IgA Glomerulonephritis Research Articles

IgA Glomerulonephritis in the Setting of Immune Checkpoint Inhibitor Use Successfully Treated with Rituximab

IgA Glomerulonephritis in the Setting of Immune Checkpoint Inhibitor Use Successfully Treated with Rituximab

Drusen and Other Retinal Findings in People With IgA Glomerulonephritis

PurposeRetinal drusen have been described in people with IgA nephropathy. We examined the frequency of drusen in IgA nephropathy, and compared their location and composition with those for drusen in age-related macular degeneration. DesignImmunohistological case series of eyes of patients with IgA nephropathy, and a comparison eye with age-related macular degeneration. MethodsDonor eyes from four individuals (3 male, one female, aged 40 – 80 years) with biopsy-proven IgA nephropathy and kidney failure were examined for the presence of drusen, and location and composition using antibodies for vitronectin, IgA, IgM, IgG, C3 and C1q. Results were compared with those for drusen in macular degeneration without IgA nephropathy. ResultsAll four donors had sparse, sub-retinal pigment epithelium drusen about 55-65 μm diameter, that stained for vitronectin, but not for IgA or complement. All donors had retinal capillaries and choriocapillaris staining for IgA. The youngest donor (F, 40) had rare deposits in the outer nuclear layer that stained for IgA, but not for vitronectin. The oldest donor (M, 82) had large cyst-like spaces in the inner nuclear and plexiform layers, and smaller cysts in the outer nuclear layer, with no staining for IgA or complement. ConclusionsRetinal drusen are uncommon in IgA nephropathy, even with kidney failure. Drusen in IgA nephropathy resemble drusen found in age-related macular degeneration. IgA-staining deposits in the outer nuclear layer were likely due to systemic deposition of IgA and complement activation. The nature of cystic spaces is unknown. Further analysis of the retinae of people with glomerulonephritis is recommended.

Familial IgA Glomerulonephritis Is Commonly Caused by Pathogenic Variants Associated With Other Genetic Kidney Diseases

Familial IgA Glomerulonephritis Is Commonly Caused by Pathogenic Variants Associated With Other Genetic Kidney Diseases

Increased retinal drusen in IgA glomerulonephritis are further evidence for complement activation in disease pathogenesis

Drusen are retinal deposits comprising cell debris, immune material and complement that are characteristic of macular degeneration but also found in glomerulonephritis. This was a pilot cross-sectional study to determine how often drusen occurred in IgA glomerulonephritis and their clinical significance. Study participants underwent non-mydriatic retinal photography, and their deidentified retinal images were examined for drusen by two trained graders, who compared central drusen counts, counts ≥ 10 and drusen size with those of matched controls. The cohort comprised 122 individuals with IgA glomerulonephritis including 89 males (73%), 49 individuals (40%) of East Asian or Southern European ancestry, with an overall median age of 54 years (34–64), and median disease duration of 9 years (4–17). Thirty-nine (33%) had an eGFR < 60 ml/min/1.73 m2 and 72 had previously reached kidney failure (61%). Overall mean drusen counts were higher in IgA glomerulonephritis (9 ± 27) than controls (2 ± 7, p < 0.001). Central counts ≥ 10 were also more common (OR = 3.31 (1.42–7.73, p = 0.006), and were associated with longer disease duration (p = 0.03) but not kidney failure (p = 0.31). Larger drusen were associated with more mesangial IgA staining (p = 0.004). Increased drusen counts were also present in IgA glomerulonephritis secondary to Crohn’s disease but not with Henoch-Schonlein purpura. The finding of retinal drusen in IgA glomerulonephritis is consistent with complement activation and represents a model for better understanding glomerular immune deposition and a supporting argument for treatment with anti-complement therapies.

Immune Checkpoint Inhibitors' Associated Renal Toxicity: A Series of 12 Cases.

