bluuebunny/crossref_metadata_2025 huggingface dataset:
#5534 HIFS AND BUTS: A NETWORK META-ANALYSIS OF HIF-PH INHIBITORS AND ESAS IN NDD-CKD PATIENTS WITH ANEMIA COMPARING THEIR SAFETY AND EFFICACY
Authors: Warudkar Sandesh , Jain Amit B , Sharma Jay , Dave Nilanj , Chaturvedi Alok
Published: June 2023

Background and Aims

Hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) are a new class of oral medicines for the management of anemia in CKD patients. These agents are found to be efficacious in the management of renal anemia, however safety is still under scrutiny. While, ESAs (Erythropoietin stimulating agents) are available since long with a well-established clinical profile. This network meta-analysis aimed to compare

the safety and efficacy of HIF-PHI vs ESA in CKD patients with anemia not undergoing dialysis.

Method

An electronic database search was carried out in EBM (Evidence Based Medicine) Reviews, Cochrane Library and PubMed from inception to July 2022 for phase III clinical trials comparing six different HIF-PHIs and ESA for treating anemia in non-dialysis-dependent (NDD) CKD patients. The outcomes included the serious adverse events (SAEs) and change in hemoglobin (Hb) levels.

Results

Total 163 records were identified out of which 6 studies involving a total of 6847 patients were eligible for analysis. Compared to ESA, all HIF-PHIs increased risk for SAEs (daprodustat of RR, 1.21[95% CI, 0.825–1.77]; desidustat, 1.38[95% CI, 0.695–2.76]; enarodustat, 1.29[95% CI, 0.568–3.02]; molidustat, 1.02[95% CI, 0.585–1.74]; roxadustat, 1.29[95% CI, 0.674–2.57] and vadadustat, 1.01[95% CI, 0.693–1.47]) although these differences were statistically non-significant. When change in Hb was analyzed, there was no statistically significant difference between the two groups. The mean difference in change in HB with various HIFs as compared to ESA were: daprodustat (MD: 0.0796, 95% CI −0.676–0.838), desidustat (MD: 0.120, 95% CI: −0.626–0.883), enarodustat (MD: -0.600, 95% CI: −1.36–0.157), molidustat (MD: -0.309, 95% CI: −1.07–0.449), roxadustat (MD: -0.0702, 95% CI: −0.831–0.692) and vadadustat (MD: -0.0402, 95% CI: −0.802–0.720).

Conclusion

In terms of safety, HIF PHIs were associated with more SAEs compared to ESA although these differences are not statistically significant. Comparing efficacy, HIF-PHIs and ESA both effectively increase Hb level in NDD-CKD patients without any significant difference. Results of our network meta-analysis suggest the need for larger and long-term studies comparing HIF-PHIs with ESAs to have better understanding of their comparative efficacy and safety profiles.
#5559 BONE SPECIFIC ALKALINE PHOSPHATASE AS A POTENTIAL BIOMARKER OF AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE PROGRESSION
Authors: Jankowska Magdalena , Qureshi Abdul Rashid Tony , Haarhaus Mathias Loberg , Debska-Slizien Alicja , Stenvinkel Peter , Evenepoel Pieter , Lindholm Bengt
Published: June 2023

Background and Aims

Autosomal dominant polycystic kidney disease (ADPKD) is a systemic disease, resulting in a dysfunction of the primary cilium, a sensory organelle ubiquitously present in human cells. Ciliopathies are characterized by disorders of seemingly unrelated organs and functions, which depend on integrity of the primary cilium, among them the skeleton and the kidneys. A distinct bone phenotype has been reported in ADPKD patients in several cohort studies. Findings, however, were heterogenous. Present study aimed to measure bone turnover biomarkers in patients with ADPKD across disease severity measured by eGFR and height-adjusted total kidney volume (HtTKV).

Method

In this cross-sectional study, we included 80 ADPKD patients with different chronic kidney disease (CKD) stages (G1 and G2 (n = 39), and G3 and G4 (n = 41)) with median age 44.0 (33.5-50.5) years, 62.5% men, and BMI 25.1 (23.3-28.7) kg/m2. HtTKV was measured with magnetic resonance imaging. We measured biochemical parameters of mineral metabolism, including bone specific alkaline phosphatase (BALP) and total ALP, calcium (Ca), parathyroid hormone (PTH), and 25(OH) vitamin D (25(OH)D) and bone strength index (BSi) with microindentation, using an OsteoProbe® (Active Life Scientific, USA). Microindentation is minimally invasive technique assessing bone quality. The cortical bone at the mid-shaft of the tibia is penetrated with the indenter to measure bone resistance.

Results

Bone biomarkers expressed as median and interquartile range were as follow: Ca 9.6 (9.3-9.9) mg/dL, BALP 9.0 (7.0-12.5) ug/L, ALP 59.0 (46.0-72.0) U/L, PTH 43.5 (26.6-72.0) pg/mL and 25(OH)D 25.4 (16.6-33.5) ng/mL. Median BSi was 79.1(73.5-82.1) in men and 68.5 (62.1-78.6) in women (lower than the average score in healthy caucasians). Among analyzed bone markers only BALP significantly associated with severity of ADPKD. BALP - but not eGFR - associated with HtTKV and was different across HtTKV tertiles. BALP was also higher in the highest BSi group, but BSi did not associate with HtTKV (Figure 1).

