sup.2] , Keisuke Fujioka [sup.1] , Takashi Nagai [sup.1] , Shuji Kondo [sup.1] , Shoji Kagami [sup.1] , Masahiro Hirayama [sup.2] , Maki Urushihara [sup.1] Author [...]

Background Type 1 diabetes mellitus (T1DM) is a common endocrine disease in children. Early recognition of complications of T1DM is important for preventing long-term morbidity and mortality. We aimed to investigate whether urinary haptoglobin level is a biomarker of diabetic nephropathy in children with T1DM. Methods Ninety T1DM patients, aged between 2-18 years, and 60 healthy age-matched children were included in the study. Glycosylated hemoglobin (HbA1c), spot urine creatinine, microalbumin, protein and haptoglobin levels of all cases were measured and compared. Correlations between HbA1c level, duration of diabetes, spot urine microalbumin/creatinine (uACR), protein/creatinine (uPCR), and haptoglobin/creatinine (uHCR) ratios in the T1DM group were evaluated. Results T1DM and control groups were homogeneous in terms of age, sex, and anthropometric measurements. uACR was higher in the T1DM group than in the control group (14 mg/g vs. 6 mg/g) while uHCR was not elevated in T1DM patients. Nevertheless, uHCR was higher in the microalbuminuria group when compared to the normoalbuminuria group. In the T1DM group, moderate positive correlations between uPCR with uACR and uHCR, and weak correlation between uACR and uHCR were found (r = 0.60, p < 0.001; r = 0.55, p < 0.001; r = 0.24, p = 0.03, respectively). No significant relationship was found between diabetes duration, HbA1c levels and uACR, uPCR, and uHCR. Conclusions Although uHCR in the T1DM group was similar to the control group, uHCR was higher in the microalbuminuria group than in the normoalbuminuria group. These results show that the uHg level could be a biomarker of diabetic nephropathy, but not earlier than albuminuria in the disease course. Graphical abstract, Author(s): Digdem Bezen [sup.1] , Eren Vurgun [sup.2] , Hasan Dursun [sup.3] Author Affiliations: (1) grid.488643.5, 0000 0004 5894 3909, Department of Pediatrics, Pediatric Endocrinology, University of Health Sciences, Prof. [...]

Given the wide diversity of causes of hematuria, ranging from simple urinary tract infections with rapid recovery to severe glomerulonephritis with fast decline in kidney function, it is essential to recognize the underlying disease. The first objective of the assessment is to determine whether the cause of the hematuria is medically significant. The combination of hematuria with proteinuria, the presence of hypertension, or worsening kidney function can represent signs of progressive kidney disease. Differentiating the various causes of hematuria is often simple and obvious based on the clinical signs and gross appearance of the urine. However, in some instances, additional non-invasive investigations, such as ultrasound imaging, urinary red cell morphology, measurement of calcium and other solutes in the urine, evaluation of kidney function, and protein excretion, are needed to elucidate the nature of the hematuria. Taking a detailed family history can help in establishing the underlying cause in cases of familial hematuria. On the other hand, the decision to perform a kidney biopsy in children with asymptomatic hematuria remains a challenging issue for clinicians. Ultimately, the frequency of diagnosis of glomerular involvement causing hematuria may depend on the threshold for performing a kidney biopsy. The following review will focus on the diagnostics of hematuria, starting with difficulties regarding its definition, followed by various means to differentiate between urinary, glomerular, and other causes, and finally reviewing the most common diseases that, due to their frequency or their effect on kidney function, present a diagnostic challenge in everyday practice., Author(s): Orsolya Horváth [sup.1] , Attila J. Szabó [sup.1] , George S. Reusz [sup.1] Author Affiliations: (1) grid.11804.3c, 0000 0001 0942 9821, 1st Department of Pediatrics, Semmelweis University, , 53-54 [...]

