Mean eGFR Research Articles

#2725 Chronic kidney disease is a risk factor for hyperchloremic metabolic acidosis after plasma exchange

Abstract Background and Aims Observational studies have demonstrated that metabolic acidosis due to hyperchloremia is an often encountered metabolic disorder following plasma exchange (PE) with an albumin-saline solution. Because of the reduced capacity for acid and chloride excretion, we hypothesized that patients with chronic kidney disease have the highest risk for hyperchloremic metabolic acidosis, in particular when multiple PE sessions are performed in a limited period. Method We prospectively collected data from all patients who received PE at Amsterdam UMC, between February 2023, and January 2024. We collected data on demographics, exchanged plasma volume, replacement fluids, and collected blood for analysis of sodium, chloride and bicarbonate before and after plasma exchange. We selected patients who received ≥5 plasma exchanges in an intensive cycle (≥4.2 sessions/week). We excluded patients who received Omniplasma, intravenous sodium bicarbonate or dialysis during the PE period. We assessed the effect of PE and kidney function on plasma bicarbonate and chloride concentration throughout the PE period with repeated measures mixed ANOVA, corrected for baseline plasma bicarbonate concentration, volume of exchanged plasma and PE intensity. Results Data from 26 patients, corresponding to 130 plasma exchanges, were included in the analysis. The mean age was 56 ± 14 years and 46% was female. Mean eGFR was 45 ± 14 ml/min/1.73 m2. Patients with an eGFR ≤59 ml/min/1.73 m2 (n = 17) had a significantly lower baseline plasma bicarbonate concentration (19.0 ± 2.8 versus 24.0 ± 1.9 mmol/L; p < 0.001) and used oral bicarbonate supplements (29% versus 0%; p = 0.02) more often than patients with an eGFR ≥60 ml/min/1.73 m2 (n = 9). Despite the lower baseline plasma bicarbonate and more frequent use of oral bicarbonate supplements, the plasma bicarbonate levels decreased the most in subjects with an eGFR ≤59 ml/min/1.73 m2 (mean difference −4.2; 95% CI −7.1 to −1.3; p = 0.006; Fig. 1A) during a cycle of 5 PE sessions. Baseline plasma chloride concentration was similar in both groups (103 ± 7 vs 103 ± 4 mmol/L) and increased the most in patients with an eGFR ≤59 ml/min/1.73 m2 (mean difference −1.4; 95% CI −2.2 to 5.0; p = 0.426; Fig. 1B). Conclusion Repeated plasma exchange with albumin-saline as a replacement fluid is associated with a significant decrease in plasma bicarbonate concentration in patients with impaired kidney function. Future studies should determine whether this hyperchloremic metabolic acidosis has impact on the patients’ symptoms or long-term outcome.

#755 Endotrophin as an early marker of kidney outcomes in persons with type 2 diabetes: findings from the PROVALID study

Abstract Background and Aims Diabetic kidney disease (DKD) is driven by a set of pathophysiological processes, including fibrosis. Endotrophin (ETP), a pro-fibrotic fragment generated during collagen type VI formation, has previously been shown to be a biomarker of DKD progression. The aim of this study was to investigate, for the first time, circulating ETP as a risk marker for kidney outcomes in persons with type 2 diabetes (T2D) being taken care of at the primary level of healthcare. Method Levels of ETP were measured using the nordicPRO-C6TM ELISA in plasma at baseline from 3226 persons with T2D enrolled in the Prospective Cohort Study in Patients with Type 2 Diabetes Mellitus for Validation of Biomarkers (PROVALID). Outcomes included a composite kidney endpoint defined as a sustained 40% decline in estimated glomerular filtration rate (eGFR) < an eGFR of 60 ml/min/173 m2, sustained 30% increase in albuminuria including a transition in albuminuria stage, or kidney failure with replacement therapy or kidney death. A decline in eGFR and an increase in albuminuria were considered sustained if they persisted over at least two consecutive measurements. Crude and adjusted Cox proportional hazards regression models were applied to investigate the potential of ETP as a risk marker of the kidney endpoint. Levels of ETP were log-transformed before analysis. The Kaplan–Meier estimator was used to compare the risks of experiencing the kidney endpoint according to ETP levels split by the median in persons with baseline eGFR > 90 ml/min/1.73 m2 (n = 976). Results The cohort consisted of 57% males; median age was 64 (58-70) years, and mean eGFR was 79 ± 24 ml/min/1.73 m2. Median follow-up was 3.9 years. Higher levels of ETP were associated with a higher risk of developing the kidney endpoint, with a hazard ratio (HR) of 1.63 (p = 0.0012; n = 293/3226). After adjustment for the refined variables: age, diabetes duration, HbA1c, atherosclerotic cardiovascular disease, blood pressure, duration of hypertension, BMI, LDL-cholesterol, HDL-cholesterol, and eGFR, the HR was 1.55 (p = 0.012). In persons with an eGFR > 90 ml/min/1.73 m2, higher ETP was also associated with an increased risk of developing the kidney endpoint (p = 0.03; n = 69/976). Conclusion Plasma ETP was an independent risk marker for kidney outcomes in persons with T2D with early kidney disease. Higher levels of plasma ETP were associated with a significantly increased risk of developing the kidney endpoint in persons with eGFR > 90 ml/min/1.73 m2. These findings demonstrate that biomarkers of fibrosis, such as ETP, may serve as early markers for kidney disease progression or kidney failure in persons with T2D and apparently normal kidney function.