We present a series of twelve patients, bearing a wide range of solid malignancies, who received either PD-L1 or a combination of PD-L1 and CTLA-4 inhibitors. Following immunotherapy administration, they exhibited the clinical signs indicative of renal toxicity, including increased serum creatinine levels, proteinuria, nephrotic syndrome and/or hematuria. All patients underwent renal biopsy. Results: All cases demonstrated some degree of interstitial inflammation and tubular injury, while in five patients, glomerular alterations consistent with a specific glomerulopathy were also observed: secondary “lupus-like” membranous glomerulopathy in two cases and membranoproliferative glomerulonephritis, IgA glomerulonephritis and secondary AA amyloidosis in each of the remaining three patients. The two patients with “lupus-like” nephritis and the one with amyloidosis experienced nephrotic syndrome, while their creatinine was within normal range. In the remaining nine cases, deterioration of renal function was the main manifestation. Conclusion: Our findings harmonize with bibliographical data that identify tubulointerstitial nephritis as the most frequent histological lesion related to ICIs administration. The preferential involvement of tubulointerstitial tissue could be associated with the reported higher expression levels of PD-L1 on tubular epithelial cells, compared to glomeruli. On the other hand, glomerular involvement is probably a consequence of a systemic immune system reconstruction, induced by immune-checkpoints inhibition.

Retinal drusen counts are increased in inflammatory bowel disease, and with longer disease duration, more complications and associated IgA glomerulonephritis

Retinal drusen are deposits of inflammatory proteins that are found in macular degeneration and glomerulonephritis and result, in part, from complement activation. This was a cross-sectional observational study of individuals with inflammatory bowel disease (IBD) recruited from a Gastroenterology clinic who underwent non-mydriatic retinal photography. Deidentified images were examined for drusen, and drusen counts and size were compared with matched controls, and examined for clinical associations. The cohort with IBD comprised 19 individuals with ulcerative colitis, 41 with Crohn’s disease and three with indeterminate colitis, including 34 males (54%) and an overall median age of 48 (IQR 23) years. Their median IBD duration was 7 (IQR 10) years, median CRP level was 7 (IQR 14) mg/L, and 28 (44%) had complications (fistula, stricture, bowel resection etc.), while 28 with Crohn’s disease (68%) had colonic involvement. Drusen counts were higher in IBD than controls (12 ± 34, 3 ± 8 respectively, p = 0.04). Counts ≥ 10 were also more common (14, 22%, and 4, 6%, p = 0.02, OR 4.21, 95%CI 1.30 to 13.63), and associated with longer disease duration (p = 0.01, OR 1.06, 95%CI 1.00 to 1.13), an increased likelihood of complications (p = 0.003, OR 6.90, 95%CI 1.69 to 28.15) and higher CRP levels at recruitment (p = 0.008, OR1.02, 95%CI 1.00 to 1.05). Increased retinal drusen were found in all four individuals with Crohn’s disease and IgA glomerulonephritis. IBD and drusen may share pathogenetic mechanisms and underlying risk factors such as complement activation.

Genotype-Phenotype Correlations for Pathogenic COL4A3-COL4A5 Variants in X-Linked, Autosomal Recessive, and Autosomal Dominant Alport Syndrome.

Alport syndrome is inherited as an X-linked (XL), autosomal recessive (AR), or autosomal dominant (AD) disease, where pathogenic COL4A3 – COL4A5 variants affect the basement membrane collagen IV α3α4α5 network. About 50% of pathogenic variants in each gene (major rearrangements and large deletions in 15%, truncating variants in 20%, splicing changes in 15%) are associated with “severe” disease with earlier onset kidney failure, and hearing loss and ocular abnormalities in males with XL inheritance and in males and females with AR disease. Severe variants are also associated with early proteinuria which is itself a risk factor for kidney failure. The other half of pathogenic variants are missense changes which are mainly Gly substitutions. These are generally associated with later onset kidney failure, hearing loss, and less often with major ocular abnormalities. Further determinants of severity for missense variants for XL disease in males, and in AD disease, include Gly versus non-Gly substitutions; increased distance from a non-collagenous interruption or terminus; and Gly substitutions with a more (Arg, Glu, Asp, Val, and Trp) or less disruptive (Ala, Ser, and Cys) residue. Understanding genotype-phenotype correlations in Alport syndrome is important because they help predict the likely age at kidney failure, and the need for early and aggressive management with renin-angiotensin system blockade and other therapies. Genotype-phenotype correlations also help standardize patients with Alport syndrome undergoing trials of clinical treatment. It is unclear whether severe variants predispose more often to kidney cysts or coincidental IgA glomerulonephritis which are recognized increasingly in COL4A3-, COL4A4 - and COL4A5-associated disease.

