Adriana Sierra Ochoa

Background: Sodium-glucose cotransporter-2 inhibitors (SGLT2is) have cardioprotective and renoprotective effects. However, experience with SGLT2is in diabetic kidney transplant recipients (DKTRs) is limited. Methods: This observational multicentre study was designed to examine the efficacy and safety of SGLT2is in DKTRs. The primary outcome was adverse effects within 6 months of SGLT2i treatment. Results: Among 339 treated DKTRs, adverse effects were recorded in 26%, the most frequent (14%) being urinary tract infection (UTI). In 10%, SGLT2is were suspended mostly because of UTI. Risk factors for developing a UTI were a prior episode of UTI in the 6 months leading up to SGLT2i use {odds ratio [OR] 7.90 [confidence interval (CI) 3.63-17.21]} and female sex [OR 2.46 (CI 1.19-5.03)]. In a post hoc subgroup analysis, the incidence of UTI emerged as similar in DKTRs treated with SGLT2i for 12 months versus non-DKTRs (17.9% versus 16.7%). Between baseline and 6 months, significant reductions were observed in body weight [-2.22 kg (95% CI -2.79 to -1.65)], blood pressure, fasting glycaemia, haemoglobin A1c [-0.36% (95% CI -0.51 to -0.21)], serum uric acid [-0.44 mg/dl (95% CI -0.60 to -0.28)] and urinary protein:creatinine ratio, while serum magnesium [+0.15 mg/dl (95% CI 0.11-0.18)] and haemoglobin levels rose [+0.44 g/dl (95% CI 0.28-0.58]. These outcomes persisted in participants followed over 12 months of treatment. Conclusions: SGLT2is in kidney transplant offer benefits in terms of controlling glycaemia, weight, blood pressure, anaemia, proteinuria and serum uric acid and magnesium. UTI was the most frequent adverse effect. According to our findings, these agents should be prescribed with caution in female DKTRs and those with a history of UTI.

Abstract Background and Aims Lupus Nephritis (LN) is a severe complication of Systemic Lupus Erytemathosus (SLE). This is the main reason why identifying predisposing factors to differentiate patients at risk of developing LN is so important. Method Retrospective study of patients with SLE diagnosed between years 2008-2018 in our center. Demographic, clinical and analytical data have been collected. Results We included 171 patients, 48 (28%) with diagnose of LN. Age at diagnose of SLE was 39,51 ± 15,40 years, being more frequent in women 151 (87,5%). Time of follow-up since SLE diagnose until development of LN was of 3 ± 5, 3 years. Respectful to the LN classification we found: 4 (8%) class I LN, 6 (12.5%) class II LN, 15 (31.2%) class III LN, 19 (39.5%) class IV LN and 4 (8%) class V LN. At diagnose of SLE, the following variables, where related to developing LN: CH50 [HR: 1,039; CI (95%): 1,004-1,064; p=0,024], C3 [HR: 1,029; CI (95%): 1,016-1,042; p<0,001, titer of Anti- DNACrithidia [HR: 4,364; CI(95%): 1,26-15,064; p=0,02], AntiSM [HR: 4,634, CI (95%) 1,76-12,17, p=0,002], ACA IgG [HR: 7,5; CI (95%): 2,3 -24,449; p=0,001] and Lupus anticoagulant [HR: 4,97; CI (95%): 1,591-15,533; p=0,006]. Treatment with hidroxicloroquine is a protective factor against developing LN [HR: 0,17; CI (95%): 0,063-0,511; p=0.001]. At diagnose of LN, complement factors and titer of anti-DNA crithidia show a positive correlation when compared to the initial determinations: C3 [r= 0,605 (p<0,001]); C1q [r= 0,861 (p=0,006)]; CH50 [r= 0,981 (p<0,001), anti- DNACrithidia [r= 0,529 (p<0,001)], anti-Sm [r=0.8, )p=0.001)]. Conclusion Consumption of complement factors, high titers of anti-DNAcrithidia, Anti-SM, ACA IgG and Lupus anticoagulant are related to a future LN development at SLE diagnose. Moreover, we see an increase of their titer once we diagnose LN. Otherwise, treatment with hidroxicloroquine seems to be a protective factor.

