International Study Of Kidney Disease In Children Research Articles

Diagnostic performance of renal cortical elasticity by supersonic shear wave imaging in pediatric glomerular disease

PurposeTo explore the diagnostic performance of renal cortical elasticity expressed by Young’s modulus (YM) using the supersonic shear wave imaging (SSI) technique in pediatric glomerular disease. Materials and methodsSeventy-one children with glomerular disease confirmed by renal biopsy and sixty healthy volunteers were enrolled in this study. Conventional and SSI ultrasound examinations were performed in all individuals for both kidneys. We measured renal length, renal width, renal thickness, parenchyma thickness, interlobar arterial resistive index (RI) and the YM of the middle and lower pole. ResultsRegardless of which pole and which side of the kidney, the YM in the disease group was significantly higher than that in the control group (P < 0.001). The YM of the middle pole in the left kidney demonstrated the largest AUC (0.936, P < 0.001), and the corresponding cut-off value was 15.48 kPa with a sensitivity of 87.3% and a specificity of 86.7%. There was no significant difference in the YM among different pathological types of pediatric glomerular disease in the disease group, and the same in different grades of patients with Immunoglobulin A (IgA) nephropathy by Lee classification and the Oxford Classification as well as Henoch-Schonlein purpura nephritis (HSPN) by International Study of Kidney Disease in Children (ISKDC) classification (P > 0.05). We found positive but weak correlations between the YM and renal length (r = 0.299, P = 0.001), renal width (r = 0.408, P < 0.001), renal thickness (r = 0.299, P = 0.001), and parenchyma thickness (r = 0.212, P = 0.015), whereas the YM had no significant correlations with age, sex, BMI, interlobar arterial RI, and laboratory findings (P > 0.05). ConclusionsSSI technology is a non-invasive and feasible method for the diagnosis of pediatric glomerular disease. However, SSI did not show good performance in distinguishing different pathological types and disease grades in our study.

Value of the modified semiquantitative classification in predicting outcomes in children with Henoch–Schönlein purpura nephritis

AbstractBackgroundThe modified semiquantitative classification (SQC) is a new pathological classification for Henoch–Schönlein purpura nephritis (HSPN), and its prognostic value with regard to the outcomes of HSPN is unclear.MethodsWe performed a retrospective review of 249 patients with biopsy‐proven HSPN admitted to the Children's Hospital of Chongqing Medical University. In addition to the International Study of Kidney Disease in Children (ISKDC) classification, renal biopsy specimens were also reevaluated according to the SQC.ResultsDuring the follow‐up period of 2.9 (1.0–6.9) years, 14 (5.6%) patients reached the poor outcome at the end of follow‐up. The SQC activity and chronicity indexes were positively correlated with the clinical manifestations, conventional pathology grades, and 24‐h urinary protein (24hUP). The difference in the areas under the curve between the total biopsy SQC scores and ISKDC classification was 0.12 (p = .001, 95% CI: 0.0485–0.192). In the receiver operating characteristic (ROC) curve analysis of 1‐year, 3‐year, and 5‐year poor outcomes and total biopsy SQC scores, a total biopsy score ≥10 was associated with a higher risk of an adverse outcome.ConclusionOur study suggests that the SQC indexes are clearly correlated with the clinical and pathological findings of HSPN. The SQC is more sensitive than ISKDC classification for the prediction of the long‐term outcomes of HSPN in children.

Bowman’s capsule rupture and the Oxford MEST-C score in adult patients with Immunoglobulin a vasculitis nephritis: a single center experience