Conclusion

In patients with ADPKD and different stages of CKD, BALP associates with bone strength and kidney volume, suggesting that it may be a sensitive marker of systemic ADPKD manifestations. Further studies should elucidate whether BALP may be a more sensitive marker for ADPKD progression than GFR.
#5566 DIETARY MAGNESIUM SUPPLEMENTATION REDUCES RENAL AND CARDIAC FIBROSIS IN AN EXPERIMENTAL MODEL OF TYPE 4 CARDIORENAL SYNDROME
Authors: Muñoz-Castañeda Juan R , Muñoz Andrés Carmona , Martinez-Moreno Julio Manuel , Obrero Teresa , Lopez-Baltanas Rodrigo , Guerrero Fatima , Romero Ana Torralbo , Membrives Cristina , Ortiz Maria Encarnacion Rodriguez , Haad Cristian Rodelo , Peregrín Cayetana Moyano , de Mier M Victoria Pendon-Ruiz , Rodriguez Mariano
Published: June 2023

Background and Aims

In chronic kidney disease (CKD) patients, high serum phosphate (HP) levels are associated with the development of a cardiorenal renal syndrome type 4 (CRS4). In this syndrome, the heart is damaged by oxidative stress, inflammation, and fibrosis in renal tissue. In this study we have evaluated if dietary Mg supplementation could reduce CRS4.

Method

The in vivo studies were performed in 5/6Nx rats fed a high (0.9%) phosphate diet with high or low dietary content of Mg to evaluate: 1) The effect of dietary Mg supplementation (0.3%) on oxidative stress, inflammation and fibrosis of kidney and heart. 2) The contribution of hypomagnesemia (using a low Mg diet (0,03%) to the progression of CRS4 in Nx rats and normal rats as controls. 3) Whether dietary Mg supplementation (8 weeks) reduces renal and cardiac fibrosis in Nx rats with established CRS4. In vitro, we evaluated the effects of Mg (Mg2Cl) on mesangial and tubular cells and also cardiomyocytes cells expose to TGF-β.

Results

Dietary Mg supplementation (0,3%) improved renal function, decreased oxidative stress, FGF23 levels, hypertension, renal and cardiac fibrosis and recovered renal expression of Klotho. A low Mg diet increased FGF23 and renal fibrosis but a subsequent switch to dietary Mg supplementation did not significantly improve CRS4 parameters although it reduced the values of blood pressure. In HK2 and rat mesangial cells treated with TGFβ (100 ng/ml), high Mg levels (1,4- and 2,8-times basal levels in the medium) reduced the amount of pro-fibrotic proteins such as α-smooth muscle actin, fibronectin, or renin, recovering Klotho expression and decreasing Smad3 phosphorylation.

Conclusion

Dietary Mg supplementation is a useful tool to improve renal function and prevent CRS4, by reduction the progression of renal and cardiac fibrosis.
#5658 TUBULE-SPECIFIC CYCLIN-DEPENDENT KINASE 12 KNOCKDOWN POTENTIATES KIDNEY INJURY THROUGH TRANSCRIPTIONAL ELONGATION DEFECTS
Authors: Zhang Yilin , Wang Bin , Liu Bicheng
Published: June 2023

Background and Aims

Direct tubular injury caused by several medications, especially chemotherapeutic drugs, is a common cause of AKI. Inhibition or loss of cyclin-dependent kinase 12 (CDK12) triggers a transcriptional elongation defect that results in deficiencies in DNA damage repair, producing genomic instability in a variety of cancers. Notably, 10-25% of individuals developed AKI after treatment with a CDK12 inhibitor, and the potential mechanism is not well understood.

Method

Here, we established a cisplatin-induced AKI mouse model with CDK12 knockdown mice and created stable in vitro models with CDK12 knockdown tubular epithelial cells. Cisplatin nephrotoxicity was induced by intraperitoneal injection of cisplatin (20 mg/kg). After 2 days following cisplatin treatment, blood and kidney tissues were harvested. Renal function and histology were evaluated. DDR, tubular apoptosis, cell proliferation were evaluated by immunofluorescence assays, real-time PCR, flow cytometer and western blot analysis. Notably, we performed single-molecule real-time sequencing (SMRT), a long-read sequencing platform, to identify the formation of novel transcripts involved in the above events.

Results

We found that CDK12 was downregulated in the renal tubular epithelial cells in both patients with AKI and murine AKI models. Moreover, tubular cell-specific knockdown of CDK12 in mice enhanced cisplatin-induced AKI through promotion of genome instability, apoptosis, and proliferative inhibition, whereas CDK12 overexpression protected against AKI. Using the single molecule real-time (SMRT) platform on the kidneys of CDK12RTEC+/− mice, we found that CDK12 knockdown targeted Fgf1 and Cast through transcriptional elongation defects, thereby enhancing genome instability and apoptosis.

Conclusion

These data demonstrated that CDK12 knockdown could potentiate the development of AKI by altering the transcriptional elongation defect of the Fgf1 and Cast genes, and more attention should be given to patients treated with CDK12 inhibitors to prevent AKI.
#5665 C3 GLOMERULOPATHY CURRENT THERAPY AND REAL-WORLD MANAGEMENT - INTERIM RESULTS FROM A MULTI-COUNTRY STUDY
Authors: Proudfoot Clare , Pannagl Katharina , Ndife Briana , King Andrea , Murphy Kathleen , Libby Susanna , Lafayette Richard
Published: June 2023

Background and Aims

C3 glomerulopathy (C3G) is a rare form of glomerulonephritis, with an estimated incidence of 1 – 2 per million per year. C3G is associated with a high risk of disease progression with approximately 50% of patients reaching kidney failure within 10 years of diagnosis. No treatments have been proven effective through randomized controlled trials. KDIGO glomerular disease guidelines recommend treating with renin-angiotensin-aldosterone system inhibitors (RAASi) to reduce blood pressure and proteinuria, and, in select patients, utilization of immunosuppressants such as mycophenolate mofetil and corticosteroids. Newer agents, such as eculizumab, are also sometimes used off-label. The aim of this analysis was to better understand the current management of C3G in the US, Europe, and Asia.

Method

An analysis was conducted using interim data from the Adelphi C3G Disease Specific Programme (DSP), a cross-sectional survey of C3G-treating nephrologists in US, EU5 (France, Germany, Italy, Spain, UK), China and Japan (study ongoing since August 2022; interim analysis based on data until November). Nephrologists completed structured forms administered via online links for consecutive patients presenting with C3G. Forms included information on current and most recent therapy.

