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

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

Podocyte Injury in Diabetic Kidney Disease in Mouse Models Involves TRPC6-mediated Calpain Activation Impairing Autophagy.

SIGNIFICANCE STATEMENT: Autophagy protects podocytes from injury in diabetic kidney disease (DKD). Restoring glomerular autophagy is a promising approach to limit DKD. This study demonstrates a novel regulatory mechanism of autophagy that blocks this critical protection of the glomerular filtration barrier. We demonstrated that TRPC6 induced in podocytes in mouse models of diabetes mediates calpain activation, thereby impairing podocyte autophagy, causing injury and accelerating DKD. Furthermore, this study provides proof of principle for druggable targets for DKD because restoration of podocyte autophagy by calpain inhibitors effectively limits glomerular destruction. BACKGROUND: Diabetic kidney disease is associated with impaired podocyte autophagy and subsequent podocyte injury. The regulation of podocyte autophagy is unique because it minimally uses the mTOR and AMPK pathways. Thus, the molecular mechanisms underlying the impaired autophagy in podocytes in diabetic kidney disease remain largely elusive. METHODS: This study investigated how the calcium channel TRPC6 and the cysteine protease calpains deleteriously affect podocyte autophagy in diabetic kidney disease in mice. We demonstrated that TRPC6 knockdown in podocytes increased the autophagic flux because of decreased cysteine protease calpain activity. Diabetic kidney disease was induced in vivo using streptozotocin with unilateral nephrectomy and the BTBR ob/ob mouse models. RESULTS: Diabetes increased TRPC6 expression in podocytes in vivo with decreased podocyte autophagic flux. Transgenic overexpression of the endogenous calpain inhibitor calpastatin, as well as pharmacologic inhibition of calpain activity, normalized podocyte autophagic flux, reduced nephrin loss, and prevented the development of albuminuria in diabetic mice. In kidney biopsies from patients with diabetes, we further confirmed that TRPC6 overexpression in podocytes correlates with decreased calpastatin expression, autophagy blockade, and podocyte injury. CONCLUSIONS: Overall, we discovered a new mechanism that connects TRPC6 and calpain activity to impaired podocyte autophagy, increased podocyte injury, and development of proteinuria in the context of diabetic kidney disease. Therefore, targeting TRPC6 and/or calpain to restore podocyte autophagy might be a promising therapeutic strategy for diabetic kidney disease.

Optimizing COVID-19 Vaccination Strategy in Pediatric Kidney Transplant Recipients: Humoral and Cellular Response to SARS-CoV-2 mRNA Vaccination.

In this retrospective cohort study, we analyze the early humoral and cellular response in 64 adolescents KTx recipients, after two or three doses of mRNA vaccine BNT162b2 against different variants of COVID-19. After 2 doses, 77.8% % of children with no history of infection had a positive humoral response with a median anti-S IgG level of 1107 (IQR, 593-2,658) BAU/mL. All the patients with a history of infection responded with a higher median IgG level (3,265 (IQR, 1,492-8,178) BAU/mL). In non-responders after 2 doses, 75% responded after a third dose with a median Ab titer at 355 (IQR, 140-3,865 BAU/mL). Neutralizing activity was significantly lower against the delta and the omicron variants compared to the wild-type strain and did not improve after a 3rd dose, while infection did provide higher levels of neutralizations against the variants. T cell specific response correlated with humoral response and no patient displayed a cellular response without a humoral response. Adolescent KTx recipients exhibit a high seroconversion rate after only two doses. A third injection, induces a response in the majority of the non-responders patients but did not counterbalance the strong decrease in neutralizing antibody activities against variants highlighting the need for boosters with specific vaccines.

Successful global anti-B-cell strategy with daratumumab in a patient with post-transplant nephrotic syndrome recurrence unresponsive to immunoadsorption and obinutuzumab.