Background Randomized controlled trials in pediatric kidney transplantation are hampered by low incidence and prevalence of kidney failure in children. Real-World Data from patient registries could facilitate the conduct of clinical trials by substituting a control cohort. However, the emulation of a control cohort by registry data in pediatric kidney transplantation has not been investigated so far. Methods In this multicenter comparative analysis, we emulated the control cohort (n = 54) of an RCT in pediatric kidney transplant patients (CRADLE trial; ClinicalTrials.gov NCT01544491) with data derived from the Cooperative European Paediatric Renal Transplant Initiative (CERTAIN) registry, using the same inclusion and exclusion criteria (CERTAIN cohort, n = 554). Results Most baseline patient and transplant characteristics were well comparable between both cohorts. At year 1 posttransplant, a composite efficacy failure end point comprising biopsy-proven acute rejection, graft loss or death (5.8% ± 3.3% vs. 7.5% ± 1.1%, P = 0.33), and kidney function (72.5 ± 24.9 vs. 77.3 ± 24.2 mL/min/1.73 m.sup.2P = 0.19) did not differ significantly between CRADLE and CERTAIN. Furthermore, the incidence and severity of BPAR (5.6% vs. 7.8%), the degree of proteinuria (20.2 ± 13.9 vs. 30.6 ± 58.4 g/mol, P = 0.15), and the key safety parameters such as occurrence of urinary tract infections (24.1% vs. 15.5%, P = 0.10) were well comparable. Conclusions In conclusion, usage of Real-World Data from patient registries such as CERTAIN to emulate the control cohort of an RCT is feasible and could facilitate the conduct of clinical trials in pediatric kidney transplantation. Graphical abstract, Author(s): Christian Patry [sup.1] , Lukas D. Sauer [sup.2] , Anja Sander [sup.2] , Kai Krupka [sup.1] , Alexander Fichtner [sup.1] , Jolanda Brezinski [sup.2] , Yvonne Geissbühler [sup.3] , [...]

Background Cystinuria is an inherited metabolic disease involving the defective transport of cystine and the dibasic amino acids in the renal proximal tubules that causes the formation of stones in the urinary system. In our regional child health program, cystinuria is included in newborn metabolic screening. Our objectives are the phenotypic characterization of our cystinuric pediatric cohort and to present our experience in neonatal cystinuria screening. Methods The study of clinical cases of pediatric patients diagnosed with cystinuria over a period of 32 years. All patients were studied at demographic, clinical, laboratory, radiological, and therapeutic levels. Results We diagnosed 86 pediatric patients with cystinuria; 36% of them had the homozygous biochemical phenotype. 95.3% of the patients were detected by neonatal metabolic screening. We performed urine biochemical analyses of parents with additional diagnoses of 63 adult patients. The mean follow-up time was 16.8 ± 8.5 years. 11.6% of patients developed one or more episodes of urinary tract infection during that period. Chronic kidney disease, proteinuria, and hypertension were uncommon (1.2%). 10.5% developed kidney stones at the mean age of presentation of 7.78 ± 7.6 years; 33% were recurrent. The risk of developing lithiasis was higher for homozygous biochemical-phenotype patients. Hypercalciuria was a significant risk factor in the development of lithiasis. Conclusions Our clinical data suggest that diagnosing cystinuria through neonatal screening could be a useful strategy for the detection of presymptomatic cases, in order to establish preventive measures, as well as for the detection of relatives at risk. Graphical abstract, Author(s): Juan Alberto Piñero-Fernández [sup.1] , Carmen Vicente-Calderón [sup.1] , María José Lorente-Sánchez [sup.1] , María Jesús Juan-Fita [sup.2] , José María Egea-Mellado [sup.2] , Inmaculada C. González-Gallego [sup.2] Author [...]