Interleukin-33 Exacerbates IgA Glomerulonephritis in Transgenic Mice Overexpressing B Cell Activating Factor.

The cytokine IL-33 is an activator of innate lymphoid cells 2 (ILC2s) in innate immunity and allergic inflammation. B cell activating factor (BAFF) plays a central role in B cell proliferation and differentiation, and high levels of this protein cause excess antibody production, including IgA. BAFF-transgenic mice overexpress BAFF and spontaneously develop glomerulonephritis that resembles human IgA nephropathy. We administered IL-33 or PBS to wild-type and BAFF-transgenic mice. After treating Rag1-deficient mice with IL-33, with or without anti-CD90.2 to preferentially deplete ILC2s, we isolated splenocytes, which were adoptively transferred into BAFF-transgenic mice. BAFF-transgenic mice treated with IL-33 developed more severe kidney dysfunction and proteinuria, glomerular sclerosis, tubulointerstitial damage, and glomerular deposition of IgA and C3. Compared with wild-type mice, BAFF-transgenic mice exhibited increases of CD19+ B cells in spleen and kidney and ILC2s in kidney and intestine, which were further increased by administration of IL-33. Administering IL-33 to wild-type mice had no effect on kidney function or histology, nor did it alter the number of ILC2s in spleen, kidney, or intestine. To understand the role of ILC2s, splenocytes were transferred from IL-33-treated Rag1-deficient mice into BAFF-transgenic mice. Glomerulonephritis and IgA deposition were exacerbated by transfer of IL-33-stimulated Rag1-deficient splenocytes, but not by ILC2 (anti-CD90.2)-depleted splenocytes. Wild-type mice infused with IL-33-treated Rag1-deficient splenocytes showed no change in kidney function or ILC2 numbers or distribution. IL-33-expanded ILC2s exacerbated IgA glomerulonephritis in a mouse model. These findings indicate that IL-33 and ILC2s warrant evaluation as possible mediators of human IgA nephropathy.

Clinical and pathologic analysis of kidney damage in patients with nephrotic syndrome in the Republic of Srpska

Background / Aim: Nephrotic syndrome (NS) is a clinical syndrome characterised by massive proteinuria &gt; 3.5 g in 24 h urine, hypoalbuminaemia, hyperlipidaemia and oedema. Aim of this study was to determine the aetiology and frequency of kidney diseases that occur as the cause of NS in adults in the Republic of Srpska and the progression of renal insufficiency, disease outcomes and efficacy of applied therapy. Methods: The retrospective study included patients aged 18 to 80 hospitalised between 2014 and 2018 due to clinically and laboratory-manifested NS. In patients with suspected primary glomerular disease, a kidney biopsy with immunofluorescent dyeing was performed. The first examination involved hospital admission and the next check-up six months after the first hospitalisation. Basic clinical parameters were followed: creatinine, clearance creatinine, albumin, total protein, cholesterol, total protein in 24 h urine and microscopy of urine during the first hospitalisation and repeated same laboratory findings on control. The progression of kidney failure during this period was assessed, as well as the efficacy of immunosuppressive therapy. Results: In primary NS category membranous glomerulonephritis (MGN) was present at 40.7 % of patients, followed by focal segmental glomerulosclerosis (FSGS) 21.7 %, membranoproliferative glomerulonephritis (MPGN) 11.9 % and IgA glomerulonephritis (IgAN) 11.9 %. Nephroangiosclerosis was verified as the most common cause of secondary NS with 28.8 % and lupus nephritis 21.2 %, followed by ANCA-associated GN (11.5 %) and diabetic nephropathy (11.5 %). Thirty-four patients (21 %) died during the follow-up. Thirty-four patients (18.6 %) progressed to end stage renal disease during the five-year follow-up. Conclusion: The pathology of kidney disease in older patients is often very complex; therefore, a kidney biopsy should be conducted at an early stage of kidney disease for the purpose of obtaining an accurate diagnosis, determining appropriate treatment and thus improving the prognosis of the patient.