Objective Bowman’s capsule rupture (BCR) is a glomerular pathological change, but it is still not well recognized in immunoglobulin A vasculitis nephritis (IgAV-N). The Oxford MEST-C score is a classification for IgA nephropathy; however, its clinical correlation and prognostic value in adult patients with IgAV-N are unclear. Methods A retrospective study of 145 adult patients with IgAV-N diagnosed by renal biopsy was conducted. Clinical manifestations, pathological changes and the prognosis of IgAV-N patients were compared depending on the presence or absence of BCR, International Study of Kidney Disease in Children (ISKDC) classification and MEST-C score. The primary endpoint events were end-stage renal disease, renal replacement therapy and all-cause death. Results In total, 51 of 145 (35.17%) patients with IgAV-N presented with BCR. Patients with BCR had more proteinuria, lower serum albumin, and more crescents. Compared with IgAV-N patients with crescents only, 51/100 patients with crescents combined with BCR had a higher proportion of crescents in all glomeruli (15.79% vs. 9.09%; p = 0.003). Patients with higher ISKDC grades had more severe clinical presentation, but it did not reflect the prognosis. However, the MEST-C score not only reflected clinical manifestations but also predicted prognosis (p < 0.05). BCR contributed to the effectiveness of the MEST-C score in predicting the prognosis of IgAV-N (C-index: 0.845 to 0.855). Conclusions BCR is associated with clinical manifestations and pathological changes in patients with IgAV-N. The ISKDC classification and MEST-C score are related to the patient’s condition, but only the MEST-C score is correlated with the prognosis of patients with IgAV-N, while BCR can improve its predictive ability.

Steroid- and immunosuppressant-based protocol of Henoch-Schönlein purpura nephritis without angiotensin inhibitors in the acute phase.

The Kidney Disease: Improving Global Outcomes (KDIGO) guidelines suggest initially using angiotensin-converting-enzyme inhibitors (ACE-Is) and/or angiotensin receptor blockers (ARBs) to treat Henoch-Schönlein purpura nephritis (HSPN). However, these guidelines might overlook the potential benefits of aggressive therapy. Therefore, we evaluated the efficacy of an HSPN protocol that primarily uses steroids and immunosuppressants, without ACE-Is or ARBs. We determine treatment intensity based on International Study of Kidney Diseases in Children (ISKDC) grading. Fifty-one patients were treated with our protocol that primarily uses steroids and immunosuppressants. ACE-Is and ARBs were not used in the acute phase, including before renal biopsy. We evaluated the proteinuria disappearance rate, duration to proteinuria disappearance, and estimated glomerular filtration rate (eGFR) at the time of last observation and compared them to those in previous reports. Proteinuria disappeared in 49 patients (96%) within a median of 5 months. The median eGFR was 116.0 mL/min/1.73 m2 at the time of last observation. Six of 51 patients had acute kidney injury (eGFR<90 mL/min/1.73 m2) before treatment, but all recovered during the observation period (median 52 months). Our steroid- and immunosuppressant-based protocol without ACE-Is or ARBs in the acute phase of HSPN had almost equivalent efficacy to that in previous studies that used ACE-Is and/or ARBs with steroids and immunosuppressants.

The first randomized controlled trial in pediatric nephrology: the history of the International Study of Kidney Disease in Children (ISKDC).

The International Study of Kidney Disease in Children (ISKDC), begun in 1966, conducted the first international collaborative randomized blinded controlled trial in pediatric nephrology and one of the first in either pediatrics or nephrology. For this trial, the ISKDC developed the criteria, such as those for response and relapse, used today to describe the clinical course of the nephrotic syndrome, and the trial generated the nephropathologic terminology and criteria which largely remain the current standards. Over an approximately 20-year span, the ISKDC followed the natural history and evaluated the therapeutic effectiveness of therapies in over 500 children with the nephrotic syndrome from three continents. It published 14 peer-reviewed studies and several reports and commentaries, many of which helped create current standards of practice for therapy of childhood nephrotic syndrome and consequently remain highly cited today. The ISKDC continues to be an important model for subsequent collaborative studies and was the impetus for the development of regional and national pediatric nephrology societies leading to the recognition and growth of pediatric nephrology as a separate subspecialty. A higher resolution version of the Graphical abstract is available as Supplementary information.

Clinico-Biochemical Profile and Identification of Independent Risk Factors of Frequent Relapse in Childhood-Onset Steroid-Sensitive Nephrotic Syndrome.