Results

In this interim analysis, 88 nephrologists had completed records for 277 patients, including 95 in US, 120 in EU5, 39 in China and 23 in Japan. Median patient age at time of the survey was 44, and 60% were male. 80% had C3 glomerulonephritis (C3GN) and 19% had dense deposit disease (DDD). At the time of the survey, 82% out of 277 patients were receiving treatment. The majority (69%) of 228 treated patients were receiving RAASi, 27% were receiving mycophenolate mofetil/ mycophenolate sodium, 48% corticosteroids, and biologics were used in almost a third of patients. At the time of the survey, mean proteinuria was 2.1 g/day, with 60% of patients having proteinuria ≥1 g/day (Table 1).

Conclusion

C3G is a rapidly progressing glomerulonephritis for which there is no approved therapy. Most patients in this real-world study were receiving treatment, with both conventional immunosuppressants and biologics frequently added to RAASi. Despite this, proteinuria remained high, with the majority of patients having proteinuria ≥1 g/day. This highlights the need for novel therapies to actively treat C3G.
#5672 CORTICAL IRON DEPOSITION ASSESSED BY MAGNETIC RESONANCE IMAGE IS ASSOCIATED WITH KIDNEY FIBROSIS
Authors: Couceiro Carlos , Codina Sergi , Sandoval Diego , Oliveras Laia , Puig Isabel , De Lama Eugenia , Sola Anna , Manonelles Anna , Melilli Edoardo , Montero Nuria , Coloma Ana , Favà Alexandre , Maus Mate , Serrano Manuel , Cruzado Josep
Published: June 2023

Background and Aims

Fibrosis is responsible for the loss of kidney function as a result of several insults, such as ischemia-reperfusion injury or hyperfiltration. This process can continue even after cessation of the primary insult, as documented in acute kidney injury to chronic kidney disease. Recently, we discovered that iron accumulation is a hallmark of fibrotic diseases [1]. We found that in mouse models, iron deposition in the kidney accompanies the progression of the disease. Based on these results, we propose that chronic-low grade hemolysis produced in situation like ischemia-reperfusion injury may be one of the drivers of fibrosis through the damage that the filtrated hemolytic iron cause to the kidneys. Early detection of this iron could help the detection of ongoing fibrogenesis and improve the outcomes by prompt intervention. The challenge of this approach is the lack of non-invasive markers of fibrosis. We evaluated if magnetic resonance image (MRI)-based detection of iron levels in the kidney are correlated to fibrosis in biopsies from kidney transplant recipients.

Method

After approval from the Institutional Revision Board, we carried out a transversal study in our center between 2020 and 2021. We evaluated iron deposits through MRI in patients who underwent a kidney biopsy (per protocol or by clinical indication) and its association with histological parameters. MRI was performed at the same period the biopsy was done. Iron deposits were estimated by using the R2* sequence considering the Grassedonio protocol [2].

Results

We collected data from 15 kidney transplant recipients. Mean age was 58.3 years old. Mean time from kidney transplant to the biopsy was 4.3 years and mean eGFR was 44.4 ml/min/1.73 m2.We analyzed by MRI the R2* signal in the kidney cortex, and their level of fibrosis measured on the biopsies (IFTA score, interstitial fibrosis and tubular atrophy). We found that patients with high IFTA score (2 and 3) presented with significantly higher R2* signal (p = 0.005), than patients with low IFTA score (0 and 1). We also found positive and significant correlation between IFTA (0-3) and iron deposits (Spearman correlation index: r = 0.7537, p = 0.0012).

Conclusion

Iron deposits in the kidney are higher in patients with more fibrosis, and its detection through MRI could be considered a non-invasive marker.
#5679 PATIENT OUTCOME IN A SWEDISH SINGLE-CENTRE COHORT OF ANCA-ASSOCIATED VASCULITIS WITH RENAL INVOLVEMENT
Authors: Ostlund Ylva , Saeed Aso , Mihovilovic Karlo
Published: June 2023

Background and Aims

End-stage kidney disease and premature death are common in patients with antineutrophil cytoplasmic antibody (ANCA) -associated vasculitis (AAV) with renal involvement. Poor patient outcome is attributed to multiple factors comprising a delay in diagnosis and treatment, inadequate efficacy of treatments, and complications due to toxic effects of given immunosuppressive therapy. The aim of the present study was to evaluate clinical and prognostic features of a Swedish cohort of patients with renal AAV and to investigate the pattern of immunosuppressive treatment and predictors of renal and patient survival.

Method

Ninety-one patients diagnosed with AAV with renal involvement between 01 March 2002 and 30 October 2018 in a single-centre were included in the present retrospective study.

Results

Among these ninety-one patients, 52 (57%) were diagnosed with PR3-ANCA, and 39 (43%) with MPO-ANCA. Patients with PR3-ANCA and MPO-ANCA were received comparable induction therapy. However, the frequency of PLEX was significantly higher in patients with PR3-ANCA versus MPO-ANCA (44% vs. 21% respectively; P = 0.025). Overall renal survival at 1- and 5-year was 91% and 69% respectively with no significant differences between patients with PR3-ANCA and MPO-ANCA. Overall, 1-year and 5-year patient survival was 92% and 77% respectively. The overall survival time mean was11.5 years and 95% confidence interval (CI) of 9.9 to 13.0 years. Mean survival time in patients with PR3-ANCA was 10.8; 95% CI 8.8 to 12.7 years versus 11.7; 95% CI 9.6 to 13.8 years in those with PR3-ANCA. Cox regression analysis showed that advancing age significantly predicted higher mortality risk, whereas MPO-ANCA subtype significantly predicted lower mortality risk (Figure 1). Infection (25%), malignancy (22%), and cardiovascular events (16%) were the major causes of death in the present cohort. In a subgroup of thirty-two patients with eGFR <15 ml/min per 1.73 m2 or undergoing dialysis at time of diagnosis. Twenty-three patients (72%) were treated with PLEX, whereas 9 patients (28%) did not receive PLEX as a part of remission induction therapy. Treatment with PLEX had no effects on overall 1-year patient and renal survival