#493 CKDG4/5 with K-elevated metabolic acidosis under RAAS inhibitor use show a slow renal decline and preservation of response to alkalizing therapy

Abstract Background and Aims Renin-angiotensin-aldosterone system inhibitors (RAASi) are well-established renoprotective agents, but can induce serum potassium (K) elevation and metabolic acidosis (MA). MA contributes to the progression of chronic kidney disease (CKD), thus the renoprotective potential of RAASi is unknown in advanced CKD with MA due to the use of RAASi. MA with elevated serum K may discourage the use of RAASi. In highly advanced CKD, besides factors such as age, proteinuria, and diabetes, it is still debatable under what conditions the continued use of RAASi is favorable for renal prognosis. Furthermore, no studies have focused on the relationship between the response to alkalizing therapy for MA and renal prognosis in advanced CKD with MA and serum K elevation under RAASi use. Method In this single-center retrospective observational study, CKDG4 or G5 outpatients with MA ([HCO3−] < 22 mM) and elevated K (serum [K]≥5.0 mEq/L) at our center and who had started alkalinizing therapy (i.e., sodium bicarbonate and/or low-dose trichlormethiazide plus fludrocortisone) for MA were included. A total of 45 patients were selected, excluding those who had already been prepared for renal replacement therapy at the start of treatment. The RAASi group (Ri group, N = 39) and the non-RAASi group (non-Ri group, N = 16) were divided by the presence or absence of continued RAASi use prior to alkalizing therapy for MA, and the two groups were followed and compared up to 2 years after treatment. Background factors including age, sex, cause of CKD, estimated glomerular filtration rate (eGFR), CKD stage, diabetes, urinary protein (g/gCr), serum [K]/ [HCO3−]/[Na]/[CL]/albumin/phosphate, hemoglobin levels, and the use of K binders, diuretics were investigated. The endpoints were rapid response to alkalizing therapy (i.e., changes in serum [HCO3−], [K], [Na]-[CL] levels 2 months after the start of alkalinizing therapy, and percentage of patients achieving [HCO3−] ≥22 mM at 2 months after the start of alkalizing therapy) and incidence of renal events (>30% reduction in eGFR or renal replacement therapy). Results In all 45 subjects, the mean age was 71.3±11.8 years, 84% were male, mean eGFR was 18.3 ± 5.6 mL/min/1.73 m2, G4 67%/G5 33%, primary disease was diabetic nephropathy 31%, nephrosclerosis 40%, K binders and diuretics use was 25% and 24%, respectively. Mean serum [HCO3−] was 17.9 ± 2.3 mM and mean serum [K] was 5.5 ± 0.4 mEq/L. Comparison of background factors showed no significant difference between the two groups. The changes in serum [K], [HCO3−], [Na]-[CL] 2 months after the start of alkalinizing therapy and the percentage of patients achieving [HCO3−] ≥22 mM after 2 months of starting alkalizing therapy did not differ at all between the Ri and non-Ri groups (Table 1). Cumulative renal survival (non-renal events) was significantly higher in the Ri group than in the non-Ri group(p = 0.010) (Figure 1). None of the rapid responses to alkalizing therapy (i.e., changes in serum[HCO3−], [K], [Na]-[CL], and the percentage of patients achieving [HCO3−] ≥22 mM) were significantly associated with cumulative renal survival (p = 0.186, p = 0.266, p = 0.65, p = 0.114). In a Cox proportional hazards multivariate model adjusted for age, sex, eGFR, cause of CKD, diabetes, urinary protein(g/gCr), method of alkalizing therapy, and rapid response to alkalizing therapy, the risk of renal events without RAASi use was significantly higher (Table 2). Conclusion In CKDG4/5 with MA with elevated serum K under RAASi use, renal function declines more slowly than with non-RAASi use, ensuring a rapid response to alkalizing therapy for MA.

#636 A phase 4, open label, multicenter prospective study of the safety and efficacy of agalsidase beta in Chinese patients with Fabry disease

Abstract Background and Aims Fabry disease (FD) is a rare inherited lysosomal storage disease caused by pathogenic GLA gene variants which result in a deficiency of the enzymatic activity of α-galactosidase A. Enzyme replacement therapy (ERT) is the mainstay of FD-specific treatment, but there are currently no reported clinical trials of ERT for FD in the Chinese population. This is the first phase 4 study to evaluate the safety and efficacy of ERT for FD in China since the approval of agalsidase beta in China in 2019. Method A 54-week, phase 4, open label, single arm, prospective, post-marketing surveillance (PMS) study of agalsidase beta (NCT05054387) was performed at 6 sites in China. Twenty-two Chinese ERT-naïve FD participants (≥8 years) with estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2 were enrolled and received infusions of agalsidase beta (Fabrazyme®, Sanofi) at a dose of 1.0 mg/kg every 2 weeks for up to 48 weeks. The primary endpoint was safety and tolerability of agalsidase beta. The endpoints of clinical efficacy included the changes of plasma globotriaosylceramide (GL-3), globotriaosylsphingosine (Lyso-GL-3), FD symptoms (including angiokeratoma, hypohidrosis, anhidrosis, abdominal pain, headache, tinnitus, heat tolerance, and activity tolerance), and eGFR from baseline to week 48. A post-hoc subgroup analysis was conducted to explore the differences in ERT efficacy between two subgroups of different ages (<30 years and ≥30 years). Results All 22 patients completed the study intervention. There were 18 males (81.8%) and the mean age of ERT initiation was 29.0 ± 13.5 years. Treatment-related adverse events (AEs) and infusion-associated reactions (IARs) were reported in 8 participants (36.4%), which was less than ∼60% as previously reported for IARs. Most AEs were mild or moderate and no AE caused permanent treatment discontinuation or death. The mean plasma GL-3 and Lyso-GL-3 levels decreased remarkably at week 6 and remained stable throughout the trial, with the mean percentage reduction from baseline to week 6 through week 48 ranged from −34.6% ± 27.4% to ­41.9% ± 14.9% and −58.8% ± 20.2% to ­64.9% ± 12.7%, respectively (Fig. 1a and b). The reduction was more remarkable for the classic male patients (n = 18; GL-3: 7.99 ± 2.19 ug/mL at baseline and 4.31 ± 1.71 ug/mL at week 48, −46.0% ± 18.4%; Lyso-GL-3: 83.11 ± 25.69 ng/mL at baseline and 25.89 ± 13.43 ng/mL at week 48, −67.8% ± 17.6%). Thirteen (59.1%) participants experienced improved FD symptoms at week 48, with no cases of worsening symptoms. The mean eGFR was 115.6 ± 37.3 mL/min/1.73 m2 at baseline and 118.4 ± 42.9 mL/min/1.73 m2 at week 48, with a change of 0.0 ± 12.4 mL/min/1.73 m2 from baseline to week 48 (Fig. 1c). In the subgroup analysis, participants were divided into the younger group with age <30 years (n = 11) and the older group with age ≥30 years (n = 11) according to their age of ERT initiation. At week 48, the reduction of mean plasma GL-3 (−47.1% ± 23.6% vs −22.0% ± 26.0%) and Lyso-GL-3 levels (−72.4 ± 17.3% vs −48.2% ± 19.8%), the stabilization of renal function (the mean change of eGFR from baseline to week 48: 5.2 ± 7.9 mL/min/1.73 m2 vs −5.2 ± 14.1 mL/min/1.73 m2) and the percentage of symptom improvement (81.8% vs. 36.4%) were generally more remarkable in the younger group than in the older group (Table 1). Conclusion This first phase 4 study of ERT for Fabry disease in China demonstrates that agalsidase beta is safe and well tolerated with a relatively low IAR rate, and effective in reducing plasma GL-3 and Lyso-GL-3, improving symptoms, and stabilizing renal function in Chinese patients with FD. Furthermore, the present study implies that patients who initiate ERT at a younger age benefit more from the therapy. Funding: Commercial support - Sanofi Pharmaceuticals.

