Biopsy-proven IgA Nephropathy Research Articles

Hydroxychloroquine blood concentrations and effects in Chinese patients with IgA nephropathy.

Hydroxychloroquine (HCQ) is recommended for Chinese patients with immunoglobulin A nephropathy (IgAN). However, the relationship between HCQ blood concentration and the therapeutic effect for IgAN has not yet been defined. This study investigates the optimal and efficacious range of HCQ blood concentrations in Chinese patients with IgAN. Seventy-three patients with biopsy-proven IgAN who were at risk of progression were included in this study. Thirty-eight patients with IgAN were treated with HCQ plus an optimized renin-angiotensin-aldosterone system inhibitor (RAASi), and thirty-five patients received only RAASi. Blood HCQ concentration and 24-h proteinuria were examined at three and six months after treatment. The baseline proteinuria levels were comparable between the RAASi and HCQ groups. The HCQ group had lower 24-h proteinuria than the RAASi group three months after treatment, though the difference was not significant (p = 0.38). After six months, the median proteinuria level was significantly lower in the HCQ group than in the RAASi group (p < 0.05). The percentage reduction in 24-h proteinuria in the HCQ group was greater than that in the RAASi group at three (p < 0.05) and six months (p < 0.05). Hydroxychlorquine blood concentration and efficacy were positively correlated at three months (r = 0.428, p < 0.05) and six months (r = 0.48, p < 0.05). Moreover, the optimal blood concentration of HCQ for three-month efficacy was 418.96ng/mL and that for six-month efficacy was 582.48ng/mL. No serious adverse events were reported during HCQ treatment. Hydroxyhloroquine safely reduces proteinuria in Chinese patients with IgAN. The efficacy of HCQ is positively correlated with its blood concentration.

Prognostic Value of Inflammation Scores and Hematological Indices in IgA and Membranous Nephropathies: An Exploratory Study

Background and Objectives: Systemic-inflammation-based prognostic scores and hematological indices have shown value in predicting outcomes in various clinical settings. However, their effectiveness in predicting outcomes specifically for IgA nephropathy (IgAN) and membranous nephropathy (MN), the most common primary glomerular diseases diagnosed by kidney biopsy, has not been thoroughly investigated. Materials and Methods: We conducted a retrospective, observational study involving 334 adult patients with biopsy-proven IgAN (196 patients) and MN (138 patients) from January 2008 to December 2017 at a tertiary center. We assessed six prognostic scores [Glasgow prognostic score (GPS), modified GPS (mGPS), prognostic nutritional index (PNI), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-C-reactive protein ratio (LCRP)] and two hematological indices [red blood cell distribution width (RDW), platelet distribution width (PDW)] at diagnosis and examined their relationship with kidney and patient survival. Results: End-stage kidney disease (ESKD) occurred more frequently in the IgAN group compared to the MN group (37% vs. 12%, p = 0.001). The mean kidney survival time was 10.7 years in the IgAN cohort and 13.8 years in the MN cohort. After adjusting for eGFR and proteinuria, lower NLR and higher LCRP were significant risk factors for ESKD in IgAN. In the MN cohort, no systemic-inflammation-based scores or hematological indices were associated with kidney survival. There were 38 deaths (19%) in the IgAN group and 29 deaths (21%) in the MN group, showing no significant difference in mortality rates. The mean survival time was 13.4 years for the IgAN group and 12.7 years for the MN group. In the IgAN group, a lower PLR was associated with a higher mortality after adjusting for age, the Charlson comorbidity score, eGFR, and proteinuria. In patients with MN, higher NLR, PLR, and RDW were associated with increased mortality. Conclusions: NLR and LCRP are significant predictors of ESKD in IgAN, while PLR is linked to increased mortality. In MN, NLR, PLR, and RDW are predictors of mortality but not kidney survival. These findings underscore the need for disease-specific biomarkers and indicate that systemic inflammatory responses play varying roles in the progression and outcomes of these glomerular diseases. Future studies on larger cohorts are necessary to validate these markers.

Uromodulin and Progression of IgA Nephropathy

Abstract Background This study investigates the link between genetic variants associated with kidney function and IgA nephropathy (IgAN) progression. Methods We recruited 961 biopsy-proven IgAN patients and 651 non-IgAN end-stage renal disease (ESRD) patients from Ruijin Hospital. The clinical and renal pathological data were collected. The primary outcome was the time for ESRD. A healthy population was defined as eGFR &amp;gt; 60 ml/min/1.73m2 without albuminuria or hematuria. Fifteen single-nucleotide polymorphisms (SNPs) were selected from a genome-wide association study of kidney function and genotyped by the SNaPshot. Immunohistochemistry in renal tissue and ELISA in urine samples were performed to explore the potential functions of genetic variations. Results The rs77924615-G was independently associated with an increased risk for ESRD in IgAN patients after adjustments for clinical, pathologic indices, and treatment (adjusted Hazard Ratio, 2.10; 95% CI, 1.14 to 3.88). No significant differences in ESRD-free survival time among different genotypes in non-IgAN ESRD patients (log-rank, p = 0.480). Moreover, rs77924615 exhibited allele-specific enhancer activity by dual-luciferase reporter assay. Accordingly, the urinary uromodulin-creatinine ratio (uUCR) was significantly higher in healthy individuals with rs77924615 AG or GG than in individuals with AA. Furthermore, uromodulin expression in tubular epithelial cells was higher in patients with rs77924615 AG or GG. Finally, we confirmed that an increased uUCR (p = 0.009) was associated with faster IgAN progression. Conclusion The SNP rs77924615, which modulates the enhancer activity of the UMOD gene, is associated with renal function deterioration in IgAN patients by increasing uromodulin levels in both the renal tubular epithelium and urine.

A preliminary probabilistic nomogram model for predicting renal arteriolar damage in IgA nephropathy from clinical parameters.

IgA nephropathy (IgAN) is a significant contributor to chronic kidney disease (CKD). Renal arteriolar damage is associated with IgAN prognosis. However, simple tools for predicting arteriolar damage of IgAN remain limited. We aim to develop and validate a nomogram model for predicting renal arteriolar damage in IgAN patients. We retrospectively analyzed 547 cases of biopsy-proven IgAN patients. Least absolute shrinkage and selection operator (LASSO) regression and logistic regression were applied to screen for factors associated with renal arteriolar damage in patients with IgAN. A nomogram was developed to evaluate the renal arteriolar damage in patients with IgAN. The performance of the proposed nomogram was evaluated based on a calibration plot, ROC curve (AUC) and Harrell's concordance index (C-index). In this study, patients in the arteriolar damage group had higher levels of age, mean arterial pressure (MAP), serum creatinine, serum urea nitrogen, serum uric acid, triglycerides, proteinuria, tubular atrophy/interstitial fibrosis (T1-2) and decreased eGFR than those without arteriolar damage. Predictors contained in the prediction nomogram included age, MAP, eGFR and serum uric acid. Then, a nomogram model for predicting renal arteriolar damage was established combining the above indicators. Our model achieved well-fitted calibration curves and the C-indices of this model were 0.722 (95%CI 0.670-0.774) and 0.784 (95%CI 0.716-0.852) in the development and validation groups, respectively. With excellent predictive abilities, the nomogram may be a simple and reliable tool to predict the risk of renal arteriolar damage in patients with IgAN.