Background and aimNephrotic syndrome is one of the commonest glomerular diseases in children, and the majority of them have minimal change lesions in histology with a favorable outcome. Most children with minimal change disease (MCD) are steroid-sensitive, but half of them have a frequent relapse and a prolonged course. This study was conducted to evaluate the clinical manifestations and biochemical profile and to determine independent risk factors of frequent relapse in children with steroid-sensitive nephrotic syndrome (SSNS).MethodsThis was a tertiary care hospital-based observational study conducted at the pediatric department of Kalinga Institute of Medical Sciences (KIMS), Bhubaneswar, India, from October 2017 to September 2019. Fifty-three children from age one to 15 years admitted with steroid-sensitive nephrotic syndrome diagnosed as per the International Study of Kidney Disease in Children (ISKDC) criteria were enrolled in the study. On admission, history-taking, physical examination, and routine hematological and biochemical tests were carried out. Children who had no infection were started oral prednisolone at the dose of 2 mg/kg/day for six weeks, followed by 1.5 mg/kg/day on alternate days for six weeks with daily follow-up for evidence of proteinuria till remission. The parameters evaluated were age at presentation, sex, type of presentation, precipitating factors, laboratory findings, and rapidity of steroid response. All children were followed up for one year, and those with no relapse over a period of one year after remission served as the control group to determine the risk factors for relapse. Data were analyzed using standard statistical software (Stata version 13.1, StataCorp LLC, College Station, Texas, USA).ResultsOf the 53 cases, 47% of the children had a relapse. In the relapse category, 88% were male, and 67% were between one and 5.5 years. The clinical manifestations during the first episode in the relapse group were similar to the no relapse group. Investigations revealed that 64% of the children with relapse had serum total protein ≤ 4.2 g/dL (p = 0) and that 59% had serum albumin ≤ 1.8 g/dL (p = 0.004). In the relapse group, 41% of the children went into remission within two weeks of initiation of therapy as compared with 80% in the no relapse group.ConclusionThe risk factors determined for relapse in SSNS are male sex, younger age, low serum albumin, low serum total protein, and delayed response to steroid therapy.

Leflunomide therapy for IgA vasculitis with nephritis in children

BackgroundHenoch-Schönlein purpura (HSP), also called IgA vasculitis, is a systemic vasculitis characterized by deposits of immunoglobulin A in blood vessels. Renal impairment of these patients is the main determinant of prognosis. The optimal treatment of HSP nephritis (HSPN) in children remains controversial, but many clinicians administer an immunosuppressive agent with a corticosteroid. A previous study reported that leflunomide (LEF) with a corticosteroid was effective for adult patients with HSPN and nephrotic proteinuria. However, data on this treatment in pediatric patients is limited.MethodsWe described our experience at a single center on the use of LEF in 5 pediatric patients who had IgA vasculitis with proteinuria that was nearly 50 mg/kg (nephrotic range) and remained high despite administration of intravenous steroid, and biopsy-proven nephritis. All patients had class II to IIIb lesions based on the International Study of Kidney Disease in Children (ISKDC).ResultsWe successfully treated all 5 children who had IgA vasculitis with nephritis using LEF with a corticosteroid. Four patients achieved a complete remission of proteinuria, and 1 patient had significantly reduced proteinuria. The children received LEF for 6 months to 12 months, and none of them had severe adverse events.ConclusionsTo our knowledge, this is the first case series to report successful treatment of pediatric HSPN with LEF in combination with a corticosteroid.

Changing Histopathological Trends in Idiopathic Steroid Resistant Nephrotic Syndrome in Pediatric Population

Objective: This study aims to determine the most prevalent histopathological subtype of nephrotic syndrome in children and assess the response to corticosteroids therapy in different histological patterns. Methodology: A cross-sectional analysis of 64 patients was conducted from february 2018 to june 2019 at Pakistan Institute of Medical Sciences Hospital (PIMS), Islamabad. Patients were clinically assessed and investigated using criteria determined by International Study of Kidney Disease in Children (ISKDC). Renal biopsies were performed where indicated and samples were examined with the help of light microscopy and immunofluorescence. IBM SPSS 24 and Excel 2010 were used for data interpretation and illustration. Results: The study comprised of 64 patients including 32 (50%) females and 32 (50%) males, ranging from 2 years to 12 years, with a mean age of 6.78 years. The results showed FSGS (28.13%)  and MCD (28.13%)  as the most common pattern on histopathology followed by MPGN (15.63%), Mesengioproliferative Glomerulonephritis (9.38%), Membranous glomerulonephritis (9.38%), Diffuse Proliferative glomerulonephritis (DPGN) (3.13%), Lupus Nephritis (LN) (3.13%), IgM nephropathy (IgMN) (3.13%). 87.5% children were observed to be resistant to corticosteroid therapy, whereas, the rest of the 12.5% patients responded to corticosteroid treatment. Conclusion: Resistance to steroids has become more prevalent in all variants of nephrotic syndrome in children. FSGS and Minimal change disease are the most frequently seen histopathological patterns observed in the pediatric population of Pakistan, having Steroid resistant nephrotic syndrome (SRNS). Furthermore, an increase in the frequency of FSGS was observed in our population, in comparison to prior studies.