Background As there are no large-scale reports of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) mRNA vaccination in patients with nephrotic syndrome using immunosuppressive agents, we conducted the prospective study. Methods SARS-CoV-2 mRNA vaccines were administered to patients with nephrotic syndrome receiving immunosuppressive agents. The titers of SARS-CoV-2 spike protein receptor-binding domain antibodies were measured before and after vaccination. We evaluated factors associated with antibody titers after vaccination and analyzed adverse events. Results We enrolled 40 patients and evaluated vaccine immunogenicity in 35 of them. Seroconversion (> 0.8 U/mL) was achieved in all patients, and the median antibody titer was 598 U/mL (interquartile range, 89-1380 U/mL). Patients using mycophenolate mofetil (MMF) showed lower antibody titers than those who were not (median: 272 U/mL vs. 2660 U/mL, p = 0.0002), and serum immunoglobulin G (IgG) levels showed a weak linear relationship with antibody titers (R.sup.2 = 0.16). No breakthrough infections were noted. Three patients (7.5%) suffered from a relapse of nephrotic syndrome (2 and 3 days, respectively, after the first dose and 8 days after the second dose), two of whom had a history of relapse within 6 months before the vaccination. Conclusions The SARS-CoV-2 mRNA vaccine was immunogenic in patients with nephrotic syndrome using immunosuppressive agents, although the use of MMF and low levels of serum IgG were associated with lower antibody titers after vaccination. Patients with high disease activity may experience a relapse of nephrotic syndrome after vaccination. Graphical abstract A higher resolution version of the Graphical abstract is available as Supplementary information, Author(s): Koichi Kamei [sup.1] , Masao Ogura [sup.1] , Mai Sato [sup.1] , Kentaro Nishi [sup.1] , Kensuke Shoji [sup.2] , Takanori Funaki [sup.2] , Chikara Ogimi [sup.2] , Shuichi [...]

Background The most well-known and common long-term complication in children with renal parenchymal scarring (RPS) is hypertension (HT). The present study aimed to evaluate the presence of HT in children with RPS based on ambulatory blood pressure monitoring (ABPM) and to compare the patients' blood pressure (BP) to that in healthy controls matched for age, gender, and BMI. Methods The study included 55 patients aged < 18 years diagnosed with RPS who were followed up for [greater than or equal to] 1 year and 48 healthy controls matched for age, gender, and BMI. Results Mean age in the RPS group was 12.8 ± 3.3 years, and 49.1% of the group were female. Among the RPS patients, 28 were diagnosed with HT based on ABPM, of which 18 (32.7%) had an office BP 95 percentile for age, gender, and height. The difference in detection of HT based on ABPM between the two groups was significant (P = 0.00). Conclusions Early diagnosis of HT via ABPM can help prevent development of kidney failure and cardiovascular disease in patients with RPS, significantly reducing the rates of morbidity and mortality. All children with RPS should be evaluated via ABPM, even if office BP measurements are normal. Graphical abstract, Author(s): Deniz Karakaya [sup.1] [sup.2] , Evrim Kargin Çakici [sup.1] , Fatma Yazilitas [sup.1] , Tülin Güngör [sup.1] , Evra Çelikkaya [sup.1] , Esra Baglan [sup.1] , Mehmet Bülbül [sup.1] [...]

Background Reports on long-term complications of childhood-onset nephrotic syndrome (NS), such as obesity, osteoporosis, growth failure, and hypertension, are mostly from developed countries not representing South Asian ethnicities. Furthermore, data on cardiovascular health among patients with childhood-onset NS are limited. Methods This was an observational study involving patients attending a tertiary care center. Patients aged 15 years and older were examined for long-term complications and remission of NS at their visit in December 2021. Childhood-onset NS meant onset of NS before 10 years of age. Long-term complications included obesity, growth failure, low bone mineral density (BMD) Z score, hypertension, and increased carotid intima-media thickness (cIMT). Long-term remission was defined as no relapse for the last [Formula omitted] 3 consecutive years without immunosuppressive medication to maintain remission. Results Of 101 patients studied (~ 80% with frequent relapsing (FR)/steroid-dependent (SD) NS), the mean age was 17.6 (± 2.4) years at the time of study. Long-term complications were noted in 89.1% of patients which included one or more of the following: obesity (22.7%), growth failure (31.7%), low BMD Z score (53.5%), hypertension (31.7%), and high cIMT (50.5%). Thirty-nine patients (38.6%) were in long-term remission at the time of the study. Growth failure and low BMD Z scores were less frequent in patients with long-term remission compared to those without long-term remission. Conclusions In patients with childhood-onset NS (predominantly FR/SDNS) who were studied at [Formula omitted] 15 years of age, ~ 90% had long-term complications which included high cIMT in 50%. Only ~ 40% were in long-term remission. Graphical abstract, Author(s): Joyita Bharati [sup.1] , Karalanglin Tiewsoh [sup.2] , Lesa Dawman [sup.2] , Tarvinder Singh [sup.3] , Ujjwal Gorsi [sup.3] , Arun Prabhahar Rajarajen [sup.1] , Aakanksha Sharma [sup.1] , [...]