BACKGROUND: Steroid-resistant nephrotic syndrome recurrence post-transplant unresponsive to immunoadsorption is a dilemma, and no reliable treatment strategy has been identified to induce remission so far. CASE PRESENTATION: A 2-year-old girl presented first with idiopathic nephrotic syndrome. She did not reach remission after 30 days of oral steroids and remained resistant to steroid pulses, oral tacrolimus, IV cyclosporine, and to 30 sessions of plasma exchange. Bilateral nephrectomy was performed because of extrarenal complications. Two years later, she received an allograft from a deceased donor and idiopathic nephrotic syndrome relapsed immediately post-transplantation. She did not reach remission after immunosuppressive therapy including tacrolimus, mycophenolate mofetil, methylprednisolone pulses, daily immunoadsorption, and B-cell depletion. She received obinutuzumab 1 g/1.73 m2 injections weekly for 3 weeks and then daratumumab 1 g/1.73 m2 weekly for 4 weeks. One week after the last daratumumab infusion, urine protein/creatinine ratio began to decrease. Proteinuria was negative for the first time at Day 99. Immunoadsorption was stopped 147 days after, and she remained relapse-free at last follow-up (18 months post-transplantation). The treatment was complicated by a pneumocystis jirovecii pneumonia with a favorable outcome and persistent hypogammaglobulinemia. CONCLUSION: A obinutuzumab and daratumumab combination seems to be a promising strategy in post-transplantation SRNS recurrence without response to standard treatment options.

Outcome of children with IgA vasculitis with nephritis treated with steroids: a matched controlled study.

BACKGROUND: IgA vasculitis (IgAV) is the most common vasculitis in children. IgAV long-term prognosis depends on kidney involvement or IgA vasculitis with nephritis (IgAVN). To date, steroid treatment (oral steroids or methylprednisolone pulses) has not proven to be formally efficient. This study aimed to assess the role of steroids on IgAVN outcome. METHODS: All children with IgAVN diagnosed 2000-2019 in 14 French pediatric nephrology units with minimal follow-up of 6 months were retrospectively included. Outcomes of patients treated with steroids were compared with those of a control group of untreated patients matched for age, sex, proteinuria, eGFR, and histological features. The primary endpoint was IgAVN remission defined as urine protein-to-creatinine ratio < 20 mg/mmol without impaired eGFR one year after disease onset. RESULTS: A total of 359 patients with IgAVN were included with a median follow-up time of 249 days (range 43-809). One hundred eight (30%) patients received oral steroids alone, 207 (51%) patients received three methylprednisolone pulses followed by oral steroids, and 44 patients (12.5%) did not receive steroids. Thirty-two children treated with oral steroids alone were compared with 32 matched control patients who did not receive steroids. One year after disease onset, IgAVN remission proportion was not different between these two groups: 62% versus 68%, respectively. Ninety-three children treated with oral steroids alone were compared with 93 matched patients treated with three methylprednisolone pulses followed by oral corticosteroids. IgAVN remission proportion was not different between these two groups: 77% versus 73%, respectively. CONCLUSION: The benefit of oral steroids alone and methylprednisolone pulses could not be established based on this observational study. Randomized controlled trials are thus required to determine the efficacy of steroids in IgAVN. A higher resolution version of the Graphical abstract is available as Supplementary information.

Renal vein thrombosis in neonates: a case series of diagnosis, treatment and childhood kidney function follow-up.

BACKGROUND: Neonatal renal vein thrombosis (NRVT) is a rare condition with little data available. METHODS: We retrospectively analyzed newborns diagnosed with NRVT admitted to 3 pediatric nephrology units in Paris from 2005 to 2020. RESULTS: Twenty-seven patients were analyzed (male = 59%). The median age at diagnosis was 2.5 days (1 - 4.5). Diagnosis was suspected based on at least one of the three cardinal signs of renal vein thrombosis in 93%: flank mass (67%), hematuria (67%) and thrombocytopenia (70%). In all patients, diagnosis was confirmed by ultrasound. All patients had at least one known perinatal risk factor. A prothrombotic risk factor was found in 13 patients (48%). NRVT was unilateral in 70%, involving the left renal vein in 58%. Among 25 treated patients, 19 (76%) received low molecular weight heparin (LMWH) as initial therapy, 2 (8%) received unfractionated heparin and 4 (16%) received fibrinolysis. Median duration of treatment was 8 weeks (4 - 12). Bleeding occurred significantly more often with fibrinolysis than with LMWH/supportive therapy (3 of 4: 75% vs 0 of 4: 0%, p = 0.05). Clot resolution in patients treated with fibrinolysis did not differ significantly from those treated with LMWH/supportive therapy. After a median follow-up of 5.7 years (3 years - 9.9 years), pathological kidney features were observed in 73% of the patients (19 of 26), kidney atrophy in 18 (69%), hypertension in 2 (8%), chronic kidney disease (CKD) in 1 (4%) and proteinuria in 2 (8%). CONCLUSIONS: NRVT remains a challenging condition, which still requires further study because of its associated morbidity. A higher resolution version of the Graphical abstract is available as Supplementary information.