#2740 Pregnancy outcomes in patients with IgA nephropathy and the impact of pregnancy on the renal disease

Abstract Background and Aims IgA nephropathy (IgAN), the predominant primary glomerulonephritis in adults,, frequently affects women in childbearing age. There is a dearth of information about the impact of pregnancy on the outcome in IgAN especially in the Indian population where it is known to have an aggressive disease phenotype. This retrospective cohort study examines pregnancy outcomes in women with biopsy-proven IgAN and the impact on renal outcome. Method In a retrospective cohort study, we assessed the medical records of women in child bearing age (18-40 years) diagnosed with biopsy proven primary IgAN from 2012-2022. Patients with end stage kidney disease (ESKD) at the time of biopsy and/or at time of conception and those who had undergone kidney transplantation were excluded. Maternal (pre-eclampsia, relapse, renal disease progression, etc.) and fetal outcomes (neonatal death, preterm delivery, intra-uterine growth retardation-IUGR, etc.) were recorded. Relapse was defined as increase in proteinuria to ≥1 g/day during pregnancy and renal disease progression as &amp;gt;40% sustained decline in eGFR and/or ESKD. Results Of 75 women assessed, 25 were lost to follow up. 34 did not conceive after biopsy. 20 pregnancies were documented in 14 patients. Three (15%) were medically terminated, 7 (35%) resulted in spontaneous abortions, and 10 (50%) culminated in live births. There was one neonatal death. 6/20(30%) pregnancies occurred while the patient was on ACEi/ARBs of which 5 pregnancies resulted in live births. 7/10 (70%) births were premature, 5 being moderate preterm (34-37 weeks) and 2 late preterm (32-34 weeks). IUGR below the 5th percentile affected 7/10(70%) of births. The mode of delivery was evenly split between vaginal (5, 50%) and Caesarian (5, 50%). From a maternal perspective, preeclampsia affected 3/10 (30%) patients. 5/10(50%) patients who delivered had a relapse during pregnancy with 2 developing nephrotic range proteinuria. 4 of them receiving steroids during pregnancy. All relapsed patients had persistent proteinuria &amp;gt;1 g/day postpartum. In 2 (20%) pregnancies, relapse developed during immediate post-partum period. In 4 patients, eGFR decreased by &amp;gt; 40 percent compared to their baseline (at biopsy) following the pregnancy. Conclusion Pregnancy is associated with adverse maternal and fetal outcomes in women with IgA nephropathy. eGFR, estimated glomerular filtration rate. IUGR, Intra-uterine growth restriction (based on birth weight percentile, adjusted for gender and gestational age). *Serum creatine of one patient during pregnancy is not available, analysis is done using values of other 9 patients. **Urine Protein of one patient is not available at the latest follow-up, analysis is done using values of 9 other patients.

#1701 IgA nephropathy in numbers: the experience of a single center

Abstract Background and Aims IgA nephropathy is probably the most common glomerular disease worldwide and kidney histology is recognized to significantly impact the risk of progressive kidney failure. Method This is a retrospective cohort study of adult patients diagnosed with biopsy-proven IgA nephropathy during the last decade in the nephrology department of a tertiary hospital. Results In total, 75 patients with biopsy-proven IgA nephropathy were identified and data from 53 of them were analyzed [mean age 48 ± 16 [SD] years, 81% males, 60% hypertensives, 19% diabetics, baseline serum creatinine 2.03 ± 1.80 mg/dl, baseline estimated glomerular filtration rate (eGFR) 60.9 ± 31.4 ml/min/1.73 m2, baseline proteinuria 2.76 ± 2.44 gr/24 h]. Eventually, 6 patients were submitted to chronic dialysis. 50% of the patients received RAAS blockers and 14% received SGLT2-inhibitors. The most frequently used immunosuppression regimens were glucocorticoids alone (33%), glucocorticoids plus cyclophosphamide and azathioprine (13%), budesonide (9%). Relapse was identified in 9% of the patients and it was treated with glucocorticoids alone or budesonide. 25% of the patients had elevated serum IgA levels. Crescents were identified in 36% of the patients and interstitial and mesangial inflammation were observed in 83% and 64% of the patients respectively. Approximately all of the patients had arterial vessels with hyalinosis or fibroelastosis. Concerning immunofluorescence, the dominant findings were IgA, IgM, c3, λ light chain, while all other components were merely found. The median duration of follow-up was 2 years and the follow-up minus baseline serum creatinine, eGFR, and proteinuria differences were 0.35 ± 1.77 mg/dl, −4.0 ± 22.2 ml/min/1.73 m2, and −1.46 ± 2.39 gr/24 h, respectively. Median follow-up minus baseline eGFR was higher for diabetics (1.5 vs 0 ml/min/1.73 m2, p = 0.04). Participants receiving treatment with glucocorticoids were found to present a reduction of serum creatinine during follow-up (follow-up minus baseline median serum creatinine −0.1 vs 0.2 mg/dl for participants receiving vs not receiving glucocorticoids, p = 0.02) and a non-reduction of eGFR (follow-up minus baseline median eGFR 0 vs −3 ml/min/1.73 m2 for participants receiving vs not receiving glucocorticoids, p = 0.01). Participants receiving treatment with SGLT2 inhibitors were also found to have stable median eGFR during follow-up (follow-up minus baseline median eGFR 0 vs −11 ml/min/1.73 m2 for participants receiving vs not receiving SGLT2 inhibitors, p = 0.01). In multivariable linear regression analysis, follow-up minus baseline serum creatinine was independently associated with baseline proteinuria (β = 0.38, p &amp;lt; 0.01), administration of glucocorticoids (β= −1.23, p = 0.01), and the S component of MEST-c score (β = 1.27, p = 0.04), after adjustment for age, sex, baseline serum creatinine, diabetes, hypertension, MEST-c score, and percentage of interstitial fibrosis. In multivariable linear regression analysis, follow-up minus baseline eGFR was independently associated with baseline eGFR (β= −0.43, p &amp;lt; 0.01), baseline proteinuria (β= −2.54, p &amp;lt; 0.05), and hypertension status (β= −18.93, p = 0.02), after adjustment for age, sex, diabetes, treatment with glucocorticoids, MEST-c score, and percentage of interstitial fibrosis. Conclusion These preliminary data indicate that patients with IgA nephropathy who were treated with glucocorticoids or SGLT2 inhibitors present better course concerning the renal function, and the S component of MEST-c score was the only element of the kidney biopsy associated with the kidney outcome.

