bluuebunny/crossref_metadata_2025 huggingface dataset:
#3045 Understanding BK polyomavirus: surveillance and clearance in kidney transplant recipients
Authors: González-Rojas Ángela , Marcos Maria Angeles , Juarez Jordi Rovira , Cacho Judit , Leal Agustin , Cucchiari David , Revuelta Ignacio , Pujol Federico Cofan , Cuadrado Elena , Rodríguez Diana , Arana Carolt , Diekmann Fritz
Published: May 2024

Background and Aims

BK virus allograft nephropathy (BKVN) can develop graft loss. The aim of this study was to describe BK viraemia and BKVN related factors, our experience in treatment and the impact in graft survival.

Method

We introduce a retrospective cohort of 78 kidney transplant recipients (KTRs) with BKV viraemia between January 2013 from January 2020 and with follow-up until December 31, 2022 in our center.

Results

Thirty-four (43%) were living donor KTRs, 30 (38.5%) DBD, 11 (14.1%) DCD III, and 2 (4.3%) DCD II. Twenty-seven (34.6%) of recipients were sensitized. Immunosuppressive induction was based on Anti-CD25 in 33 (42.3%), and antilymphocytes antibodies in 44 (56.4%). Basal treatment was TAC+MPA+PDN in 44 (56.4%) and TAC+iMTOR+PDN in 31 (39.7%). Median FK levels were 7.9 (ng/ml) in the first replication. Median BK load at first replication was 3636 [1030-97151]cp/ml. Median time to replication from transplant was 6 months, and from highest load 9 months.

Immunosuppression adjustment after replication was switch to imTOR+FK 25 (32.1%), low FK 17 (21.8%), imTOR 4 (5.1%). Only surveillance was chosen in 27 (35.9%). Others therapies were Leflunomide 4 (5.1%), IVIG 6 (7.7%) or both 3 (3.8%). Photopheresis was used in 2 cases.

Viraemia was cleared in 17/24 (70.8%) of the cases in which conversion to mTOR was performed as an immunosuppression adjustment strategy, versus 9 (56.3%) in which it was decided to lower FK and in 3 (75%) with low MMF. Ten cases in which surveillance was carried out became negative for viremia, possibly because they were patients with a lower replicative load.

BKN occurred in 28/78 (36%) cases, interstitial fibrosis (ci>2) was found in 14/28 (48.27%). Graft rejection after BKN was developed in 11/28 (37.9%). Graft loss occurred in 26/78 (33.3%) of cohort and in 19 (65%)of patients with BKN, reaching a significant value. Viraemia clearance was reached in 41 (60.3%) in mean time of 10 months [4-27]. Mean time since BKVN until graft loss was 22.3 months [10.2-34.2].

Exitus occurred in 7/78 (9%) of replication cases and in 3/28 (10.7%)of BKN patients.

Maximum BK load Exp β; [1-1], p 0.033, first replication load >10.000 (cp/ml) and deceased donor status (Exp β; 6,9 [2.43-19.57] and 2.98 [1.10-8.07] p 0.031, were related to BKVN in bivariate analysis. No significant differences were found between therapy in BKVN and graft loss, maybe due to low BKVN cases.

Conclusion

In our cohort, maximum BK load, first replication load >10,000 (cp/ml), and deceased donor status appear to be related to nephropathy.

No significant differences were found between induction, basal or adjuvant therapy and graft loss.

The current challenge is to stop replication before fibrosis, without increasing the risk of rejection.
#701 Occult hepatitis B infection in kidney transplant recipients and their donors
Authors: Musialik Joanna , Kolonko Aureliusz , Wiecek Andrzej Jan
Published: May 2024

Background and Aims

Occult hepatitis B infection (occult HBV infection—OBI) in kidney transplant recipients (KTRs) poses a potential risk of transforming into an overt process during immunosuppressive therapy. We aimed to evaluate the frequency of OBI occurrence in KTRs population and in the corresponding cohort of kidney donors.

Method

We analyzed 1222 consecutive KTRs transplanted between Jan 2012 and Jun 2023 and their 670 deceased donors. The diagnosis of seropositive OBI was based on the presence of anti-HBc antibodies without detectable HBs antigen. In eligible KTRs with pre-transplant OBI, the status of HBV infection was examined including the HBV-DNA and calculated aspartate aminotransferase to platelet ratio index (APRI) and Fibrosis-4 (FIB-4) indexes to assess the degree of liver fibrosis.

Results

Prior to transplantation, OBI was diagnosed in 178 (14.9%) KTRs [median age 49 (IQR, 38-59) years] and in 72 (10.7%) donors [median age 49 (38-58)]. OBI was significantly more frequent in KTRs than in general population (χ2=6.4, p<0.05). In a long-term follow-up period [median 84 (47-117) months], 5 out of 85 pre-transplant OBI patients (5.9%) presented the negative HBc status, whereas HBV viremia and HBs antigen, as determined using the high-sensitive method, were absent in all subjects. Among 85 pre-transplant OBI subjects, anti-HBs antibodies >10 mIU/ml were present in 84.7% and no liver fibrosis was found by APRI and FIB-4 indexes calculation.