#1037 Urinary marinobufagenin reflects the severity of renal disease in non-advanced CKD: a pilot study

Abstract Background and Aims The identification of new biomolecules involved in the pathogenesis of chronic kidney disease (CKD) which may improve clinical understanding remains a research priority. Marinobufagenin (MBG) is an endogenous cardiotonic steroid endowed with natriuretic and vasoactive properties, which altered levels trigger fibrosis of various organs, including the kidney. The kidney plays a central role in regulating the systemic MBG balance through its urinary excretion (uMBG) but the impact of a reduced clearance due to CKD remains unknown. In this pilot study, we analyzed the clinical and diagnostic significance of uMBG in a cohort of CKD patients with mild-to-moderate CKD (stage 2-4) Method uMBG was measured in 108 CKD patients (mean age 71.6 ± 10 yrs, 70.4% male; mean eGFR 40.54 ± 17 mL/min/1.73 m2) together with a series of clinical, anthropometric, laboratory and instrumental parameters to identify clinical predictors in this cohort. Additionally, uMBG was measured in 25 healthy matched subjects. Results CKD patients displayed lower uMBG values as compared with controls (0.37 [IQR 0.25-0.45] vs. 0.64 [0.46-0.78] nmol/L; p = 0.004). Clinical, independent predictors of uMBG in our study cohort were eGFR (β = 0.248; p = 0.01), the use of statins (β=-0.326; p = 0.001), diabetes (β = 0.243; p = 0.009) and urinary sodium (β = 0.204; p = 0.01). At logistic regression analysis, higher uMBG levels were associated with a lower probability of having an eGFR ≤30 mL/min (OR 0.868; 95% CI 0.798-0.986; p = 0.03). At ROC analyses, uMBG displayed a good diagnostic capacity in identifying patients with more advanced CKD (AUC 0.675; 95% CI 0.578 to 0.762; p = 0.002; Fig. 1). Conclusion Conclusions: Overall, CKD patients display a reduced uMBG excretion which parallels the severity of renal clearance impairment. Sodium intake, diabetes and the assumption of statins may modulate such relationship. Additional studies are needed to confirm the diagnostic usefulness and biological meaning of measuring uMBG as a way to assess CKD severity.

#2865 The impact of glomerular C3 deposition in membranous nephropathy prognosis

Abstract Background and Aims Membranous nephropathy (MN) is one of the most frequent causes of nephrotic syndrome in non-diabetic adults. Studies on MN have suggested a preponderant role of the complement. C3 deposits are common in primary and secondary MN and appear to be related to increased proteinuria. The prognostic role of proteinuria is well established, but the importance of C3 glomerular deposition in disease course is not clear. Our study aims to investigate the role of glomerular C3 deposition in the evolution of membranous nephropathy. Method We conducted a single-center retrospective study including 39 patients with histological diagnosis of MN. The patients were assembled in two groups according C3 deposition intensity in kidney biopsy: low intensity (C3+) and high intensity (C3 2 or more ++). The primary outcome was the development of end-stage kidney disease (ESKD). The rate of remission, the rate of relapse and a decreased of at least 30% of the estimated glomerular filtration rate (eGFR) was defined as secondary outcomes. Results Thirty-nine patients were included, 26 (66.7%) were male with a mean age at biopsy of 54 ± 17.5 years. Twenty-six (66.7%) patients had hypertension at diagnosis and four patients had a thrombotic event. The mean eGFR was 88.7 ± 34.3 ml/min/1.73 m2, and median UPCR was 5.55 g/g. Most patients had primary MN (82.1%). The patients with higher C3 deposition were more likely to response to ACEi/ARB (72.2% vs 42.9%, p = 0.06) and 29 patients did immunosuppression therapy during the follow-up period. There were no significant differences between groups, except the body mass index (BMI), which it was higher in the high C3 group (25.52 ± 3.14 vs 27.42 ± 5.45, p = 0.03) and the presence of thrombosis, which all occurred in the high C3 group (0 vs 4, p = 0.023). During a mean follow-up of 6 ± 4.2 years, 7 (17.9%) patients developed ESKD and 11 (33.3%) patients had a decreased of at least 30% eGFR at five years. The group with low C3 deposition had a higher rate of remission (81.0% vs 61.1%, p = 0.03), reaching remission earlier (9.75 ± 322.92 vs 17.8 ± 32, p = 0.021) comparing with the high C3 deposition. The rate of relapse was similar in both groups. Conclusion There is growing evidence that complement activation has a role in the pathophysiology and, probably, in prognosis of MN. Previous studies have correlated low serum C3 levels with poor long-term renal survival. In our study, the extensive C3 deposition in kidney biopsies was associated with lower and delayed remission rate. Furthermore, it was associated with more thrombotic complications. More patients of the higher C3 deposition group developed ESKD. It was not statistically significant, probably because of the small size of the sample, a limitation of our study. Nonetheless, we believe that C3 deposition is indicative of a worse prognosis of MN and therapeutic modulation of the complement can be a promising treatment strategy in MN.

