ANCA detection with solid phase chemiluminescence assay: diagnostic and severity association in vasculitis.

ANCA-associated vasculitis (AAV) comprises a group of necrotizing vasculitis that mainly affects small- and medium-sized vessels. Serum anti-neutrophil cytoplasmic antibodies (ANCA), mainly anti-myeloperoxidase (anti-MPO) and anti-proteinase 3 (anti-PR3), levels may correlate to severity, prognosis, and recurrence of the disease. A retrospective analysis of 101 patients with MPO-positive and 54 PR3-positive vasculitis was performed, using laboratory established cut-off value, measured by chemiluminescence. Furthermore, data of renal disease and pulmonary involvement were collected at vasculitis diagnosis, as well as the progress, requiring dialysis, transplant, or mortality. For anti-MPO antibodies with a diagnosis of vasculitis (n = 77), an area under the curve (AUC) was calculated (AUC = 0.8084), and a cut-off point of 41.5 IU/ml was determined. There were significant differences in anti-MPO levels between patients with renal or pulmonary dysfunction (n = 65) versus those without them (n = 36) (p = 0.0003), and a cut-off threshold of 60 IU/ml was established. For anti-PR3 antibodies with a diagnosis of vasculitis (n = 44), an area under the curve (AUC) was calculated (AUC = 0.7318), and a cut-off point of 20.5 IU/ml was determined. Significant differences in anti-PR3 levels were observed between those patients with renal or pulmonary dysfunction (n = 30) and those without them (n = 24) (p = 0.0048), and a cut-off threshold of 41.5 IU/ml was established. No significant differences between those patients who had a worse disease progression and those who did not were found for anti-MPO and anti-PR3. Anti-MPO and anti-PR3 levels at the moment of vasculitis diagnosis are related with disease severity but not with disease outcome or vasculitis recurrence.

Sodium-glucose cotransporter 2 inhibition in primary and secondary glomerulonephritis.

BACKGROUND: The role of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in the management glomerular/systemic autoimmune diseases with proteinuria in real-world clinical settings is unclear. METHODS: This is a retrospective, observational, international cohort study. Adult patients with biopsy-proven glomerular diseases were included. The main outcome was the percentage reduction in 24-h proteinuria from SGLT2i initiation to 3, 6, 9 and 12 months. Secondary outcomes included percentage change in estimated glomerular filtration rate (eGFR), proteinuria reduction by type of disease and reduction of proteinuria ≥30% from SGLT2i initiation. RESULTS: Four-hundred and ninety-three patients with a median age of 55 years and background therapy with renin-angiotensin system blockers were included. Proteinuria from baseline changed by -35%, -41%, -45% and -48% at 3, 6, 9 and 12 months after SGLT2i initiation, while eGFR changed by -6%, -3%, -8% and -10.5% at 3, 6, 9 and 12 months, respectively. Results were similar irrespective of the underlying disease. A correlation was found between body mass index (BMI) and percentage proteinuria reduction at last follow-up. By mixed-effects logistic regression model, serum albumin at SGLT2i initiation emerged as a predictor of ≥30% proteinuria reduction (odds ratio for albumin <3.5 g/dL, 0.53; 95% CI 0.30-0.91; P = .02). A slower eGFR decline was observed in patients achieving a ≥30% proteinuria reduction: -3.7 versus -5.3 mL/min/1.73 m2/year (P = .001). The overall tolerance to SGLT2i was good. CONCLUSIONS: The use of SGLT2i was associated with a significant reduction of proteinuria. This percentage change is greater in patients with higher BMI. Higher serum albumin at SGLT2i onset is associated with higher probability of achieving a ≥30% proteinuria reduction.

BAFF, APRIL and BAFFR on the pathogenesis of Immunoglobulin-A vasculitis.