Guidelines for Genetic Testing and Management of Alport Syndrome.

Genetic testing for pathogenic COL4A3-5 variants is usually undertaken to investigate the cause of persistent hematuria, especially with a family history of hematuria or kidney function impairment. Alport syndrome experts now advocate genetic testing for persistent hematuria, even when a heterozygous pathogenic COL4A3 or COL4A4 is suspected, and cascade testing of their first-degree family members because of their risk of impaired kidney function. The experts recommend too that COL4A3 or COL4A4 heterozygotes do not act as kidney donors. Testing for variants in the COL4A3-COL4A5 genes should also be performed for persistent proteinuria and steroid-resistant nephrotic syndrome due to suspected inherited FSGS and for familial IgA glomerulonephritis and kidney failure of unknown cause.

Association between anti-complement factor H antibodies and renal outcome in primary membranous nephropathy.

The complement factor H (CFH) is a regulator for the alternative complement pathway. The prevalence and roles of anti-CFH antibodies in the clinical outcome of primary membranous nephropathy (MN) patients remain unclear. A total of 106 biopsy-proven kidney disease patients and 18 healthy controls were retrospectively investigated in this study. 36 patients had primary MN and 70 patients were diseased controls (31 minimal change nephrotic syndrome (MCNS), 19 rapidly progressive glomerulonephritis (RPGN), and 20 IgA glomerulonephritis (IgAGN)). Serum anti-CFH antibody titers were measured by enzyme-linked immunosorbent assay. 77.8% of MN patients were positive for anti-CFH antibodies. However, only 27.1% of diseased control patients and 5.6% of healthy controls were positive for anti-CFH antibodies. Moreover, median anti-CFH antibody titers were significantly higher in MN patients (4.69 AU/mL) than in diseased control patients (MCNS patients (0 AU/mL, p<0.01), RPGN patients (0 AU/mL, p<0.05), IgAGN patients (0 AU/mL, p<0.01)), and healthy controls (0 AU/mL, p<0.01). Anti-CFH antibody titer was selected as an independent unfavorable predictor of renal dysfunction by Cox proportional hazards analysis. These data suggest that anti-CFH antibodies may be involved in the deterioration of renal function in primary MN.

POS-328 THE BURDEN OF HYPERKALEMIA IN PATIENTS WITH CHRONIC KIDNEY DISEASE: A REPORT FROM THE DISCOVER CKD RETROSPECTIVE COHORT

Hyperkalemia (HK), defined as serum potassium (sK+) >5.0 mmol/L, is a potentially fatal condition most often observed in patients with chronic kidney disease (CKD), heart failure (HF) or diabetes and exacerbated by medications that inhibit the renin-angiotensin aldosterone system (RAASi). This real-world study describes characteristics of patients with and without HK in a large international observational study of patients with CKD. The DISCOVER CKD retrospective cohort was extracted using the US TriNetX hospital-EMR, UK Clinical Practice Research Datalink (CPRD) linked to hospital data, the US Dialysis Outcomes and Practice Patterns Study (DOPPS) and Japan Medical Data Vision (JMDV) databases. The study cohort included patients aged >18 years (>20 in JMDV database) with a diagnostic CKD code (stage 3a+ to stage 5 including renal replacement therapy) or 2 estimated glomerular filtration rate (eGFR) measures <75 mL/min/1.73 m2 at least 90 days apart between January 2008 and March 2020. For patients with eGFRs 60–75 mL/min/1.73 m2, one or more of the following was also required inclusive or prior to the second eGFR measurement: CKD diagnostic code, history/presence of albuminuria, history of kidney transplant, or confirmed cause of CKD, including any of the following: IgA nephropathy, glomerulonephritis, lupus nephritis, ANCA nephritis, or polycystic kidney disease. The index date for patients with HK was 2nd sK+measurement >5.0 mmol/L and for non-HK patients, date of CKD. Descriptive analyses were used. In patients with CKD, 125,196 with HK (48.5% female, mean±SD age 68.0±14.1 years, mean±SD sK+ 5.3±0.5 mmol/L) and 1,672,595 without HK (57.6% female, mean±SD age 63.6±14.0 years, mean±SD sK+ 4.2±0.05 mmol/L) were identified (Table 1). Compared to CKD patients without HK, patients with HK were older, had substantially higher proportions of comorbidities and about 25 mL/min/1.73 m2lower eGFR which decreased with increasing comorbidity burden. Diuretic and K+ binder use increased with additional comorbidities in HK and was greatest in patients with CKD + T2D + HF. Even among patients with comorbid HF, the highest proportion of RAASi use was 57.7%. This large cohort of patients with CKD demonstrates the high burden of HK even though HK was generally mild. Patients with HK and CKD + T2D + HF had the greatest CKD burden as evidenced by AKI, albuminuria, and diabetic nephropathy, though similar sK+ ranges were seen across groups. The use of HK treatments was low overall. Use of RAASi, representing life-saving guideline recommended therapy for patients with CKD and HF, was absent in >40% of patients regardless of the presence of HK.