Prevalence and Etiologies of Renal and Urinary Manifestations in a Large Cohort of Children With Inflammatory Bowel Disease.

BACKGROUND AND OBJECTIVES: Renal and/or urinary manifestations (RUM) have been reported in pediatric patients with inflammatory bowel disease (IBD) but their incidence is unknown. The aims of this study were to assess the prevalence and causes of these manifestations in children with IBD and determine the causal link with 5-aminosalicylic acid (5-ASA) treatment. METHODS: A retrospective observational study was performed with children with diagnosis of IBD. All children with RUM during follow-up and/or impaired renal function [estimated glomerular filtration rate (eGFR) < 90 mL/min/1.73 m 2 ] were identified. RESULTS: Of 228 included patients, 9 (3.9%) had a RUM during follow-up [follow-up: 5 years (1-12 years)] at a median age of 16 years (8-17 years). It concerned 7 of 171 patients with Crohn disease and 2 of 57 with ulcerative colitis. Seven patients were taking 5-ASA at the time of the RUM. Only 1 of them had an iatrogenic renal complication related to this treatment. Patients with RUM had a more severe disease with increased anti-tumor necrosis factor-α use ( P = 0.031), more abscesses ( P = 0.003), and a higher rate of digestive surgery ( P = 0.04). For the whole cohort, a significant decrease in eGFR was found during follow-up (121 vs 107 mL/min/1.73 m 2 , P < 0.001). At the end of follow-up, 38 of 202 (19%) patients had an eGFR < 90 mL/min/1.73 m 2 . CONCLUSION: In children with IBD, RUM can occur, independently of treatment with 5-ASA. During follow-up, a significant decrease in eGFR was observed. We suggest monitoring renal function in all patients with IBD.

Predictive factors for survival in patients with oligohydramnios secondary to antenatal kidney disease.

BACKGROUND: Renal oligohydramnios (ROH) is caused by bilateral congenital abnormalities, either of renal parenchymal or obstructive origin. ROH is a poor prognostic factor of neonatal survival; lung hypoplasia is reported to be the main cause of mortality. We aimed to describe the fetal morbidity and pre- and postnatal mortality in case of ROH due to renal congenital pathologies and to find predictive risk factors for morbidity and mortality. METHODS: All data were collected in Trousseau Hospital in the obstetric, neonatology, and pediatric nephrology units, from 2008 to 2020. RESULTS: We included 66 fetuses with renal parenchymal pathologies posterior urethral valves (PUV) (N = 25), bilateral kidney agenesis (N = 10), hypodysplasia (N = 16), and polycystic kidney disease (N = 10) causing oligohydramnios identified on antenatal ultrasound. Total pre- and postnatal mortality was 76% (50/66). Mortality, excepting termination of pregnancy (TOP), was 65%. The presence of pneumomediastinum and pneumothorax was not different in survivors and non-survivors. Fetuses with kidneys having features of hypodysplasia on ultrasound at T2 and those with oligohydramnios before 32 weeks GA had a higher risk of death. There was a significant difference in plasma creatinine of the surviving patients compared to the deceased patients, from day 3 onwards (183 µmol/L [88; 255] vs. 295 µmol/L [247; 326]; p = 0.038). CONCLUSIONS: The main differences between survivors and non-survivors among patients with "renal oligohydramnios" were oligohydramnios detection before 32 weeks GA, dysplasia detection on the second trimester ultrasound, and increase of serum creatinine from day 3 onwards. A higher resolution version of the Graphical abstract is available as Supplementary information.