#913 Impact of retinal photography-based deep learning system on risk stratification for chronic kidney disease progression

Abstract Background and Aims We had previously developed a deep-learning-based risk evaluation system from retinal photographs, Reti-CKD, for stratifying chronic kidney (CKD) development risk in kidney function preserved people. This study aims to evaluate whether Reti-CKD can improve risk assessment of kidney disease progression in diabetic patients with prevalent CKD. Method Total of 5348 diabetic patients from two tertiary hospitals in Korea were evaluated. Patients with estimated glomerular filtration rate (eGFR) <90 ml/min/1.73 m2 or albuminuria were included. Those with missing data for retinal photograph, serum creatinine, or albuminuria were excluded. Patients were categorized into low-risk, moderate-risk, and high-risk groups according to the KDIGO criteria for prognosis of CKD. The KDIGO groups were additionally dichotomized based on Reti-CKD score (Reti-CKD <20 and ≥20). CKD progression was compared between the categories using Cox regression models. Primary outcome was CKD progression, defined as incremental progression to a higher NKF-KDOQI CKD stage. Results The mean age of the patients was 62.4 ± 11.4 years and 60.6% were male. Mean eGFR was 86.6 ± 15.3 mL/min per 1.73 m2 and albuminuria was present in 46.9%. During a median follow-up of 5.0 (interquartile range, 2.5-7.8) years, primary outcome developed in 1379 (25.8%) patients. The primary outcome incidence rate gradually increased with higher KDIGO and Reti-CKD combined risk categories. The risk for CKD progression progressively increased in KDIG moderate-risk and high-risk groups compared to low-risk. When Reti-CKD was incorporated to the KDIGO category, significant stratification of CKD progression risk was noted in the KDIGO low-risk and moderate-risk groups (Table and Figure). Additionally, the combination of KDIGO and Reti-CKD classification showed better discrimination power compared to the KDIGO only classification (delta c-statistics, 0.03; 95% CI 0.02 to 0.040). Conclusion Retinal photography-based deep learning system (Reti-CKD) further stratifies the risk of CKD progression and improves predictability in diabetic patients with reduced renal function.

#2600 Idiopathic full-house non-lupus nephropathy

Abstract Background and Aims A full-house pattern at immunofluorescence (IF) in kidney biopsies is usually associated with Lupus Nephritis (LN). However, it can be also secondary to other causes, such as infections, or it can idiopathic, without a defined origin. Idiopathic Full House non-lupus Nephropathy (iFH-N) represents a rare entity previously identified in small cohorts of patients, with different clinical features and outcomes. A limited number of the described cases developed overt systemic lupus erythematosus (SLE) during follow up, while renal outcome varied across different studies. A retrospective observational study aimed at evaluating clinical presentation and outcomes of patients with iFH-N in a Tertiary Center has been performed. Long-term renal function and development of overt SLE have been considered as main outcomes of the study. Method All native kidney biopsies performed from January 2012 to December 2022 in our Institution were considered. Full-house pattern was defined as simultaneous positivity for IgG, IgM, IgA, C3 and C1q staining at IF. Inclusion criteria were: age ≥18, full-house pattern at kidney biopsy, patients not meeting criteria for SLE diagnosis according to American College of Rheumatology (ACR) 1997 classification or Systemic Lupus International Collaborating Clinics (SLICC) 2012 criteria. Exclusion criteria: diagnosis of SLE, secondary causes of full-house pattern at kidney biopsy. We considered histological, clinical and laboratory features, performed therapies, renal function and SLE development during follow up. Results In the considered period, 2110 patients underwent a native kidney biopsy at our Institution. Of these, 91 patients had a histological finding of full-house nephropathy and were initially included for further evaluation. Of the 91 patients, 84 had received a diagnosis of SLE and were excluded, while 7 did not meet the criteria for a diagnosis of SLE. Two of these 7 were further excluded, having a full house pattern secondary to other conditions. Five patients were finally labelled as iFH-N. At kidney biopsy, all 5 included subjects had a Membranous Nephropathy, with extracapillary proliferation in 2 cases. They were all females, 4 Caucasians (80%), 1 Black (20%). At presentation, mean age was 28.2 years (range 21–40). All had impairment of kidney function, 2 of 5 had a full-blown nephrotic syndrome, 3 of 5 a nephrotic range proteinuria. Mean serum creatinine was 2.1 mg/dl (SD± 0.47), mean eGFR 35.2 ml/min/1.73 m2 (SD ±11), mean proteinuria 7.1 gr/24 h (SD ±3.3). Antinuclear antibodies (ANA) were negative in 4 of 5 patients; anti-dsDNA, anti-extractable nuclear antigens (ENAs) and antiphospholipid antibodies were negative in all subjects; slightly low C3 was present in 3 of 5 subjects. All patients received immunosuppressive therapy, including high dose intravenous (iv) steroids in association with cyclophosphamide (CYC) or mycophenolate mofetil, or Intensified B Cell Depletion Protocol (i.e. iv steroids + CYC and Rituximab). Mean follow-up from the time of kidney biopsy was 7.4 year (SD ± 2.4) (range 3–10 years). During follow up, 4 patients (80%) developed end stage renal disease (ESRD) needing renal replacement therapy, 3 of them within 24 months after presentation. The two patients with crescents had a severe prognosis, starting dialysis within 10 months after presentation. The fifth patient developed chronic kidney disease stage 4. One patient formally developed an ACR negative, SLICC positive SLE two years after presentation, with new positivity for ANA and anti-dsDNA antibodies at high titer and low C3, in addition to renal involvement. Conclusion All patients with iFH-N had similar presentation, being all young females, with a Membranous Nephropathy, nephrotic proteinuria and impairment of kidney function. They all had an aggressive form of kidney disease, refractory to different regimens of immunosuppression and with poor long-term renal outcome. Only one case developed SLE on the long term, although without systemic signs. The relationship between idiopathic full-house nephropathy and SLE remains controversial.

