The relationship between glomerular IgG staining and poor prognostic findings in patients with IgA nephropathy: the data from TSN-GOLD working group

Background Galactose-deficient IgA1 (Gd-IgA1) has an increased tendency to form immunocomplexes with IgG in the serum, contributing to IgAN pathogenesis by accumulating in the glomerular mesangium. Several studies showed that glomerular IgG deposition in IgAN is an important cause of mesangial proliferation and glomerular damage. This study aims to determine the association of the positivity of IgG and the intensity of IgG staining with a poor renal prognosis. Methods A total of 943 IgAN patients were included in the study. Glomerular IgG staining negative and positive patients were compared using Oxford classification scores, histopathological evaluations, proteinuria, eGFR, albumin, blood pressures. IgG positive patients were classified as (+), (++), (+++) based on their staining intensity, and the association with the prognostic criteria was also evaluated. Results 81% (n = 764) of the patients were detected as IgG negative, while 19% (n = 179) were positive. Age, gender, body mass index, blood pressure, proteinuria, eGFR, uric acid values were similar in IgG positive and negative patients who underwent biopsy (p > 0.05). Intensity of glomerular IgG positivity was not found to be associated with diastolic and systolic blood pressure, urea, uric acid, age, eGFR, albumin, proteinuria (p > 0.05 for all, r = − 0.084, r = − 0.102, r = − 0.006, r = 0.062, r = 0.014, r = − 0.044, r = − 0.061, r = − 0.066, r = 0.150, respectively). There was no difference for histopathological findings between IgG (+), IgG (++), IgG (+++) groups (for all, p > 0.05). Conclusion Glomerular IgG negativity and positivity detected by routine IFM in IgAN patients is not associated with poor renal prognostic risk factors.

IgA Vasculitis with Nephritis in Adults: Histological and Clinical Assessment

Patients with IgA vasculitis (IgAV), an immune complex-mediated disease, may exhibit kidney involvement—IgAV with nephritis (IgAVN). The kidney-biopsy histopathologic features of IgAVN are similar to those of IgA nephropathy, but little is known about histopathologic disease severity based on the interval between purpura onset and diagnostic kidney biopsy. We assessed kidney histopathology and clinical and laboratory data in a cohort of adult patients with IgAVN (n = 110). The cases were grouped based on the interval between the onset of purpura and kidney biopsy: Group 1 (G1, <1 month, n = 14), Group 2 (G2, 1–6 months, n = 58), and Group 3 (G3, >6 months, n = 38). Glomerular leukocytes were more common in G1 than in the other groups (p = 0.0008). The proportion of neutrophils among peripheral-blood leukocytes was the highest in the patients biopsied within a month after onset of purpura (G1: 71 ± 8%). In the patients with an interval >6 months, the neutrophil proportion was lower, 60%. Moreover, the glomerular mesangial proliferation score correlated with the serum total IgA concentration (p = 0.0056). In conclusion, IgAVN patients biopsied <1 month from purpura onset showed an elevated percentage of blood neutrophils and glomerular leukocytes, consistent with an acute-onset inflammatory reaction. In all IgAVN patients, the mesangial proliferation score correlated with the serum IgA level.

A Rare Case of Immunotactoid Glomerulopathy Associated with Hodgkin Lymphoma

Immunotactoid glomerulopathy (ITG) is characterized by Congo red-negative microtubular deposits, and it has been reported as a rare paraneoplastic syndrome due to hematologic malignancies, viral infections, or autoimmune diseases. In hematologic malignancies, multiple myeloma and other mature B-cell malignancies are the most common hematologic malignancies, and Hodgkin lymphoma (HL) is extremely rare. A 59-year-old woman was admitted to our hospital because of a pulmonary mass and proteinuria. Computed tomography-guided lung biopsy confirmed the presence of HL stage IIA. Immunofixation of peripheral blood was positive for immunoglobulin G (IgG) kappa. Renal biopsy showed mesangial proliferation with deposits in the subendothelial lesion and no invasion of the HL. These deposits were positive for IgG3, C3, and kappa light chain but negative for C1q and lambda light chain. Electron microscopy showed randomly aligned tubular structures with a diameter of approximately 50 nm. We diagnosed the patient with immunotactoid nephropathy and HL. After systemic chemotherapy, the patient achieved a complete response and loss of proteinuria. On the contrary, her serum monoclonal gammopathy was observed after chemotherapy. The existence of a monoclonal antibody itself might not be a sufficient factor for ITG in some cases, and an additive trigger is necessary for development.