Benefits of BNP/NT-proBNP serum level evaluation for dry weight adjustment in pediatric hemodialysis patients.

BACKGROUND: Dry weight (DW) adjustment in children on hemodialysis (HD) can be challenging. It relies on clinical evaluation and additional supports. Our aim was to study the benefits of cardiac biomarker assessment, in addition to the more commonly used technique, bioimpedance spectroscopy (BIS), and clinical signs for DW prescription in pediatric HD patients. METHOD: Observational study including 41 children on HD in three pediatric HD centers in the Paris region. During one session, BIS was performed before the session and serum levels of BNP and NT-proBNP were analyzed before and after the session. RESULTS: Median pre-dialysis level of BNP was 87 ng/L [24-192] and NT-proBNP 968 ng/L [442-4828]. Cardiac biomarker levels showed positive correlation with the BIS hydration status evaluation (p = 0.004). The most appropriate cutoff for pre-dialysis BNP to detect significant overhydration (OH) was 165 ng/L (sensitivity 0.67, specificity 0.84). Based on the BIS evaluation, only 32% of patients with high blood pressure (BP) had OH, whereas in the normal BP group, 33% had significant OH. CONCLUSIONS: DW prescription for children on HD should not only rely on clinical evaluation, particularly BP, but should also include additional helpful parameters. BIS is well-validated in children, but it has limitations in non-cooperative patients, and its cost can limit its use in some settings. Cardiac biomarkers, especially BNP, were well-correlated to hydration status evaluated by BIS, and thus could add valuable information for individual patient management and DW assessment. A higher resolution version of the Graphical abstract is available as Supplementary information.

Management of IgA Vasculitis with Nephritis.

Immunoglobulin A (IgA) vasculitis (IgAV), previously called Henoch-Schönlein purpura, is characterized by IgA-dominant immune deposits affecting small vessels and often involves the skin, gastrointestinal tract, joints, and kidneys. IgAV is the most common cause of systemic vasculitis in children. The long-term prognosis is dependent on renal involvement: IgAV with nephritis (IgAVN) can progress to renal failure. IgAVN is an inflammatory disease, providing a rationale for the use of corticosteroids. However, data supporting the use of corticosteroids in patients with established IgAVN of any severity remain limited, although most clinicians use them. Even in patients with severe forms of IgAVN, methylprednisolone pulses added to oral corticosteroids appears to improve renal outcomes. Considering the multihit hypothesis for the pathogenesis of IgAVN, involving many other immune agents, there is a strong rationale for the use of other immunosuppressive drugs in patients with IgAVN, including mycophenolic acid, cyclophosphamide, rituximab, calcineurin inhibitors, and complement inhibitors. Thus, these immunosuppressive treatments have also been evaluated in IgAVN, usually in corticosteroid-dependent or corticosteroid-resistant forms and in small retrospective studies. However, their efficacy has not been proven. Thus, the risk of progression to renal failure and the ongoing debate about the best management of IgAVN justifies the interest in investigating and identifying treatments that can potentially preserve renal function in patients with IgAVN. This review reports on the efficacy of the different drugs currently used for the treatment of IgAVN in adults and children.

Procalcitonin serum levels in stage 5 chronic kidney disease children on hemodialysis.

BACKGROUND: Infections are responsible for morbidity and mortality in children on hemodialysis (HD). Procalcitonin (PCT) is rarely used in this population, even though it is an efficient biomarker of infection and sepsis. Our aim was to study PCT baseline level in uninfected children with stage 5 chronic kidney disease (CKD 5) on HD, and determine how to use it in this population. METHODS: Prospective observational study including 40 uninfected children on classical HD or hemodiafiltration (HDF) in three pediatric HD centers in the Paris region. PCT was monitored before and after three consecutive sessions within 1 week. RESULTS: Median pre-dialysis PCT was 0.60 ng/mL [0.36-1.15], median post-dialysis PCT was 0.23 ng/mL [0.10-0.47], PCT reduction rate was 59.8% [37.5-75.8]. Seventy percent of pre-dialysis PCT were <1 ng/mL. Anuric patients had higher pre-dialysis PCT than those with residual urine output (0.70 [0.42-1.30] vs. 0.48 [0.30-0.93] ng/mL, p=0.01). HDF was more efficient than HD to clear PCT during sessions (reduction rate 75% [67-80] vs. 37 [31-50]), p<0.001). CONCLUSION: PCT levels in pediatric HD patients without infection are higher than normal, but this increase is relatively moderate compared to massive increases of PCT in children with bacterial infections on HD. If PCT is measured after dialysis sessions, the specific technique-dependent reduction rates should be taken into consideration. Moderately increased PCT levels around 2 ng/ml should be interpreted with caution; however, higher PCT serum levels can be used to motivate rapid start of antibiotic treatment in pediatric HD patients.