#1881 Association of circulating autoantibodies to erythropoietin receptor with anaemia in patients with type 2 diabetes and chronic kidney disease

Abstract Background and Aims Anaemia is a risk factor for cardiovascular and kidney prognosis in patients with type 2 diabetes and it is important to identify patients at high risk of anemia. We have previously reported that autoantibodies to erythropoietin receptor (anti-EPOR antibodies) may functionally neutralize the activity of erythropoietin and are associated with haemoglobin (Hb) in patients with lupus nephritis, and hypo responsiveness to erythropoiesis-stimulating agents (ESAs) in patients undergoing haemodialysis. This study assessed the association between anti-EPOR antibodies and anaemia in patients with type 2 diabetes and chronic kidney disease. Method This cohort study included patients with type 2 diabetes and chronic kidney disease who were diagnosed between 1989 and 2014 at our hospital. The presence of anti-EPOR antibodies at baseline were assessed by ELISA in stocked serum. To investigate the association between anti-EPOR antibodies and anaemia, odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression analysis adjusted for multiple covariates. We then estimated hazard ratios (HR) and 95% CIs using Cox regression models to investigate the association between anti-EPOR antibodies and the risk of iron deficiency, defined as transferrin saturation below 20% in those with follow-up measurements of iron metabolism. Results The mean age was 63 years, the mean eGFR was 42 ml/min/1.73 m2 and the median urinary protein to creatinine ratio (UPCR) was 1.8 g/gCr. Anti-EPOR antibodies were detected in 26 out of 110 patients (24%). At baseline, most patients with anti-EPOR antibodies had anaemia (n=24, 92%) and severe anaemia with Hb<10 g/dl (n=16, 62%) and used ESAs (n=16, 62%). The presence of anti-EPOR antibodies was independently associated with severe anaemia (OR 9.3; 1.2-70.1, p=0.03) after adjustment for baseline covariates including HbA1c, eGFR, UPCR, iron, and CRP. During a mean follow-up of 6.5 years, 6 of 10 patients (60%) developed iron deficiency in anti-EPOR antibodies positive patients, while 3 of 20 patients (15%) in negative patients. Patients with anti-EPOR antibodies were associated with an higher risk of iron deficiency compared to those without (HR 76.0; 95% CI 1.2-4721.7, p=0.04). Conclusion In patients with type 2 diabetes and chronic kidney disease, the presence of anti-EPOR antibodies was associated with a risk of severe anaemia and iron deficiency independently of kidney function. These results suggest that anti-EPOR antibodies may be useful in predicting the risk of anaemia and establishing therapeutic strategies of anaemia in people with type 2 diabetes.

#2861 Real-life efficacy of tolvaptan for polycystic kidney disease (PKD) and association with patient adherence in London North-West specialist clinic

Abstract Background and Aims Tolvaptan is approved by NICE in the treatment of PKD afterrandomised controlled trials demonstrated a reduction in decline in eGFR. Aquaresis occurs as an effect, and this may limit tolerability as the second dose in a day causes nocturia and disturbed sleep. Thirty-three patients in our specialist PKD clinic were treated based on criteria of bipolar renal length >=15cm and decline in eGFR by > −5 ml/min/yr. We evaluated their real-life outcome regarding measures of adherence including an adapted Basel Assessment of Adherence to Immunosuppressive Medication Scale © (by permissions.nursing.unibas.ch/) originally validated for immunosuppression medications in transplant patients. A further 24 patients had finished treatment at our centre and were excluded as BAASIS could not be applied in hindsight. However, they illustrated a notably high level of intolerance leading to cessation in 16/24 (9 with nocturia, 4 transaminitis, 1 angioedema, 1 rash, 1 fatigue) emphasizing the importance of this work on adherence and response. Method BAASIS addresses recall of treatment adherence in the preceding 4 weeks, all 33 patients currently treated as of 16/1/24 were screened on telephone by two independent auditors with a standard non-judgemental introductory script designed to result in candid engagement. Investigators were blinded to renal outcomes. A decline in eGFR of less than 5 ml/min/yr was defined as treatment response. Results Of the 33 patients included, 14 males and 19 females, median age 49yrs (range 32-72), were on treatment for a mean of 2.7yr (SD 2.2, range 0.3-7.5). Mean eGFR (CKD-EPI) was 58 ml/min (SD 19, range 28-110) at start and 48 ml/mi (SD 23, range 17-102) at end of treatment. Median total daily dose was 120 mg/d (range 60-120). Attendance at clinic for monitoring was 100%. 18/33 patients had responded to treatment, with delta eGFR –0.1 ml/min/year (SD 3.4) versus non-responders’' delta eGFR –13 ml/min/year (SD 8.7) There was a total of 35 instances of non-implementation in 23/33 patients with missed (20 instances), delayed (13 instances) or self-alteration in doses (2 instances). Only 10/33 patient made no failure to implement Tolvaptan at any time. There were 9 patients with non-persistence of Tolvaptan treatment. Associative analysis of renal outcome with adherence was made for all 31 patients who had more than 6 months treatment, 2 patients being excluded because treatment had been too short-term. 25/31 had non-adherence defined by non-implementation or non-persistence or both, but this did not statistically associate with treatment failure ChiSq 1.951 p = 0.16. The element of non-implementation alone was however associated with treatment failure ChiSq 4.949 p = 0.03, this term includes patient behaviour of not taking and mistiming drug taking, and patient-initiated dose reduction and drug holidays. Conclusion Just over half (55%) of currently treated patients had made a clinical response to Tolvaptan. 23/33 patients had non-implementation within the 4 weeks preceding the validated adherence survey, and this was significantly associated with treatment failure. This study is limited to a small single-centre patient cohort but could easily be applied more widely. This study informs shared-decision making and we should encourage our patients to take this high-cost drug in the right amount and at the right times, and notably not to miss doses, thereby to achieve higher clinical response rates.

#2511 Usefulness of cystatin C in measuring renal function in patients with liver cirrhosis

Abstract Background and Aims Liver cirrhosis (LC) is often accompanied by acute kidney injury, and renal function is known to be a significant factor in mortality of patients with LC. However, LC is a representative protein-energy-wasting disease, and there are limitations in measuring renal function using muscle based creatinine (Cr). Therefore, this study tried to investigate the discrepancy in the estimated glomerular filtration rate (eGFR) using conventional serum Cr and cystatin C in patients with LC Method In total, 121 patients were enrolled, and eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation based on both serum Cr and cystatin C levels. Each eGFR was classified into three categories with GFR < 10 mL/min/1.73 m2 (group A), 10-50 mL/min/1.73 m2 (group B), and > 50 mL/min/1.73 m2 (group C) mL/min/1.73 m2, distribution was evaluated according to Child-Pugh classification. Results Of the 121 patients, 69 were Child-Pugh A, 32 were Child-Pugh B, and 20 were Child-Pugh C. The mean eGFR using serum Cr was 85.35 mL/min/1.73 m2, which was higher than the eGFR using cystatin C of 69.52 mL/min/1.73 m2 (p < 0.05) After converting eGFRcr to eGFRcystatinC, the number of patient with group change was 11 (15.9%) in the Child-pugh A, 8 (18%) in Child-Pugh B and 5(25%) in Child-Pugh C (Child-Pugh A: 9 in A↔B, 2 in B→C, Child-Pugh B: 5 in A↔B, 3 in B→C, Child-Pagh C: 4 in A→B, 1 in B→C). Except for 2 patients, eGFR decreased when converting eGFRcr to eGFRcystatinC (p < 0.05). Conclusion In patients with LC, the eGFRcystatinC is significantly lower than that of eGFRcr. And this was significant in cirrhotic patient with a high Child-Pugh class.