#1638 Long-term mortality trends in IgA nephropathy: a study of an Eastern European cohort

Abstract Background and Aims IgA Nephropathy (IgAN), recognized as the most prevalent form of primary glomerulonephritis, has been thoroughly researched in terms of renal outcomes. However, there is a scarcity of data regarding patient survival, especially in Eastern Europe. Our study focuses on exploring the long-term survival rates of IgAN patients and identifying associated risk factors within an Eastern European population. Method In our retrospective study, we analyzed 215 patients with biopsy proven IgAN (median age 44 years, 71% male, median eGFR 40.9 mL/min/1.73 m2, median proteinuria 1.24g/g) diagnosed at a tertiary center in Romania from 2010 to 2017. Our study primarily focused on all-cause mortality and secondarily on the development of ESKD (start of kidney replacement therapy or renal transplantation). The follow-up for patients continued until they reached either of these endpoints or until January 1, 2022, whichever came first. Results During a median follow-up of 7.3 years, 20% of the patients died. The main causes of death were cardiovascular diseases (60%), followed by infectious (19%), gastroenterological (12%), and neoplasia (9%) diseases. Mean survival of the entire cohort was 117.5 months (95% CI: 111.2, 123.8) and mean kidney survival was 98.4 months (95% CI: 90.5, 106.2). Survival rates at 1 year, 5 years and 10 years were 93%, 84% and 77% respectively, and kidney survival rates at 1 year, 5 years and 10 years were 87%, 72% and 58% respectively. When compared to the survivors, deceased patients were significantly older (60 vs 42 years, p 0.001) and had an increased prevalence of diabetes mellitus (26 vs 4%, p 0.001) and higher Charlson comorbidity index (5 vs 2, p 0.001). Deceased patients also had significantly higher serum creatinine levels (3.3 vs 1.6 mg/dL, p 0.001), lower eGFR (18 vs 46 mL/min, p 0.001), and more haematuria (230 vs 183cells/HPF, p 0.01). There was no significant difference in proteinuria between the two groups (1.1 vs 1.2g/g, p 0.3). In the univariate Cox regression analysis, all-cause mortality was significantly associated with several factors: advancing age (HR 1.08, 95% CI: 1.05, 1.11), an increased Charlson comorbidity index (HR 1.60, 95% CI: 1.42, 1.80), the presence of diabetes mellitus (HR 5.13, 95% CI: 2.57, 10.25), lower eGFR (HR 0.95, 95% CI: 0.93, 0.97), increased proteinuria (HR 1.12, 95% CI: 1.00, 1.25), the presence of haematuria (HR 1.26, 95% CI: 1.03, 1.53), lower serum albumin (HR 0.35, 95% CI: 0.22, 0.56), higher MEST-C score (HR 1.38, 95% CI 1.13, 1.69) and absence of renin-angiotensin-system inhibitors (RASI) (HR 0.32, 95% CI 0.17, 0.60). However, in the multivariate analysis, only an increased Charlson comorbidity index (HR 1.31, 95% CI: 1.09, 1.57), lower eGFR (HR 0.98, 95% CI: 0.96-1.00) and absence of RASI (HR 0.21, 95% CI: 0.15, 0.28) retained their statistical significance. Conclusion We report a 20% mortality rate in our Eastern European IgAN cohort, primarily due to cardio-vascular diseases. Death correlates with increased age, comorbidity burden, decreased renal function at diagnosis, and absence of RASI use. RASI treatment may potentially improve survival, highlighting its importance in managing IgAN.

#153 The risk of post-transplant recurrent immunoglobulin A nephropathy: the association with post-transplant steroid use

Abstract Background and Aims Immunoglobulin A nephropathy (IgAN) is the most common cause of kidney failure among glomerulopathies worldwide and it is reported that approximately 6-7% of all kidney transplantation is due to IgAN. It is well known that IgAN can recur in the kidney allograft and previous studies suggest that recurrent IgAN is the third most common cause of graft loss in patients with IgAN as primary disease. There is currently no effective treatment for recurrent IgAN, and the main goal is therefore to prevent recurrence in the allograft. Post-transplant steroid therapy is a cornerstone in many immunosuppressive regimens, but steroid treatment also come with several side effects leading to the use of steroid-free protocols. Controversy remains as to whether the use of steroid affects the risk of recurrent IgAN. Previous, retrospective studies report widely divergent associations between the use of steroids and the risk of recurrent IgAN and thus, more research on the association between steroid use and the risk of recurrent IgAN is warranted. We examined this by taking advantage of the fact that two different standard immunosuppression protocols have been employed at two Danish transplantation centers, of which one included steroids and the other did not. The patients treated at the two transplantations centers were otherwise similar with respect to ethnicity, socio-economic status and other aspects of treatment differing only by regional residency. This provided a unique opportunity to compare the association between steroid use, recurrence rate and graft survival. We furthermore aimed to identify potential risk factors for recurrent IgAN. Method A retrospective cohort study including all adult patients (age ≥ 18 years) with biopsy-proven IgAN and a first-time kidney-only transplantation from 1990 to 2020 at either Aarhus University Hospital or Odense University Hospital using a steroid containing or a steroid free post-transplant immunosuppressive protocol, respectively. Renal transplant patients with IgAN were identified from the Danish Nephrology Registry and data on medical treatment, graft survival and histopathological evidence of recurrent IgAN were extracted from electronic medical journals. Data is presented by Aalen-Johansen and Kaplan-Meier plot, and associations between risk factors for recurrent IgAN were analyzed by cox-regression. Results A total of 120 first-time kidney recipients were included in the study. Biopsy-proven, recurrent IgAN was identified in 17 (14.2%) recipients. The median time from transplantation to recurrence was 2.91 years (IQR 0.89−5.60). Only one of 18 (15%) recipients adhering to steroid-free protocol was diagnosed with recurrent IgAN during the study period. The accumulated use of steroid as part of the immunosuppression regime was not associated with the risk of recurrent IgAN (unadjusted HR (95% CI) =1.02 (0.94−1.12)). Transplantation with genetically related living donor was associated with a greater risk of recurrent IgAN compared with non-genetically related ((unadjusted HR (95% CI) = 3.90 (1.37−11.10)) and recipients with recurrent IgAN were more likely to be younger at time of been diagnosed with IgAN and had a shorter time from being diagnosed to kidney failure when compared to recipients with non-recurrent IgAN. There were no associations between the risk of recurrent IgAN and induction therapy or HLA-mismatches. The 10-year death censored graft survival was 45% for recipients with recurrent IgAN, compared to 80% for recipients with non-recurrent IgAN. Conclusion The risk of recurrent IgAN after kidney transplantation was not associated with the use of steroids as part of the immunosuppression protocol, whereas recipients receiving a kidney from a genetic related donor appeared to have a higher risk of recurrent IgAN.