¿Ha mejorado la supervivencia renal en la glomerulonefritis IgA en las últimas tres décadas?

Aim: To have the knowledge of the incidence, clinical, analytical and histological presentations, the kidney survival mean and the contribution of treatments to it. Methods: A descriptive, observational and transversal study over 156 patients who were diagnosed of primary IgA glomerulonephritis between 1994 and 2018 in the Nephrology department of Reina Sofía Hospital in Córdoba. Variables were analysed globally and compared between group 1 (G1) 1994-2002, group 2 (G2) 2002-2010 and group 3 (G3) 2010-2018. Results: Annual incidence 8,4 cases/million, 69,2% men, age mean 35,4±15,2 years old, serum creatinine mean 1,7±1,2 mg./dl., proteinuria mean 1,9±2,4 g./24h., macroscopic hematuria 41,4%, arterial hypertension 61,5%, ACEI/IIARA 87,5% and corticosteroids 33,7%. Kidney biopsy, mesangial proliferation 71,1%, sclerosis 49,2%, severe fibrosis 27,1%. The kidney survival at 10 and 20 years was 80,6% and 77,3%, respectively. GROUPS. The annual incidence increased in G3 (9,9 cases/million VS 6,9 cases/million G1), higher age mean (39,4±16,5 years old VS 31,5±14,9 years old G1, p=0,011), lower macroscopic hematuria (27,5% VS 58,8% G1, p=0,021) and worse prognosis histological characteristics, S1 (59,6% VS 25% G1, p=0,005) y F2 (21,7% VS 20% G1, p=0,016). The kidney survival at 8 years was identical in three groups (p=0,16). Conclusion: The incidence of biopsies with IgA nephropathy in Cordoba was increased between 2010 and 2018, with older patients, lower macroscopic hematuria and worse prognosis histological characteristics. Treatments and kidney survival at 8 years have not varied in three groups, making a different therapeutic approach necessary in order to improve the prognosis of the disease.

Renal disease associated with myeloproliferative neoplasms and myelodysplastic syndrome/myeloproliferative neoplasms.

Renal changes in patients with myeloproliferative neoplasms (MPNs) or myelodysplastic syndrome (MDS)/MPNs have been addressed by few, respectively no, reports. The aim of this study was to focus on a systematic evaluation of renal biopsies in patients with MPNs or MDS/MPNs. The cohort comprised 29 patients (23 men) aged 67±11years (mean±standard deviation), diagnosed with chronic myeloid leukaemia (n=5), polycythaemia vera (n=9), primary myelofibrosis (n=5), essential thrombocythaemia (n=2), or chronic myelomonocytic leukaemia (n=4), as well as MPNs or MDS/MPNs not otherwise specified (n=4). Patients manifested with proteinuria (93%), partially in the nephrotic range (46%), haematuria (72%), and impaired kidney function (93%). The most prominent histological findings included double-contoured glomerular basement membranes (71%), acute endothelial damage (68%), intracapillary platelet aggregation (62%), mesangiolysis (21%), thrombotic microangiopathy (24%), segmental glomerulosclerosis (66%), mesangial hypercellularity and sclerosis, extramedullary haematopoiesis (17%), and also IgA nephropathy (21%) and glomerulonephritis (GN) with features of infection-related GN (21%). MPN and MDS/MPN patients showed significantly more chronic changes than age-matched and sex-matched controls, including global and segmental glomerulosclerosis, mesangial sclerosis, and hypercellularity, whereas the extent of arteriosclerosis was comparable. MPN and MDS/MPN patients show glomerular scarring that exceeds age-related phenomena. Ongoing endothelial damage, growth factors released by platelets and deposition of immune complexes are probably the causative mechanisms. Early recognition of renal failure heralded by proteinuria and haematuria, and consequent control of risk factors for kidney failure, should be recommended for MPN and MDS/MPN patients.