Background Viral upper respiratory tract infections trigger nephrotic syndrome relapses. Few data exist on the impact of the SARS-CoV-2 pandemic on the risk of relapse in children with idiopathic nephrotic syndrome (INS). Methods In a Belgian and Italian cohort of children with INS, we performed a retrospective analysis on the number and duration of relapses observed in 3 different periods in 2020: first COVID period, February 15-May 31; second COVID period, June 1-September 14; third COVID period, September 15-December 31. Relapse rates were compared to those of the previous 5 years (PRECOVID period). For the years 2019 and 2020, all causes and INS relapse-related hospitalizations were recorded. Hospitalizations and deaths due to SARS-CoV-2 infection were also recorded. In the Belgian cohort, SARS-CoV-2 serologies were performed. Results A total of 218 patients were enrolled, and 29 (13.3%) were diagnosed with new-onset INS during the COVID period. Relapse rates per 1000 person-days were as follows: 3.2 in the PRECOVID period, 2.7 in the first COVID period, 3.3 in the second COVID period, and 3.0 in the third COVID period. The incidence rate ratio for the total COVID period was 0.9 (95%CI 0.76 to 1.06; P = 0.21) as compared to the PRECOVID period. During 2020, both the proportion of patients hospitalized for recurrence (14.2% vs. 7.6% in 2019; P = 0.03) and the rate of hospitalization for recurrence (IRR 1.97 (95%CI 1.35 to 2.88); P = 0.013) were higher compared to 2019. In December 2020, anti-SARS-CoV-2 antibodies were detected in 31% of the Belgian cohort. Patients with positive and negative SARS-CoV-2 serology did not differ significantly in relapse rate (2.4 versus 4.2 per 1000 person-days). The number of new INS cases remained similar between 2020, 2019, and 2018. Conclusion The first year of the SARS-CoV-2 pandemic did not significantly affect the relapse rate in children with INS. No serious infections were reported in this population of immunosuppressed patients. Graphical abstract A higher resolution version of the Graphical abstract is available as Supplementary information, Author(s): Benedetta Chiodini [sup.1] , Anita Sofia Bellotti [sup.2] , William Morello [sup.2] , Chiara Bulgaro [sup.2] , Ilaria Farella [sup.3] , Mario Giordano [sup.3] , Giovanni Montini [sup.2] , [...]

Background Children with underlying kidney diseases display a mild course of SARS-CoV-2 infection, but they only accounted for a minority of cases until the spread of the Omicron variant. Nonetheless, idiopathic nephrotic syndrome (INS) has been advocated as a predictor of worse outcome. Methods We investigated the spread, severity, and risk of relapse related to SARS-CoV-2 infection among children with INS. The incidence and characteristics of SARS-CoV-2 infections, immunosuppression, and vaccination status were retrospectively collected from the beginning of the pandemic to May 31, 2022. Results We enrolled 176 patients (73 females, median age 10.22 years); 28 had a steroid-resistant disease, and 108 (61.4%) were on immunosuppressive therapy. Sixty-one (34.7%) patients reported a SARS-CoV-2 infection, with incidence peaking between December 2021 and January 2022. No hospitalization or deaths were reported, and symptoms were absent or mild. The rate of SARS-CoV-2 infection was similar in children with and without immunosuppression (33.8% vs 35.2%; p = 0.85). None of the 38 immunosuppressed patients discontinued the therapy, but they had a longer time to negativization (13.31 vs. 10.04 days; p = 0.03). Proteinuria was detected in 7 patients, but only one had a relapse requiring steroid therapy, with prompt remission and a mild course. Conclusions After the spread of the Omicron variant, the rate of SARS-CoV-2 infection in children with INS was much higher than previously reported. In this large cohort, symptoms were mild, even in immunosuppressed patients and those with proteinuria. During the infection, transient proteinuria was common with a low rate of relapses. Graphical abstract, Author(s): William Morello [sup.1] , Federica Alessandra Vianello [sup.1] , Chiara Bulgaro [sup.1] , Giovanni Montini [sup.1] [sup.2] Author Affiliations: (1) grid.414818.0, 0000 0004 1757 8749, Pediatric Nephrology, Dialysis and [...]