#812 Phase 2b ORIGIN study open label extension with atacicept in patients with IgA nephropathy and persistent proteinuria: week 72 interim analysis

Abstract Background and Aims IgA nephropathy (IgAN), the most common primary glomerulonephritis and a significant contributor to ESKD worldwide, is characterized by elevated serum levels of galactose-deficient IgA1 (Gd-IgA1). The production of Gd-IgA1 and its autoantibodies is driven by both the B-cell Activating Factor (BAFF) and A PRoliferation-Inducing Ligand (APRIL) signaling pathways that stimulate maturation, differentiation, and effector function of B cells and plasma cells. Atacicept is a fusion protein targeting both BAFF and APRIL in clinical development for IgAN treatment. The Phase 2b ORIGIN study met the primary endpoint with statistically significant urine protein:creatinine ratio (UPCR) reduction at 24 weeks vs placebo. At 36 weeks, atacicept 150 mg achieved statistically significant and clinically meaningful UPCR reduction, eGFR stabilization, and Gd-IgA1 reduction vs placebo, with similar safety to placebo. This interim analysis reports 72-week results from the open-label extension period. Method The randomized, double-blind, placebo-controlled Phase 2b ORIGIN study included 116 participants with biopsy-proven IgAN, 24 h urine protein &amp;gt;0.75 g/day or UPCR &amp;gt;0.75 g/g, and eGFR ≥30 mL/min/1.73 m2 despite optimized renin–angiotensin system blockade. Participants were randomized to atacicept 150, 75, or 25 mg, vs placebo (2:2:1:2), self-administered by subcutaneous injection once weekly for up to 36 weeks. The double-blind randomized treatment period was followed by an open-label extension in which participants could receive atacicept 150 mg for up to 60 additional weeks, for a total of 96 weeks. For this interim analysis, changes from baseline in eGFR, natural log transformed UPCR, and Gd-IgA1 through 72 weeks were analyzed using a mixed-effects model for repeated measurements. Microscopic hematuria was evaluated on urine dipstick and participants with hematuria grade 1+ or higher at baseline were evaluated for resolution, defined as a decrease to negative/trace, at 72 weeks. Results Of 116 randomized participants in the double-blind period, 106 participants (91%) completed 72 weeks of treatment. At 72 weeks, eGFR total slope estimate was 0.0 mL/min/1.73m2/year and eGFR change from baseline was 0 mL/min/1.73m2 in all participants originally randomized to atacicept (all-atacicept group; n = 82). After switching to open-label atacicept 150 mg, the original placebo group showed eGFR stabilization with −3.2 mL/min/1.73m2 change from baseline at 72 weeks vs −4.9 mL/min/1.73m2 at 36 weeks (Figure 1). At 72 weeks, UPCR change from baseline was −45% in the all-atacicept group and the placebo switch group showed a −47% UPCR change from baseline at 72 weeks vs +3% at 36 weeks (Figure 2). Open-label atacicept 150 mg was also associated with rapid Gd-IgA1 reduction in the placebo switch group at 48 weeks that was sustained through 72 weeks. Hematuria resolution was observed at 72 weeks in 81% (35/43) of participants in the all-atacicept group and 59% (10/17) in the placebo switch group. Atacicept was generally well tolerated during the open-label extension, with a similar rate of infections compared to the double-blind period and one study drug-related serious adverse event. Conclusion At 72 weeks, treatment with atacicept 150 mg was associated with sustained eGFR stability and deepening UPCR reductions, as well as a reversal of the downward eGFR decline in the placebo switch group. Sustained reductions in hematuria were also observed. The open-label extension showed a favorable safety profile similar to the double-blind period. These results support atacicept 150 mg as a potential disease-modifying treatment for IgAN.

#123 Impact of atacicept on hematuria in IGA nephropathy: post-hoc analysis of the phase 2b ORIGIN study

Abstract Background and Aims Patients with IgA nephropathy (IgAN) and persistent hematuria during follow up have a greater decline in renal function than those with minimal or no hematuria, while hematuria resolution has been independently associated with less decline in renal function [1, 2]. Atacicept is a fusion protein targeting both BAFF and APRIL in clinical development for IgAN. The Phase 2b ORIGIN study met the primary endpoint with statistically significant urine protein:creatinine ratio (UPCR) reduction at 24 weeks for atacicept vs placebo. At 36 weeks, atacicept 150 mg achieved statistically significant and clinically meaningful UPCR reduction, eGFR stabilization, and robust reduction of galactose-deficient IgA1 vs placebo, with similar safety to placebo. This post-hoc analysis evaluates changes in hematuria during treatment with atacicept vs placebo over 36 weeks. Method The randomized, double-blind, placebo-controlled Phase 2b ORIGIN study included 116 participants with biopsy-proven IgAN, 24h urine protein &amp;gt;0.75 g/day or UPCR &amp;gt;0.75 g/g, and eGFR ≥30 mL/min/1.73 m2 despite optimized renin–angiotensin system blockade. Participants were randomized to atacicept 150, 75, or 25 mg vs placebo (2:2:1:2) self-administered by subcutaneous injection once weekly for up to 36 weeks. Microscopic hematuria was evaluated at weeks 2, 4, 12, 24, and 36 via urine dipstick at a centralized lab, and hematuria levels were graded negative/trace, 1+, 2+, or 3+. Hematuria improvement was defined as a decrease by ≥1 grade, and resolution was defined as a decrease to negative/trace. Results In the intent-to-treat population, 15 of 33 (45%) participants who received atacicept 150 mg and 19 of 34 (56%) who received placebo had hematuria (1+ or greater) at baseline. Of these, 87% (n = 13/15) on atacicept 150 mg had improved hematuria at 36 weeks vs 32% (n = 6/19) on placebo (p = 0.002), with 80% (n = 12/15) on atacicept 150 mg achieving resolution to negative/trace hematuria vs 5% (n = 1/19) on placebo (p &amp;lt; 0.0001) (Figure). The atacicept 150 mg group steadily improved to lower hematuria grades over 36 weeks, with improvement occurring as early as 4 weeks, while the placebo group had no improvement in hematuria over time. The majority of participants without hematuria at baseline maintained negative or trace levels at 36 weeks. Conclusion In a post-hoc analysis, atacicept treatment was associated with hematuria resolution at 36 weeks in a substantially greater percentage of participants as compared with placebo, with improvements seen as early as 4 weeks. These results add to the growing body of evidence supporting atacicept as a potential disease-modifying treatment for IgAN. Atacicept 150 mg is currently being evaluated in a global Phase 3 randomized placebo-controlled trial.

#1392 MEST-C score correlation with proteinuria reduction after SGLT2i treatment in patients with IgA nephropathy

