C3 Glomerulopathy Research Articles

#2663 Assessment of in situ alternative and classical convertases as indicators of ongoing glomerular complement activation in IgA nephropathy

Abstract Background and Aims Complement activation is involved in IgA nephropathy (IgAN), opening up new avenues for complement-targeting therapies. However, precise patient selection and optimal timing for these therapies are essential. Current diagnostic methods of complement activation in IgAN, based on immunostaining, lack precision in identifying specific pathway(s) involved and distinguishing ongoing from past complement activation. Method Complement deposition analysis was conducted on kidney biopsy samples from 53 patients with primary IgAN at diagnosis (NCT05234463). Glomerular complement deposition was assessed through immunohistochemistry for C4d and C5b-9 and immunofluorescence for C3b/iC3b and C1q. In situ detection of C3/C5 convertases complexes from complement classical/lectin (C4b2b) and alternative pathways (C3bBb) was performed on paraffin-embedded kidney biopsies from 33 patients using a proximity ligation assay (Duolink®, Sigma). Kidney biopsies from patients with lupus nephritis (LN) and C3 glomerulopathy (C3G) were used as positive controls for classical/lectin and alternative convertases staining, respectively. The signals corresponding to the convertases were quantified using QuPath® Software and correlated with clinical parameters, MEST-C score and C5b-9 staining. Results At diagnosis, all 53 IgAN patients (100%) exhibited C3 mesangial deposition. Additionally, 51.2% were positive for C4d, 16.5% had C1q deposition and 62.7% had C5b-9 deposition. In situ analysis of C3/C5 convertases revealed the presence of glomerular C3bBb convertases in 20/33 (60.6%) patients, with a median positive area of 14.9 [2.5-26.5]%o of glomerular surface. C4b2b convertases were detected in 21/33 patients (63.6%), with a median glomerular positive area of 8.1 [3.4-12.1]%o. Both C3bBb and C4b2b convertases were detected in 13/33 (39.4%) patients (Fig. 1). By contrast, no convertases were detected in 5/33 (15.2%) patients despite positive C3b/iC3b deposition. The intensity of C3bBb staining positively correlated with terminal pathway C5b-9 glomerular deposits (p = 0.0011, r2 0.29). Patients with MEST-C score S1 lesions and/or interstitial fibrosis/tubular atrophy (T1-2) exhibited a more pronounced intensity of C3bBb at diagnosis (p = 0.0093). Conclusion Our study, for the first time, presents evidence of ongoing complement activation at the tissue level in IgA nephropathy (IgAN), showing variable intensities among patients. The visualization of in situ C3/C5 convertases could enhance the functional aspect of pathological examination, helping identify patients with ongoing complement activation, making them potential candidates for complement inhibitors. Further research is necessary to investigate the kinetics of this staining over the natural course of IgAN and its implications for IgAN progression.

Primary immunodeficiency as a cause of immune-mediated kidney diseases.

Primary immunodeficiency (PID) is no longer defined by infections alone, and autoimmunity is an accompanying manifestation of PID. Recurrent infections may trigger autoimmunity through molecular mimicry, bystander activation, or superantigens. The diagnosis of PID is still challenging, but genetic analysis reveals the underlying link between PID and autoimmunity. Mutations in relevant genes affecting central and peripheral immune tolerance, regulatory T-cell function, expansion of autoreactive lymphocytes, antigen clearance, hyperactivation of type I interferon, and NF-κB pathways have all been implicated in triggering autoimmunity in PID. Autoimmunity in PID leads to chronic inflammation, tissue damage, and organ failure and increases the mortality of patients with PID. The kidneys are inextricably linked with the immune system, and kidney diseases can be mediated by both infection and autoimmunity/inflammation in PID patients. The manifestations of kidney involvement in PID patients are very heterogeneous and include lupus nephritis, C3 glomerulopathy, kidney thrombotic microangiopathy, vasculitis, and interstitial nephritis.Patients with PID-caused kidney diseases have defined immune function defects and may benefit from pathway-based biologics, stem cell transplantation, or gene therapy. Early diagnosis and appropriate treatment of PID are crucial for reducing the mortality rate and improving organ function and quality of life.