Conclusion

1. OBI is still a significant clinical problem not only in KTRs, but also in the general population, despite the widespread access to preventive vaccinations against HBV. 2. A separate analysis is necessary to evaluate the influence of OBI on kidney graft and liver function in KTRs.
#833 Spectrum of tuberculosis after kidney transplantation: a case-control study in a middle-endemic area
Authors: Cherif Tehir Mohamed , Lylia Trima
Published: May 2024

Background and Aims

Tuberculosis (TB) is the leading cause of infectious-disease death worldwide. Post-transplant TB is a problem in successful long-term outcome of kidney transplantation recipients (KT) and is often associated with high morbidity and mortality. The aim of this study was to assess the clinical features, risk factors, and outcome of TB after kidney transplantation in a middle-prevalence area.

Method

We performed a retrospective analysis of a cohort of adult KT recipients from 2015 to 2020 at the Annaba University Hospital with follow-up until October 2022.

Results

Among 152 KT recipients evaluated, 8 developed TB, the prevalence was 5.26%. Median time to diagnosis was 28.4 months, with 25% of the cases occurring in the first Two year. Pulmonary TB represented 75% of the cases, including disseminated disease. Two patients received isoniazid prophylaxis for latent TB infection and developed active infection. Median duration of treatment was 12 months. However TB was associated with a significant reduction in patient and graft survival (74% vs. 90.2% in 5 years for patient survival, P=0.001; and 58.6% vs. 80.2% in 5 years for graft survival, P<0.001). Death and graft loss occurred in the first 6 months after diagnosis in one-third of the patients, 38.8% of them with disseminated disease. Disseminated disease was significantly associated with mortality compared to local disease (41.8% vs. 9.7%, P=0.035). It should also be pointed out that Algeria is a country with an intermediate level of tuberculosis endemicity.

Conclusion

TB is the archetype of opportunistic infection in KT, with significant impact on patient and graft survival. Our results emphasize the need for systematic screening for LTBI in all patients awaiting transplant. Treatment challenges in KT recipients with TB, drug interactions, drug toxicities and therapeutical adherence must be considered.
#2292 Incremental peritoneal dialysis: an individualized therapy with better clinical outcomes and reduced environmental and economic impact
Authors: Domingos Diogo , Ávila Gonçalo , Carnevale Andreia , Francisco Diogo , Fernandes Adriana , Calça Rita , Branco Patrícia , Matias Patrícia
Published: May 2024

Background and Aims

Incremental peritoneal dialysis (IPD) is based on the prescription of a dose lower than the standard “full dose” (SPD). The achievement of individualized clearance goals is based on the combination of peritoneal and renal clearance. IPD as the initial PD strategy seems to be a convenient and resource-sparing technique, but its impact in long term outcomes and in the environment lacks evidence.

The aim of this study is to evaluate IPD outcomes and to analyze the potential impact of this initial approach on costs, total and plastic waste, and water consumption.

Method

Single-center observational retrospective study that included a cohort of 87 prevalent PD adults. Patients were assigned in two groups according to their initial PD prescription—IPD group [continuous ambulatory PD (CAPD): less than 4 dwells daily, less than 2L dwell volume, and/or PD less than 7 days/week; automated PD (APD): without a long dwell, less than 10 L delivered, and/or PD for less than 7 days/week] and SPD group. Primary outcomes were residual kidney function preservation, technique survival and mortality. Secondary outcomes were peritonitis rate and hospitalizations. The reductions related to costs, total and plastic waste, and water usage were also compared between groups.

Results

In 57 (65%) of the patients IPD was the initial therapy, while 30 (35%) patients were prescribed SPD. The median follow-up was 23 months and the median transition time from 2 to 3 and from 3 to 4 exchanges were 6 and 14 months in CAPD, respectively. APD patients transitioned to SPD after a median of 9 months.

Patients in IPD group had a higher glomerular filtration rate (7 vs. 3.7, mL/min/1.73 m2, p < 0.001) in the first 6 months, and after 24 months (4.8 vs. 1.9, mL/min/1.73 m2, p = 0.002. IPD was also associated with a longer technique survival (p = 0.026), lower hospital admissions per year (0.23 vs. 0.5, p = 0.001), and lower mortality (1.8% vs. 13.3%, p = 0.027).

Compared to SPD, 2 and 3 exchanges per day led to a reduction in costs of approximately 8500 or 4100 euros/patient-year, total waste of 266 or 143 kg/year/patient, in plastic waste of 159 or 69 kg/year/patient, and water savings of 28,620 or 12,420 L/year/patient, respectively.

In APD, IPD led to a reduction of 4400 euros/ patient-year in cost, 211 kg/year/patient in total and of 139 kg/year/patient in plastic waste, and water savings of 25,020 L/year/patient.

Conclusion

Prescription of initial individualized IPD is associated with better clinical outcomes in patients with substantial RKF. This approach was a significant economic and environmental impact, with a reduction in total and plastic waste, and water consumption.
#2307 Serum NGAL, MMP-9 and suPAR in the assessment of kidney impairment and cardiovascular risk in children and adolescents with type 1 diabetes or obesity
Authors: Kostopoulou Eirini , Kalavrizioti Dimitra , Davoulou Panagiota , Vamvakas Sotirios , Papachristou Evangelos , Spiliotis Bessie , Goumenos Dimitrios , Papasotiriou Marios
Published: May 2024

Background and Aims

Type 1 diabetes mellitus (DM1) and obesity represent two chronic paediatric diseases with worryingly rising incidence, characterized by chronic inflammation, endothelial dysfunction and increased risk for kidney impairment and cardiovascular disease. The aim of this cross-sectional study was to explore the potential usefulness of serum Neutrophil Gelatinase-Associated Lipocalin (NGAL), Matrix Metalloproteinase-9 (MMP-9) and Soluble Urokinase Plasminogen Activator Receptor (suPAR) for predicting early kidney injury or increased cardiovascular risk in children and adolescents with DM1 or obesity.