Background Pompe disease (PD) is a lysosomal glycogen storage disorder caused by a deficiency in acid [alpha]-glucosidase (GAA) activity. Various organs, including the skeletal muscle, cardiac muscle, and liver, are commonly involved. Early initiation of enzyme replacement therapy (ERT) with recombinant human [alpha]-glucosidase (rhGAA) can improve the outcome. However, some patients experience a poor clinical course despite ERT because of the emergence of anti-rhGAA antibodies that neutralize rhGAA. Treatment against anti-rhGAA antibodies is challenging. Case-diagnosis/treatment A 14-year-old boy with late-onset PD was referred to our hospital with proteinuria detected by school urinalysis screening. He was diagnosed with PD at the age of 4 years based on muscle biopsy and decreased GAA activity. Treatment with rhGAA was initiated, but anaphylaxis occurred frequently. Anti-rhGAA antibodies were detected and immune tolerance therapy was therefore given, but his antibody titer remained high. Kidney biopsy revealed stage II membranous nephropathy. Immunohistochemistry staining revealed anti-rhGAA antibody/rhGAA immune complexes along the glomerular capillary loop. Aggressive immunotherapy combined with bortezomib and rituximab was then initiated. Serum levels of anti-rhGAA antibodies decreased significantly and his proteinuria finally resolved. Conclusions There have been few reports of membranous nephropathy associated with ERT for PD. We clarified the cause in the current patient. Bortezomib and rituximab effectively suppressed anti-rhGAA antibody production resulting in the resolution of proteinuria and maintenance of ERT efficacy., Author(s): Keigo Sasaki [sup.1] , Toru Uchimura [sup.1] , Aya Inaba [sup.1] , Masako Otani [sup.2] , Junko Hanakawa [sup.3] , Shuichi Ito [sup.1] Author Affiliations: (1) grid.413045.7, 0000 0004 [...]

Idiopathic nephrotic syndrome is the most frequent pediatric glomerular disease, affecting from 1.15 to 16.9 per 100,000 children per year globally. It is characterized by massive proteinuria, hypoalbuminemia, and/or concomitant edema. Approximately 85-90% of patients attain complete remission of proteinuria within 4-6 weeks of treatment with glucocorticoids, and therefore, have steroid-sensitive nephrotic syndrome (SSNS). Among those patients who are steroid sensitive, 70-80% will have at least one relapse during follow-up, and up to 50% of these patients will experience frequent relapses or become dependent on glucocorticoids to maintain remission. The dose and duration of steroid treatment to prolong time between relapses remains a subject of much debate, and patients continue to experience a high prevalence of steroid-related morbidity. Various steroid-sparing immunosuppressive drugs have been used in clinical practice; however, there is marked practice variation in the selection of these drugs and timing of their introduction during the course of the disease. Therefore, international evidence-based clinical practice recommendations (CPRs) are needed to guide clinical practice and reduce practice variation. The International Pediatric Nephrology Association (IPNA) convened a team of experts including pediatric nephrologists, an adult nephrologist, and a patient representative to develop comprehensive CPRs on the diagnosis and management of SSNS in children. After performing a systematic literature review on 12 clinically relevant PICO (Patient or Population covered, Intervention, Comparator, Outcome) questions, recommendations were formulated and formally graded at several virtual consensus meetings. New definitions for treatment outcomes to help guide change of therapy and recommendations for important research questions are given., Author(s): Agnes Trautmann [sup.1] , Olivia Boyer [sup.2] , Elisabeth Hodson [sup.3] , Arvind Bagga [sup.4] , Debbie S. Gipson [sup.5] , Susan Samuel [sup.6] , Jack Wetzels [sup.7] , [...]