Moss-produced human complement factor H with modified glycans has an extended half-life and improved biological activity.

Most drugs that target the complement system are designed to inhibit the complement pathway at either the proximal or terminal levels. The use of a natural complement regulator such as factor H (FH) could provide a superior treatment option by restoring the balance of an overactive complement system while preserving its normal physiological functions. Until now, the systemic treatment of complement-associated disorders with FH has been deemed unfeasible, primarily due to high production costs, risks related to FH purified from donors' blood, and the challenging expression of recombinant FH in different host systems. We recently demonstrated that a moss-based expression system can produce high yields of properly folded, fully functional, recombinant FH. However, the half-life of the initial variant (CPV-101) was relatively short. Here we show that the same polypeptide with modified glycosylation (CPV-104) achieves a pharmacokinetic profile comparable to that of native FH derived from human serum. The treatment of FH-deficient mice with CPV-104 significantly improved important efficacy parameters such as the normalization of serum C3 levels and the rapid degradation of C3 deposits in the kidney compared to treatment with CPV-101. Furthermore, CPV-104 showed comparable functionality to serum-derived FH in vitro, as well as similar performance in ex vivo assays involving samples from patients with atypical hemolytic uremic syndrome, C3 glomerulopathy and paroxysomal nocturnal hematuria. CPV-104 - the human FH analog expressed in moss - will therefore allow the treatment of complement-associated human diseases by rebalancing instead of inhibiting the complement cascade.

Complement Terminal Pathway Activation and Intrarenal Immune Response in C3 Glomerulopathy.

C3 glomerulopathy is a rare disease resulting from an overactivation of the complement alternative pathway. Although there is also evidence of terminal pathway activation, its occurrence and consequences on the disease have been poorly studied. We retrospectively studied a cohort of 42 patients diagnosed with C3 glomerulopathy. We performed centralized extensive characterization of histological parameters. Kidney C5b-9 staining was performed as a marker of terminal pathway activation, intra-renal immune response was characterised through transcriptomic analysis. Eighty-eight percent of biopsies showed C5b-9 deposits in glomeruli. Biopsies were grouped according to the amount of C5b-9 deposits (no or low n=15/42, 36%, intermediate n=15/42, 36%, and high n=12/42, 28%). Patients with high C5b-9 deposits significantly differed from the 2 other groups patients and were characterized by a significant higher histological chronicity score (p=0.005) and lower outcome-free survival (p=0.001). In multivariable analysis, higher glomerular C5b-9 remained associated with poor kidney prognosis after adjustment. One third of the 847 studied immune genes were upregulated in C3 glomerulopathy biopsies compared to controls. Unsupervised clustering on differentially expressed genes identified a group of kidney biopsies enriched in high glomerular C5b-9 with high immune and fibroblastic signature and showed high chronicity scores on histological examination. In a cohort of patients with C3 glomerulopathy, intra-renal terminal pathway activation was associated with specific histological phenotype and disease prognosis.

Clinical characteristics and outcomes of immune-complex membranoproliferative glomerulonephritis and C3 glomerulopathy in Japanese children