Using MEST-C Scores and the International Study of Kidney Disease in Children Classification to Predict Outcomes of Henoch-Schönlein Purpura Nephritis in Children.

Introduction: Henoch–Schönlein purpura nephritis (HSPN) and IgA nephropathy (IgAN) bear similarities in some aspects. The histological classification of HSPN was built on the International Study of Kidney Disease in Children (ISKDC) criteria, while IgAN was established on the 2016 Oxford classification (MEST-C scores). The purpose of this paper was to discuss the predictive value of the ISKDC classification and MEST-C scores in children with HSPN.Methods: We performed a retrospective study of 877 children with HSPN in a single center between 2001 and 2019. The primary outcome was defined as chronic kidney disease—estimated glomerular filtration rate (eGFR) <90 ml/min/1.73 m2.Results: During the follow-up period of 23.3 (10.9–47.9) months, 51 (5.8%) patients reached the primary outcome. As revealed in a Kaplan–Meier plot, segmental glomerulosclerosis (S) (P < 0.001) and tubular atrophy/interstitial fibrosis (T) (P < 0.001) significantly predict poor renal outcome. Other Oxford lesions and the ISKDC classification, however, did not show a significant difference in a worse outcome. In a multivariate Cox model adjusted for pathological and clinical factors, eGFR [hazard ratio (HR) = 2.831, 95% confidence interval (95% CI) = 1.359–5.896], S lesion (HR = 3.936, 95% CI = 2.078–7.457), and T lesion (HR = 4.002, 95% CI = 1.733–9.242) were independent risk factors for the renal outcome.Conclusion: This series constitutes the largest series reported so far in the literature of such patients. According to our findings, S and T of the Oxford classification, which are ignored by the ISKDC classification, could be applied to predict the renal prognosis of children with HSPN.

Steroid treatment for the first episode of childhood nephrotic syndrome: comparison of the 8 and 12 weeks regimen using an individual patient data meta-analysis

Steroids are the cornerstone of the treatment of childhood nephrotic syndrome. The optimal duration for the first episode remains a matter of debate. The aim of this study is to determine whether the 8 weeks International Study of Kidney Disease in Children (ISKDC) regimen is equally effective as the 12 weeks steroid regimen from the German society of pediatric nephrology (Arbeitsgemeinschaft für Pädiatrische Nephrologie [APN]). An individual patient data (IPD) meta-analysis of randomized controlled trials reporting on prednisolone treatment for a first episode of childhood nephrotic syndrome was conducted. European trials aimed at investigating the ISKDC and/or APN steroid regimen were selected. The lead investigators of the selected trials were requested to provide the IPD of the specific treatment groups. Four trials included European cohorts using dosing schedules according to the regimens studied. IPD of two trials were available. A significant difference was found in time to first relapse after cessation of steroid treatment between the 8 and 12 weeks treatment group with a median time to relapse of 29 and 63 days, respectively. Moreover, relapse rate ratios during total follow-up were 51% higher for the 8 weeks regimen. Finally, younger children have a significantly lower time to first relapse and frequently relapsing nephrotic syndrome.Conclusions: The results of this IPD meta-analysis suggest that the 8 weeks steroid regimen for a first episode of steroid-sensitive nephrotic syndrome may not be equally effective as the 12 weeks steroid regimen. Moreover, this study highlights the importance of using uniform definitions to enable accurate comparison and interpretation of trial results.Trial registration: Registration number: CRD42020199244, date of registration 16-08-2020What is Known:• Steroids are the cornerstone of the treatment of childhood nephrotic syndrome, however the optimal duration for the first episode remains a matter of debate.• Currently, the 8 weeks ISKDC protocol and 12 weeks APN protocol are among the most frequently used protocols in Europe.What is New:• The 8 weeks steroid regimen for a first episode of steroid-sensitive nephrotic syndrome may not be equally effective as the 12 weeks steroid regimen for the treatment of a first episode of nephrotic syndrome.• Younger children have a significantly shorter time to first relapse and time to frequent relapsing nephrotic syndrome.