Method

Serum samples were obtained from children and adolescents aged <18 years old with DM1 (n=35) or obesity (n=38) and normal renal function with no history of albuminuria, as well as from healthy controls (n=23). Serum NGAL, MMP-9 and suPAR concentrations were measured using commercially available sandwich ELISA kits (NGAL: (DY1757-05), MMP-9: (DMP900); suPAR: (DUP00); R&D systems). All patients were evaluated for anthropometric indices (weight, height, BMI) while for different degrees of weight status we used the body mass index (BMI) z-score adjusted for age and sex. Estimated glomerular filtration rate (eGFR) was calculated according to the revised bedside Schwartz formula.

Results

Serum NGAL values were found significantly higher in patients with obesity but not in those with DM1. A positive correlation was found in patients with T1DM with diabetes duration (Spearman rho 0.364, p=0.044), and in all study participants with BMI z-score (Spearman rho 0.401, p=0.004). Furthermore, serum MMP-9 levels were significantly increased in patients with T1DM and in patients with obesity compared to controls. Mean serum suPAR levels were significantly higher in patients with obesity compared to patients with T1DM and controls, while children with T1DM had similar suPAR levels to controls (Table 1). Finally, serum suPAR levels showed a negative correlation with age (Spearman rho −0.359, p<0.001) and creatinine levels (Spearman rho −0.334, p=0.005), and a positive correlation with BMI z-score (Spearman rho 0.354, p=0.009).

Conclusion

Circulating NGAL, MMP-9 levels may prove useful as surrogate biomarkers to creatinine, GFR and albumin excretion rate for early detection of kidney injury, inflammation or endothelial dysfunction and cardiovascular complications in children and adolescents with T1DM or obesity. Children with obesity may have impaired inflammation status, kidney and endothelial function to a higher degree compared to children with T1DM, which may suggest that obesity may impose a greater health burden than T1DM, at least during childhood or the first years after T1DM diagnosis.
#694 Effects of nonsteroidal mineralocorticoid receptor antagonists on kidney of cirrhotic rats
Authors: Huang Hui-Chun , Chuang Chiao-Lin
Published: May 2024

Background and Aims

Aldosterone binds to renal mineralocorticoid receptors (MRs) to regulate fluid and electrolytes homeostasis. In addition, aldosterone can be deleterious as a driver of inflammation and tissue fibrosis in several organs. Thus, blockade of aldosterone represents an important option to mitigate the target-organ damage. Mineralocorticoid receptor antagonists (MRAs) have been widely used as diuretic drugs for the management of hypertension, cirrhosis, and heart failure. However, the use of MRAs is limited by adverse events such as hyperkalemia. More recently, novel nonsteroidal selective MRAs with improved safety profiles have been developed. This nonsteroidal MRA (finerenone) has higher selectivity and stronger affinity for the MR, leading to lower risk of hyperkalemia. Recent evidences showed that finerenone reduces albuminuria, risk of CKD progression, and cardiovascular events in patients with chronic kidney disease and type 2 diabetes with a low incidence of hyperkalemia related treatment discontinuation.

The pathophysiology of cirrhosis is very similar to that of cardiac failure. Decompensated cirrhosis is frequently treated with the MRAs. In addition to fluid management, MRAs showed hepatoprotective actions via reducing oxidative stress and inflammatory responses in CCl4-induced and common bile duct ligation (CBDL)-induced liver injury models. The potential beneficial effects of nonsteroidal MRA on cirrhosis had never been studied. This study aims to explore the renal protective role of nonsteroidal selective MRA and associated mechanisms in common bile duct ligation-related liver injury in rat model.

Method

CBDL was used to create liver injury in the Male Sprague-Dawley Drats. Finerenone (10 mg/kg/day) or vehicle was administered since the 1st day after CBDL. The effects of nonsteroidal selective MRA on kidneys were surveyed in two paralleled series on the 7th day (inflammation) and the 28th day (cirrhosis), respectively. The following parameters were evaluated: (a) hemodynamic parameters; (b) serum potassium, liver and renal function; (c) in-situ kidney perfusion; (d) western analyses of renal cortex and medulla.

Results

Compared with the vehicle-treated group, there was significantly lower renal vascular responsiveness to ET-1 in CBDL rats receiving 28 days of MRA (p<0.05) (Fig. 1B), but not in those receiving 7 days of MRA (Fig. 1A). MRA treatment led to no significant change in mean arterial pressure, portal pressure, serum potassium, liver, and renal function in CBDL rats (Table 1). The expressions of vasoactive mediators, such as iNOS, eNOS, ETA, and ETB in both renal cortex and medulla showed no significant change in CBDL rats following 28 days of MRA treatment (Fig. 2).