Long-term kidney and liver outcome in 50 children with autosomal recessive polycystic kidney disease.

BACKGROUND: Autosomal recessive polycystic kidney disease (ARPKD) is a rare ciliopathy characterized by congenital hepatic fibrosis and cystic kidney disease. Lack of data about long-term follow-up makes it difficult to discuss timing and type of organ transplantation. Our objectives were to evaluate long-term evolution and indications for transplantation, from birth to adulthood. METHODS: Neonatal survivors and patients diagnosed in postnatal period with ARPKD between 1985 January and 2017 December from 3 French pediatric centers were retrospectively enrolled in the study. RESULTS: Fifty patients with mean follow-up 12.5 ± 1 years were enrolled. ARPKD was diagnosed before birth in 24%, and at mean age 1.8 years in others. Thirty-three patients were < 1 year of age at first symptoms, which were mostly kidney-related. These most often presented high blood pressure during follow-up. Portal hypertension was diagnosed in 29 patients (58%), 4 of them with bleeding from esophageal varices. Eight patients presented cholangitis (> 3 episodes in three children). Liver function was normal in all patients. Nine children received a kidney transplant without liver complications. A 20-year-old patient received a combined liver-kidney transplant (CLKT) for recurrent cholangitis, and a 15-year-old boy an isolated liver transplant for uncontrollable variceal bleeding despite portosystemic shunt. CONCLUSIONS: Long-term outcome in patients with ARPKD is heterogeneous, and in this cohort did not depend on age at diagnosis except for blood pressure. Few patients required liver transplantation. Indications for liver or combined liver-kidney transplantation were limited to recurrent cholangitis or uncontrollable portal hypertension. Liver complications after kidney transplantation were not significant.

Acute Renal Failure after Abdominal Trauma: Renal Artery Spasm Hypothesis in Ischemic Infarction in a 12-Year-Old Girl.

Posttraumatic renal failure is often due to postischemic renal infarction, caused by identified vascular lesions. In our patient, a 12-year-old girl with acute anuric renal failure requiring hemodialysis after severe abdominal trauma, no vascular lesion or thrombosis was identified. Nevertheless, CT-scan and renal biopsy showed typical lesions of diffuse bilateral renal ischemic necrosis. The main hypothesis is a severe bilateral arterial vasospasm after a blunt abdominal trauma. The patient recovered only partially with persisting chronic renal failure.

Setting reasonable objectives for improving preemptive kidney transplantation rates in children.

BACKGROUND: This study aims to develop a method to estimate the potential of preemptive kidney transplantation (PKT) by identifying patients who were transplanted after a dialysis period (non-preemptive kidney transplantation (NPKT)) despite being medically suitable for PKT. METHODS: All children (< 18 years old) starting kidney replacement therapy (KRT) in France, between 2010 and 2016 and transplanted before December 31, 2017, were included. A propensity score (PS) of receiving PKT was estimated by multivariate logistic regression based on recipient medical characteristics. Healthcare use during the 24 months prior to KRT initiation was extracted from the French National Health Insurance database, and a pre-KRT follow-up of more than 18 months was considered sufficient to allow preemptive transplantation. RESULTS: Among 643 patients who started KRT, 149 (23.2%) were preemptively transplanted. Using PS stratification, among 391 NPKT patients, we identified 145 patients (37%) suitable for PKT, according to clinical characteristics. Mean age was 12.3 years, 67% were males, and 56% had urological abnormalities. Among those 145 patients, we identified 79 NPKT patients who started on dialysis despite early referral to a nephrologist (more than 18 months prior to KRT initiation). CONCLUSIONS: This method estimates a potential of 228 (149 + 79) PKT (35%) among pediatric patients in France. A similar method could be used in adults or in other countries. Estimation of the rate of patients with CKD stage 5 medically suitable for PKT will be of interest for health policy makers when setting up objectives for improvement in preemptive kidney transplant access.