BackgroundMembranoproliferative glomerulonephritis (MPGN) can be divided into immune-complex MPGN (IC-MPGN) and C3 glomerulopathy (C3G), which includes dense deposit disease (DDD) and C3 glomerulonephritis (C3GN). These conditions result from abnormalities in different complement pathways and may lead to different prognoses. However, there are limited studies describing the respective clinical courses.MethodsIn this study, Japanese pediatric patients diagnosed with MPGN based on kidney biopsies conducted between February 2002 and December 2022 were reclassified as having IC-MPGN or C3G (DDD or C3GN). We retrospectively analyzed the clinical characteristics and outcomes of these patients.ResultsOut of 25 patients with MPGN, three (12.0%) were diagnosed with DDD, 20 (80.0%) with C3GN, and two (8.0%) with IC-MPGN. There were 13 (65.0%) patients and one (33.3%) patient in remission after treatment for C3GN and DDD, respectively, and no patients with IC-MPGN achieved remission. The median follow-up period was 5.3 (2.5–8.9) years, and none of the patients in either group progressed to an estimated glomerular filtration rate < 15 ml/min/1.73 m2. Patients with C3GN presenting mild to moderate proteinuria (n = 8) received a renin-angiotensin system inhibitor (RAS-I) alone, and these patients exhibited a significant decrease in the urinary protein creatinine ratio and a notable increase in serum C3 levels at the last follow-up.ConclusionsMost patients with MPGN were diagnosed with C3GN. The remission rate for C3GN was high, and no patients developed kidney failure during the approximately 5-year follow-up. Additionally, patients with C3GN with mild to moderate proteinuria had good outcomes with RAS-I alone, but continued vigilance is necessary to determine long-term prognosis.Graphical abstractA higher resolution version of the Graphical abstract is available as Supplementary information

Recurrent disease after pediatric renal transplantation.

Recurrent disease after kidney transplant remains an important cause of allograft failure, accounting for 7-8% of graft loss and ranking as the fifth most common cause of allograft loss in the pediatric population. Although the pathophysiology of many recurrent diseases is incompletely understood, recent advances in basic science and therapeutics are improving outcomes and changing the course of several of these conditions. Review of the literature. We discuss the diagnosis and management of recurrent disease. We highlight new insights into the pathophysiology and treatment of post-transplant primary hyperoxaluria, focal segmental glomerulosclerosis, immune complex glomerulonephritis, C3 glomerulopathy, lupus nephritis, atypical hemolytic uremic syndrome, and IgA nephropathy.

Successful Treatment of Posttransplant Monoclonal Gammopathy-associated C3 Glomerulopathy With Plasma Cell Clone-directed Therapy.

Successful Treatment of Posttransplant Monoclonal Gammopathy-associated C3 Glomerulopathy With Plasma Cell Clone-directed Therapy.

Diagnostic Challenges and Emerging Pathogeneses of Selected Glomerulopathies.

Recent progress in glomerular immune complex and complement-mediated diseases have refined diagnostic categories and informed mechanistic understanding of disease development in pediatric patients. Herein, we discuss selected advances in 3 categories. First, membranous nephropathy antigens are increasingly utilized to characterize disease in pediatric patients and include phospholipase A2 receptor (PLA2R), Semaphorin 3B (Sema3B), neural epidermal growth factor-like 1 (NELL1), and protocadherin FAT1, as well as the lupus membranous-associated antigens exostosin 1/2 (EXT1/2), neural cell adhesion molecule 1 (NCAM1), and transforming growth factor beta receptor 3 (TGFBR3). Second, we examine advances in techniques for paraffin and light chain immunofluorescence (IF), including the former's function as a salvage technique and their necessity for diagnosis in adolescent cases of membranous-like glomerulopathy with masked IgG kappa deposits (MGMID) and proliferative glomerulonephritis with monotypic Ig deposits (PGNMID), respectively. Finally, progress in understanding the roles of complement in pediatric glomerular disease is reviewed, with specific attention to overlapping clinical, histologic, and genetic or functional alternative complement pathway (AP) abnormalities among C3 glomerulopathy (C3G), infection-related and post-infectious GN, "atypical" post-infectious GN, immune complex mediated membranoproliferative glomerulonephritis (IC-MPGN), and atypical hemolytic uremic syndrome (aHUS).