Abstract Background and Aims Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are associated with better cardiovascular outcomes and with nephroprotection independent of diabetes status. Recent data suggest that SGLT2i significantly reduce proteinuria in patients with IgA nephropathy (IgAN). Data available for the use of the MEST-C score to determine if treatment would benefit IgAN patients is scarce. The aim of our study was to assess the degree of proteinuria reduction after SGLT2i treatment in IgAN and its possible association with the MEST-C score. Method 63 adult patients with biopsy-proven IgA nephropathy, eGFR ≥ 30 mL/min/1.73 m2 (CKD-epi), and total urine protein of &amp;gt;0.5 grams/day at screening were included. Patients with secondary IgAN and crescents were excluded. All receiving maximally tolerated RASi for at least 12 weeks. All patients started dapagliflozin 10 mg once per day after baseline data were registered. The total follow-up was 12 months. The main outcome was the decline in eGFR and the reduction in 24-hour proteinuria from SGLT2i initiation to 1,3, 6, 9, 12 months, end-stage renal disease, or kidney or cardiovascular death. Three repeated measurements of proteinuria (mg/24H) were performed, 90 days before SGLT2i treatment initiation, and only patients with stable proteinuria were enrolled in the study. Results 49 patients (35/14 M/F), with mean age of 41,9 ± 19,6 years, completed follow up. 8 patients discontinued treatment due to adverse events attributed to dapagliflozin. At baseline eGFR was 68.21±18,1 ml/min/1.73 m2 and Upr: 2196±1091 mg/24H. The MEST-C scores were correlated with the serum creatinine level, proteinuria, and hematuria. The mean serum creatinine level was higher in M1, E1, S1, and T1 compared with score “0”. It was statistically significant (p = 0.03) only in the T-score. The mean proteinuria level was again higher in M1, S1, and T1 but reached statistical significance (p = 0.037) in only the T1-score. E1 has higher hematuria. The Upr/24H difference for dapagliflozin was −24.7% (95% CI −27.5, −23.2; p &amp;lt; 0.001) at the end of follow-up (month 12). Proteinuria reduction was similar across all eGFRs, age, and baseline proteinuria. Among MEST-C score parameters, T1 had a negative impact on the antiproteinuric effect of dapagliflozin (p = 0.01) No hypoglycemic events were reported and no deaths occurred. Conclusion In the present study, the use of SGLT2i was associated with a significant reduction of proteinuria in patients with IgA nephropathy and maximally tolerated RASi. We analyzed renal outcomes in association with pathologic features. We established that the presence of the T1 score has a negative impact on proteinuria reduction after SGLT2i treatment. Further studies are needed to investigate the impact of the use of the Oxford Classification score for developing individual treatment therapies.

#1679 Relationship between initial eGFR DIP with proteinuria after SGLT2i treatment, in patients with IgA nephropathy. A real-world clinical study

Abstract Background and Aims Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are associated with better cardiovascular outcomes and with nephroprotection independent of diabetes status. Recent data suggest that SGLT2i significantly reduce proteinuria in patients with IgA nephropathy (IgAN). However, they often cause an initial decline in estimated glomerular filtration rate (eGFR). The aim of our study was to assess the degree of proteinuria reduction after SGLT2i treatment in IgAN and its possible association with the initial functional dip in eGFR. Method 63 adult patients with biopsy-proven IgA nephropathy, eGFR ≥ 30 mL/min/1.73 m2 (CKD-epi), and total urine protein of &amp;gt;0.5 grams/day at screening were included. Patients with secondary IgAN were excluded. All receiving maximally tolerated RASi for at least 12 weeks. All patients started dapagliflozin 10 mg once per day after baseline data were registered. The total follow-up was 12 months. The main outcome was the decline in eGFR and the reduction in 24-hour proteinuria from SGLT2i initiation to 1,3, 6, 9, 12 months, end-stage renal disease, or kidney or cardiovascular death. Results 55 patients (38/17 M/F), with mean age of 44,2±18,3 years, completed follow up. 8 patients discontinued treatment due to adverse events attributed to dapagliflozin. At baseline eGFR was 66.17±19,7 ml/min/1.73 m2 and Upr: 2356±1023 mg/24H. There was a transient decline in eGFR, 30 days after initiation of dapagliflozin (66.17±19,7 min/1.73 m2 at baseline to 57 ml/min/1.73 m2) but then, there was an improvement at month 3 from baseline. The Upr/24H difference for dapagliflozin was −25.1% (95% CI −27.5, −23.2; p &amp;lt; 0.001) at the end of follow-up (month 12). Proteinuria reduction was similar across all eGFRs. Notably, a significant correlation was found between the initial eGFR dip and percentage proteinuria reduction in the 12th month. (R = –0.23; p = 0.03). Consistent results of dapagliflozin treatment on proteinuria were found in all analysis subgroups including sex, baseline proteinuria, systolic blood pressure, and body mass index. No hypoglycaemic events were reported and no deaths occurred. Conclusion In the present study, the use of SGLT2i was associated with a significant reduction of proteinuria in patients with IgA nephropathy in patients with maximally tolerated RASi. Higher initial eGFR dip after treatment initiation was a predictor of a significantly higher reduction in proteinuria at the end of follow-up. The correlation between eGFR dip and proteinuria reduction perhaps reflects the intraglomerular pressure reduction, mediated by tubuloglomerular feedback, one of the numerous.

#2042 Efficacy and safety of telitacicept in IgA nephropathy: a retrospective study

Abstract Background and Aims Telitacicept is a novel fusion protein composed of a recombinant transmembrane activator, calcium modulator, and cyclophilin ligand interactor (TACI) receptor fused with the fragment crystallizable (Fc) region of human immunoglobulin G (IgG). Telitacicept inhibits the differentiation of immature B cell and survival of long-lived plasma cells by neutralizing the activity of B Lymphocyte Stimulator (BlyS) and A Proliferation-Inducing Ligand (APRIL). It was approved for the treatment of patients with Systemic Lupus Erythematosus (SLE) in China in March 2021. Given that BlyS/APRIL overexpression has also been identified in IgA nephropathy (IgAN), telitacicept is in clinical trials for the treatment in IgAN. In this study, we aim to retrospectively evaluate the efficacy and safety of telitacicept in patients with IgAN. Method In this retrospective study, 27 patients with primary IgAN were enrolled from Nephrology Department of Renmin hospital of Wuhan university in China from February 2022 to March 2023. Patients were administered 160 mg telitacicept by subcutaneous injection based on the previous treatment once a week at least 4 weeks, and were followed up. Adults 20–75 years of age who met the following criteria were included: biopsy-proven primary IgAN and 24-hour proteinuria &amp;gt;0.75 g. Patients were excluded if they had secondary causes of IgAN, 24 h proteinuria &amp;lt;0.75 g or immunocompromised state. Changes in proteinuria, serum creatinine, estimated glomerular filtration rate (eGFR), serum immunoglobulins, complement protein (in blood serum), albumin, urine erythrocyte, blood leukocyte and hemoglobin were analyzed during treatment. Key assessment time points were at 2, 4, 8, 12, 16 and 24 weeks after the first administration. Results In this study, duration of telitacicept exposure ranged from 4 weeks to 32 weeks, the median of which was 16 weeks. After administration of telitacicept, baseline 24 h proteinuria of 3.37 g/d decreased to 1.05 g/d at the Week 24 (z = −4.46, p &amp;lt; 0.05), with reductions statistically significant by Week 4. During telitacicept treatment, the median eGFR showed stable trend without sudden decline. Compared to the baseline eGFR of 68.34 ml/(min 1.73 m2), the eGFR at Week 24 was 72 ml/(min 1.73 m2). Changes in immunoglobulin A (IgA), immunoglobulin G (IgG) and immunoglobulin M (IgM) all showed downward trend while complement protein 3 (C3) and complement protein 4 (C4) maintained stable trend. Specifically, IgA decreased from 2.51 g/L at baseline to 1.41 g/L at Week 24, there was a significant reduction by Week 4 (P = 0.001). The median of IgG decreased from 8.31 g/L at baseline to 6.71 g/L at Week 24, with reductions statistically significant by Week 4 (P = 0.008). IgM decreased significantly at Week 2 from baseline of 1.13 g/L to 1.05 g/L (P = 0.017) and was 0.64 g/L at Week 24. The median C3 was stable from baseline to Week 24 (0.92 g/L, 0.87 g/L, respectively), and C4 were 0.22 g/L and 0.23 g/L, in order. Patients had a significant increase in albumin from baseline to Week 2 (P = 0.009) and the Week 24. (36.7 g/L, 37.1 g/L and 41.8 g/L, respectively). Conversely, there was a continuous reduction in urine erythrocyte, from baseline of 62.46/μL to 7.68/μL at Week 24. There remained stable in blood leukocyte from baseline to Week 24 (8.48 × 109/L, 8.67 × 109/L, respectively), with no significant changes. By the end of the study, 10/27 patients was in complete remission (CR) and 8/27 patients had achieved partial remission (PR). The overall remission rate of primary IgAN with telitacicept treatment reached 67%. Telitacicept was generally well tolerated in patients with IgAN in this study. No treatment-emergent adverse events (AEs) occurred in all 27 patients, such as respiratory tract infection, urinary tract infections and injection site allergic. Conclusion In conclusion, based on the retrospective analysis with a small sample, telitacicept, a novel BLyS/APRIL dual inhibitor, effectively decreases proteinuria in IgAN with stable renal function. In addition, it demonstrates a favorable safety profile in patients. The data are supportive of further study with telitacicept in IgAN.