#615 Generalisability of cardiovascular RCTs to patients with chronic kidney disease in clinical practice: a comparison between RCTs and real-world data

Abstract Background and Aims Randomised controlled trials (RCTs) often apply stringent eligibility criteria, which could limit the external applicability of RCTs to patients in routine clinical practice. This is specifically troublesome in the setting of chronic kidney disease (CKD) given that kidney disease is commonly used as an ineligibility criterion in RCTs. In this pilot study we estimated the eligibility of patients with CKD in routine clinical practice in five major cardiovascular outcome trials - CREDENCE, DAPA-CKD, CIBIS II, CIBIS III, and AUGUSTUS - and described reasons for ineligibility. Method We included patients with CKD (defined as an estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2 or an urinary albumin creatinine ratio (UACR) >3 mg/mmol present for >3 months) from the Utrecht Patient Oriented Database (UPOD) who visited a cardiovascular outpatient clinic in the University Medical Centre Utrecht between 2012 and 2019. The eligibility criteria were extracted from the selected RCTs and consequently modelled on the patients from UPOD. The percentage of eligible patients and reasons for ineligibility were described descriptively. The percentage of eligible patients for CIBIS II and CIBIS III were only calculated for patients with heart failure, and for the AUGUSTUS trial for patients with coronary artery disease as patients with these conditions were targeted. Patients could not fulfil multiple inclusion criteria and or meet multiple exclusion criteria or both. Results In total, 9005 UPOD patients with CKD were included. Patients had a mean age of 65 ± 14 years, 42% was female, mean eGFR was 49 ± 17, 1741 (19%) had a history of atherosclerotic cardiovascular disease, and 765 (8%) of heart failure. Overall, 0.05% of patients would be eligible for the DAPA-CKD trial and 0% for the CREDENCE trial. Of included patients with heart failure, 2% would have been eligible for CIBIS II and 3% for CIBIS III. Of included patients with coronary artery disease, 2% would have been eligible for the AUGUSTUS trial. Main reasons for ineligibility for DAPA-CKD were not fulfilling the inclusion criteria for UACR (52%), eGFR (20%), or the prescription of RAAS-inhibitors (arb) (49%) or meeting the exclusion criteria for primary kidney disease (PRD, 6%), or a kidney transplant (15%), or other comorbidities. Similarly, patients were often ineligible for the CREDENCE trial because they did not fulfill the inclusion criteria for UACR (48%), eGFR (18%), HbA1c (35%), or prescription of a RAAS-inhibitor (43%) or met one of the exclusion criteria for PRD (29%), cardiovascular disease (23%), or prescription of a mineralocorticoid receptor antagonist (10%). For CIBIS II, main reasons for ineligibility were not fulfilling the inclusion criteria for left-ventricular ejection fraction (LVEF, 50%) or prescription of an ace-inhibitor (42%) or diuretic (33%) or meeting the exclusion criteria of coronary artery disease (17%) or prescription of a calcium-channel blocker (16%). For CIBIS III, patients were also ineligible because they were not fulfilling the inclusion criteria for age (46%), LVEF (46%), or prescription of diuretics (31%) or met the exclusion criteria for serum creatinine (9%) or prescription of an angiotension receptor blocker (14%). Lastly, for the AUGUSTUS trial, patients were mainly ineligible due to not fulfilling the inclusion criteria of atrial fibrillation (79%) or percutaneous coronary interventions (PCI, 91%) or meeting the eGFR exclusion criteria (14%). Conclusion Based on this pilot study, less than 3% of patients with CKD in routine clinical practice would be eligible to participate in cardiovascular RCTs. Patients were often ineligible because they did not fulfil the inclusion criteria and a substantial number of patients was ineligible due to kidney disease. The low eligibility rate of patients with CKD in cardiovascular trials could limit the generalisability of results to patients with CKD treated in practice. To improve generalisability, RCTs in patients with CKD should aim to include more patients who reflect the patients with CKD treated in practice.

#1486 Looking for a new role of known players: the additional value of plasmatic C3 and C4 in predicting IgA Nephropathy prognosis, an observational study

Abstract Background and Aims IgA Nephropathy (IgAN) is the most common glomerular disease worldwide [1]. Complement system activation through the alternative and lectin pathways is crucial in its pathogenesis and leads to worse outcome, eliciting the need for (new) biomarkers to assess risk of disease progression and potential response to new targeted treatments [2, 3]. Only few works have correlated serum C3 and C4 with disease activity and prognosis [4, 5]. Our work explores the potential advantages of incorporating serum C3 and C4 levels into a standardized prognostic model to assess kidney outcome in IgAN. Method This retrospective study, conducted at Sant'Orsola University Hospital in Bologna, investigated the prognostic value of serum complement C3 and C4 in patients with IgAN. The primary outcome was defined as a 40% decline in eGFR or the onset of kidney failure. The study aimed to evaluate whether the addition of serum C3 and C4 to an established predictive model, incorporating variables from the International IgA Prediction Tool (IntIgAPT), enhances the accuracy of outcome prediction. We computed the measures of goodness of fit for each model: Akaike Information Criterion (AIC) and Bayesian Information Criterion (BIC), Nagelkerke R2 test (NR2) that depicts the% explained variation of the outcome based on the set of variables included, and Likelihood Ratio Test (LRT); discrimination with the c-index. Furthermore, we aimed to evaluate the characteristics of patients stratified by baseline serum C3 levels (Low <90 mg/dl, Medium 90-140 mg/dl, High >140 mg/dl). Results 101 patients were included in the cohort. 90% were Caucasian and 65.3% were male with a mean age of 42.6 years. As reported in Table 1, mean eGFR and median proteinuria levels at baseline were 70.4 ml/min/1.73 m² and 1.04 g/24 h respectively. Mean serum C3 was 114.9 mg/dL. The Low group had lower values of eGFR at baseline (47.0 vs 75.67 and 68.64 ml/min/1.73 m², p = 0.015), while the Medium group had lower values of uProt (0.75 vs 1.81 and 1.46 g/24 h, p = 0.004). During a median 54.28 months follow-up, the Low group exhibited significantly higher primary outcome incidence (16.3 events vs 2.9 and 1.7 events x 100 pts/year, p = 0.003). We computed a first model (M1) based upon IntIgAPT variables and then a second model (M2) as the same of M1 plus serum C3 and C4 at baseline (Table 2). C3 showed a negative association with outcome (OR 0.88, CI 0.78 to 0.99, p = 0.05) whereas C4 had a positive one (OR 1.21, CI 1.02 to 1.48, p = 0.05). M2 had an improved prediction accuracy than M1, as evidenced by lower AIC (49.1 vs 53.8), higher c-index (0.74 vs 0.65), and NR2 (0.76 vs 0.65). Likelihood ratio test was significant between the two (p = 0.008). Conclusion The inclusion of serum C3 and C4 in a validated prognostic model enhances prediction accuracy and improves the percentage of events explained, highlighting complement's inherent informativeness. In our population lower C3 and higher C4 levels were associated with poorer prognosis in IgAN, characterizing a more ‘Complement-Pathic’ subset of patients. This result expands the current evidence, for the first time to our knowledge, in a Caucasian-prevalent study population.