Tolvaptan therapy to treat severe hyponatremia in pediatric nephrotic syndrome.

BACKGROUND: Tolvaptan is a selective oral vasopressin V2-receptor antagonist. Some data have implicated stimulation of arginine vasopressin (AVP) as an important factor in oedema formation in a rodent model of nephrotic syndrome (NS) and adult NS patients. We report case of pediatric NS with severe hyponatremia efficiently treated by tolvaptan. CASE/DIAGNOSIS - TREATMENT: A 22-month-old girl presented first with NS. She remained nephrotic after a 30-day course of oral steroids. Tacrolimus was inefficient and there was no response to plasma exchanges (15 sessions on a daily basis). She had severe oedema and ascites. Thus, in addition to immunosuppressive therapy, she received diuretics, furosemide 5 mg/kg/day, and amiloride 1 mg/kg/day, and required water restriction. She was hypertensive and was treated with a full dose of calcium inhibitor (amlodipine 0.5 mg/kg/day). After2 months of treatment, serum sodium reached 116 mmol/L and urinary osmolarity 547 mosmol/L, suggesting an inappropriate AVP secretion. Tolvaptan was introduced at 0.3 mg/kg/day and progressively increased to 3 mg/kg/day on day 4, leading to a partial correction of serum sodium (130 mmol/l) and a urinary osmolarity decrease to 90 mosmol/L. Tolvaptan was then continued at the dose of 3 mg/kg/day with unchanged serum sodium, without hypernatremia or dehydration. Her weight decreased from 14.8 k to 14 k, but oedema still persisted. CONCLUSION: Tolvaptan was very efficient in this case of hyponatremia associated with steroid-resistant NS. Tolvaptan should be considered in the management of therapy-resistant hyponatremia in patients with NS.

Immunoglobulin serum levels in rituximab-treated patients with steroid-dependent nephrotic syndrome.

BACKGROUND: Rituximab (RTX) is efficient in steroid-dependent nephrotic syndrome (SDNS) in pediatric and adult patients. The aim of this study is to describe hypogammaglobulinemia as a side effect of RTX treatment. METHODS: All pediatric patients (< 18 years old) of four French pediatric nephrology centers who received RTX for SDNS between 2010 and 2015 have been included. Clinical and biological data have been analyzed retrospectively before, during, and after RTX treatment. Hypogammaglobulinemia was defined as an IgG level < - 2 standard deviations for patient age. RESULTS: A total of 107 pediatric patients have been included, 65.9% were boys, median age at nephrotic syndrome diagnosis was 3.1 interquartile range [IQ 2.24-5.45] years and age at RTX introduction was 11.7 [IQ 8.6-14.2] years. Twenty-one patients had hypogammaglobulinemia before the initiation of RTX. Of the patients, 25/86 had at least one hypogammaglobulinemia during B cell depletion or after B cell recovery while IgG levels at initiation were normal with a persisting hypogammaglobulinemia for 13 patients 1 year after B cell recovery. Patients who developed hypogammaglobulinemia were younger at RTX initiation with a median age of 8.2 years [IQ 6.3-12.4]. Among all the 46 patients with hypogammaglobulinemia during follow-up, 13 had a concomitant infection. CONCLUSIONS: Hypogammaglobulinemia is a frequent complication of RTX treatment in younger children treated for SDNS. The use of RTX in children has to be carefully evaluated and their clinical and biological follow-up should be adapted to the age-dependent risk profile for hypogammaglobulinemia.

Histological prognostic factors in children with Henoch-Schönlein purpura nephritis.