Conclusion

MRA treatment led to no significant effects on hemodynamics, liver, and renal function, but lower renal vascular responsiveness to ET-1 in CBDL rats receiving 28 days of MRA. The exact mechanisms remained to be further studied.
#348 Neutrophil membrane-derived nanovesicles deliver IL-37 to repair renal endothelial cells in ischemia‒reperfusion injury
Authors: MA Wenjie , Zhou Changcheng , Wu D I , Long Chengcheng , Liu Jingyu , Jia Ruipeng
Published: May 2024

Background and Aims

Renal ischemia‒reperfusion injury (IRI) is one of the most important causes of acute kidney injury (AKI). Interleukin (IL)-37 is a novel anti-inflammatory factor, but its application is still limited by its low stability and delivery efficiency. In recent years, engineered extracellular vesicles (EVs) have attracted substantial attention as an emerging drug delivery system. The aim of this study was to investigate the reparative effect of neutrophil membranes-derived nanovesicle (N-MV)-delivered IL-37 on renal IRI and its mechanism of action.

Method

The density gradient centrifugation method was used to extract peripheral blood neutrophils from rats, and the differential centrifugation method was used to extract neutrophil membranes. Cell membranes and IL-37 were then extruded with polycarbonate porous membranes with different pore sizes using a mini extruder to prepare IL-37 that was coated with neutrophil membrane (N-MV@IL-37). Subsequently, the physical and chemical properties and in vitro biological functions were identified. The in vivo distribution of N-MV@IL-37 as well as the renal function and inflammatory response in rats were further evaluated in a rat renal IRI model, and the targeting and anti-inflammatory mechanisms of N-MV@IL-37 were further explored.

Results

N-MV@IL-37 not only enhanced the stability of IL-37 but also targeted endothelial cells via P-selectin glycoprotein ligand-1 (PSGL-1) on neutrophil membrane surfaces. In vitro experiments showed that N-MV@IL-37 inhibited endothelial cell apoptosis and inflammatory factor production and promoted endothelial cell viability and angiogenesis. In the rat renal IRI model, N-MV@IL-37 inhibited renal cell apoptosis and alleviated inflammatory responses, thereby improving renal function in IRI rats.

Conclusion

N-MVs provide an effective method of delivering IL-37, thereby alleviating the inflammatory response due to renal IRI and repairing renal endothelial cells; these vesicles could be a potential system for the treatment of renal IRI. Meanwhile, N-MVs also provided a drug delivery platform to provide a new strategy for the treatment of other IRI-like diseases.
#2468 2-Step-Scores with optional histopathology for the prediction of delayed graft function and 1-year transplant loss in Eurotransplant
Authors: Becker Jan Ulrich , Ernst Angela
Published: May 2024

Background and Aims

The decision for acceptance or discard of the increasingly rare and marginal deceased donor kidneys in Eurotransplant (ET) countries has to be made without solid evidence. Thus, we developed and validated flexible clinicopathological scores we call 2-Step Scores for the prognosis of delayed graft function (DGF) as 2-Step-DGF and one-year death-censored transplant loss (1y-tl) as 2-Step-1y, reflecting current practice of six ET countries including Croatia and Belgium.

Method

The training set was n = 620 for DGF and n = 711 for 1y-tl, with validation sets n = 158 and n = 162. In step 1, stepwise logistic regression models including only clinical predictors were used to estimate the risks. In step 2, risk estimates were updated for statistically relevant intermediate risk percentiles with nephropathology.

Results

Step 1 revealed an increased risk of DGF with increased cold ischaemia time, donor and recipient BMI, dialysis vintage, number of HLA-DR mismatches or recipient CMV IgG positivity. On the training and validation set, c-statistics were 0.672 and 0.704, respectively. At a range between 18% and 36%, accuracy of DGF-prognostication improved with nephropathology including number of glomeruli and Banff cv (updated overall c statistics of 0.696 and 0.701, respectively).

Risk of 1y-tl increased in recipients with cold ischaemia time, sum of HLA-A. -B, -DR mismatches and donor age. On training and validation sets, c-statistics were 0.700 and 0.769, respectively. Accuracy of 1y-tl prediction improved (c-statistics = 0.706 and 0.765) with Banff ct. Overall, calibration was good on the training, but moderate on the validation set; discrimination was at least as good as established scores when applied to the validation set. Receiver operating characteristics of both 2-Step-DGF and 2-Step-1y compared to established scores are shown in Figs 1 and 2.

Conclusion

Our flexible 2-Step Scores with optional inclusion of time-consuming and often unavailable nephropathology should yield good results for clinical practice in ET, and may be superior to established scores. Our scores are adaptable to donation after cardiac death and perfusion pumps use.
#2139 Non-lupus full house nephropathy: a debatable entity
Authors: Uzzo Martina , Kronbichler Andreas , Alberici Federico , Bajema Ingeborg
Published: May 2024

Background and Aims

The presence of a full house (FH) pattern at immunofluorescence on kidney biopsy in a patient without clinical and laboratory features of systemic lupus erythematosus (SLE) has led to the descriptive term non-lupus full house nephropathy (NLFHN). This systematic review and meta-analysis focus on NLFHN nomenclature, clinical findings and outcomes.

Method

In a reiterative process, all identified terms for NLFHN and other MeSH terms were searched in PubMed. Out of 344 results, 57 records published between 1982 and 2022 were included in the analysis. Clinical data of single patients from different reports were collected and analysed.