MO1028EFFECTIVENESS AND KIDNEY PROGNOSIS IN THE TREATMENT OF CORTICORRESISTANT NEPHROTIC SYNDROME IN PEDIATRICS

Background and Aims To report the response to different treatments and the renal prognosis in a cohort of patients with corticosteroid-resistant nephrotic syndrome (CRNS). Method Retrospective observational study in patients with CRNS. For this, the results of the histology, the different treatment guidelines used in each case and the evolution of renal function were collected, determining the results in terms of remission and renal survival in the different groups. Results Of the initial cohort of 37 patients, 33 were included, excluding 4 patients with Finnish-type genetic CRNS. The mean age at diagnosis was 6.1 years. 54.5% were women. Regarding the initial biopsy, 45.5% corresponded to minimal changes (15 patients), 27.3% (9) focal and segmental glomerulosclerosis, 15.1% (5) diffuse mesangial proliferation and 12.1% (4) others. The mean follow-up was 53 months (3-115 months). 27 patients (84.4%) received cyclosporine (CyA), 66.7% (18) of them presented complete remission and 22.2% (6) partial response. Of the patients in complete remission, 33% had at least one relapse after 17 months of treatment (7–27 months). Rituximab was administered in 12 patients (37.5%), of which 7 had not previously responded to immunosuppressants. 100% of frequent relapsers presented complete remission after administration of Rituximab, although 3 had subsequent relapses (60%) after 21 months of treatment (12-34 months). 57% of the patients who did not respond to immunosuppressants did not respond to Rituximab either, with Ofatumumab allowing complete remission in one of them. When relating the results with the histology, we saw how the remission in minimal changes and diffuse mesangial proliferation was 100% and 80%, respectively, although it was 33.3% in focal and segmental glomerulosclerosis. Similarly, renal failure was more frequent in patients with focal segmental glomerulosclerosis (77.7%). Of the remissions (24; 72.7%), 3 were partial (9.1%) and 6 (18.2%) did not respond to any immunosuppressive treatment, with the need for kidney transplantation in 2 of them (6%) and with 1 deceased due to an infectious cause (3%). Conclusion Histology and, especially, focal and segmental glomerulosclerosis, play a prognostic role in the CRNS with a lower remission rate and a greater deterioration in renal function and the need for associated kidney transplantation.

A case of lupus podocytopathy and a review of the literature

Nephrotic syndrome in systemic lupus erythematosus patients with histological evidence of minimal change disease, mesangial proliferation or focal and segmental glomerulosclerosis on light microscopy, represents a distinct clinical entity – lupus podocytopathy. This entity is characterized by a diffuse foot process effacement on electron microscopy and by absence of subepithelial or subendothelial immune -complex deposition. We report the case of a 49 -year -old woman admitted on suspicion of lupus nephritis flare, characterized by nephrotic syndrome and acute kidney injury, whose renal biopsy revealed histological features of lupus podocytopathy. Six months after discharge, under prednisolone and azathioprine, she presented 300 mg/day proteinuria, normal kidney function, without hematuria. A review of the pathogenesis, clinical features, diagnostic criteria, treatment and prognosis of lupus podocytopathy is provided. This case highlights the mounting evidence that lupus podocytopathy encompasses distinct clinical and morphological features, that should be included in the upcoming pathological classification of lupus nephritis.

Has the kidney survival improved in the IgA glomerulopathy in the last three decades?

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.

P1822CLINICAL AND BIOCHEMICAL DIFFERENCES IN PATIENTS WITH CORTICODEPENDENT, CORTICORRESISTENT NEPHROTIC SYNDROME AND FRECUENT RECAIDS THAT DEVELOPED DISEASE CHRONIC RENAL DISEASE