Background There are few reports on kidney complications after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) messenger RNA (mRNA) vaccination, especially in the pediatric population. We report a pediatric case diagnosed with crescentic glomerulonephritis (CrGN) after the second dose of the SARS-CoV-2 mRNA vaccine. Case-diagnosis/treatment A 16-year-old girl was admitted due to dyspnea and headache approximately 6 weeks after receiving the second SARS-CoV-2 mRNA vaccine (Pfizer-BioNTech). She had previously experienced fever, nausea, vomiting, and dyspnea after the first vaccination, which persisted for a week. On admission, her blood pressure was 155/89 mmHg with a 7 kg weight gain in a month. She had microhematuria and proteinuria. Laboratory findings were as follows: blood urea nitrogen/creatinine, 66/9.57 mg/dL; and brain natriuretic peptide, 1,167 pg/mL. Anti-neutrophil cytoplasmic antibody (ANCA), anti-glomerular basement membrane (GBM) antibody, and antinuclear antibody findings were negative. Kidney doppler sonography revealed swelling and increased echogenicity of both kidneys with increased resistive index. Cardiac magnetic resonance imaging results showed early minimal fibrosis of myocarditis. We then started hemodialysis. Kidney biopsy showed diffuse extra capillary proliferative glomerulonephritis with diffuse crescent formation. We treated the patient with methylprednisolone pulse therapy with subsequent oral steroids and mycophenolate mofetil. Although dialysis was terminated, the patient remained in the chronic kidney disease stage. Conclusions This is the first case of ANCA-negative CrGN after SARS-CoV-2 mRNA vaccination in the pediatric population. As children are increasingly vaccinated with SARS-CoV-2 mRNA vaccines, monitoring for kidney complications is warranted., Author(s): Sujeong Kim [sup.1] , Jiwon Jung [sup.1] , Haeyon Cho [sup.2] , Jina Lee [sup.1] , Heounjeong Go [sup.2] , Joo Hoon Lee [sup.1] Author Affiliations: (1) grid.267370.7, 0000 [...]

Background CD151 is a cell-surface molecule of the tetraspanin family. Its lateral interaction with laminin-binding integrin É3[beta]1 is important for podocyte adhesion to the glomerular basement membrane (GBM). Deletion of Cd151 in mice induces glomerular dysfunction, with proteinuria and associated focal glomerulosclerosis, disorganisation of GBM and tubular cystic dilation. Despite this, CD151 is not routinely screened for in patients with nephrotic-range proteinuria. We aimed to better understand the relevance of CD151 in human kidney disease. Methods Next-generation sequencing (NGS) was used to detect the variant in CD151. Electron and light microscopy were used to visualise the filtration barrier in the patient kidney biopsy, and immunoreactivity of patient red blood cells to anti-CD151/MER2 antibodies was performed. Further validation of the CD151 variant as disease-causing was performed in zebrafish using CRISPR-Cas9. Results We report a young child with nail dystrophy and persistent urinary tract infections who was incidentally found to have nephrotic-range proteinuria. Through targeted NGS, a novel, homozygous truncating variant was identified in CD151, a gene rarely reported in patients with nephrotic syndrome. Electron microscopy imaging of patient kidney tissue showed thickening of GBM and podocyte effacement. Immunofluorescence of patient kidney tissue demonstrated that CD151 was significantly reduced, and we did not detect immunoreactivity to CD151/MER2 on patient red blood cells. CRISPR-Cas9 depletion of cd151 in zebrafish caused proteinuria, which was rescued by injection of wild-type CD151 mRNA, but not CD151 mRNA containing the variant sequence. Conclusions Our results indicate that a novel variant in CD151 is associated with nephrotic-range proteinuria and microscopic haematuria and provides further evidence for a role of CD151 in glomerular disease. Our work highlights a functional testing pipeline for future analysis of patient genetic variants. Graphical abstract A higher resolution version of the Graphical abstract is available as Supplementary information, Author(s): Richard W. Naylor [sup.1] , Elizabeth Watson [sup.2] , Samantha Williamson [sup.3] , Rebecca Preston [sup.1] , J Bernard Davenport [sup.1] , Nicole Thornton [sup.4] , Martin Lowe [sup.5] [...]

The syndrome of thrombotic microangiopathy (TMA) is a clinical-pathological entity characterized by microangiopathic hemolytic anemia, thrombocytopenia, and end organ involvement. It comprises a spectrum of underlying etiologies that may differ in children and adults. In children, apart from ruling out shigatoxin-associated hemolytic uremic syndrome (HUS) and other infection-associated TMA like Streptococcus pneumoniae-HUS, rare inherited causes including complement-associated HUS, cobalamin defects, and mutations in diacylglycerol kinase epsilon gene must be investigated. TMA should also be considered in the setting of solid organ or hematopoietic stem cell transplantation. In this review, acquired and inherited causes of TMA are described with a focus on particularities of the main causes of TMA in children. A pragmatic approach that may help the clinician tailor evaluation and management is provided. The described approach will allow for early initiation of treatment while waiting for the definitive diagnosis of the underlying TMA., Author(s): Lilian Monteiro P. Palma [sup.1] , Maria Helena Vaisbich-Guimarães [sup.2] , Meera Sridharan [sup.3] , Cheryl L. Tran [sup.4] , Sanjeev Sethi [sup.5] Author Affiliations: (1) grid.411087.b, 0000 0001 [...]