Conclusion

In this cohort of patients with AAV with renal involvement the overall 1-year renal and patient survival were high. Advancing age significantly predicted higher mortality risk, while MPO-ANCA subtype significantly predicted lower mortality risk. Treatment with PLEX had no effects on 1-year patient and renal survival in a subgroup of patients with severe renal involvement with AAV.
#5743 ALTERNATIVES TO DAYTIME IN-CENTER HEMODIALYSIS AND EMPLOYMENT AMONG PATIENTS WITH KIDNEY FAILURE
Authors: Perez Jose , Niu Jingbo , Winkelmayer Wolfgang , Cavanaugh Kerri , Pappadis Monique , Erickson Kevin
Published: June 2023

Background and Aims

Maintaining employment is a priority for many patients with kidney failure. In addition to its economic benefits, employment is associated with physical and psychological wellbeing. Yet, only 30-35% of working aged patients with advanced chronic kidney disease in the United States (US) report employment prior to starting dialysis and many patients stop working at the onset of kidney failure. While access to a dialysis treatment schedule outside of working hours may help patients to remain employed, the effects of alternative dialysis options on employment after starting dialysis are not well understood.

Method

We analyzed data from the US National Dialysis Registry to determine whether access to nearby facilities offering evening dialysis shifts and home dialysis increases the likelihood that patients are able to continue working after they start dialysis. Our cross-sectional analysis included working-aged patients (ages 18-54) receiving dialysis in US facilities in 2016. We combined information reported at the levels of individual patients and dialysis facilities. In a negative binomial regression model, we examined the associations among exposures of interest (the presence of facilities offering home dialysis and/or evening dialysis shifts in a patient's locality) and the number of employed working-aged adults at each dialysis facility. The multivariable regression model adjusted for observed patient, dialysis facility, and geographic characteristics, including patient health and demographic characteristics, information about individual patient employment at the onset of dialysis, local unemployment rates, and the number of working-aged patients at a given dialysis facility.

Results

We identified 4,860 US dialysis facilities with information about patient employment in 2016. Median employment among working-aged adults at these facilities was 17.9% (interquartile range 8.8% to 28.6%). In multivariable, fully adjusted, regression models, the presence of at least one facility offering an evening dialysis shift in a county was associated with a 5% increase in the relative rate of maintaining employment among all working-aged patients receiving dialysis in the county (risk ratio (rr) 1.05; 95% Confidence Interval (CI) 1.01 to 1.09; p = 0.02). The presence of at least one facility offering home dialysis in a county was associated with a 26% increase in the relative rate of maintaining employment (RR 1.26; 95% CI 1.18 to 1.34; p<0.001). The likelihood of employment did not increase with additional facilities in a county offering home dialysis.

Conclusion

Access to dialysis schedules outside of regular working hours – evening dialysis shifts and home dialysis – is associated with increased employment among patients with kidney failure. Efforts to increase access to these alternative dialysis treatments could help patients to continue working.
#5769 MEASURING PROTEINURIA AT 12 MONTHS IN LUPUS NEPHRITIS: A USEFUL TOOL?
Authors: Braga Beatriz Gil , Cunha Ana , Sousa Sofia , Ventura Sofia , Correia Sofia , Campos Andreia , Santos Josefina
Published: June 2023

Background and Aims

Lupus nephritis is a well know manifestation of systemic lupus erythematosus (SLE) and it can progress to end stage kidney disease (ESKD) in 10-30% of patients [1]. Several studies have been conducted to find out whether proteinuria detected earlier in the course of lupus nephritis is associated with worse kidney related outcomes, such as progression to chronic kidney disease [2].

Method

We retrospectively reviewed a cohort of 67 patients referenced to our center with the diagnosis of lupus nephritis until 2019. We evaluated proteinuria (g/g) in a random urine sample measured 12 months after diagnosis and beginning of treatment of lupus nephritis and divided patients into two groups: those with proteinuria less than or equal to 0.3 g/g– group 1(n = 11; 35%) and those with proteinuria superior to 0.3 g/g– group 2 (n = 20; 65%) that had measures of our variables of interest. These groups were compared regarding a continuous variable: serum creatinine measured in the 7th year of follow up, as evaluated in previous studies [3]. We compared the median of serum creatinine values between group 1 and group 2 using Mann-Whitney test, due to the absence of normal distribution of serum creatinine. We also compared the median of serum creatinine in the 7th year to proteinuria measured at 3 and 6 months.

Results

Mean follow up was 13.36 ± 7.8 years and 81.7% (n = 57) were women, with a median age of 33.0 ±12.85 years. A total of 8 patients (11.9%) progressed to ESKD defined by the need for renal replacement therapy or being submitted to renal transplantation. Only 1 patient died due to a nosocomial infection. We had a sample of 31 patients, 26 women and 5 men (p = 0.591) (missing n = 36). Baseline median serum creatinine in group 1 was 0,95 mg/dl and in group 2 was 0.78 mg/dl (p = 0.086). We obtained a median serum creatinine of 0.69 mg/dl (Interquartile range (IQR): 0.61-0.87) in group 1 versus0.92 mg/dl (IQR: 0.66-1.25) in group 2 (p = 0.04). Medians of serum creatinine in the 7th year regarding proteinuria measured at 3 and 6 months were not significantly different (p>0.05).