#553 Renal tubular damage is an independent risk factor for all-cause and cardiovascular mortality in a community-based population: the Takahata Study

Abstract Background and Aims Renal tubulointerstitial damage is a risk for renal failure. However, the association between renal tubulointerstitial damage and all-cause and cardiovascular mortality in the general population remains unclear. In this prospective cohort study, we examined this point using urinary β2-microglobulin/creatinine ratio (UBCR) as a marker of renal tubulointerstitial damage in the general Japanese population. Methods We examined the association between UBCR values at entry and all-cause and cardiovascular mortality during the follow-up period (median 9.2 years) in 3 427 residents (mean age 62.5 years, 45.1% male, mean eGFR 81.6 ml/min/1.73 m², ≥1+ protein 4.4%) of Takahata Town in Japan. Results Study participants were divided into two groups (low < 300 μg/gCre, high ≥300 μg/gCre) based on UBCR at entry. Kaplan-Meier analysis showed a significantly higher incidence of all-cause and cardiovascular mortality in the high UBCR group (Log-rank P < 0.01). A multivariate Cox proportional hazards analysis adjusted for age, sex, eGFR, urinary protein level, comorbidities, smoking status, and other background factors showed a hazard ratio of 1.47 (95% CI 1.09-2.00, P = 0.01) for all-cause mortality and a hazard ratio of 1.82 (95% CI 1.06-3.12, P = 0.03) for cardiovascular death in the high-UBCR group. The addition of high UBCR to conventional risk factors, including eGFR and urinary protein level, significantly improved the net reclassification improvement (NRI) for all-cause and cardiovascular mortality (P < 0.01). Conclusions UBCR, a marker of tubulointerstitial damage, was identified as a risk factor for all-cause and cardiovascular mortality in the general population independent of eGFR and urinary protein levels.

#2979 Patients referred to nephrology consultation from African countries of Portuguese official language: a Portuguese single-center cohort study

Abstract Background and Aims Chronic kidney disease (CKD) is a main cause of morbidity and mortality worldwide, with African population being at increased risk. Nevertheless, access to treatment for CKD is restricted in African countries resulting in premature death. The latest statistics point to an annual referral to Portugal of around 900 patients from those countries for medical reasons—of which only 5% corresponds to Nephrology referrals. However, this protocol is burdened with high social and economic impact, consuming 50% of the funds budgeted by the Portuguese government (estimated at 3 million euros annually). The aim of this study was to describe the clinical characteristics, reasons for the referral and outcomes of patients from African Countries of Portuguese Official Language (ACPOL) to a nephrology consultation in a tertiary hospital in Portugal under a cooperation protocol. Method Single-center retrospective analysis of 131 African patients referred to our nephrology department between 2014 and 2023. Results Only 84 patients (64%) ended up being evacuated from their country of origin and attended the nephrology consultation in Portugal. The mean age was 46 ± 14 years and 55% were male. Thirty-two patients were from Guinea-Bissau (38%), 24 from São Tomé and Príncipe (29%), 22 from Cape Verde (26%), and 6 from Angola (7%). The motives for referral to a tertiary center were advanced CKD in 58 patients (69%), nephrotic syndrome in 21 patients (25%), and hemodialysis (HD) vascular access dysfunction in 5 of the cases (6%). In the group of patients referred with advanced CKD the mean eGFR was 16 ± 10 ml/min, all patients had hypertension, 20% had diabetes and 9% presented heart failure. More than half (56%) needed hospitalization with urgent need of dialysis and all patients started HD with a central venous catheter. During the follow-up, four patients died (5%), two patients (2.3%) transitioned to peritoneal dialysis and 70% were on kidney transplant waiting list. Patients referred with nephrotic syndrome had a mean eGFR of 71 ± 49 ml/min/1,73 m2 and a median urine albumin/creatinine ratio (uACR) of 6.9 [IQR 4.7-8.8] g/g. Kidney biopsy was performed in 90% of the cases, with membranous nephropathy (37.5%) and focal segmental glomerulosclerosis (25%) being the two most frequent diagnosis. Only two patients returned to their origin country; the remaining prolonged their stay due to unavailability of resources for appropriate treatment in their country of origin. Conclusion These data emphasize the inequality in access to healthcare in African countries and highlights the urgent need for investment, especially in CKD, as it contributes to serious consequences in these patients’ survival and morbidity. With the cooperation protocol, Portugal provides the possibility for these patients to be evacuated and treated in specialized nephrology departments, improving their outcomes. However, our study shows that there is still a lot to be done since just over 60% of referred patients manage to reach Portugal. The entire evacuation process remains extremely delayed, a fact shown by the need for patients to start urgent HD and that more than half of them require hospitalization upon arrival at the nephrology department, with a high economic burden.