Risk factors associated with renal crescentic formation in pediatric Henoch\u2013Sch\xf6nlein purpura nephritis: a retrospective cohort study

BackgroundThe long-term prognosis of Henoch-Schönlein purpura (HSP) depends on the severity of renal involvement, and crescent formation is considered an important risk factor for poor prognosis of Henoch-Schönlein purpura nephritis (HSPN). The objective of this study was to evaluate factors affecting crescent formation in children with HSPN.MethodsDemographic factors, clinical characteristics, and laboratory data of children with HSPN with or without crescents were retrospectively analyzed. Univariate and multivariate logistic regression analyses were used to determine the risk factors of crescent formation in HSPN.ResultsA total of 191 children with HSPN were enrolled in the study. There were 107 (56%) males and 84 (44%) females, with a median age of 7 years (range: 2 years–15 years). International Study of Kidney Disease in Children (ISKDC) grading was used to divide subjects into two groups: those without glomerular crescent formation (ISKDC grades I–II, n = 146 cases) and those with glomerular crescent formation (ISKDC grades III–V, n = 45 cases). Logistic regression analysis showed that higher urinary white blood cell (WBC) count (OR = 3.300; 95% CI, 1.119–9.739; P = 0.0306) and higher urinary microalbumin/creatinine ratio (ACR) (OR = 25.053; 95% CI, 1.354–463.708; P = 0.0305) were independent risk factors for the formation of crescents in HSPN. The area under the receiver operating characteristic curve of urinary WBC and ACR were 0.753 and 0.698 respectively, with the Hosmer and Lemeshow goodness-of-fit test (P = 0.0669, P > 0.05).ConclusionThese results suggest that higher urinary WBC count and ACR should be strictly monitored for children with HSPN. Adequate clinical intervention for these risk factors may limit or prevent renal crescent formation.

Biopsy-proven Henoch-Sch\xf6nlein purpura nephritis: a single center experience

BackgroundKnowledge on normal progress and treatment of Henoch-Schönlein purpura nephritis (HSPN) is limited. This study reviews outcome, clinical, pathological, and therapeutic factors affecting the prognosis of HSPN patients.MethodsForty-nine children with biopsy-confirmed HSPN diagnosed between September 2008 and 2018 were included. Demographics, clinical and laboratory data, treatment, and outcome were recorded at the time of biopsy, 3, 6, 12, and 24 months and at last visit. Clinical outcome was graded according to Meadow’s criteria.ResultsThe median age at time of biopsy was 10.1 years (IQR:5.7) and female/male ratio 24/25. At presentation, 40.8% of patients had nonnephrotic proteinuria, 18.4% nephrotic syndrome (NS), 4.1% nephritic syndrome (NephrS), and 36.7% NephrS+NS. There were 11 patients with an estimated glomerular filtration rate below 90 ml/min/1.73 m2. Biopsy specimens were classified according to International Study of Kidney Diseases in Children (ISKDC) and Oxford Classification MEST-C scoring systems. Forty-one patients received angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, 37 patients steroids, and 35 patients other immunosuppressive medications. At last visit, 24 patients had stage 1 chronic kidney disease (CKD), three stage 2 CKD, and two had stage 5 CKD. Neither clinical parameters nor ISKDC biopsy grade or treatment modalities effected the final outcome. The Oxford classification showed significantly increased segmental glomerulosclerosis in patients with unfavorable outcome. Favorable outcome was associated with shorter time from kidney involvement to biopsy and start of treatment.ConclusionA large proportion of patients continued to show signs of CKD at last follow-up while only a small proportion developed stage 5 CKD.