Conclusion

In our cohort, the group with a higher persistent proteinuria (> 0.3 g/g), one year after lupus nephritis diagnosis, had a significantly higher serum creatinine (7 years after diagnosis). Although previous studies have shown that reducing proteinuria to less than 0.5–0.8g/d 3 by 1 year of treatment predicts good long-term kidney outcomes, our particular data suggest that further reducing to less than 0.3 g/g may provide additional benefit in the long run [2], even though, due to our reduced sample, more investigation is required. From the above mentioned, one may consider 12 months proteinuria as a potential predictor to long-term renal outcomes with lupus nephritis. More studies are necessary to validate this hypothesis.
#5943 THE VALUE OF THE HISTOLOGICAL CLASSIFICATIONS OF ANCA ASSOCIATED VASCULITIS IN PREDICTING LONG TERM KIDNEY SURVIVAL
Authors: Stella Matteo , Locatelli Laura , Sala Filippo Maria , Calatroni Marta , Reggiani Francesco , Moroni Gabriella Luisa , Sinico Renato Alberto
Published: June 2023

Background and Aims

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) are a group of multisystemic autoimmune diseases characterized by necrotizing inflammation of small vessels, with a predilection for the kidney. The prognostic value of histological classification of ANCA-glomerulonephritis (ANCA-GN) is discussed. In 2010, Berden and colleagues proposed a prognostic classification based on glomerular involvement; in 2018, Brix et al. introduced the ANCA Renal Risk Score, which includes histological features and glomerular filtration rate; in 2017 the Mayo Clinic Chronicity Score, that considers chronic histological lesions, was designed and assessed in ANCA-GN. We aimed to identify which score is the best tool to predict end-stage kidney disease or death in a cohort of ANCA-GN patients.

Method

Patients who underwent kidney biopsy in two Italian centers within 32 years were retrospectively collected. Inclusion criteria: age >18 years, and at least one year of follow-up. A minimum of 10 glomeruli was considered adequate for a biopsy. Renal biopsies were classified according to Berden's classification, Renal Risk Score and Mayo Clinic Chronicity Score. The primary end point of the study was the development of end-stage kidney disease (ESKD) at 5 years, defined as the chronic need of renal replacement therapy (RRT) or glomerular filtration rate (GFR) <15 ml/min. The secondary endpoint was a composite endpoint of ESKD or death for all causes.

Results

Of the 152 patients 84 were male, the median age was 63.8 years (Figure 1). Mean eGFR at diagnosis was 21.32 ml/min/1.73 m2. 32.2% of patients were PR-3 positive, 50.6% were MPO positive, 17.2% were ANCA-negative. After a mean follow-up of 71.7 ± 66.7 months, 59 patients (38.8%) were on chronic dialysis or with a GFR <15 ml/min; among them, 20 patients died. The pure kidney survival rate (without ESKD or GFR<15 ml/min) was 79% at 1 year, 65% at 5 years, 59.8% at 10 years. Figure 2 reported the pure kidney survival rates of the patients assigned to every class of the three scores that we considered in this study. Fig. 3, Fig. 4, Fig. 5 show Kaplan-Meyer curves for the secondary outcome (ESKD+death); patients are classified according to the Berden's score (Fig. 2), the Renal Risk Score (Fig. 3) and Mayo Clinic Chronicity Score (Fig. 4).

Conclusion

Berden histopathological classification and Renal Risk Score are predictive of renal prognosis when we consider the primary outcome (ESKD or eGFR<15 ml/min) and when we consider the composite outcome (ESKD + death). The Mayo Clinic Chronicity Score allows a reliable stratification of the patients only when we consider the composite outcome (ESKD and death).
#6019 DEVELOPMENT, APPLICATION, AND VALIDATION OF A HISTOLOGICAL CLASSIFICATION AUTOMATION SYSTEM FOR KIDNEY ALLOGRAFT PRECISION DIAGNOSTICS
Authors: Yoo Daniel , Goutaudier Valentin , Divard Gillian , Gueguen Juliette , Aubert Olivier , Raynaud Marc , Demir Zeynep , Hogan Julien , Investigators Ktd-Innov , Investigators Eu-Train , Haas Mark , Lefaucheur Carmen , Rabant Marion , Loupy Alexandre
Published: June 2023

Background and Aims

The Banff histological classification is the gold standard for allograft rejection diagnostics but has become considerably more complex over the past three decades, leading to misclassifications. We aimed to develop an automated rejection classification system and demonstrate its ability to improve rejection diagnoses.

Method

We built a consortium consisting of pathologists, physicians, and developers to translate all Banff classification rules until the latest version published in 2019 into an algorithm, further embedded in an application which automatically assigns diagnoses. We then tested the Banff Automation System's ability to reclassify rejection diagnoses on 4,409 kidney transplant biopsies from 3,054 adult and pediatric patients, from multicenter cohorts and clinical trials, totaling 20 transplant referral centers in Europe and North America. The impact of diagnostic reclassifications on graft survival was evaluated.

Results

We devised a system that generates automatic reports with diagnoses and a decision tree. In the adult kidney transplant biopsies, the Banff Automation System reclassified 83 of 279 (29.75%) antibody-mediated rejection (AMR) cases and 57 of 105 (54.29%) T-cell mediated rejection (TCMR) cases, while 237 of 3,239 (7.32%) biopsies with non-rejection-related diagnoses were reclassified as rejection. The rejection reclassification rates were 8 of 26 (30.77%) and 12 of 39 (30.77%) for AMR and TCMR, respectively, in the pediatric cohort. Finally, we found that the non-rejection diagnoses according to the pathologists which were reclassified as rejections by the Banff Automation System had similar outcomes as those of confirmed rejection cases.

Conclusion

We built the first comprehensive Banff Automation System and confirmed its ability to reclassify rejection diagnoses. This decision support system might help for training and standardizing diagnoses in routine care and clinical trials.
#6171 SEROPREVALENCE OF COVID-19 INFECTION BASED ON IGG ANTIBODY AGAINST NUCLEOCAPSID PROTEIN (NP) AND SPIKE PROTEIN (S) IN HEMODIALYSIS PATIENTS
Authors: Bhoumik Sukhinath , Iqbal Masud , Morshed Raquib , Alam Sohrab , Waheed Shahryar , Alam Kazi Shahnoor , Islam MD Nazrul , Banerjee Sajal Krishna , Hassan Ms , Arslan MI
Published: June 2023

Background and Aims

Maintenance hemodialysis (MHD) patients have been identified as a high-risk group for COVID-19 infection. Serological testing can be used to monitor disease prevalence & evaluate screening measures & protocols aiming at limiting transmission within dialysis units. This study was conducted to observe the sero prevalence of COVID-19 infection among maintenance hemodialysis patients.