BAFF, APRIL and BAFF-R are key proteins involved in the development of B-lymphocytes and autoimmunity. Additionally, BAFF, APRIL and BAFFR polymorphisms were associated with immune-mediated conditions, being BAFF GCTGT>A a shared insertion-deletion genetic variant for several autoimmune diseases. Accordingly, we assessed whether BAFF, APRIL and BAFFR represent novel genetic risk factors for Immunoglobulin-A vasculitis (IgAV), a predominantly B-lymphocyte inflammatory condition. BAFF rs374039502, which colocalizes with BAFF GCTGT>A, and two tag variants within APRIL (rs11552708 and rs6608) and BAFFR (rs7290134 and rs77874543) were genotyped in 386 Caucasian IgAV patients and 806 matched healthy controls. No genotypes or alleles differences were observed between IgAV patients and controls when BAFF, APRIL and BAFFR variants were analysed independently. Likewise, no statistically significant differences were found in the genotype and allele frequencies of BAFF, APRIL or BAFFR when IgAV patients were stratified according to the age at disease onset or to the presence/absence of gastrointestinal (GI) or renal manifestations. Similar results were disclosed when APRIL and BAFFR haplotypes were compared between IgAV patients and controls and between IgAV patients stratified according to the clinical characteristics mentioned above. Our results suggest that BAFF, APRIL and BAFFR do not contribute to the genetic network underlying IgAV.

[Measurement of galactosyl-deficient IgA1 by the monoclonal antibody KM55 contributes to predicting patients with IgA nephropathy with high risk of long-term progression]. / La determinación de IgA1 galactosil deficiente mediante el anticuerpo monoclonal KM55 contribuye a predecir a los pacientes con nefropatía IgA con alto riesgo de progresión a largo plazo.

BACKGROUND AND OBJECTIVE: About 25% of patients with IgA nephropathy (IgAN) progress to stage 5 chronic kidney disease (CKD) after years of evolution. Various tools have been developed in recent years designed to predict which of the patients will had poorer outcomes. The value of circulating galactosyl-deficient IgA1 (Gd-IgA1) has been related to a worse evolution of IgAN in several studies. There are also some publications that relate higher APRIL values with a worse evolution. Recently, a new method has been developed that allows measuring the value of circulating Gd-IgA1 in a simpler way than those previously available. The objective of this study is to analyze the influence of circulating Gd-IgA1, measured by this method, on the progression of IgAN. MATERIALS AND METHODS: Forty-nine patients with a diagnosis of IgAN demonstrated by renal biopsy were selected in our center, without having received prior immunosuppressive treatment, for whom frozen serum was available. The median follow-up was 4 years. Gd-IgA1 was measured by lectin-independent ELISA with the monoclonal antibody KM55 (IgA1 kit Cat. No. 30111694. IBL Int., Hamburg, Germany). Likewise, APRIL levels were also measured in these patients. RESULTS: 19 (38.8%) patients reached stage 5 CKD. The fourth quartile of circulating Gd-IgA1 was related to a higher cumulative risk of reaching stage 5 CKD in the Kaplan-Meier analysis (risk at the 5th year 39.4% vs. 24.3%, log rank p=0.019). The Gd-IgA1 value was related to an increased risk of CKD stage 5 (HR 1.147, 95% CI 1.035-1.270, p=0.009), regardless of glomerular filtration rate, proteinuria, the percentage of sclerosed glomeruli and the value of segmental sclerosis. We did not find significant differences in the APRIL values. CONCLUSIONS: The value of circulating Gd-IgA1 measured by the monoclonal antibody KM55 is related to a worse evolution of patients with IgAN independently of other variables, so it could be included in the study of patients to improve the prediction of the risk of disease progression.

Measurement of galactosyl-deficient IgA1 by the monoclonal antibody KM55 contributes to predicting patients with IgA nephropathy with high risk of long-term progression.

BACKGROUND AND OBJECTIVE: About 25% of patients with IgA nephropathy (IgAN) progress to stage 5 chronic kidney disease (CKD) after years of evolution. Various tools have been developed in recent years designed to predict which of the patients will had poorer outcomes. The value of circulating galactosyl-deficient IgA1 (Gd-IgA1) has been related to a worse evolution of IgAN in several studies. There are also some publications that relate higher APRIL values with a worse evolution. Recently, a new method has been developed that allows measuring the value of circulating Gd-IgA1 in a simpler way than those previously available. The objective of this study is to analyze the influence of circulating Gd-IgA1, measured by this method, on the progression of IgAN. MATERIALS AND METHODS: Forty-nine patients with a diagnosis of IgAN demonstrated by renal biopsy were selected in our center, without having received prior immunosuppressive treatment, for whom frozen serum was available. The median follow-up was 4 years. Gd-IgA1 was measured by lectin-independent ELISA with the monoclonal antibody KM55 (IgA1 kit Cat. No. 30111694. IBL Int., Hamburg, Germany). Likewise, APRIL levels were also measured in these patients. RESULTS: 19 (38.8%) patients reached stage 5 CKD. The fourth quartile of circulating Gd-IgA1 was related to a higher cumulative risk of reaching stage 5 CKD in the Kaplan-Meier analysis (risk at the 5th year 39.4% vs. 24.3%, log rank p=0.019). The Gd-IgA1 value was related to an increased risk of CKD stage 5 (HR 1.147, 95% CI 1.035-1.270, p=0.009), regardless of glomerular filtration rate, proteinuria, the percentage of sclerosed glomeruli and the value of segmental sclerosis. We did not find significant differences in the APRIL values. CONCLUSIONS: The value of circulating Gd-IgA1 measured by the monoclonal antibody KM55 is related to a worse evolution of patients with IgAN independently of other variables, so it could be included in the study of patients to improve the prediction of the risk of disease progression.