Results

Out of the 57 records, 61% were case reports. NLFHN was addressed with 17 different names; the same name used by different authors could refer to different entities. We identified 148 patients: 75 (51%) were males; median age 35 (23-58) years. Serum creatinine and proteinuria at onset were 1.4 (0.8-2.5)mg/dL and 5.7 (2.7-8.8)g/day. Overall, about half of patients achieved complete response.

A causative agent was identified in 51 (44%) patients, predominantly infections(41%). Secondary NLFHN was mostly non-relapsing with worse kidney function at onset compared to idiopathic NLFHN (P = 0.001). Among the 57 (50%) patients with idiopathic NLFHN, complete response was comparable between patients treated with immunosuppression and supportive therapy; however, proteinuria and creatinine at onset were higher in patients treated with immunosuppression (P = 0.089 and P = 0.066). The remaining 7 (6%) patients developed SLE after a median follow-up of 5.0 (1.9-9.0) years.

Conclusion

The place of NLFHN among glomerular diseases is still uncertain, due to the lack of high-quality evidence and consensus on nomenclature. NLFHN can be evaluated as initial manifestation of SLE, isolated manifestation of SLE or a new disease unrelated to SLE. Data support the classification of SLE and NLFHN as distinct clinical entities, with comparable outcome. However, RCTs are needed to drive strong conclusions on treatments and outcomes.
#2699 Rare glomerular microangiopathy: clinicopathological characteristics and prognosis
Authors: Liu Hanshu , Xia Peng , Wen Yu-Bing , Ye Wei , Ye Wenling , Zhang Lu , Wang Ying , Chen Limeng
Published: May 2024

Background and Aims

Different from the typical histologic changes of thrombotic microangiopathy (TMA), we identified a group of patients whose pathology with glomerular involvement without blood vessel lesions, which was rare and known as glomerular microangiopathy (GMA).

Method

In Peking Union Medical College Hospital, a total of 33 patients were diagnosed as GMA with proliferation and swelling of glomerular endothelial cells, fragmented red blood cells, fibrin or platelet thrombi in the capillary lumen, thickening of the basement membrane, stenosis or occlusion of capillary lumen, but no abnormalities in the endothelium of renal small vessels. The pathology and clinical data were from the medical records and analyzed.

Results

The patients were 66.7% male with a mean of 45 years (14 to 74 years). The primary diseases were Castleman's disease (CD, 30.3%), POEMS syndrome (21.2%), cancer patients receiving agents targeting vascular endothelial growth factor (21.2%), and others. All the patients showed various degrees of proteinuria, with an average 24-hour urinary protein of 2.66 g/d, hematuria (63.6%), and acute kidney injury (AKI, 39.4%). The median serum creatinine (SCr) was 142 (107.5, 169) μmol/L. The AKI patients had lower Alb (P < 0.0001), PLT (P = 0.0192), higher high-sensitivity C-reactive protein (hs-CRP) (P = 0.0199), and reduction of IgA (P = 0.0021). There is no significant difference in SCr and proteinuria among patients with different etiologies. The CD patients exhibited higher hs-CRP and D-Dimer. Treatment included targeting therapy of underlying hematological disorders, glucocorticoid combination with or without immunosuppressant, and supportive treatment. After treatment, we observed proteinuria remission (66.7%), partial improvement (27.3%), or complete recovery (45.5%) of renal function.

Conclusion

In Castleman's disease, POEMS syndrome, and patients receiving agents targeting VEGF, initial attention to GMA might improve the prognosis and shed light on the study of the mechanisms.
#1444 Albuminuria and subsequent risk of kidney events in patients with IgA nephropathy: a nationwide cohort study
Authors: Faucon Anne-Laure , Lundberg Sigrid , Lando Stefania , Wijkström Julia , Segelmark Mårten , Evans Marie , Carrero Juan-Jesus
Published: May 2024

Background and Aims

KDIGO recommends proteinuria <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 <0.3, 0.3-0.5, 0.5-1.0, 1.0-1.5, 1.5-2.0 and >2.0 g/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 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 <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 > 30% eGFR decline. In multivariable analyses, and compared with uACR <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>2g/g. Similar graded relationships were observed for KRT (HR ranging from 1.39 to 4.65), and for >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.
#1342 Updated results from the RUBY-3 study of povetacicept, an enhanced dual BAFF/APRIL antagonist, in autoantibody-associated glomerulonephritis
Authors: Madan Arvind , Park Inwhee , Yalavarthy Rajesh , Mandayam Sreedhar , Kulkarni Hemant , Barratt Jonathan , Davies Rupert , Enstrom Amanda , Thomas Heather , LI Jiahua , Peng Stanford L , Tumlin James
Published: May 2024

Background and Aims

Inhibition of BAFF and/or APRIL has shown promise in IgA nephropathy (IgAN), systemic lupus erythematosus (SLE), lupus nephritis (LN), and primary membranous nephropathy (pMN), and has the potential to exert a disease-modifying effect. Povetacicept (ALPN-303) is an Fc fusion protein of a variant TACI domain engineered for more potent dual BAFF/APRIL inhibition than wild-type TACI or anti-BAFF or anti-APRIL antibodies. In a previous report, povetacicept 80 mg every 4 weeks was initially well tolerated and demonstrated promising, clinically meaningful reductions in urine protein to creatinine ratio (UPCR) and Gd-IgA1 in participants with IgAN (Tumlin J, et al. Poster TH-PO1125 presented at ASN 2023). Updated data are reported here.