BACKGROUND: The management of IgA vasculitis with nephritis (IgAVN) remains controversial because of the difficulty to identify prognostic factors. This study reports the prognosis of children with IgAVN in relation to histological parameters. METHODS: All children with IgAVN diagnosed between 2000 and 2015 in three pediatric nephrology centers were included. The following histological parameters were analyzed: mesangial proliferation (MP), endocapillary proliferation (EP), crescents, active, or chronic tubular and interstitial lesions (TIa lesions/TIc lesions), and segmental glomerulosclerosis (GS). Clinical and biological data were collected at the time of renal biopsy. The primary endpoint was IgAVN remission defined as a proteinuria < 200 mg/l without renal failure. RESULTS: One hundred fifty-nine children were included with a median age of 7.6 years. Acute glomerular or TI lesions including MP, EP, crescents, and TIa lesions were observed, respectively, in 81%, 86%, 49%, and 21% of patients. Chronic glomerular lesions including GS and TIc lesions were observed in 6 and 7% of patients. Median initial proteinuria was 330 mg/mmol, albuminemia 32 g/l, and eGFR 110 ml/min/1.73 m2. One hundred twelve (70%) patients were in remission at the end of a median follow-up of 37.4 months. Chronic lesions were significantly associated with the absence of remission in multivariate analysis, whereas EP, crescents and TIa were not associated with a poor prognosis. CONCLUSIONS: Of children with IgAVN, 30% present a persistent renal disease at the end of a 3-year follow-up. Chronic histological lesions, but not EP or crescents, are associated with a bad prognosis and must be evaluated in IgAVN histological classification.

Infrequent tacrolimus-induced nephrotoxicity in French patients with steroid-dependent nephrotic syndrome.

BACKGROUND: Chronic nephrotoxicity with potentially irreversible lesions is a major concern regarding calcineurin inhibitor (CNI) treatment in children with severe forms of idiopathic nephrotic syndrome (INS). CASE-DIAGNOSIS/TREATMENT: We retrospectively included all children on CNI for steroid-dependent INS with a duration of CNI treatment of more than 1 year. Only patients in whom CNI could not be replaced by mycophenolate mofetil were included. All included patients underwent a kidney biopsy. All results were expressed as median and range. Twenty-one children (6 girls) were included. Age at disease onset was 49 (29-66) months and treatment duration on CNI was 30 (20-45) months. Age at kidney biopsy was 108 (78-170) months. Number of relapses was 7 (3-9) since disease onset. Serum creatinine level was transiently and moderately increased in two patients. Kidney biopsy revealed minimal change disease in 20/21 patients and focal segmental glomerulosclerosis in 1/21. Evidence for chronic CNI nephrotoxicity was found in one patient revealed by arteriolar hyalinosis and fibrosis in 50% of glomeruli. CONCLUSIONS: CNI-induced chronic nephrotoxicity was infrequent. In patients who require long-term and/or high-dose CNI treatment, kidney biopsies might be useful to exclude chronic CNI-induced lesions.

Quality of life in children with severe forms of idiopathic nephrotic syndrome in stable remission-A cross-sectional study.

AIM: Severe forms of idiopathic nephrotic syndrome (INS) require immunosuppressive therapy: oral treatment or intravenous therapy (rituximab, RTX). The main objective was to describe quality of life (QOL) in these specific patients. METHODS: Cross-sectional, multicentre, observational study analysed QOL using a standardised questionnaire in children from 7 to 17 years, with a steroid-dependent or steroid-resistant INS in stable remission. The questionnaire consisted of 30 questions concerning physical and emotional well-being, self-esteem, family, friends, school and disease resulting in a global score of 0-100. RESULTS: A total of 110 patients with a mean age of 11.6 years from three French paediatric nephrology centres were included. A total of 71 patients had oral immunosuppressive treatment, 27 had RTX, and 12 had both. 13.6% of patients had a steroid-resistant INS. The mean number of relapses was 5.8. Seventy-eight patients answered the questionnaire. The global score in the whole study population was 74.7; 72.6 in the RTX group, 76.2 in the oral drugs group, (P = 0.49). The results of sub-dimension 'school' were statistically lower in RTX group (61.6 ± 19.5) compared with oral drugs group (71.4 ± 16; P = 0.02). CONCLUSION: Global QOL score was high in 'difficult-to-treat' patients with INS in stable remission on oral immunosuppressive or RTX treatment.