Low-dose corticosteroid with mizoribine might be an effective therapy for elderly-onset ISKDC grade VI IgA vasculitis

Both the diagnosis of elderly-onset IgA vasculitis (IgAV) and its prognosis can be difficult because of its rarity and the likely presence of comorbidities. Furthermore, the treatment of elderly-onset IgAV remains controversial: the ideal dosages of corticosteroid and/or immunosuppressants have not been determined. In the elderly, corticosteroid adverse effects can lead to severe outcomes, and a consensus regarding its benefit and risk balance has not been reached. We report a case of IgAV in an 89-year-old patient who was admitted to our hospital to investigate a 30-day history of palpable purpura and pitting edema on her leg. A renal biopsy showed membranoproliferative glomerulonephritis with IgA deposits (The International Study of Kidney Disease in Children (ISKDC) grade VI), which is a predictor of a poor prognosis; these findings led to early intervention with low-dose corticosteroid (15mg/day) and mizoribine. As a result, a complete remission without obvious adverse effects was obtained. Early intervention with low-dose corticosteroid and mizoribine based on renal histopathology results might be an effective treatment for elderly-onset ISKDC grade VI IgAV.

Prediction of renal outcome in Henoch\u2013Sch\xf6nlein nephritis based on biopsy findings

BackgroundIn Henoch–Schönlein nephritis (HSN), a risk factor for unfavorable outcome is prolonged proteinuria, but the value of renal biopsies in prognosis assessment is debatable.MethodsWe evaluated serial renal biopsies from 26 HSN patients. Follow-up biopsy occurred at median 2.1 years after diagnostic biopsy. Patients formed two groups at the follow-up biopsy: patients without proteinuria (group I; n = 11) and with proteinuria (group II; n = 15). Biopsies underwent evaluation according to three classifications: International Study of Kidney Disease in Children (ISKDC), Oxford (MEST-C), and semiquantitative classification (SQC) including an activity and chronicity score. Analysis also included expression of pro-fibrotic (alpha-smooth muscle actin and vimentin) and inflammatory (P-selectin glycoprotein ligand-1) molecules in the diagnostic biopsy specimens. Definition of unfavorable outcome was active renal disease or reduced renal function at last follow-up.ResultsBetween the biopsies, SQC chronicity score increased in 22 (85%) patients, whereas activity score and ISKDC grade decreased in 21 (81%) and 17 (65%), respectively. Of the MEST-C parameters, endocapillary proliferation (from 83 to 13%; p < 0.001) and crescents (from 63 to 25%; p = 0.022) showed significant reduction, and segmental glomerulosclerosis (from 38 to 79%; p = 0.006) significant increment. These changes occurred similarly in groups I and II. Expression of the pro-fibrotic and inflammatory molecules showed no clinically significant differences between groups I and II. None in group I and five (33%) patients in group II had unfavorable outcome (p = 0.053).ConclusionsOur results suggest that follow-up biopsies provide limited additional information to clinical symptoms in HSN outcome prediction.

Patient Outcomes of Henoch–Schönlein Purpura Nephritis According to the New Semiquantitative Classification

Background: A new semiquantitative classification (SQC) for pediatric Henoch–Schönlein nephritis (HSN) was defined recently. The outcomes of pediatric HSN patients are reevaluated according to the new classification. Methods: Primary kidney biopsies from 80 HSN patients were scored using the new SQC. The International Study of Kidney Disease in Children (ISKDC) and SQC classifications were compared in terms of the patient outcomes. Outcomes were defined as: Outcome A (n = 44) patients with no sign of renal disease, Outcome B (n = 32) patients with minor urinary abnormalities, and Outcome C (n = 4) patients with active renal disease. Results: The patients with outcome C had significantly higher biopsy scores and chronicity indices than patients in group A. There was no significant difference in areas under the curve between total biopsy SQC scores and ISKDC findings. Conclusions: Our results suggest that the modified SQC is not more sensitive than ISKDC classification for predicting the outcome in HSN cases.

Clinical significance of ANCA positivity in patients with IgA vasculitis: a retrospective monocentric study.