Bilateral Anterior Ischaemic Optic Neuropathy as First Manifestation of Henoch-Schönlein Purpura (IgA Vasculitis).

A 46-year-old man was referred to our department complaining of a bilateral progressive decrease in his visual acuity. Fundus examination revealed bilateral optic disc oedema, indicative of anterior ischaemic neuropathy (AION), and a macular star in the right eye. Laboratory analysis showed low haematocrit and haemoglobin, elevated creatinine, and increased erythrocyte segmentation rate and C-reactive protein level. Physical examination revealed the presence of purpuric rash on the trunk and the extremities. During the investigation we performed a complete laboratory and imaging examination for autoimmune collagen diseases, vasculitides and infectious diseases, which were all negative. Histologic findings of renal biopsy were compatible with IgA glomerulonephritis and thus Henoch-Schönlein purpura (HSP) diagnosis was established. The patient was treated with methylprednisolone and cyclophosphamide. Six months later, his renal function and his visual acuity had improved, and the rash had subsided. This is a rare case of AION in a patient with HSP.

P0245PERCUTANEOUS RENAL BIOPSY IN FRAIL AND HIGH RISK PATIENTS

Abstract Background and Aims: Many patients with End Stage Kidney Disease do not undergo percutaneous kidney biopsy (KB) and do lack a definite diagnosis. Whether KB is beneficial in the extreme patients’ categories, i.e., age &amp;gt;75 years and very late referrals with kidney disease requiring renal replacement therapy at the first evaluation, remains controversial. Aim: To analyse the benefit/risk balance in terms of therapeutic options and general outcome of KB procedure in these borderline categories. Method Files for all biopsies performed in our Centre between 2013 and 2019 (# 903 inpatients’ native kidney) were retrospectively analysed with special focus on histological diagnosis, biopsy complications, and post-biopsy patient’s outcome. Two groups of high risk patients were identified 1. &amp;gt;75 years old patients, and 2. patients requiring dialysis at the first clinical evaluation. A rigorous protocol of screening of the bleeding risks was adopted. Results Of the 903 biopsies, 217 cases (24%) had group 1, and 92 (10%) group 2 criteria. Group 1: mean age 80 years (range 75-92), main histological diagnoses: ANCA associated vasculitis (AAV) (12,4%); membranous nephropathy (MN) (11,5%), diabetic nephropathy (10,1%), IgA glomerulonephritis (IgAGN) (9,2%), cast nephropathy (9,2%), renal amyloidosis (9.2%), focal segmental glomerulosclerosis (FSGS - 7,8 %). Group 2: mean age 60 years (range 20-92), most frequent histological diagnosis: AAV (26,1%); cast nephropathy (19,6 %), nephroangiosclerosis (9,8%), IgAGN (7,6 %), diabetic nephropathy (6,5%), renal amyloidosis (5,4%); FSGS (4,3%). Five major complications (2,3%), including AV fistula with spontaneous resolution in 4 patients and 1 case of severe bleeding requiring arterial embolization, and 14 minor complications (6,5%), including post biopsy haematomas &amp;lt;2cm in 12 patients and haematuria in 2 patients were observed in group 1. Only 1 (1%) major complication (AV fistula) and 4 minor complications (4,3%), including post biopsy &amp;lt;2cm haematomas in group 2 were identified in group 2. Histological diagnosis conditioned or changed treatment strategy in 71% of elderly patients (group 1), and 63% of patients in dialysis (group 2). Dialysis discontinuation was achieved in 30 out of 92 patients (36,6%) with a sparing of over 1 million euro/year. Conclusion Given its high diagnostic value (especially in patients who are willing to be transplanted), the prognostic significance (and the assessment of the extent of the renal sclerotic changes), and the potential impact on the treatment policy, indications to percutaneous kidney biopsy in elderly and dialysis patients should be probably revised.