#1444 Albuminuria and subsequent risk of kidney events in patients with IgA nephropathy: a nationwide cohort study

Abstract Background and Aims KDIGO recommends proteinuria &amp;lt;1 g/d as a treatment target in patients with immunoglobulin A nephropathy (IgAN) because of high-risk of progression to kidney failure. However, long-term kidney outcomes in patients with low-grade proteinuria remain poorly studied. Method We enrolled patients with biopsy-proven primary IgAN from the Swedish Renal Registry and analyzed associations between first-recorded urinary albumin-to-creatinine ratio (uACR, in categories &amp;lt;0.3, 0.3-0.5, 0.5-1.0, 1.0-1.5, 1.5-2.0 and &amp;gt;2.0 g/g) and the occurrence of major adverse kidney events (MAKE, a composite of kidney replacement therapy [KRT] and &amp;gt;30% decline in eGFR). We also explored the risk of MAKE associated with the fold-change in uACR within a year. Results We enrolled 1269 patients with primary IgAN (74% men, median 53 years, mean eGFR 33 mL/min/1.73 m², median uACR 0.7 g/g). Compared to patients with uACR &amp;lt;0.3 g/g, those with higher uACR levels were younger, more often men, had a higher prevalence of hypertension, diabetes, acute kidney injury, lower eGFR and serum albumin level, and were less often prescribed RASi. Over median follow-up of 5.5 [2.8;9.2] years, 667 MAKE and 517 KRT events occurred, and 528 patients experienced &amp;gt; 30% eGFR decline. In multivariable analyses, and compared with uACR &amp;lt;0.3 g/g, any higher uACR category strongly and incrementally associated with the risk of MAKE (Figure), with Hazard Ratios (HR) ranging from 1.56 [95% CI 1.14-2.14] in patients with uACR 0.3-0.5 g/g to 4.53 [3.36-6.11] in patients with uACR&amp;gt;2g/g. Similar graded relationships were observed for KRT (HR ranging from 1.39 to 4.65), and for &amp;gt;30% decline in eGFR (HR ranging from 1.76 to 3.47). In the 785 patients who had repeated uACR measurements within a year, and compared with stable uACR, the risk of kidney events was lower if uACR decreased by 2-fold (HR ranging from 0.47 to 0.49), and higher if uACR increased by 2-fold (HR from 1.18 to 2.56), irrespective of baseline uACR. Conclusion Our findings show substantial risk of adverse kidney outcomes among patients with IgAN and uACR between 0.3 and 1.0 g/g, a population currently considered at low-risk of CKD progression. Reduction in uACR is associated with better kidney outcomes, irrespective of baseline uACR.

#1257 Complement system is overactivated in patients with IgA nephropathy after COVID-19

Abstract Background and Aims Since the coronavirus disease of 2019 (COVID-19) pandemic swept across the world, the flare of immune-mediated disease following SARS-CoV-2 infection has emerged rapidly. IgA nephropathy (IgAN), which has been confirmed as a complement mediated autoimmune disease, is also one of the common glomerulonephritis associated with COVID-19. Here, we aim to investigate the clinical and immunological characteristics of patients with IgAN after COVID-19. Method From December 2022 to April 2023, 33 patients with renal biopsy-proven IgAN (Group CoV) at Beijing Anzhen hospital who had experienced COVID-19 before renal biopsy were enrolled. Meanwhile, 44 patients with IgAN (Group non-CoV) diagnosed from December 2018 to April 2019 (the same period in the previous year, with no COVID-19) were enrolled as control. Plasma FHR-5, MBL, C5a, soluble C5b-9, serum Gd-IgA1 and IgA immune complex were detected by enzyme-linked immunosorbent assay. Glomerular staining for FHR-5, C3c, MAC and Gd-IgA1 were detected by immunofluorescence. SARS-CoV-2 nucleocapsid was detected by immunohistochemistry. Clinicopathological and immunological features between the two groups were analyzed. Results The median time between onset of COVID-19 symptoms and the time of renal biopsy was 12 (6, 18) weeks, ranging from 1 to 26 weeks. SARS-CoV-2 nucleocapsid antigen expression in the renal tubular epithelial cells were observed in 11/33 (33.3%) patients. Compared with Group non-CoV, the level of eGFR was significantly lower in Group CoV[67.30 (52.94, 96.43) ml/min per 1.73 m2 vs. 101.04 (74.35, 120.98) ml/min per 1.73 m2, p = 0.010]. Histologically, compared with Group non-CoV, Group CoV presented with more percentages of segmental glomerulosclerosis/adhesion (p = 0.003) and less percentages of mesangial hypercellularity (p = 0.017). The level of plasma level of C5a [16.45 (10.48, 22.07) ng/ml vs. 3.68 (2.70, 4.47) ng/ml], soluble C5b-9 [614.43 (481.66, 770.02) ng/ml vs. 358.08 (304.83, 471.77) ng/ml], FHR5 [4.01 (3.51, 4.48) ug/ml vs. 2.73 (2.25, 3.21) ug/ml]were all significantly higher in Group CoV compared with Group non-CoV, respectively (p &amp;lt; 0.001). Although the plasma level of MBL showed no difference in Group CoV and Group non-CoV, the proportion of high levels of MBL in Group CoV was higher than in Group non-CoV (p = 0.025). Compared with Group non-CoV, the intensity of glomerular MAC deposition was much stronger in Group CoV. There were no significant differences in serum levels of IgA, Gd-IgA1, IgA immune complex between two Groups. However, a greater intensity of Gd-IgA1 deposition in glomerular mesangial and capillary areas has been exhibited in Group CoV than those in Group non-CoV (p = 0.005). Conclusion For IgAN after COVID-19, mucosal immune responses to SARS-CoV-2 infection may result in the overactivation of systemic and renal local complement system, which is the first hit, and increased glomerular deposition of Gd-IgA1 is the second hit. We think that these two hits may lead to renal dysfunction and promote renal progression in IgAN patients. It is crucial to emphasize the necessity for long term follow-up in these patients of IgAN after COVID-19. Additionally, we propose that inhibitors targeting the mediators of complement activation might be a promising therapy for these IgAN patients after SARS-CoV-2 infection.