We assessed the detection rate of antineutrophil cytoplasmic antibody (ANCA) and investigated the clinical significance of ANCA positivity at diagnosis in patients with IgA vasculitis (Henoch-Schönlein purpura). We retrospectively reviewed their medical records of 86 IgA vasculitis patients. We divided IgA vasculitis patients based on ANCA positivity and compared variables at diagnosis and poor outcomes and medication during follow-up between the two groups. All-cause mortality, relapse, chronic kidney disease (CKD) (stage 3-5) and end-stage renal disease (ESRD) were defined as poor outcomes. We assessed the renal histological features based on the International Study of Kidney Disease in Children (ISKDC) classification and Oxford classification. Comparison of cumulative survivals was analysed by the Kaplan-Meier survival analysis. Five of 86 IgA vasculitis patients (5.8%) had ANCA and all ANCA-positive patients had myeloperoxidase (MPO)-ANCA. IgA vasculitis patients with ANCA exhibited pulmonary and nervous involvement of IgA vasculitis more frequently than those without. There was no significant difference in renal involvement between the two groups. There were no significant differences in renal histological features and poor outcomes related to renal function between IgA vasculitis patients with and without ANCA. In addition, 5 IgA vasculitis patients did not meet the classification criteria for ANCA-associated vasculitis (AAV). Particularly, there were no significant differences in CKD and ESRD-free survival rates between IgA vasculitis patients with and without ANCA. 5.8% of IgA vasculitis patients had MPO-ANCA and poor outcomes of IgA vasculitis were not affected by the presence of ANCA.

MON-308 MANAGEMENT OF HENOCH-SCHONLEIN PURPURA NEPHRITIS IN AUSTRALIA AND NEW ZEALAND: DOES IT DIFFER FROM KIDNEY DISEASE IMPROVING GLOBAL OUTCOMES GUIDELINES?

Henoch-Schönlein purpura (HSP) is the most common systemic vasculitis in children, with renal involvement occurring in 40-60% of paediatric patients within 4 to 6 weeks of the initial presentation. Majority of paediatric patients with HSP nephritis (HSPN) have mild disease, however a small proportion of patients present with renal impairment, nephrotic syndrome, or both. Kidney Disease Improving Global Outcomes (KDIGO) guidelines assist with management of different severities of HSPN but with low level of evidence. We aimed to evaluate the variance in current practice in management of paediatric HSPN by paediatric nephrologists in Australia and New Zealand. We designed an electronic survey consisting of various clinical scenarios of different severities in paediatric patients with HSPN. All of the questions were in multiple-choice format; majority allowing for participants to provide multiple management choices if required. The link to the survey was e-mailed to all members (trainees and consultants) of the Australian and New Zealand Paediatric Nephrology Association (ANZPNA). Survey was sent to 55 members of ANZPA. The responses were collated and analysed. The response rate was 30%, majority of the respondents being Staff Specialists of more than 10 years of experience. Majority of the respondents would commence treatment for mild HSPN with angiotensin converting enzyme inhibitors (ACEi), which is consistent with KDIGO guideline. Prednisolone was added in conjunction with ACEi for HSPN International Study of Kidney Diseases in Children (ISKDC) classification II and above. More complex HSPN including macroscopic haematuria and nephrotic-range proteinuria highlighted variability in practice amongst the ANZPNA group. For ISDKC classification IIIb and more, a non-steroid based immunosuppressive therapy was added to other therapies, but there was no consistency in treatment of choice. Rapidly progressive glomerulonephritis (RPGN) scenario was usually treated with IV methylprednisolone and cyclophosphamide with occasional use of plasma exchange. The majority of Australia and New Zealand Paediatric Nephrologists follow the KDIGO recommendations for treatment of mild HSPN. There is a wide variation in practice for moderate-to-severe HSPN with no consistency in choice of non-steroid immunosuppression, based on clinical presentation or histological findings except for RPGN. The wide variation in clinical practice highlights the lack of current evidence-based recommendations for HSPN treatment.

Updated Oxford classification and the international study of kidney disease in children classification: application in predicting outcome of Henoch-Sch\xf6nlein purpura nephritis

BackgroundHenoch-Schönlein purpura nephritis (HSPN) shares many similarities with IgA nephropathy. We aimed to analyze the predictive value of the International Study of Kidney Disease in Children (ISKDC) classification and the updated Oxford classification for IgA nephropathy in HSPN patients.MethodsData of 275 HSPN patients (aged≥14 years) were retrieved, and all of them underwent a renal biopsy. We re-classified the biopsies according to the ISKDC classification and the updated Oxford classification to analyze their correlations with clinical features and renal outcomes. The renal endpoints were defined as ≥30% reduction in baseline estimated glomerular filtration rate (eGFR) in 2 years, doubling of serum creatinine (Scr) or end stage renal disease.ResultsDuring follow-up period of 56(30,86) months, 30(10.9%) patients reached renal endpoints. Segmental sclerosis was the only pathological feature independently associated with renal endpoints (HR 4.086, 95%CI 1.111–15.026, P = 0.034). Tubular atrophy/ interstitial fibrosis was associated with eGFR and Scr levels, and its correlation with renal endpoints was found by univariate analysis. Endocapillary hypercellularity was associated with 24 h urine protein and is of prognostic value in univariate analysis. Mesangial hypercellularity was not associated with clinical features or renal endpoints. Crescents were associated with 24 h urine protein, Scr and eGFR levels, but both ISKDC and updated Oxford classifications of crescents were not associated with renal endpoints by multivariate analysis.ConclusionsThe updated Oxford classification can help in disease management and renal outcome prediction of HSPN.