C3 glomerulopathy associated with peripheral retinal drusen: Case report and review of the literature

A 46-year-old female was admitted with complaints of fever and generalized bodily swelling and a working phenotypic diagnosis of nephrotic syndrome. Renal function was mildly impaired. A fundus examination revealed multiple whitish-yellow drusen scattered in the inferior mid-periphery of both eyes with an underlying retinal depigmentation/atrophy. A kidney biopsy was repeated, and the cores were examined. Immunofluorescence staining for IgA, IgM, and IgG was negative, but strongly positive C3 staining was seen in the capillary walls and mesangium. These findings were strongly suggestive of C3 glomerulopathy. The detection of drusen led to the use of the appropriate testing and correct diagnosis. The use of fundus examination may provide diagnostic assistance in cases of unexplained glomerulopathy.

374 C3 glomerulopathy mimic induced by mycoplasma infection

374 C3 glomerulopathy mimic induced by mycoplasma infection

Prognostic factors and validation of the histologic chronicity score for C3 glomerulopathy: a registry analysis.

Data on the prognostic factors for C3 glomerulopathy (C3G) are limited, and validation of the new C3G histologic index (C3G-HI) in different settings is still needed. We aimed to evaluate the chronicity score of C3G-HI and probable prognostic factors in our population. In this registry study, 74 patients from 20 centers with adequate follow-up data were included. Total chronicity score (TCS) was calculated according to percentages of glomerulosclerosis, interstitial fibrosis, tubular atrophy, and presence of arterio- and arteriolosclerosis. Primary composite outcome was defined as doubling of serum creatinine from baseline, undergoing dialysis or transplantation, development of stage 5 chronic kidney disease, or death. Median age was 34 [interquartile range (IQR) 24-46] years, and 39 patients (52.7%) were male. Median follow-up duration was 36 (IQR 12-60) months, and median TCS was 3 (IQR 1-5). Overall, 19 patients (25.7%) experienced primary composite outcome. Multivariate Cox regression model showed that only hemoglobin [adjusted HR (aHR) 0.67, 95% confidence interval 0.46-0.97, P=.035] predicted primary composite outcome, and TCS fell short of the statistical significance (aHR 1.26, 0.97-1.64, P=.08). Receiver operating characteristic analysis demonstrated that TCS showed an area under the curve value of 0.68 (0.56-0.78, P=.028) in discriminating primary composite outcome at 3 years, and 3-year kidney survival was lower in patients with TCS ≥4 (72.4%) compared with TCS <4 (91.1%) in Kaplan-Meier analysis (P=.036). Low hemoglobin levels predicted dismal outcomes in patients with C3G. TCS ≥4 was associated with a worse 3-year kidney survival, which validated the 3-year prognostic value of the TCS of C3G-HI in our population.

Apolipoprotein E is enriched in dense deposits and is a marker for dense deposit disease in C3 glomerulopathy

C3 glomerulopathy (C3G) is a rare disease resulting from dysregulation of the alternative pathway of complement. C3G includes C3 glomerulonephritis (C3GN) and dense deposit disease (DDD), both of which are characterized by bright glomerular C3 staining on immunofluorescence studies. However, on electron microscopy (EM), DDD is characterized by dense osmiophilic mesangial and intramembranous deposits along the glomerular basement membranes (GBM), while the deposits of C3GN are not dense. Why the deposits appear dense in DDD and not in C3GN is not known. We performed laser microdissection (LCM) of glomeruli followed by mass spectrometry (MS) in 12 cases each of DDD, C3GN, and pretransplant kidney control biopsies. LCM/MS showed marked accumulation of complement proteins C3, C5, C6, C7, C8, C9 and complement regulating proteins CFHR5, CFHR1, and CFH in C3GN and DDD compared to controls. C3, CFH and CFHR proteins were comparable in C3GN and DDD. Yet, there were significant differences. First, there was a six-to-nine-fold increase of C5-9 in DDD compared to C3GN. Secondly, an unexpected finding was a nine-fold increase in apolipoprotein E (ApoE) in DDD compared to C3GN. Most importantly, immunohistochemical and confocal staining for ApoE mirrored the dense deposit staining in the GBM in DDD but not in C3GN or control cases. Validation studies using 31 C3G cases confirmed the diagnosis of C3GN and DDD in 80.6 % based on ApoE staining. Overall, there is a higher burden of terminal complement pathway proteins in DDD compared to C3GN. Thus, our study shows that dense deposits in DDD are enriched with ApoE compared to C3GN and control cases. Hence, ApoE staining may be used as an adjunct to EM for the diagnosis of DDD and might be valuable when EM is not available.