P1670GLOMERULAR C4D IN POST-TRANSPLANT IG-A GLOMERULONEPHRITIS IS ASSOCIATED WITH DECREASED ALLOGRAFT SURVIVAL

Abstract Background and Aims Post transplant (pTX) glomerulonephritis (GN) is an important factor contributing to early and late allograft failure. De novo or recurrent IgA GN are the most frequent pTX-GN forms, however little is known about the optimal risk and therapeutic assessment. Recently, immunopathological evidence of glomerular C4d staining has been suggested as a prognostic tool in native glomerular kidney disease, in particular IgA GN. While peritubular capillary C4d is an accepted diagnostic criterion for antibody mediated rejection (ABMR), the role of glomerular C4d in pTX-GN is unkown. The primary hypothesis was that the finding of immunohistochemical glomerular C4d may be associated renal graft survival in post TX IgA GN. Method This large retrospective cohort study included all indication biopsies performed for cause in 885 kidney allografts from 1999-2006. Cases were screened for biopsy verified de novo or recurrent pTX-GN. GN cases were re-assessed by a single nephropathologist (NK). Primary endpoint was death-sensored graft survival followed until 01.01.2017. Results The prevalence of pTX-GN was 9.6% (n=85/885). De novo or recurrent IgA-GN was the most common pTX GN form with 40%. Of the 34 cases with pTX IgA GN, 27 had adequate material for interpretation of immunohistochemical glomerular C4d in the biopsy specimen. Eighteen of the 27 cases (66%) with pTx-IgA GN showed positive immunohistochemical C4d staining along glomerular capillary walls. There was no difference in renal function at biopsy or after one year comparing glomerular C4d positive vs. C4d negative pTX IgA GN. In univariate KM analysis glomerular C4d positive pTX-IgA GN showed significantly worse renal allograft survival rates (28%) compared to glomerular C4d negative pTX IgA GN (50%) or cases without GN (66%), p&amp;lt;0.001, respectively. In a multivariate Cox-Regression analysis including baseline covariates as well C4d+ABMR, Borderline lesion and TCMR, C4d+pTX IgA-GN remained independently associated with death censored graft-loss (HR 2.92, 95% CI 1.51-5.64, p=0.001). Conclusion Glomerular C4d staining in post transplant IgA glomerulonephritis is an independent risk factor for worse allograft survival and may provide a valuable risk assessment tool for prognostic and therapeutic decisions in post transplant glomerulonephritis.

P0436REFRACTORY IGA NEPHROPATHY. A MULTICYTOKINE NORMALIZED LEVELS THERAPY FOR T CELLS IMBALANCE

Abstract Background and Aims Interleukine-17(IL-17) is a pro-inflammatory cytokine which influences in glomerulonephritis (GN) in animal models. IgA nephropathy (IgAN) is a primary GN with auto-inflammatory and autoimmune features. Imbalances in Th1/Th17 and Treg/Th17 have been associated with the pathogenesis of the IgAN. We evaluated the effect of sequential treatment with a selective vitamin D receptor activator and with an IL-17 blocker in patients with refractory IgA GN (r-IgAN). Method Five patients with r-IgAN (previously treated with steroids, mycophenolate, tacrolimus and a renin-angiotensin-aldosterone system inhibitor) were treated initially with paricalcitol and six months later with secukinumab (IL-17A blocker) with the objective to improve anti-inflammatory and subsequentially inhibit pro-inflammatory milieu, respectively. We evaluate the evolution of the proteinuria, haematuria, plasma creatinine and urinary N-acetyl-beta-D-glucosaminidase: u-NAG, as a measure of lysosomal activity during the first month of treatment (induction phase) and at month 3 after treatment. We also evaluate the evolution of the evolution of the Th1/Th17 and Treg/Th17 ratio in whole blood. We evaluated the changes at month (M) 0, 1 and 3. Results Five males were included. Age: 43±11 years. Proteinuria (24h-collected) decreased along the study from 3.5, 2.1 to 1.6g (P&amp;lt;0.01) at M0, M1 and M3 respectively. Four (80%) patients who presented haematuria at month 0 disappeared at month 3. Creatinine did not show changes over time (1.84, 1.88 and 1.95 mg/dl for M0, M1 and M3, P=0.44). uNAG increased after induction phase from 7.2 to 9.8(P= 0.01) and finally decreased to 8.3 at month 3(P=1, respect to month1). Uric acid decreased but not significantly from 8.0, 7.1 and 7.6g/dl at any time point. The ratio Th1/Th17 and Treg/TH17 changed from the month 0 to month 3, from 1.8 to 2.6 (P =0.25) and 0.23 to 0.32 (P=0.16), respectively. Conclusion Sequential treatment was associated with a reduction in proteinuria and haematuria was well controlled. The changes in u-NAG suggest and intensive initial effect on the lysosomal activity since no changes in renal function was observed. The theoretical benefit of the Th1/Th17 and Treg/Th17 ratio represents a new modality of treatment that need to be rigorously evaluated for its clinical implication in r-IgAN patients.

