FCGG renal biopsy network : first epidemiological report on pediatric renal diseases

Objective: In 2016, a regional renal biopsy network was founded as a collaboration between renal pathologists and nephrologists in order to standardize diagnosis and therapy. Uniform renal biopsy request and renal biopsy report forms were introduced, together with a new comprehensive list of renal pathology diagnoses for coding. The 2017-2018 epidemiological data of the pediatric patients (age= 0-17 years) are presented. Methods: Following informed consent and in compliance with GDPR, data registration consists of basic patient and categorical renal data, semi-structured medical information of renal histopathology and the clinical renal disease. Results: In 2017-2018, 92 renal biopsies were reported in pediatric patients or 3.6 per 100,000 pediatric inhabitants per year. Three clinical patterns were equally represented: only proteinuria >1g/day; only hematuria; and combination of proteinuria and hematuria. Acute or chronic renal failure were rare. In the youngest age group (0-5 years; N=26) minimal change disease predominated, followed by Henoch-Schönlein nephritis. The middle age group (6-11 years; N=32) mainly presented with disease characterized by hematuria: IgA nephropathy, Henoch-Schönlein nephritis and Alport’s disease. A more diverse renal disease spectrum was present in the highest age group (12-18 years; N=34): IgA nephropathy, different forms of proliferative glomerulonephritis and of nephrotic syndrome of childhood. Patients with a Caucasian descent presented with IgA nephropathy, while a nephrotic syndrome was more common in those without a Caucasian descent. Alport’s disease was particularly diagnosed in female patients, IgA nephropathy in male patients, and the gender distribution was equal in minimal change disease. Conclusion: The FCGG network provides an better cross-talk between renal pathologists and nephrologists. For the first time, reliable estimates of pediatric renal diseases based on histology are available. Genetic analyses are not yet included. Efforts to coordinate clinical care of pediatric renal diseases are ongoin

FCGG Renal Biopsy Network: first epidemiological report on pediatric renal disease in Flanders

FCGG Renal Biopsy Network: first epidemiological report on pediatric renal diseases Sevasti Karamaria1, Johan De Meester2, Amélie Dendooven3, Elena Levtchenko4, Noel Knops4, Koen Van Hoeck5, Dominique Trouet5, Reiner Mauel6, Ben Sprangers7, Wim Laurens8, Johan Vande Walle1, on behalf of the FCGG – NBVN working group 1 Department of Pediatrics, UZ Gent, Ghent; 2NBVN, Antwerp; 3Pathology Department, UZ Gent, Ghent; 4Department of Pediatrics, UZ Leuven, Leuven; 5Departement of Pediatrics, UZ Antwerpen, Antwerp; 6Department of Pediatrics, UZ Brussel, Brussels; 7Department of Nephrology, UZ Leuven, Leuven; 8Department of Nephrology, AZ Nikolaas, Sint-Niklaas. Objective: In 2016, a regional renal biopsy network was founded as a collaboration between renal pathologists and nephrologists in order to standardize diagnosis and therapy. Uniform renal biopsy request and renal biopsy report forms were introduced, together with a new comprehensive list of renal pathology diagnoses for coding. The 2017-2018 epidemiological data of the pediatric patients (age= 0-17 years) are presented. Methods: Following informed consent and in compliance with GDPR, data registration consists of basic patient and categorical renal data, semi-structured medical information of renal histopathology and the clinical renal disease. Results: In 2017-2018, 92 renal biopsies were reported in pediatric patients or 3.6 per 100,000 pediatric inhabitants per year. Three clinical patterns were equally represented: only proteinuria >1g/day; only hematuria; and combination of proteinuria and hematuria. Acute or chronic renal failure were rare. In the youngest age group (0-5 years; N=26) minimal change disease predominated, followed by Henoch-Schönlein nephritis. The middle age group (6-11 years; N=32) mainly presented with disease characterized by hematuria: IgA nephropathy, Henoch-Schönlein nephritis and Alport’s disease. A more diverse renal disease spectrum was present in the highest age group (12-18 years; N=34): IgA nephropathy, different forms of proliferative glomerulonephritis and of nephrotic syndrome of childhood. Patients with a Caucasian descent presented with IgA nephropathy, while a nephrotic syndrome was more common in those without a Caucasian descent. Alport’s disease was particularly diagnosed in female patients, IgA nephropathy in male patients, and the gender distribution was equal in minimal change disease. Conclusion: The FCGG network provides an better cross-talk between renal pathologists and nephrologists. For the first time, reliable estimates of pediatric renal diseases based on histology are available. Genetic analyses are not yet included. Efforts to coordinate clinical care of pediatric renal diseases are ongoing

Adult-Onset ANCA-Associated Vasculitis in SAVI: Extension of the Phenotypic Spectrum, Case Report and Review of the Literature.

STING-associated vasculopathy with onset in infancy (SAVI) is an autosomal dominant disorder due to gain-of-function mutations in STING1, also known as TMEM173, encoding for STING. It was reported as a vasculopathy of infancy. However, since its description a wider spectrum of associated manifestations and disease-onset has been observed. We report a kindred with a heterozygous STING mutation (p.V155M) in which the 19-year-old proband suffered from isolated adult-onset ANCA-associated vasculitis. His father suffered from childhood-onset pulmonary fibrosis and renal failure attributed to ANCA-associated vasculitis, and died at the age of 30 years due to respiratory failure. In addition, an overview of the phenotypic spectrum of SAVI is provided highlighting (a) a high phenotypic variability with in some cases isolated manifestations, (b) the potential of adult-onset disease, and (c) a novel manifestation with ANCA-associated vasculitis

The association between use of proton-pump inhibitors and excess mortality after kidney transplantation:A cohort study