Method

RUBY-3 is an open-label, multiple ascending dose, phase 1b/2a study of povetacicept 80 or 240 mg administered subcutaneously once every 4 weeks. Eligible participants are aged ≥18 years with biopsy-confirmed IgAN, LN, or pMN and on maximally tolerated ACE inhibitor/ARB therapy, with well-controlled blood pressure, and disease-specific immunosuppressive therapy where applicable. The primary objective is safety; secondary objectives include pharmacokinetics, pharmacodynamics, immunogenicity, biomarkers, and efficacy.

Results

As of 1 Dec 2023, 12 participants with IgAN have enrolled and received povetacicept 80 mg, with 7 (58%) having received ≥24 weeks of treatment. Povetacicept continues to be well tolerated, with the majority of treatment-emergent adverse events being of low grade. There have been no incidences of severe hypogammaglobulinemia (IgG <3 g/L) or severe infections. Povetacicept 80 mg was associated with a UPCR reduction of 52.6% at 24 weeks (n = 7). Reductions in Gd-IgA1, stable renal function, and pharmacodynamically expected decreases in immunoglobulin levels were also observed. Additional results from the 80 mg cohort with longer duration of follow-up, as well as initial results from the 240 mg dosing cohort, are planned to be presented.

Conclusion

Povetacicept remains well tolerated with multiple dosing and continues to demonstrate very promising activity in IgAN, strongly supporting further study in IgAN as well as other glomerulonephritis and autoantibody-associated diseases.
#123 Impact of atacicept on hematuria in IGA nephropathy: post-hoc analysis of the phase 2b ORIGIN study
Authors: Floege Jürgen , Barratt Jonathan , Maes Bart , Cooper Kerry , Lin Celia , Wei Xuelian , Barbour Sean , Phoon Richard , Kim Sung Gyun , Tesar Vladimir , Jha Vivekanand , Wadhwani Shikha , Lafayette Richard
Published: May 2024

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 >0.75 g/day or UPCR >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 < 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.
#2640 Hyperuricemia in Gitelman syndrome 132 patients
Authors: Lyu Ning , Zhang Lei , Ji Peili , Xu Lubin , Chen Limeng
Published: May 2024

Background and Aims

Thiazide diuretics, the most common prescription for hypertension, were partly restricted by the hyperuricemia induced by the impairment of uric acid clearance serum uric acid. Gitelman syndrome (GS, OMIM263800), caused by mutations of the SLC12A3 gene encodes the thiazide-sensitive human Na–Cl co-transporter (hNCC), might shed light on the precision mechanism of hyperuricemia induced by Thiazide diuretics.

Method

We retrospectively reviewed 132 GS patients and pertinent articles and analyzed their clinical and genetic characteristics with or without hyperuricemia. Our study also employed Illumina Human Asian Screening Array-24 + v1.0 (ASA) gene chips to screen available samples from 87 patients with Gitelman Syndrome, which included a subgroup of 17 individuals exhibiting elevated uric acid levels characteristic of GS.

Results

The average uric acid level of 132 genetic-confirmed GS patients was 351.4 ± 95.1 µmol/l, with 21.2% hyperuricemia (mean 482.1 µmol/l) and 2 cases of gout. The GS patients with hyperuricemia had higher BMI (24.3 ± 3.9 vs. 21.6 ± 3.5 kg/m2, P = 0.001), lower FEUA (4.6 ± 1.0 vs. 7.0 ± 2.7%, P < 0.001), urinary calcium/creatinine (0.05 vs. 0.11 mmol/mmol, P = 0.01), and△FECl (0.6 ± 0.4% vs 1.2 ± 1.1%, P = 0.02) of the HCT test, indicating more severe NCC function injury. Fisher's exact test yielded non-significant associations of the ten uric acid-predicting SNPs between the patients with or without hyperuricemia at the conventional P-value cut-off of 0.05.

Conclusion

The prevalence of hyperuricemia in GS patients exceeds that observed in the general population. GS patients with hyperuricemia might be because of a high body mass index (BMI) and more severe impairment of NCC function, which suggested the crosstalk between NCC and Uric acid transporter.
#2644 Clinical impact of proteinuria and hematuria remission criteria in IgA nephropathy patients defined by the Japanese Society of Nephrology
Authors: Yasuda Yoshinari , Kaihan Ahmad Baseer , Kaihan Ahmad Naseer , Tanaka Akihito , Imaizumi Takahiro , Maeda Kayaho , Kato Noritoshi , Kosugi Tomoki , Maruyama Shoichi
Published: May 2024

Background and Aims

IgA nephropathy (IgAN) is one of the most common glomerulonephritis worldwide, especially in the Pacific Rim and Mediterranean countries. Hematuria is almost inevitable clinical findings and massive proteinuria is well established risk factor in IgAN. However, a few studies reported hematuria and proteinuria remission in IgAN, and their definition varies in clinical studies. The Japanese Society of Nephrology (JSN) defined new criteria for hematuria and proteinuria remission and relapse for IgAN patients. The objective of the present study was to analyze the utility of JSN criteria to predict renal prognosis among IgAN patients after immunosuppressive treatment.