Method

The study was conducted during the 3rd wave of covid-19 infection. Total 194 in-center MHD patients were included from three dialysis centers. Relevant history regarding covid-19 symptom, testing, managements and vaccination were collected. During our study a serum sample was collected to test IgG antibody against nucleocapsid protein (NP) (cut-off positive when >1.5) and spike protein (S) (cut-off positive when >50 AIU/L) of COVID-19 infection and tested by Chemiluminescent microparticle immunoassay (CMIA) method developed by Abbott (FDA-EUA approved).

Results

Mean age of the MHD subjects was 48±12 years where male was 60%. Duration of MHD was 31±22 (6-120) months. Renal pathology was DN in 31%, possible GN 31%,HTN 19% and rest from others .From records past covid infection was clinically diagnosed in 39% of which 10% based on RT-PCR and another 29% fell into suspected category (i.e. symptom with/or suggestive serology). Presentation pattern was mild in 75%, moderate 15% (requiring oxygen), severe in 5% (requiring hospitalization) and asymptomatic rest 5%. Vaccine against covid-19 was availed by 38%. In vaccinated vs. non-vaccinated patients the IgG for NP was positive in 63% vs. 561%(P = 0.65) and IgG for S in 99% vs. 98%(P = 0.56). These indicate naturally acquired immunity in most before any vaccination. The IgG titer against spike (S) protein between vaccinated and non-vaccinated groups was 7743±8920 and 5386± 6839 AIU/L (p = 0.06). The correlation study showed that IgG titer against S has no correlation with dialysis duration, age, BMI, Hb%, serum albumin or Kt/V. Similarly IgG titer against NP shows mostly no significant correlation with laboratory parameters.

Conclusion

These data demonstrate that seroprevalence in hemodialysis population based on antibody against nucleocapsid protein shows only half infected by SARS-CoV-2 where as antibody against spike protein indicates larger number of patients are naturally infected even before vaccinated. Therefore for seroprevalence studies both antibody testing should be used to identify greater population infected until more sensitive tools are established.
#6379 EFFECTS OF SODIUM-GLUCOSE CO-TRANSPORTER 2 INHIBITORS ON CARDIOVASCULAR MORTALITY INCHRONIC KIDNEY DISEASE: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Alexandrou Maria Eleni , Pella Eva , Tsitouridis Alexandros , Theodorakopoulou Marieta , Sampani Erasmia , Georgiou Areti , Kamperidis Vasileios , Papagianni Aikaterini , Sarafidis Pantelis
Published: June 2023

Background and Aims

In studies of patients with chronic kidney disease (CKD), recommended nephroprotective therapy with ACE-inhibitors or ARBs has not been shown to reduce cardiovascular (CV) events or mortality. Sodium-glucose co-transporter 2 (SGLT-2) inhibitors reduce cardiovascular events and death in patients with diabetes and established CV disease; evidence from studies in populations with CKD has been inconsistent. The aim of this meta-analysis was to evaluate the effect of SGLT-2 inhibitors on cardiovascular (CV) mortality in patients with CKD.

Method

Studies were identified by search in major electronic databases (PubMed/MEDLINE, Scopus, Cochrane Library and Web of Science) (PROSPERO ID: CRD42022382863). We included randomized controlled trials assessing the effect of SGLT-2 inhibitors on the primary outcome, time to cardiovascular death, in patients with CKD at baseline. Secondary outcomes included all-cause mortality and major adverse cardiac events (MACE).

Results

Eleven studies with 83,203 participants with CKD were eligible for inclusion in the meta-analysis. Treatmentwith SGLT-2 inhibitors, compared to placebo, reduced the risk of CV death by 14% (hazard ratio [HR] 0.86;95%CI 0.79-0.94), of all-cause death by 15% (HR 0.85; 95%CI 0.79-0.91) and of MACE by 13% (HR 0.87; 95%CI0.81-0.93). A consistent treatment effect on the primary outcome was observed with all SGLT-2 inhibitors(canagliflozin: HR 0.84; 95%CI 0.69-1.02, dapagliflozin: HR 0.89; 95%CI 0.78-1.01, empagliflozin: HR 0.82;95%CI 0.69-0.97 sotagliflozin: HR 0.90; 95%CI 0.73-1.12) studied (p-subgroup-differences = 0.85). Sensitivity analysis pooling data from studies including only diabetic patients with CKD yielded similar results (HR 0.86;95%CI 0.77-0.97).

Conclusion

Treatment with SGLT-2 inhibitors led to a significant reduction in the risk for CV and all-cause mortality in CKD patients. These findings support the use of these agents also for protection against cardiovascular events and death in CKD.
#6424 DIAGNOSTIC ACCURACY OF BONE TURNOVER MARKERS IN PATIENTS WITH VARIOUS DEGREES OF KIDNEY DYSFUNCTION AND PRIMARY OSTEOPOROSIS
Authors: Abdalbary Mohamed
Published: June 2023

Background and Aims

There are limited data available on the validity of bone turnover markers (BTMs) to predict bone turnover in patients with kidney dysfunction and primary osteoporosis.

Method

This is a cross-sectional retrospective study of patients with primary osteoporosis and eGFR<90 ml/min/1.73 m2 who had bone biopsy for clinical purposes for a time period of 8 years. CKD-EPI equation 2021 was used to calculate eGFR based on the mean serum creatinine readings. Bone biopsy samples were evaluated qualitatively using KDIGO TMV classification.

Routine laboratory data were collected in addition to alkaline phosphatase, iPTH, cyclase activating (CAP) PTH, osteocalcin, bone specific alkaline phosphatase (BSAP), and N-telopeptide collagen (NTX).