Background and Aims Nephrotic syndrome not responding to steroids (corticodependent, corticorresistant, frequent relapses) in children is a disease with significant morbidity and mortality. The evolution to chronic kidney disease has a relationship with time to histopathological diagnosis, the treatment performed, its duration, the early identification of risk factors being of utmost importance. Method An observational-retrospective study was carried out with transverse temporality, the universe of study was patients with a diagnosis of nephrotic syndrome from 2007 to 2017 with outcome to chronic kidney disease, information was obtained from the clinical files and their subsequent Bivariate analysis of qualitative variables with linear Chi and quantitative variables of normal distribution with ANOVA and abnormal distribution with Kruskas Wails. Results The clinical and biochemical differences of 121 patients with a diagnosis of non-steroidal nephrotic syndrome were determined. The clinical presentation of corticorresistant was the most frequent in 89 (73.6%), corticodependents 16 (13.2%) and frequent relapses 16 (13.2%), being the association with the major histopathological type of corticorresistant with GEFS 60 (83.3% ), mesangial proliferation 13 (61.9%) and minimum changes 9 (60%) with a p 0.05. The sex that was determined most frequently were men 83 (68.6%), women 38 (31.4%) p 0.8. The age at diagnosis had a frequency of 60 (49.6%) between 2.1 to 10 years of age and 60 (49.6%) in those over 10.1 years of age p 0.7. The evolution to chronic kidney disease was determined in 27 (22.3%), being greater its relationship with GEFS 21 (29.2%), diffuse mesangial proliferation 2 (9.5%), minimum changes 1 (6.7%) p 0.05. The time of evolution to chronic kidney disease between 0 and 3 years was 20 (16.5%), between 4 and 7 years was 4 (3.3%), and greater than 7 years 3 (2.5%), finding a greater relationship with GEFS between the 0 to 3 years that were 15 (20.8%) p 0.1. It was determined that the type of treatment most commonly used were anticalcineurinics (Cyclosporine-Tacrolimus), cyclosporine in 51 (42.1%), tacrolimus in 54 (44.6%), mycophenolate 10 (8.3%), and without treatment 6 (5% ) with a higher GEFS ratio of the use of cyclosporine 32 (44.4%) and tacrolimus 32 (44.4%) p.0.017. The use of ACEI and ARA II as antiproteinurics determined only ACEI in 8 (6.6%), ARA II 9 (7.4%) and IECA + ARA II in 52 (43%), none in 52 (43%), with a ratio of use of ACEI + ARA II in patients with GEFS in 35 (48.6%) p 0.5. Conclusion In this study, similar results were found in frequency of age, sex, progression to chronic kidney disease, histopathological type, treatment with anticalcineurinics and use of antiproteinurics in patients with nephrotic syndrome not responding to steroids to those reported in the literature, being the first in Mexico should be the beginning of different cohorts (response, duration of treatment, complications of the disease) in this type of patients.

Abstract 173: Chronic Cerebral Hypoperfusion Induces Cognitive Impairment and Aggravates the Progression of Cardiac and Renal Dysfunction

Background: Vascular contributions to cognitive impairment and dementia (VICD) are major health problems worldwide. Heart-kidney deficit and dementia frequently coexist, but little is known whether VICD induces cardiac and kidney deficit absent from primary heart and kidney deficit. The purpose of this study was to investigate the effect of VCID on white matter (WM) injury and cognitive impairment, as well as how VCID affects heart and kidney function at 2 and 8 months after bilateral common carotid artery stenosis (BCAS) in a mouse model of VICD. Methods: Adult male C57BL/6J (8-months) mice were subjected to Sham and BCAS surgery using micro coils with inner diameter of 0.16 mm. Cognitive functional tests and cardiac function were measured before mice were sacrificed at 2 months post BCAS (2M-BCAS) and at 8 months post BCAS (8M-BCAS), respectively. The brains, hearts and kidneys were then harvested for histological and immunohistochemical (IHC) staining. Significant statistics were determined as p<0.05. Results: Compared to Sham group, mice in 2M-BCAS and 8M-BCAS group both exhibit significantly: 1) increased cognitive deficits identified by decreasing the novel object recognition (NOR) test, social interaction test and Morris water maze test. 2) increased axonal/WM injury by decreasing Bielschowsky silver and Luxol fast blue density. 3) decreased left ventricular ejection fraction (LVEF) measured by echocardiogram. 4) increased heart iba-1, cardiac and renal fibrosis indicated by picrosirius red (PSR) staining. 5) increased mesangial proliferation and thickening of the glomerular basement membrane (GBM). Compared to 2M-BCAS, 8M-BCAS mice exhibit significantly: 1) worse axonal/WM injury. 2) worse LVEF and fractional shortening (FS). 3) increased heart iba-1 expression as well as cardiac and renal fibrosis. 4) induced severer mesangial proliferation and thickening of GBM. Conclusions: Our data indicate that BCAS not only induces progressive long-term cognitive impairment and WM/axonal damage, but also induces progressive cardiac and renal dysfunction compared to sham control mice.