Method

One hundred IgAN patients were recruited between 2003 and 2014 at Nagoya University Hospital and followed up until December 2017. According to JSN criteria, hematuria remission (HR) and proteinuria remission (PR) are defined as < 5 RBC/HPF, and < 0.3 g/g Cr, in three consecutive urine exams over six months of observation, respectively. Clinical remission (CR) is defined as both HR and PR in 3 consecutive urinalysis over six months. HR, PR and CR were analysed with 30% eGFR decline as a renal outcome.

Results

Baseline proteinuria, serum creatinine, and eGFR were 1.3g/day, 0.8 mg/dL, and 80 mL/min/1.73 m2. The mean age was 34.7 ± 12.5 years old, and 61% of the study population was female. Seventy-two percent of patients received intensive methylprednisolone pulse therapy (mPSL), and the incidence of HR, PR and CR were 76, 50 and 46%, 50%, respectively. Kaplan-Meier curves analyses showed a significant difference between HR and non-HR, PR and non-PR, and CR and non-CR groups (Fig.). In univariate analyses, hypertension, eGFR, HR, PR, CR, and T-score in the Oxford classification of IgAN were significantly associated with renal outcome. In multivariate Model-A, HR, and PR were significant factors for renal outcome after adjusting with sex, hypertension, eGFR and T-score. While in multivariate model-B, CR was also significantly associated with renal outcome after adjustment (Table). However, 36% and 46% of patients demonstrated hematuria and proteinuria relapses after remission.

Conclusion

JSN novel criteria for HR and PR predict renal outcomes in IgAN patients. Further studies are required to verify their clinical utility of JSN criteria in a larger sample size with different ethnicities.
#972 A Novel Single Compound from Chinese Herbs as a Potential Candidate for Reducing obesity induced diabetic nephropathy via ATF3-RARRES1 axis pathway
Authors: Wu Yueh-Lin , Chen Hsi-Hsien , Lin Heng
Published: May 2024

Background and Aims

Billions of people have obesity induced diabetic nephropathy. Promoting the browning of white adipose tissue has been suggested as a potential strategy for, but a drug still needs to be identified.

Method

First, WT and ATF3 knockout mice fed a high-fat diet were treated with STZ to determine that ATF3 plays an important role in obesity-induced diabetic nephropathy. Second, DBA mice fed a high-fat diet were infused with STZ, and db/db KO mice were fed a high-fat diet, and the two mouse models were injected intraperitoneally with or without the ATF3 inducer ST32da (the structure is a single drug designed based on the traditional Chinese medicine Salvia miltiorrhiza). After about one and a half months, all related kidneys function values were measured.

Results

After analysis the relationship between ATF3 and diabetic nephropathy in human GEO DataSet Browser indicated that the gene expression of ATF3 was lower in patients groups. Genetic deletion of activating transcription factor 3 (ATF3−/−) in mice under a high-fat diet (HFD) and STZ treatment resulted in more aggravated nephropathy phenomenon syndrome including higher urine albumin, lower creatinine clearance and high risk in death. ST32da, a synthetic ATF3 inducer isolated from Salvia miltiorrhiza, promoted ATF3 expression to downregulate inflammatory genes and ameliorated foot process effacement resulting in reduced diabetic nephropathy by suppressing the podocyte apoptosis via interleukin (IL)-6 and retinoic acid receptor responder protein 1 (RARRES1) axis.

Conclusion

Our study identified the ATF3 inducer ST32da and Salvia miltiorrhiza extraction, may as a promising therapeutic drug for treating diet-induced obesity induced diabetic nephropathy.
#1802 Treatment with potassium binders in central Sweden—an observational study based on the DEMONSTRATE database
Authors: Eriksson Svensson Maria K , Furuland Hans , Larsson Anders , Uhde Milica , Almstedt Matilda , Cars Thomas
Published: May 2024

Background and Aims

Hyperkalemia (HK), defined as a plasma potassium level (> 5.0 mmol/L), is associated with adverse outcomes, including cardiac arrhythmias and mortality. Until recently, HK was managed mainly with sodium polystyrene sulfonate (SPS) (first generation potassium binders) but concerns regarding the safety profile warranted new alternatives. The second-generation potassium binders, patiromer and sodium zirconium cyclosilicate (SZC) were introduced in Sweden in 2018 and 2019 respectively. The aim of this observational study was to understand the current use of new potassium binders, the related potassium values triggering treatment and to describe the clinical characteristics of patients treated with first- and second-generation potassium binders (SPS and patiromer/SZC respectively) in Sweden.

Method

An observational study based on laboratory data from six regions in central Sweden (18% of the Swedish population), linked to national health registry data, comprising information on clinical events and pharmacy drug dispensations. All treatment episodes of potassium binders between 01 July 2005 and 31 December 2022 were selected and restricted to patients with information on potassium values. A new treatment episode was defined as a gap of at least 120 days to the prior pharmacy dispensations of potassium binders. We analyzed potassium values (up to 60 days prior to initiation of potassium binders), demographics, comorbidities and treatments. Results are mainly presented by treatment episodes and strata of; (a) all, (b) first- and (c) second-generation potassium binders.