Results

Study included 156 patients with mean age of 64.7 years. The majority of patients were females (93.6%). The mean BMI was 26.2 kg/m2. The mean eGFR was 70 ml/min with 78% of patients had eGFR from 60-90 ml/min/1.73 m2. CKD stage III was found in 19%, and 3% of patients had CKD stage IV. HTN was found in 47%, history of kidney stones in 9%, and fragility fractures in 77%. Bisphosphonates were the most used pre-biopsy bone specific medication (66%). Teriparatide was used in 10.9% and SERM was used in 7.7% of patients, while 31.4% of patients did not receive any bone anti-resorptive or anabolic medication “treatment naiive”. Bone cortical thickness and cancellous volume were low in 94.2%, while high bone turnover (HBT) was found in 42.9% and low bone turnover (LBT) in 57.1%. Mineralization was defective only in 9.6%, while osteoid thickness was increased in 5.8%. Figure 1 shows the distribution of bone turnover among study group. Baseline characteristics and routine laboratory data were not different between HBT and LBT. PTH, especially PTH CAP, and alkaline phosphatase tended to be higher in HBT but did not reach statistical significance. While BTMs (osteocalcin, BSAP and NTX) were significantly higher in HBT (Table 1). Using ROC curve analysis, the area under the curve (AUC) for BSAP, NTX and osteocalcin were 0.605, 0.660, 0.642, respectively. Combining the NTX with either BSAP or osteocalcin did not result in increasing the AUC. This was also the same when the three of them were combined. BTMs were able to discriminate bone turnover status only among patients with eGFR≥60 ml/min/1.73 m2 (Table 2).

Conclusion

Low bone turnover was found in 43% in treatment naïve patients with primary osteoporosis, with a higher prevalence among patients with eGFR≥60. In the study group, PTH and total alkaline phosphatase were not able to discriminate LBT from HBT, while BTMs showed a modest ability to discriminate the turnover status only among patients with eGFR≥60.
#6428 PERCUTANEOUS RENAL BIOPSY (PRB) IN METASTATIC RENAL CELL CARCINOMA (MRCC) PATIENTS WITH ACUTE KIDNEY INJURY (AKI) ON SYSTEMIC ANTICANCER THERAPY
Authors: Milanez Tomaž , Arnol Miha , Premru Vladimir , Kojc Nika , Ocvirk Janja , Ovcaricek Tanja , Jaimes Edgar
Published: June 2023

Background and Aims

PRB is relatively contraindicated in patients with solitary kidney (SK) due to the perception that PRB is a risky procedure in this patient population. There are however situations in which a renal biopsy is essential to assess renal toxicity of systemic therapy and/or to identify the underlying kidney disease in the remaining kidney. Data on pathological findings of the kidney disease in mRCC patients receiving systemic anticancer therapy is scarce and it may influence the cancer treatment plan. The main aim of this study was to characterize the pathological findings of PRB in patients with SK undergoing systemic therapy.

Method

We retrospectively analyzed the pathological findings of mRCC patients with AKI who underwent PRB during systemic treatment with antiangiogenic tyrosine kinase inhibitors (TKIs) and/or immune check point inhibitors (ICIs) at the Institute of Oncology Ljubljana between 2018 and 2022. All biopsies were performed under ultrasound guidance by the treating nephrologist in patients with clinical evidence of AKI and no other formal contraindications for PRB.

Results

A total of 11 PRBs were performed in 10 patients, eight of whom had SK (Table 1). Six patients were treated with TKIs and ICIs, three with ICIs and one with a TKI alone. None of the patients had major bleeding or required any additional intervention as a consequence of the PRB. Histology revealed thrombotic microangiopathy (TMA) in three, diabetic nephropathy in three, acute interstitial nephritis in two and focal segmental glomerulosclerosis in three patients. Based on pathological findings, the therapy was discontinued after seven PRBs. One patient with TMA showed progressive loss of renal function (RF) after discontinuation of antiangiogenic therapy while the other two had either stable or improved RF.

Conclusion

Our results indicate that PRB is a safe procedure in patients with SK undergoing systemic treatment for mRCC. The pathological findings in our patients guided the decision either to continue or to discontinue the treatment, which resulted in improvement or stabilization of RF in the vast majority of patients. This study suggests that in patients with SK, PRB can provide important information, which may have a significant impact on the oncological and the nephrological therapeutic approaches.
#6545 URINARY FETUIN-A FRAGMENT EXCRETION IN PATIENTS WITH TYPE 2 DIABETES AND ITS CORRELATION WITH RENAL FUNCTION
Authors: Bandi Varun Kumar , Narilla Naga Sai Sri Harsha , Chaganti Sindhu , Yarlagadda Sirisha , Eadala Suresh
Published: June 2023

Background and Aims

Fetuin-A is associated with production of pro-inflammatory cytokines, which can lead to progression of vascular complications in patients with diabetes. We planned a study to evaluate the correlation of urinary excretion of post translationally modified fetuin-A fragment (PTM Fetuin A) with albuminuria and chronic kidney disease.

Method

We conducted a cross-sectional study between July to August 2022 in patients with type 2 diabetes. The baseline characteristics such as Age, Gender, history of Diabetes Mellitus, Hypertension, Cardiac disease, and CKD were obtained. The subject's blood pressure, Haemoglobin, Random blood sugar, Creatinine, was obtained, and eGFR (Glomerular Filtration Rate) was calculated using the CKD-EPI equation. The spot urine was tested for urine albumin to creatinine ratio (UACR) and PTM-Fetuin-A: Creatinine ratio (FCR). PTM-Fetuin A was measured by an ELISA using DNlite-IVD103 ELISA test kit, Bio Preventive Medicine Corp, Taiwan.

Results

A total of 68 subjects were included, with 37 being men (54.4%). The mean age, eGFR, UACR, and FCR were 55 ± 11.4 years, 61.9 ± 37.5 ml/min/1.73 m2, 1060.7 ± 1550 mg/g, and 522.2 ± 915.1 ng/g respectively. There was significant positive correlation between FCR and UACR (p<0.005), serum creatinine (p<0.005), and eGFR (p<0.001). There was a trend noted of increasing PTM-Fetuin A levels and UACR with worsening eGFR. The AUROC for UACR and FCR for predicting patients with CKD stage 3 onwards were 0.703 and 0.789 respectively (Figure 1). In our study, the significance of predicting CKD stage 3 onwards with a UACR cut-off of 300 mg/g, UACR cut-off of 1150 mg/g and a FCR cut-off of 123 ng/g were p = 0.008, p = 0.003, and p<0.0001 respectively.