#1170 Efficacy and safety of telitacicept in IgA nephropathy: a real-world study

Abstract Background and Aims IgA nephropathy (IgAN) is the most common primary glomerular disease in the world, and the specific therapeutic methods are limited in IgAN. Telitacicept is a humanized fusion protein composed of a transmembrane activator and calcium-modulating cyclophilin ligand interactor receptor and human IgG. This study was designed to evaluate the efficacy and safety of telitacicept in adult patients with IgAN in a real-world study. Method Biopsy-proven IgAN patients with 24-hour proteinuria greater than 0.5 g/day who received telitacicept 240 mg once a week were recruited in this study and 1:1 matched with patients who received supportive treatment only or immunosuppressive treatment by propensity score matching. The primary outcome was the change from baseline in 24-hour proteinuria over the 3-month follow-up. Results Twenty-one patients in each group were enrolled. The mean eGFR was 80.1 ml/min/1.73 m2, and the median 24-hour urine protein level was 1.48 g/day. At the end of the 3-month follow-up period, telitacicept reduced median proteinuria by 0.72 g/d (54.6%) from baseline, compared with a reduction of 0.18 g/d (20%) in the supportive treatment group (P &amp;lt; 0.001), and 1.12 g/d (72.1%) in the immunosuppressive treatment group (P = 0.814). Preserved eGFR levels were observed in the telitacicept group (1.9 ml/min/1.73 m2 [4.3%]), while the eGFR level declined in the supportive treatment group (- 2.9 ml/min/1.73 m2 [- 5.8%]) and immunosuppression group (- 6.1 ml/min/1.73 m2 [- 8.4%]). No serious adverse events were observed in the telitacicept treatment group. Injection site reactions were more prevalent in the telitacicept group (8/21 [38.1%]), meanwhile immunosuppression group had more respiratory tract infections (7/21, [33.3%]). Conclusion Telitacicept can reduce proteinuria in patients with IgAN and showed a favourable safety profile in patients with IgAN.

#683 Utility of urinary soluble CD163 as a novel biomarker for the detection of IgA nephropathy

Abstract Background and Aims IgA nephropathy (IgAN) is an immune mediated disease and a leading cause of biopsy proven glomerulonephritis (GN) worldwide. CD163 is a membrane protein localised on the surface of monocytes and macrophages. Its soluble form, sCD163, produced by enzymatic splitting of the ectodomain of inflammatory cells when activated, is found in increased concentrations in acute inflammatory diseases such as sepsis and vasculitis. Urinary sCD163 levels have also been reported to be a useful biomarker of glomerular inflammation in lupus nephritis (LN) and anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Yet, few studies have evaluated the role of urinary sCD163 as a biomarker in IgAN, and comparing it across different GN subtypes. This study aims to explore the utility of urinary sCD163 as a non-invasive biomarker for IgAN, and across different immune mediated GN types. Method This is a retrospective and prospective cohort study from a single tertiary hospital. Frozen urine samples from patients with GN and healthy controls from the Asian Kidney Disease Study and Singapore Kidney Function Study respectively were utilised for the retrospective cohort. The prospective cohort consists patients with biopsy-proven IgAN recruited from May to December 2023 with informed consent taken. Urinary sCD163 was measured using enzyme-linked immunosorbent assay (ELISA). Univariate analyses were performed and urinary sCD163 values were plotted on receiver-operating characteristic (ROC) curve and the area under the curve (AUC) was calculated. This study obtained Institutional Ethics Board Approval (DSRB 2022/00698). Categorical variables were represented by n (%). Continuous variables with a parametric distribution were represented by their means ± standard deviation, non-parametric variables were expressed as their medians with interquartile ranges. Chi-square test and ANOVA were performed between categorical variables, while a student's t-test was performed for continuous variables. P-value of &amp;lt; 0.05 was taken as statistically significant. A ROC curve was performed for sCD163 values in IgAN and controls, and the AUC calculated. Results In total, urine samples of 59 subjects were analysed (IgAN n = 10; LN n = 5; healthy controls n = 44). There were 30 male subjects (50.8%) and 29 female subjects (49.2%). Median age was 41.0 (IQR 31.0-52.0) years. Median serum creatinine was 78.0 (IQR: 60.0-91.0) µmol/L. Mean urine sCD163 value was 0.32 (±0.19) ng/ml. There were no baseline differences in demographics, comorbidities and medication between groups. Prospective cohort patients with IgAN were more likely to have received steroids (p = 0.03), and there were no patients of the Malay Ethnicity in the prospective cohort (p = 0.05). Median urine protein (g/day) in IgAN was 0.66 (IQR 0.16 to 3.29)¸ 0.159 in LN (IQR 0.09 to 0.26) and 0.12 in controls (IQR 0.07 to 0.20). Using Mann-Whitney U test to compare median proteinuria between IgAN and controls showed significant difference (p = 0.001), whereas median proteinuria between IgAN and LN was not statistically significant (p = 0.08). On univariate analysis compared to healthy controls, IgAN patients had a significantly higher serum creatinine (p = 0.04), compared to LN patients against controls (p = 0.30). Urine sCD163 levels were significantly higher in IgAN patients compared to controls (0.54 ± 0.26, p = 0.02). Patients with LN do not have a significant urinary sCD163 level difference compared to controls (0.21 ± 0.20, p = 0.40), which also correlates with creatinine and degree of proteinuria. There were no other significant baseline differences against controls. On the ROC curve for IgAN patients, urine sCD163 of 0.38 ng/ml has a 70% sensitivity, and 75% specificity in distinguishing IgAN against controls (AUC 0.77; 95% CI: 0.59-0.96, p = 0.008). For LN, urine SCD163 did not distinguish between LN and controls (AUC 0.29; 95% CI: 0.000-0.58, p = 0.12). Conclusion Urine sCD163 is elevated in patients with IgAN compared to controls and LN. Urine sCD163 is useful in the diagnosis of IgAN. A urine sCD163 level of 0.38 ng/ml has a 70% sensitivity and 75% specificity in identifying IgAN against healthy subjects.