Results

In total, we identified 13 441 treatment episodes of which 13 218 episodes (n = 7086 individuals), were attributed to first generation potassium binders (throughout the study period) and 223 episodes (n = 151 individuals) to second-generation potassium binders (from 2018-2022) (Table 1). Baseline characteristics are presented by treatment episodes. Baseline potassium value prior to treatment was 5.6 (0.8) mmol/L for first and 5.6 (0.7) for second generation potassium binders. Mean eGFR prior to treatment was 22.3 (16.3) ml/min/1.73 m2 for first and 18.7 (16.0) for second-generation potassium binders. Compared to first generation, second-generation potassium binders were prescribed to patients with more comorbidities (41.7% vs 32.1% for heart failure, 88.3% vs 81.7% for hypertension, and 39.5% vs 28.9% for dialysis) and more frequently from cardiology/internal medicine units (41.7% vs 30.0%). Distribution of potassium levels at baseline is shown in Fig. 1.

Conclusion

Compared to first- generation potassium binder, we observed fewer treatment episodes with second generation potassium binders, of which majority had a more severe comorbidity profile. There was no difference in potassium values prior to treatment between first- and second-generation potassium-binders.
#1672 High level of HDL-C is associated with a higher risk of ESRD and all-cause mortality in patients with DM and CKD
Authors: Zou Yutong , Liu Fang
Published: May 2024

Background and Aims

Previous studies have regarded high-density lipoprotein cholesterol (HDL-C) as ‘good cholesterol’; however, recent research has unveiled a higher incidence of adverse events among individuals with extremely elevated HDL-C levels.

Method

Two cohorts of subjects were analyzed in this study. In the first cohort, a total of 375 participants with DKD who underwent renal-biopsy between January 2008 and September 2020, from West China Hospital T2DM-DKD cohort, were enrolled for the longitudinal observational study. Additionally, 3,262 participants with DM and chronic kidney disease (CKD) from the National Health and Nutrition Examination Survey (NHANES) 1999-2018 were included. Kaplan-Meier curves and Cox proportional hazard models were used to analyze the association between HDL-C concentration and the incidence of end-stage renal disease (ESRD) as well as all-cause mortality.

Results

Patients were divided into three groups based on HDL-C levels. After a median follow-up of 36 months, 44% of the patients developed ESRD in T2DM-DKD cohort. Patients in Group 3 (HDL-C ≥1.55 mmol/L) exhibited a higher risk of ESRD compared to Group 1 (HDL-C <1.03 mmol/L). After adjusting for confounders, Group 3 patients still had a significantly higher risk of ESRD (adjusted HR: 1.68, 95% CI: 1.03, 2.71). Analysis of HDL subfractions revealed that a higher HDL3/HDL2 ratio was associated with a lower risk of ESRD. Furthermore, in the NHANES cohort, higher HDL-C levels were linked to a higher risk of all-cause mortality during a median follow-up of 75 months as the result of the weighted Kaplan-Meier curves (p = 0.02). Notably, in patients with CKD stages 1-2, Group 3 participants had a significantly higher hazard ratio (HR: 1.61, 95% CI: 1.19, 2.19) after adjusting for confounders.

Conclusion

This study challenges the notion of HDL-C as ‘good cholesterol’ in patients with DKD, as higher HDL-C levels were associated with increased risks of ESRD and all-cause mortality. Additionally, the study highlights the potential protective effect of a higher HDL3/HDL2 ratio against ESRD. These findings contribute to reevaluating the role of HDL-C and its subfractions in DKD patients.
#950 Conservative care management in chronic kidney disease: a value for the money?
Authors: Farinha Ana , Barata Pedro
Published: May 2024

Background and Aims

In Portugal, in 2021 the Directorate General of Health proposed the implementation of conservative care management (or kidney palliative care) as an option to handle frail Chronic Kidney Disease (CKD) patients or those who opt not to proceed to Kidney Replacement Therapy Options (KRT). A guideline regulated the clinical framework for this proposal but its socioeconomic evaluation and subsequent reimbursement has not been established. This has become a barrier to its application by public and private providers. This work intends to evaluate the limitations of costs and outcomes analysis in context of end-of-life care in CKD patients and propose indicators to compare cost effectiveness in dialysis and conservative care management.

Method

A narrative review from the literature have been made to evaluate epidemiological, social, individual and economic burden of ESKD and its treatment modalities. A reflection has been made on the benefits of Conservative Care (CC) and the limitations to evaluate cost effectiveness for this option compared to dialysis.

Results

Cost-effectiveness analysis is a method of comparing costs and effects of two or more alternatives in health or social care interventions to an outcome. Conceptual models of cost-effectiveness analysis evaluate outcomes compared to costs. Quality-adjusted life-years (QALYs) is a popular measure of outcome, but its use is problematic in ESKD. Costs of care are mostly elevated at the end of life and the way they are calculated is also debatable (Fig. 1). Some indicators may be used to compare CC and dialysis (Fig. 2).

Conclusion

The health policies should guarantee access to the health care, with quality, effectiveness and safety in the provision of services with efficiency but at the same time to assure financial sustainability and patients’ satisfaction. For some patients CC may embody an option that represents value for the money. To prove this reality, a cost-effectiveness evaluation must be implemented based on pre-specified indicators that override the limitations of this analysis in this specific context.