Background: IgG glycome composition is a key regulator of immune system modulating inflammation at multiple levels. It has been associated to aging, infections response, autoimmune diseases or early kidney failure. Its role in KT has not been studied. Our aim was to analyze the prognostic and diagnostic value of IgG_glycans in renal function after 1year of KT and in antibody-mediated rejection (AMR) Methods: We analyzed 24 essential IgG glycans by Highperformance Liquid Chromatography grouped them by biological function, according to the proportion of Galactosylated, Agalactosylated, Sialicylated, Fucosylated and Bisecting-GlcNAc structures. We measured baseline IgG_glycans and one year after KT in 248 recipients (62%M:38%M) of 55.9±13.6 years, 36 with AMR. Association models were adjusted by donor characteristics, baseline renal function, age/sex, BMI, ATN-postKT and comorbidities Results: Differences between IgG_glycans at baseline and 1year values were associated with the achieved renal function: Higher Sialization (Coeff [95% CI] 2.07 [0.23-0.3.9]) and Galactosylation (1.84 [0.0-3.6]), the better renal function and higher proportion of agalactosylated glycans associated worse renal function -2.02 [-4.1- -0.34]. AMR occurred more frequently in patients with a higher proportion of Agalactosylated glycans (OR [95% CI]) 1.7 [1.15-2.51] and less in those with a greater proportion of Galactosylates 0.59 [0.4-0.87], Sialicylates 0.67 [0.45-0.9] and Bisecting-GlcNAc 0.66 [0-45-0.99] (Figure) Conclusions: Glycans, that modulate the IgG function, are a potential prognostic tool for renal function in KT and as a diagnostic support in the identification of patients who develop AMR

Abstract Background and Aims Between the 2-8% of pregnancies suffer preeclampsia (PE). In the literature, there have been reported cases of glomerulopathy debuted by pregnancy (GDP) which are initially missdiagnosed as PE. These cases are unusual and not well-defined. We aimed to evaluate clinical and analytical factors that allow us to suspect that a PE masks a GDP. Method Retrospective study that included pregnant patients with a postpartum histological diagnosis of glomerulopathy who had been missdiagnosed as PE during pregnancy. We compared them with patients who suffered PE with full recovery after childbirth. We evaluate demographic variables of pregnant women and newborns, clinical variables related to pregnancy and childbirth, blood pressure (BP) and analytical variables before pregnancy and postpartum (serum creatinine (sCrea), estimated glomerular filtration rate by CKD-EPI equation (eGFR), serum uric acid (sUA), ratio of urine protein to creatinine (UPCR)). Results Thirty patients were included in the study ,10 patients with a postpartum histological diagnosis of glomerulopathy who had been diagnosed as PE during the pregnancy and 20 patients with a diagnosis of PE without GDP, baseline characteristics are described in attached table. Glomerulopathy was diagnosis through renal biopsy, main indication of renal biopsy was the persistence of proteinuria and/or sediment abnormalities after 4 months of childbirth. The diagnoses were: IgA nephropathy (3, 33.3%), focal and segmental hyalinosis (2, 22.2%), X-linked Alport syndrome (2, 22.2%), diabetic nephropathy (1, 11.1%), lupus nephritis (1, 11.1%) and chronic interstitial nephropathy (1, 11.1%). Pregnant women with GDP showed higher prevalence of smoking habit and major value of sCrea and sUA (figure). Regarding to pregnancy factors, patients with GDP had significant higher prevalence of primiparous gestation (100% vs 40%, p=0.002), twin gestation (20% vs 0%, p=0.03), premature newborn (50% vs 15%, p=0.01) and higher weight gain during pregnancy (13.9±5.8 vs 9.5±3.6 kg, p=0.01). Furthermore, in the postpartum data we objected a higher value of systolic/diastolic BP (145.6±10.3 / 89.4±12.1 vs 128.5±10.0 / 80.0±6.3 mmHg, p<0.05), sCrea (0.83±0.3 vs 0.54±0.2 mg/dl, p=0.02), sUA (5.8±1.3 vs 3.4±0.8 mg/dl, p<0.001) and UPCR (3046 [613-4179] vs 802 [281-948] mg/g, p=0.05) in patient with NPD. Conclusion Our results suggest that clinical and analytical variables in pregnancy and post-partum allow clinicians suspect a glomerulopathy in the setting of PE. Patients diagnosed as PE who develop GDP had higher prevalence of smoking habit, primiparous gestation, twin gestation and premature newborns. In addition, they also have higher weight gain during pregnancy, worse renal function and major sUA before pregnancy and after childbirth, and major UPCR and BP after childbirth; compared with patients with PE and full recovery after childbirth.