Conclusion

PTM-Fetuin A is significantly associated with worsening renal function. It has very significant correlation with the albuminuria, and at a FCR cut-off of 123 ng/g, it could significantly differentiate CKD stages, compared to UACR. Further prospective studies are needed to evaluate the correlation between PTM-Fetuin A levels and rate of progression of nephropathy.
#6576 SERUM INTERLEUKIN-6 LEVELS AS A PREDICTOR OF ALL-CAUSE MORTALITY IN MAINTENANCE HEMODIALYSIS PATIENTS WITH COVID-19-OMICRON INFECTION: AN OBSERVATIONAL STUDY
Authors: Song Qirong , Luo Yuxin , Fu Sha , Wang Xiaohong , Tang Ying , Chen Junzhe , Liu Aiqun
Published: June 2023

Background and Aims

Interleukin-6 (IL-6) is a key mediators of inflammation and has been linked to the severity and mortality of COVID-19-Omicron in the general population. With higher mortality rates observed in maintenance hemodialysis (MHD) patients infected with COVID-19-Omicron, the study aimed to examine the correlation between IL-6 levels and mortality in this patient population and to indentify the optimal IL-6 level for predicting the risk of death.

Method

The retrospective observational study was conducted in MHD patients diagnosed with COVID-19-Omicron infection between December 01, 2022 and January 31, 2023 at the Third Affiliated Hospital of Southern Medical University during the first wave of infection in COVID-19-Omicron outbreak in China. Clinical and biochemical data were collected during the infection, IL-6 levels of the patients were measured before consecutive dialysis sessions by a commercial kit. The Cox model was used to investigate the risk factors of mortality, meanwhile, ROC curve to determine the cut off value of IL-6 levels on mortality.

Results

A total of 162 MHD patients infected with COVID-19-Omicron were included in this study. During a median follow-up period of 40 days, 10 (6.2%) deaths occurred due to COVID-19 infection. IL-6 levels were significantly higher in patients who died. Univariate Cox regression analyses showed that the risk factors associated with death included IL-6 levels (HR: 1.009; p<0.001), C-reactive protein (HR: 1.01; p = 0.016), serum potassium (HR: 2.258; p = 0.015, procalcitonin(PCT) (HR: 1.01; p = 0.048), and the Charlson comornidity index(CCI)(HR: 1.34; p = 0.002). However, in multivariate analysis, only IL-6 levels was independently associated with all-cause mortality(HR: 1.01; p = 0.001).The ROC curve and Kaplan-Meier survival analysis revealed a significantly worse survival risk among MHD patients with higher serum IL-6 levels (≥104.87 pg/mL) (sensitivity:100%; specificity:78.2%; AUC: 0.92; p = 0.001).

Conclusion

Serum IL-6 levels greater than 104.87 pg/mL were associated with an increased risk of all-cause mortality in MHD patients infected with COVID-19-Omicron. Hemoperfusion or hemofiltration to remove IL-6 may provide appropriate treatment options for hemodialysis patients with COVID-19-Omicron.
#6608 CHARACTERIZING THE RESIDUAL VOLUME IN PERITONEAL DIALYSIS PATIENTS
Authors: Lindholm Elin , Oberg Carl , Bergling Karin
Published: June 2023

Background and Aims

Peritoneal dialysis (PD) is the most common home dialysis treatment, and is associated with lower societal costs and increased patient autonomy. During routine PD, the exact amount of fluid inside the peritoneal cavity is in general unknown, and the peritoneal catheter may also change position, which may lead to a large residual volume, inefficient dialysis, and potentially harmful overfill. A practical, clinical method to estimate the residual volume is from the dilution of a marker molecule before and after fill of a known volume of fresh dialysis fluid. However, ultrafiltration and transport of the marker molecule during the fill phase may introduce large errors, especially when low molecular weight marker molecules are utilized.

Method

Here we performed a retrospective analysis of clinical data consisting of 56 residual volume estimations utilizing either 1.5% glucose (n = 28) or 4.25% glucose fluid (n = 28). Residual volumes were estimated using creatinine, urea and albumin. The contribution of ultrafiltration and mass transport of the marker molecules were quantified using the Three-pore model.

Results

During the fill phase, the median ultrafiltration volume was 16 mL (IQR 3 to 31) in 1.5% glucose dwells, compared to 52 mL (IQR 38 to 66) during 4.25% glucose dwells (Fig. 1). Assuming that 40% of the ultrafiltration occurs as free-water transport, the median difference between Three-pore model and albumin dilution equation residual volumes were only -1 mL (-8 to 5.5) in 1.5% glucose dwells and 1 mL (-3 to 6) in 4.25% glucose dwells (Fig. 2A). Dilution-based calculations using creatinine overestimated residual volumes by 121 mL (IQR 103 to 149) during fill of 1.5% glucose fluid and 255 mL (IQR 208 to 323) during 4.25% glucose fluid fill (Figure 2B). Overestimation of a similar magnitude was observed in urea calculated residual volumes (Figure 2B). Comparison of intraperitoneal creatinine and urea mass before and after fill revealed a median creatinine mass increase of 37% (creatinine) and 48% (urea) during the fill phase.

Conclusion

This analysis highlights the inherent limitations of residual volume estimations using low molecular weight marker molecules, as both ultrafiltration and dilution marker mass transfer influence results. Since mass transfer rates correlate with molecular size, albumin-based dilution equation residual volumes conformed closely with three-pore model residual volumes, while creatinine and urea, which are subject to mass transfer to a greater extent, overestimated residual volumes. Albumin is superior to both creatinine and urea, but the latter markers may provide reasonable residual volume estimates, especially if the purpose is to exclude a large residual volume.