Is it possible to predict the evolution of IgAN? Validation of the IgA nephropathy progression calculator and its relationship with MEST-C score in our population. / ¿Es posible predecir la evolución de la nefropatia IgA? Validamos la calculadora de progresión de nefropatia IgA y su relación con Oxford score en nuestra población.

INTRODUCTION: IgA nephropathy (IgAN) is the most common and heterogeneous glomerular nephropathy. Several strategies have been used to determine the risk of progression to ESRD. We evaluate the prognostic significance and correlate the IgAN progression calculator (IgANPC) and the Oxford/MEST-C score in our population. MATERIAL AND METHODS: We performed a retrospective study of biopsied patients with diagnosis of IgA nephropathy from 1990 to 2015. We classified the biopsies using MEST-C score and we correlated the score to clinical evolution. We also calculated the risk of progression with the online IgANPC at the time of the biopsy. RESULTS: We analysed 48 biopsies, 83% of which were men with a mean age of 45 years at the time of the biopsy. Patients with a biopsy E1 according to MEST-C score had a higher IgANPC score than those with E0 (P=.021). The Pearson's correlation for the percentage of crescents and the IgANPC risk score was statistically significant (P=.014) with r=0.357. The percentage of patients with eGFR above 30 ml/min at 10 years was 100% for the low-risk group (group 1 of IgANPC), and 0% for the high-risk group (group 3), log rank P=0.001. The log rank comparison for variables of the MEST-C score, presented statistically significant results between E (0.036) and S (0.022) and the eGFR time<30 ml/min. A statistically significant relationship was also observed between T1 and eGFR<30 ml/min. The multivariate Cox regression analysis for IgANPC and eGFR<30 ml/min demonstrated a strong correlation (P=.016) between the risk group and eGFR <30 ml/min. CONCLUSION: In our study population, the IgANPC predicts the time to eGFR<30 ml/min, and adds information independent of the MEST. The MEST-C classification and IgANPC are useful and independent ÿolos for prognostic prediction, but more studies are needed to validate its use in the general population.

A proliferation-inducing ligand increase precedes IgA nephropathy recurrence in kidney transplant recipients.

BACKGROUND: IgA nephropathy (IgAN) may recur in kidney transplant recipients. B-cell-activating factor (BAFF), a proliferation-inducing ligand (APRIL), and α-defensins are involved in the pathogenesis of native IgAN; however, their role on IgAN recurrence has not been previously analyzed. METHODS: Thirty-five patients with IgAN who received a kidney transplant in our center between January 1, 1993, and December 31, 2015, were included. Recurrence was diagnosed and ruled out in 14 and 11 patients, respectively, by indication biopsies. Pre-transplant, 6-month, 1-, 3-, and 5-year sera selected to measure BAFF, APRIL, and defensin by ELISA. RESULTS: Six months post-transplantation, APRIL levels (300.1 vs 1203.8 pg/mL, P = 0.033) and the mean APRIL values from 6 months to 3 years (409.8 vs 1258.0 pg/mL, P = 0.003) were higher in recurrent patients. Both 6-month APRIL levels (AUC-ROC 0.753, P = 0.033) and mean APRIL values (AUC-ROC 0.844, P = 0.004) discriminated patients with recurrence risk. By logistic regression, APRIL at 6 months (P = 0.044) and mean APRIL (P = 0.021) related to the risk of IgAN recurrence independently. Neither BAFF nor defensin related to recurrence. CONCLUSIONS: Serum APRIL increased at 6 months and mean APRIL remained higher the first 3 years in patients in whom IgAN was going to recur.