Background Pediatric lupus nephritis (pLN) is one of the most refractory secondary kidney diseases in childhood. The treat-to-target (T2T) strategy has become the standard treatment for systemic lupus erythematosus (SLE). This study reviewed clinical features, overall remission status, and factors affecting prognosis, to guide pLN management according to T2T strategy. Methods This single-center retrospective study studied 220 children diagnosed with LN from January 2012 to December 2018, with > 6-month follow-up data on 173 and complete data on 137 patients. Primary outcome was treatment failure (deterioration or no response) at the latest follow-up. Results The most common pLN manifestation was proteinuria (81.36%). Females presented more often with rash (P Conclusions pLN usually presented with proteinuria, and class IV LN was the dominant pathology. Hypertension, nervous-system involvement, treatment non-compliance, and lower eGFR at diagnosis were independent risk factors for poor prognosis of kidney outcomes. Compared with renal remission rate and cumulative overall survival rate, the proportion of targets achieved was not ideal, suggesting T2T strategy should be used to guide pLN management. Graphical abstract, Author(s): Shiyuan Qiu [sup.1] [sup.3] , Hengci Zhang [sup.2] , Sijie Yu [sup.3] , Qin Yang [sup.3] , Gaofu Zhang [sup.3] , Haiping Yang [sup.3] , Qiu Li [sup.3] , [...]

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 m.sup.2) 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., Author(s): Ben C. Reynolds [sup.1] , Angela Lamb [sup.1] , Caroline A. Jones [sup.2] , Pallavi Yadav [sup.3] , Kay S. Tyerman [sup.3] , Colin C. Geddes [sup.4] Author Affiliations: [...]

Background Nephritis is a recognised complication of IgA vasculitis (IgAV, Henoch-Schönlein purpura) contributing to 1-2% of all chronic kidney disease (CKD) stage 5. Improved understanding may reduce irreversible damage in IgAV nephritis (IgAV-N). Objective The aim of this study was to perform a comprehensive systematic literature review to identify promising clinical and pre-clinical urine biomarkers in children with IgAV-N that could predict the presence of nephritis and/or determine its severity. Methods A systematic literature review was performed using four search engines and a predefined search term strategy. Promising biomarkers were divided in terms of clinical or pre-clinical and ability to predict the presence of nephritis or determine its severity. Results were described using statistical significance (p < 0.05) and area under the curve (AUC) values. Results One hundred twenty-one studies were identified; 13 were eligible. A total of 2446 paediatric patients were included: healthy controls (n = 761), children with IgAV-N (n = 1236) and children with IgAV without nephritis (IgAV-noN, n = 449). Fifty-one percent were male, median age 7.9 years. The clinical markers, 24-h protein quantity and urine protein:creatinine ratio, were deemed acceptable for assessing severity of nephritis (AUC < 0.8). Urinary albumin concentration (Malb) performed well (AUC 0.81-0.98). The most promising pre-clinical urinary biomarkers in predicting presence of nephritis were as follows: kidney injury molecule-1 (KIM-1) (AUC 0.93), monocyte chemotactic protein-1 (MCP-1) (AUC 0.83), N-acetyl-[beta]-glucosaminidase (NAG) (0.76-0.96), and angiotensinogen (AGT) (AUC not available). Urinary KIM-1, MCP-1, and NAG appeared to correlate with disease severity. Conclusions Longitudinal studies are needed to assess whether pre-clinical biomarkers enhance standard of care in IgAV-N., Author(s): Chloe E. C. Williams [sup.1] [sup.2] , Aileen Toner [sup.1] , Rachael D. Wright [sup.2] , Louise Oni [sup.2] [sup.3] Author Affiliations: (1) grid.10025.36, 0000 0004 1936 8470, School [...]