Abstract Background and Aims The diagnostic utility of ANCA antibodies in ANCA associated-vasculitis (AAV), antiproteinase 3 (PR3) and myeloperoxidase (MPO) testing is now undisputed, but the clinical utility of serial MPO/PR3 testing to predict relapses, remain controversial. The aim of this study was to analyze the relevance of serum MPO and PR3 antibody level assessment in the management of AAV. We sought to determine whether MPO and PR3 antibody levels correlated with renal disease activity, and whether an increase could predict a nephritis flare. Method Retrospective multicenter study including AAV-patients with renal involvement from 7 nephrology departments belonging to the Spanish Glomerular Study Group (GLOSEN). The main inclusion criteria were that MPO antibodies were detected by ELISA (Multiplex assay) and PR3 using chemioluminescence immunoassay. For statistical purpose a continuous variable were calculated, called delta MPO/PR3(ΔMPO y ΔPR3) that reflects change in antibodies levels 6 months before renal flare. Clinical data were recorded since complete remission of first nephritis diagnosis flare until second renal relapse. Results 113 AAV-patients with pauci-inmune necrotizing glomerulonephritis were included, 59 (52.2%) women, mean age (64.3±14.8 years), 85 patients (75.2%) MPO-AAV and 28 (24.8%) PR3-AAV, after a mean follow-up of 5±4.8 years, 54 renal relapses occurred in 40 (52,6%) MPO-AAV patients and in 14 (57.1%) PR3-AAVpatients. Serum MPO levels were significant higher in relapser-patients compared with non- relapser patients, 3±1.2 months before nephritis relapse [(n=32) 19.2±12.2 IA vs (n=38) 3.2±5.1 IA, p<0.001)]. Δ MPO levels were significant higher in relapse-patients compared with non-relapser patients [(n=32) 8.3±12 IA vs (n=38) 0.9±3.1.1 IA, p=0.001). The discrimination value of the MPO antibody levels 3 months before renal relapse were established by means of a ROC curve: AUC of 0.82 (95% CI 0.73 to 0.92; p<0.001) and the MPO cut-off value predicting renal relapse were established in 8.3 IA. The discrimination value of the ΔMPO were established by means of ROC curve: AUC of 0.76 (95% CI 0.63 to 0.88; p<0.001), ΔMPO cut-off value were established in an increase of MPO levels of 3.7 IA. Serum PR3 levels were significant higher in relapser-patients 2.8±1.4 months before relapse [(n=14) 58.6±6.6 IA vs (n=7) 2.0±0.6 IA, p<0.001)] and Δ PR3 levels were significant higher in relapse-patients compared with non-relapser patients [(n=14) 57.5±28.5 IA vs (n=7) 0.8±0.2. IA, p<0.001)]. The discrimination value of the PR3 3 months before flare and Δ PR3 antibody levels were established by means of ROC curve: AUC 1. Conclusion Our results show that MPO antibodies, measured by Multiplex assay, could be a useful predictor of glomerulonephritis flare in AAV-patients. MPO levels 3 months before renal flare seems a good marker confirmed by ROC curve results, MPO cut-off value with the best sensitivity and specificity in predicting renal relapse was established in 8.3 IA. Δ MPO levels show that increase in titers ≥ 3.7 IA 6 months before renal flare, predict nephritis relapse However, PR3 antibodies are not a useful predictor marker, rise in antibodies level indicate renal vasculitis activity.