Tubulointerstitial Infiltration of M2 Macrophages in Henoch-Schönlein Purpura Nephritis Indicates the Presence of Glomerular Crescents and Bad Clinical Parameters.

Henoch-Schönlein purpura (HSP) is the most common systemic vasculitis in children, and renal involvement (HSP nephritis, HSPN) is a severe manifestation. HSPN is histologically classified by the International Study of Kidney Disease in Children (ISKDC) based on mesangial hypercellularity and the extent of glomerular crescents. Macrophages, categorized as M1 or M2, frequently infiltrate in various glomerular and tubulointerstitial diseases and infiltration of specific subtypes is associated with disease progression. Therefore, to identify whether infiltration of M1 or M2 macrophages has clinical significance, we quantified the subtypes of macrophages in 49 HSPN specimens and correlated the counts with histologic features and clinical parameters. Higher tubulointerstitial M2 counts were associated with chronic renal failure (CRF), ISKDC classes III-IV, and crescents (P<0.001, 0.002, 0.001). Glomerular M2 counts were significantly related to ISKDC classes III-IV and crescents (area under curve, AUC 0.804, 0.833). Tubulointerstitial M2 counts were associated with CRF, ISKDC classes III-IV, and crescents (AUC 0.872, 0.778, 0.830). Tubulointerstitial M2 counts also revealed higher AUC than tubulointerstitial M1 counts for CRF (P=0.036) and ISKDC classes III-IV (P=0.047). Glomerular M2 counts revealed higher AUC than glomerular M1 counts for ISKDC classes III–IV (P=0.024). Tubulointerstitial M2 counts were the most powerful parameter for CRF (AUC 0.872) and revealed even higher AUC than ISKDC classification (AUC 0.716) with borderline significance (P=0.086) for CRF. In summary, tubulointerstitial M2 counts were a superior parameter to tubulointerstitial M1 counts and even to ISKDC classification indicating the presence of CRF.

Steroid- and immunosuppressant-based protocol of Henoch-Schönlein purpura nephritis without angiotensin inhibitors in the acute phase: case series with correlation to histology.

The Kidney Disease: Improving Global Outcomes (KDIGO) guidelines suggest initially using angiotensin-converting-enzyme inhibitors (ACE-Is) and/or angiotensin receptor blockers (ARBs) to treat Henoch-Schönlein purpura nephritis (HSPN). However, these guidelines might overlook the potential benefits of aggressive therapy. Therefore, we evaluated the efficacy of an HSPN protocol that primarily uses steroids and immunosuppressants, without ACE-Is or ARBs. We determine treatment intensity based on International Study of Kidney Diseases in Children (ISKDC) grading. Fifty-one patients were treated with our protocol that primarily uses steroids and immunosuppressants. ACE-Is and ARBs were not used in the acute phase, including before renal biopsy. We evaluated the proteinuria disappearance rate, duration to proteinuria disappearance, and estimated glomerular filtration rate (eGFR) at the time of last observation and compared them to those in previous reports. Proteinuria disappeared in 49 patients (96%) within a median of 5 months. The median eGFR was 116.0 mL/min/1.73 m2 at the time of last observation. Six of 51 patients had acute kidney injury (eGFR <90 mL/min/1.73 m2) before treatment, but all recovered during the observation period (median 52 months). Our steroid- and immunosuppressant-based protocol without ACE-Is or ARBs in the acute phase of HSPN had almost equivalent efficacy to that in previous studies that used ACE-Is and/or ARBs with steroids and immunosuppressants.