Complément dans les glomérulopathies à dépôts de C3 : exploration et conséquences thérapeutiques

AbstractC3 glomerulopathies are rare and chronic diseases which diagnostic is based on the presence of exclusive or predominant glomerular deposition of C3.They count for less than 5% of primitive glomerulopathies.They are severe and affect mainly children and young adults. The patients present with a glomerular syndrome at diagnosis but 30 to 50 % of them develop end stage renal disease after 10 years of evolution. C3 glomerulopathies occur secondarily to a dysregulated alternative C3 convertase leading to an excessive C3 cleavage. Thus, main of the patients exhibit low plasma levels of C3 with high soluble C5b9 in some of them. This dysregulation is mainly due to the presence of autoantibodies called C3 nephritic factor (C3NeF) and targeting the C3 convertase inducing an increase of its half life. Other autoantibodies target the components C3b and Factor B, the C5 convertase (C5 Nef) or the regulatory protein Factor H. Genetic abnormalities are rare and mainly found in familial forms.The treatment aims to decrease the glomerular inflammation and the production of the autoantibodies. Eculizumab which blocks the complement cascade at the level of C5 has shown good efficacy on the histological inflammatory lesions but heterogeneous effects at the clinical level. Multiple complement inhibitory drugs are currently tested in phase I/II and represent new hope for the C3G treatment.

Triple-fusion protein (TriFu): A potent, targeted, enzyme-like inhibitor of all three complement activation pathways

The introduction of a therapeutic anti-C5 antibody into clinical practice in 2007 inspired a surge into the development of complement-targeted therapies. This has led to the recent approval of a C3 inhibitory peptide, an antibody directed against C1s and a full pipeline of several complement inhibitors in preclinical and clinical development. However, no inhibitor is available that efficiently inhibits all three complement initiation pathways and targets host cell surface markers as well as complement opsonins. To overcome this, we engineered a novel fusion protein combining selected domains of the three natural complement regulatory proteins decay accelerating factor, factor H and complement receptor 1. Such a triple fusion complement inhibitor (TriFu) was recombinantly expressed and purified alongside multiple variants and its building blocks. We analyzed these proteins for ligand binding affinity and decay acceleration activity by surface plasmon resonance. Additionally, we tested complement inhibition in several invitro/exvivo assays using standard classical and alternative pathway restricted hemolysis assays next to hemolysis assays with paroxysmal nocturnal hemoglobinuria erythrocytes. A novel invitro model of the alternative pathway disease C3 glomerulopathy was established to evaluate the potential of the inhibitors to stop C3 deposition on endothelial cells. Next to the novel engineered triple fusion variants which inactivate complement convertases in an enzyme-like fashion, stoichiometric complement inhibitors targeting C3, C5, factor B, and factor D were tested as comparators. The triple fusion approach yielded a potent complement inhibitor that efficiently inhibits all three complement initiation pathways while targeting to surface markers.

Eculizumab dose tapering should take into account the nonlinearity of its pharmacokinetics.