Multicenter Review of Glomerular Diseases in the Emirates of Abu Dhabi: Six Years' Experience.

Glomerulonephritis (GN) is a rising paramount renal disease that varies in etiology from inherited or acquired factors. Its severity can range from asymptomatic depictions to end-stage renal disease. The aim of this study was to study the patterns of biopsy-proven GN based on the data from a multicenter in Abu Dhabi. Included kidney biopsies were from all patients above the age of 18 years, over a six-year period from 2010 to 2015, who had diagnosis of glomerular disease other than diabetes mellitus. The number of reviewed biopsies was 416. The most common type of GN among the study sample was IgA GN (22.8%) followed by focal segmental glomerulosclerosis (20.4%) and systemic lupus erythematosus (SLE) (19.7%). The least common types were pauciimmune (1.7%). There was female preponderance in lupus nephritis and pauciimmune GN. The nationality comparison did not reveal a predominate GN among Emirati nationals. The age relationship to GN types showed that majority (82.9%) of SLE patients, MCD (74.55%), and noncategorized (71.4%) patients are young aged between 18 and 39 years. On the other hand, 57.1%, 25%, and 16.7% of patients with pauciimmune, other GN types, and membranoproliferative GN, respectively, are 60 years and older. This study shows the histopathological variety of glomerular disease in Abu Dhabi. It could be a driving point to help understand GN better in the region.

Bilateral anterior ischaemic optic neuropathy with macular star as first manifestation of Henoch‐Schönlein purpura (IgA vasculitis)

AbstractPurposeTo report a case of bilateral anterior ischaemic optic neuropathy with macular star in a patient with Henoch–Schönlein purpura (HSP).MethodsA 46‐year‐old man was referred to our clinic complaining of progressive decrease in visual acuity of the right eye (OD) since the last 10 days, and since 3 days in his left eye (OS). His visual acuity was ‘hand motion’ OD and 4/10 OS. Anterior segment examination was insignificant, while fundus examination revealed optic disc edema, and bilateral macular star. A relative afferent pupillary defect was present in his right eye with normal pupillary reflexes in the left eye. Laboratory analysis showed: Hematocrit: 22.1%, ESR: 140 mm/hr, CRP: 64.80 mg/dl, Creatinine: 4.4 mg/dl. Physical examination revealed presence of erythematous rash on the trunk and the extremities. The patient was admitted to the Nephrology department for treatment of his azotemia.ResultsDuring his hospital course we performed complete laboratory and imaging examinations for autoimmune diseases, vasculitis and infectious diseases, which were negative. Histologic findings of renal biopsy were compatible with IgA glomerulonephritis and thus HSP was diagnosed. The patient received oral methylprednisolone and intravenous cyclophosphamide therapy. Six months later his renal function had improved, the rash had subsided and his visual acuity was ‘counting fingers’ OD and 10/10 OS. Standard automated perimetry showed peripheral visual field depression bilaterally.ConclusionsHenoch–Schönlein purpura (HSP) is a small vessel vasculitis which is more common in children. Based on literature, ophthalmic manifestations of HSP usually involve the anterior segment and less frequently the posterior segment. Systemic vasculitis should be included in the differential diagnosis of bilateral optic disc edema.