#1039 Characteristics and outcome of IgA nephropathy in Switzerland – a single center perspective

Abstract Background and Aims IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide leading to end-stage kidney disease (ESKD) in roughly 40% of affected patients by ten years. Geographic differences in clinical course and response to treatment may partly result from different disease entities. The purpose of this retrospective cohort analysis was to study all cases of IgAN from a single tertiary center with respect to clinical and histological characteristics, treatment practices and outcome. Method This retrospective cohort analysis identified 158 cases of adult biopsy-proven IgAN by chart review diagnosed between 1980 and 2017. Detailed phenotypisation including clinical, paraclinical, histological, treatment and outcome parameters was performed. Remission status was defined as described previously (Reich 2007). Statistical analysis was performed using Excel and SPSS software and included standard descriptive methods and included standard descriptive methods and student's t-test on a significance level of 0.05. Results Subjects were majorly male and of Caucasian descent. Mean estimated glomerular filtration rate (eGFR) according to Chronic Kidney Disease Epidemiology Collaboration formula at diagnosis was 55.3 ml/min/1.73 m2, mean proteinuria was 3.2 g/d. 70.3% of patients were hypertensive at presentation. Clinical presentation varied according to age. Thus, younger patients (18-39 years) presented more frequently with macrohematuria, asymptomatic urine abnormalities and by trend acute kidney injury whereas nephrotic syndrome and extrarenal symptoms were recorded in similar proportions of patients (Fig. 1). 28.5% of initial biopsies showed moderate to severe tubular atrophy and interstitial fibrosis (IFTA), 38% included crescents, 1.9% &amp;gt; 50% crescents. 86.1% of the patients were treated by renin-angiotensin-aldosterone-system inhibitors, 46.8% received immunosuppressive therapy including steroids in 46.2% and other immunosuppressive medications in 19.6% the most common being azathioprine (Fig. 2). There were 33.5% complete and 13.3% partial remissions. Progression to ESKD was noted in 42.1%. 51.4% of patients treated with immunosuppressive therapy experienced remission. Recurrence rate after transplantation was 18.4%. Patients treated by immunosuppressants had higher levels of baseline proteinuria (3.2 ± 2.3 vs. 1.6 ± 1.6 g/d, p &amp;lt; 0.00001), lower baseline eGFR (50 ± 31 vs. 61 ± 30 ml/min/1.73 m2, p = 0.04), higher number of crescents (9.4 ± 15.0 vs 2.3 ± 8.5%, p = 0.001), higher IFTA scores (1.7 ± 0.8 vs. 1.3 ± 0.6, p = 0.007) and higher fluorescence intensity scores for C3 (2.0 ± 0.9 vs. 1.6 ± 0.9, p = 0.02) on initial biopsy as compared to patients treated conservatively. Patients progressing to ESKD presented with higher blood pressure (146 ± 26 vs. 135 ± 18 mmHg systolic, p = 0.005; 89 ± 14 vs. 82 ± 14 mmHg diastolic, p = 0.006), lower eGFR (41 ± 29 vs. 64 ± 28 ml/min/1.73 m2, p = 0.00001), higher levels of proteinuria (3.4 ± 2.0 vs. 1.8 ± 1.9 g/d, p = 0.0001), higher number of crescents (9 ± 17 vs. 4 ± 9%, p = 0.03) and higher IFTA scores (1.8 ± 0.8 vs. 1.3 ± 0.6, p = 0.00001) as compared to patients without ESKD at last follow up. Baseline blood pressure (134 ± 18 vs. 147 ± 26 mmHg systolic, p = 0.004; 82 ± 14 vs. 89 ± 15 mmHg diastolic, p = 0.01), eGFR (60 ± 29 vs. 41 ± 27 mmHg, p = 0.0007), proteinuria (2.3 ± 1.9 vs. 3.2 ± 2.3 g/d, p = 0.03) and severity of IFTA (1.4 ± 0.6 vs. 1.8 ± 0.9, p = 0.003) differed significantly between patients who experienced any remission vs. those who did not achieve remission respectively. Conclusion This analysis gives insight into the characteristics and treatment practices of a Swiss single center cohort of IgAN patients from 1980-2017.

The predictive value of free thyroxine combined with tubular atrophy/interstitial fibrosis for poor prognosis in patients with IgA nephropathy.

IgA nephropathy (IgAN), the most common type of glomerulonephritis, has great individual differences in prognosis. Many studies showed the relationship between thyroid hormones and chronic kidney disease. However, the relationship between free thyroxine (FT4), as a thyroid hormone, and IgAN is still unclear. This study aimed to evaluate the impact of FT4 on IgAN prognosis. This retrospective study involved 223 patients with biopsy-proven IgAN. The renal composite outcomes were defined as: (1) ESRD, defined as eGFR < 15 ml/(min·1.73 m2) or initiation of renal replacement therapy (hemodialysis, peritoneal dialysis, renal transplantation); (2) serum creatinine doubled from baseline; (3) eGFR decreased by more than 50% from baseline. The predictive value was determined by the area under the curve (AUC). Kaplan-Meier and Cox proportional hazards analyses assessed renal progression and prognosis. After 38 (26-54) months of follow-up, 23 patients (10.3%) experienced renal composite outcomes. Kaplan-Meier survival curve analysis showed that the renal survival rate of the IgAN patients with FT4<15.18pmol/L was lower than that with FT4≥15.18pmol/L (P < 0. 001). Multivariate Cox regression model analysis showed that FT4 was a protective factor for poor prognosis of IgAN patients, whether as a continuous variable or a categorical variable (HR 0.68, 95%CI 0.51-0.90, P =0.007; HR 0.04, 95%CI 0.01-0.20, P <0.001). ROC curve analysis showed that FT4 combined with t score had a high predictive value for poor prognosis of IgAN patients (AUC=0.881, P<0.001). FT4 was a protective factor for IgAN. In addition, FT4 combined with tubular atrophy/interstitial fibrosis had a high predictive value for poor prognosis of IgAN.

Albuminuria predicts kidney events in IgA nephropathy.

KDIGO recommends proteinuria <1g/d as a treatment target in patients with immunoglobulin A nephropathy (IgAN) because of high-risk of progression to kidney failure. However, long-term kidney outcomes in patients with low-grade proteinuria remain insufficiently studied. We enrolled patients with biopsy-proven primary IgAN from the Swedish Renal Registry and analyzed associations between urine albumin-to-creatinine ratio (uACR, in categories<0.3, ≥0.3-0.5, ≥0.5-1.0, ≥1.0-1.5, ≥1.5-2.0 and≥2.0g/g) and the occurrence of major adverse kidney events (MAKE, a composite of kidney replacement therapy [KRT] and>30% decline in eGFR). We also explored the risk of kidney events associated with change in uACR within a year. We included 1269 IgAN patients (74% men, median 53 years, mean eGFR 33mL/min/1.73m², median uACR 0.7g/g). Over median follow-up of 5.5 [2.8;9.2] years, 667 MAKE and 517 KRT events occurred, and 528 patients experienced>30% eGFR decline. Compared with uACR<0.3g/g, any higher uACR category was strongly and incrementally associated with the risk of MAKE (adjusted HR ranging from 1.56 [95%CI 1.14-2.14] if uACR 0.3-0.5g/g to 4.53 [3.36-6.11] if uACR≥2.0g/g), KRT (HR ranging from 1.39 to 4.65), and eGFR decline>30% (HR ranging from 1.76 to 3.47). In 785 patients who had repeated uACR measurements within a year, and compared with stable uACR, the risk of kidney events was lower if uACR decreased by 2-fold (HR ranging from 0.47 to 0.49), and higher if uACR increased by 2-fold (HR from 1.18 to 2.56), irrespective of baseline uACR. There is substantial risk of adverse kidney outcomes among patients with IgAN and uACR between 0.3 and 1.0g/g, a population currently considered at low-risk of CKD progression. Reduction in uACR is associated with better kidney outcomes, irrespective of baseline uACR.