Eculizumab is a monoclonal antibody targeting complement protein C5 used in renal diseases. As recommended dosing regimen leads to unnecessarily high concentrations in some patients, tailored dosing therapeutic drug monitoring was proposed to reduce treatment cost. The objectives of the present work were (i) to investigate the target-mediated elimination of eculizumab and (ii) whether a pharmacokinetic model integrating a nonlinear elimination allows a better prediction of eculizumab concentrations than a linear model. We analysed 377 eculizumab serum concentrations from 44 patients treated for atypical haemolytic uraemic syndrome and C3 glomerulopathy with a population pharmacokinetic approach. Critical concentrations (below which a non-log-linear decline of concentration over time is evidenced) were computed to estimate the relevance of the target-mediated elimination. Simulations of dosing regimens were then performed to predict probabilities of target attainment (i.e. trough >100 mg/L). Pharmacokinetics of eculizumab was nonlinear and followed a mixture of first-order (CL = 1.318 mL/day/kg) and Michaelis-Menten elimination (Vmax = 26.07 mg/day, Km = 24.06 mg/L). Volume of distribution (72.39 mL/kg) and clearance were weight-dependent. Critical concentrations (Vmax /CL) ranged from 144.7 to 759.7mg/L and were inversely related to body weight (P = .013). Nonlinearity was thus noticeable at therapeutic concentrations. Simulations predicted that 1200 mg of eculizumab every 21 days would allow 85% and 76% of patients to maintain a therapeutic exposure, for 50 or 90 kg body weight, respectively. Our study investigates the nonlinear elimination of eculizumab and discusses the importance of accounting for eculizumab target-mediated elimination in therapeutic drug monitoring.

C3 concentrations can be normal in patients with C3 glomerulopathy secondary to C3 nephritic factor

C3 concentrations can be normal in patients with C3 glomerulopathy secondary to C3 nephritic factor

Clinical and pathological features of 52 patients with glomerulonephritis with dominant C3.

With the in-depth study of complement dysregulation, glomerulonephritis with dominant C3 has received increasing attention, with a variety of pathologic types and large differences in symptoms and prognosis between pathologic types. This study analyzes the clinical, pathological, and prognostic characteristics of different pathological types of glomerulonephritis with dominant C3, aiming to avoid misdiagnosis and missed diagnoses. The clinical, pathological, and follow-up data of 52 patients diagnosed as glomerulonephritis with dominant C3 by renal biopsy from June 2013 to October 2022 were retrospectively analyzed. According to the clinical feature and results of pathology, 15 patients with post-infectious glomerulonephritis (PIGN) and 37 patients with of non-infectious glomerulonephritis (N-PIGN) were classified. N-PIGN subgroup analysis was performed, and 16 patients were assigned into a C3-alone-deposition group and 21 in a C3-dominant-deposition group, or 27 in a C3 glomerulopathy (C3G) group and 10 in a non-C3 nephropathy (N-C3G) group. The PIGN group had lower creatinine values (84.60 μmol/L vs179.62 μmol/L, P=0.001), lower complement C3 values (0.36 g/L vs0.74 g/L, P<0.001) at biopsy, and less severe pathological chronic lesions compared with the N-PIGN group. In the N-PIGN subgroup analysis, the C3-dominant-deposition group had higher creatinine values (235.30 μmol/L vs106.70 μmol/L, P=0.004) and higher 24-hour urine protein values (4 025.62 mg vs1 981.11 mg, P=0.037) than the C3-alone-deposition group. The prognosis of kidney in the PIGN group (P=0.049), the C3-alone-deposition group (P=0.017), and the C3G group (P=0.018) was better than that in the N-PIGN group, the C3-dominant-deposition group, and the N-C3G group, respectively. Glomerulonephritis with dominant C3 covers a variety of pathological types, and PIGN needs to be excluded before diagnosing C3G because of considerable overlap with atypical PIGN and C3G; in addition, the deposition of C1q complement under fluorescence microscope may indicate poor renal prognosis, and relevant diagnosis, treatment, and follow-up should be strengthened.

Anti-factor B antibodies in atypical hemolytic uremic syndrome.