Background Chronic use of proton-pump inhibitors (PPIs) is common in kidney transplant recipients (KTRs). However, concerns are emerging about the potential long-term complications of PPI therapy. We aimed to investigate whether PPI use is associated with excess mortality risk in KTRs. Methods and findings We investigated the association of PPI use with mortality risk using multivariable Cox proportional hazard regression analyses in a single-center prospective cohort of 703 stable outpatient KTRs, who visited the outpatient clinic of the University Medical Center Groningen (UMCG) between November 2008 and March 2011 (ClinicalTrials.gov Identifier NCT02811835). Independent replication of the results was performed in a prospective cohort of 656 KTRs from the University Hospitals Leuven (NCT01331668). Mean age was 53 ± 13 years, 57% were male, and 56.6% used PPIs. During median follow-up of 8.2 (4.7-9.0) years, 194 KTRs died. In univariable Cox regression analyses, PPI use was associated with an almost 2 times higher mortality risk (hazard ratio [HR] 1.86, 95% CI 1.38-2.52, P 20 mg omeprazole equivalents/ day) compared with patients taking no PPIs (HR 2.14, 95% CI 1.48-3.09, P < 0.001) was higher than in KTRs taking a low PPI dose (HR 1.72, 95% CI 1.23-2.39, P = 0.001). These findings were replicated in the Leuven Renal Transplant Cohort. The main limitation of this study is its observational design, which precludes conclusions about causation. Conclusions We demonstrated that PPI use is associated with an increased mortality risk in KTRs, independent of potential confounders. Moreover, our data suggest that this risk is highest among KTRs taking high PPI dosages. Because of the observational nature of our data, our results require further corroboration before it can be recommended to avoid the long-term use of PPIs in KTRs

Acute kidney injury in patients treated with immune checkpoint inhibitors

Background: Immune checkpoint inhibitor-associated acute kidney injury (ICPi-AKI) has emerged as an important toxicity among patients with cancer. Methods: We collected data on 429 patients with ICPi-AKI and 429 control patients who received ICPis contemporaneously but who did not develop ICPi-AKI from 30 sites in 10 countries. Multivariable logistic regression was used to identify predictors of ICPi-AKI and its recovery. A multivariable Cox model was used to estimate the effect of ICPi rechallenge versus no rechallenge on survival following ICPi-AKI. Results: ICPi-AKI occurred at a median of 16 weeks (IQR 8-32) following ICPi initiation. Lower baseline estimated glomerular filtration rate, proton pump inhibitor (PPI) use, and extrarenal immune-related adverse events (irAEs) were each associated with a higher risk of ICPi-AKI. Acute tubulointerstitial nephritis was the most common lesion on kidney biopsy (125/151 biopsied patients [82.7%]). Renal recovery occurred in 276 patients (64.3%) at a median of 7 weeks (IQR 3-10) following ICPi-AKI. Treatment with corticosteroids within 14 days following ICPi-AKI diagnosis was associated with higher odds of renal recovery (adjusted OR 2.64; 95% CI 1.58 to 4.41). Among patients treated with corticosteroids, early initiation of corticosteroids (within 3 days of ICPi-AKI) was associated with a higher odds of renal recovery compared with later initiation (more than 3 days following ICPi-AKI) (adjusted OR 2.09; 95% CI 1.16 to 3.79). Of 121 patients rechallenged, 20 (16.5%) developed recurrent ICPi-AKI. There was no difference in survival among patients rechallenged versus those not rechallenged following ICPi-AKI. Conclusions: Patients who developed ICPi-AKI were more likely to have impaired renal function at baseline, use a PPI, and have extrarenal irAEs. Two-thirds of patients had renal recovery following ICPi-AKI. Treatment with corticosteroids was associated with improved renal recovery

The genetic architecture of membranous nephropathy and its potential to improve non-invasive diagnosis

Membranous Nephropathy (MN) is a rare autoimmune cause of kidney failure. Here we report a genome-wide association study (GWAS) for primary MN in 3,782 cases and 9,038 controls of East Asian and European ancestries. We discover two previously unreported loci, NFKB1 (rs230540, OR = 1.25, P = 3.4 × 10-12) and IRF4 (rs9405192, OR = 1.29, P = 1.4 × 10-14), fine-map the PLA2R1 locus (rs17831251, OR = 2.25, P = 4.7 × 10-103) and report ancestry-specific effects of three classical HLA alleles: DRB1*1501 in East Asians (OR = 3.81, P = 2.0 × 10-49), DQA1*0501 in Europeans (OR = 2.88, P = 5.7 × 10-93), and DRB1*0301 in both ethnicities (OR = 3.50, P = 9.2 × 10-23 and OR = 3.39, P = 5.2 × 10-82, respectively). GWAS loci explain 32% of disease risk in East Asians and 25% in Europeans, and correctly re-classify 20-37% of the cases in validation cohorts that are antibody-negative by the serum anti-PLA2R ELISA diagnostic test. Our findings highlight an unusual genetic architecture of MN, with four loci and their interactions accounting for nearly one-third of the disease risk

Pembrolizumab-related renal toxicities: diagnosis first, treatment later

Checkpoint inhibitors are increasingly used to treat different types of malignancy and have been associated with renal toxicities. In this issue, Izzedine et al. report on the incidence of pembrolizumab-associated renal toxicity in a French single-centre nephrology referral centre. They report an estimated incidence of pembrolizumab-related renal toxicities of 1.77% and most notably the most common histologic lesion was acute tubular injury (not acute tubulo-interstitial nephritis). This study further highlights the importance of performing a thorough nephrological workup including kidney biopsy in patients experiencing renal toxicities while receiving pembrolizumab treatment.status: publishe

Aetiology and management of acute kidney injury in multiple myeloma

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