The etiology of atypical hemolytic uremic syndrome (aHUS) is unknown in 30-40% of patients. Anti-factor B (FB) antibodies are reported in C3 glomerulopathy (C3G) and immune-complex membranoproliferative glomerulonephritis (IC-MPGN), though not in aHUS. We screened patients < 18-year-old from cohorts of aHUS and C3G/idiopathic IC-MPGN. Anti-FB IgG antibodies were measured by ELISA and confirmed by Western blot. Normative levels were based on antibody levels in 103 healthy blood donors. Prevalence of anti-FB antibodies was 9.7% (95% CI 6.1-14.5%; n = 21) in 216 patients with aHUS, including 11.5% (95% CI 6.4-18.5%; n = 14) in anti-FH associated aHUS and 11.8% (95% CI 4.4-23.9%; n = 6) in patients without a definitive genetic or autoimmune etiology. Patients with significant genetic variants did not show anti-FB antibodies. In patients with concomitant anti-FB and anti-FH antibodies, median anti-FH titers were higher (11,312 AU/mL vs. 4920 AU/mL; P = 0.04). Anti-FB antibody titer correlated with disease severity (hemoglobin and platelets; P < 0.05), declined following plasma exchange and increased during relapse. While 4/64 patients with C3G (6.3%) and 1/17 with IC-MPGN showed anti-FB antibodies, titers were higher in aHUS (544.8 AU/mL vs. 1028.8AU/mL; P = 0.003). Anti-FB antibodies are present in 6-10% of patients with aHUS and C3G/IC-MPGN, with higher titers in the former. The diagnostic and therapeutic implication of anti-FB antibodies in aHUS needs confirmation and further studies. The study shows propensity for autoantibody generation and co-existence of multiple risk factors for aHUS in Indian children.

New advances in pediatric nephrology: ESPN 2023 results

On September 28 — October 1, 2023, the European Society for Paediatric Nephrology (ESPN) 55th Annual Meeting was held in Vilnius, Lithuania, where new achievements in the world of pediatric nephrology were presented. The program included 66 sessions with reports, continuing medical education courses, 117 invited speakers, meetings of working groups on various issues of pediatric nephrology were held, about 450 abstracts were printed and 292 poster presentations were discussed, inclu­ding two by authors from Ukraine. Courses for young doctors, preparing them for the international exam, and 5-minute reports by well-known specialists became interesting in the organization of continuing medical education, which significantly increased the amount of presented material. Among the innovative approaches in pediatric nephrology, the following drugs have been considered: finerenone (a selective non-steroidal mineralocorticoid receptor antagonist), sparsentan (an angiotensin/endothelin receptor antagonist) for Alport syndrome, focal segmental glomerulosclerosis, IgA nephropathy, dapagliflozin (a sodium-glucose cotransporter 2 inhibitor) for chronic kidney disease and pioglitazone for proteinuria. New approaches have been introduced: to IgA nephropathy — proteinuria control with angiotensin-converting enzyme inhibitors (ACEi), tonsillectomy, rituximab, eculizumab; to focal segmental glomerulosclerosis — plasmapheresis, rituximab (CD20), ofatumumab (CD20), abatacept (CD80/86), belatacept (CD80/86), daratumumab (CD38); to membranous nephropathy — proteinuria control with ACEi, rituximab, calcineurin inhibitors, glucocorticoids, cyclophosphamide; to membranoproliferative glomerulonephritis — proteinuria control with ACEi; to C3 glomerulopathy — proteinuria control with ACEi, eculizumab. Specific provisions of the BK polyomavirus (BKPyV) guidelines were considered, in particular, monthly screening for BKPyV-DNAemia in blood plasma is suggested until month 9, then every 3 months until month 24, after which additional screening every 3 months until the end of the third year after transplantation in pediatric kidney recipients (C, weak). In pediatric patients with stable renal function and high BKPyV-DNAemia, despite reduction in immunosuppressive therapy, we suggest consideration of renal allograft biopsy, as creatinine elevation may be decreased in children with significant renal involvement, including rejection (A, strong).

Digital Ischemia as a Rare Manifestation of C3 Glomerulopathy Associated With Monoclonal Gammopathy

Digital Ischemia as a Rare Manifestation of C3 Glomerulopathy Associated With Monoclonal Gammopathy