#356 Low-dose thiazide/fludrocortisone use in advanced CKD can rapidly improve potassium-elevated metabolic acidosis with renal and cardiovascular safety

Abstract Background and Aims Advanced chronic kidney disease (CKD) is often complicated by metabolic acidosis(MA) with elevated serum potassium(K). MA is a risk factor for CKD progression, and elevated serum K forces dietary K restriction, which is also undesirable in CKD, stalling the use and escalation of renin-angiotensin-aldosterone system inhibitors (RAASi). Sodium bicarbonate(SB) and K binders, which are not well tolerated due to gastrointestinal symptoms, are often used to correct MA and hyperkalemia. On the other hand, the concurrent use of thiazide and fludrocortisone to promote urinary excretion of K and hydrogen ions has been reported in the type IV renal tubular acidosis, but its efficacy and safety in advanced CKD is unclear. Method This single-center, retrospective, observational study included CKDG3b-G5 outpatients with MA([HCO3−]<22 mM) and elevated K (serum [K]≥ 5.0 mEq/L) at our center. A total of 59 patients were selected, excluding those who had already been prepared for renal replacement therapy at the start of treatment. Patients who continued to receive trichlormethiazide (1 mg, at 1-3 day intervals) plus fludrocortisone (0.1 mg, at 1-3 day intervals) (low-T/F group, N = 10) or SB(0.5 g-5 g/day) alone (SB group, N = 49) were followed up until 2 years after the start of treatment and the two groups were compared. Background factors including age, sex, cause of CKD, estimated glomerular filtration rate (eGFR), CKD stage, urinary protein(g/gCr),serum [K]/ [HCO3−]/[Na]/[CL]/albumin/phosphate, hemoglobin levels, and the use of RAASi/K binders/diuretics were investigated. Efficacy and safety comparisons between the two groups were evaluated based on changes in serum [HCO3−]and [K] levels before and after starting of treatment (at 2, 6, 12, 18, and 24 months), percentage of patients achieving [HCO3−] ≥22 mM, change in eGFR, incidence of renal events (>30% reduction in eGFR or renal replacement therapy), the incidence of cardiovascular events, and the incidence of treatment-modified events such as initiation or increase of antihypertensive, K-binding, and uric acid-lowering agents. Results In all 59 subjects, the mean age was 72.0±11.7 years, 81% were male, mean eGFR was 19.6 ± 7.2 mL/min/1.73 m2, CKDG4/5 account for 92% (G4 60%/G5 32%), primary disease was diabetic nephropathy 30%, nephrosclerosis 43%, RAASi use 68%, mean [K] was 5.5 ± 0.4 mEq/L and mean [HCO3−] was 18.1 ± 2.2 mM. The low-T/F group consisted of patients who switched due to prior SB intolerance or in whom SB was ineffective, and included 5 patients who received concomitant SB. Comparison of background factors showed no significant difference between the two groups. The changes in the serum [HCO3−] and [K] levels 2 months after starting the treatment were significantly larger in the low-T/F group compared with the SB group ([K]after - [K]before (mEq/L):median −1.2, IQR-1.6 to −0.48 vs −0.57, −0.80 to −0.10, p = 0.036; {[K]after -[K]before}×100/[K]before(%): median −20.3, IQR −26.4 to −9.2 vs −9.3, −14.8 to −1.85, p = 0.032; [HCO3−]after-[HCO3−]before (mM):median +5.2, IQR +3.75 to +8.23 vs +3.2, +1.7 to +5.1, p = 0.022) . The percentage of patients achieving [HCO3−] ≥22 mM at 2 months after treatment was significantly higher in the low-T/F group at 88.9% (SB group 38.8%, p = 0.007). There were no renal events in the low-T/F group, and cumulative renal survival (no renal events) tended to be higher in the low-T/F group than in the SB group in the all conditions such as unadjusted condition, presence of RAASi, CKDG4/5 and matched for age, sex, primary cause of CKD and eGFR (p = 0.06, p = 0.265, p = 0.16, p = 0.14, respectively) (Figure). In patients with no renal events, the low-T/F group had a significantly better mean eGFR change of +4.2% at 6 months (SB group: −11.0%, p = 0.019). There were also no cardiovascular events in the low-T/F group, and there were no significant differences between the two groups in either cardiovascular events or treatment-modified events (Table). Conclusion Even in advanced CKD, the low-dose combination of thiazide and fludrocortisone can rapidly improve K-elevating MA and continue without adverse renal or cardiovascular outcomes.

#2278 EUROCYS, a European cystinuria registry

Abstract Background and Aims Cystinuria (OMIM 220100) is a rare autosomal recessive disorder in which high urinary cystine excretion leads to formation of cystine stones due to its low solubility at normal urinary pH. Retrospective series have been published but precise data to guide long term optimal management of these patients are lacking. Our goal was to collect consistent and comparative prospective clinical, biological, genetic and radiological data from patients (children and adults) with cystinuria followed in European centers. Method We developed EUROCYS, a multidisciplinary, European, multicenter registry of patients with cystinuria in which demographic, clinical, surgical, biological, genetic, radiological and therapeutic data are collected longitudinally. These data are recorded via the European Rare Kidney Disease Registry (ERKReg) platform. Results Enrolment started in July 2021. To date, 269 patients have been included at 29 different centers in 8 European countries. Mean age at diagnosis was 18.7 years (SD 17.3) and mean age at inclusion was 35.4 years (20.2). 86.9% of patients had less than 9 calculi extractions reported, 11.0% had between 10 to 19, and 2.0% had more than 20. 61.4% (418/680) were treated by ureteroscopy, 16.2% (110/680) by shock wave lithotripsy and 16.0% (109/680) by percutaneous nephrolithotomy. 39% of patients had a new stone expulsion or surgery during the last 12 months. At the inclusion visit, mean urinary pH was below the recommended level at 6, 8 (0.8). Only 16.3% of patients had a urinary pH between 7.5 and 8: 77.2% of patients had a urinary pH below 7.5 and 6.3% above 8. In adults, mean 24-hour urinary volume was 2653 mL (1077). 34.9% had a target urine volume above 3000 ml. Under treatment, spot urine cystine concentration was 345.5 mg/l (255.2) and 44.8% of patients had a concentration below target concentration (250 mg/l). Mean sodium urinary excretion was 147 mmol/24 h (67). Only 29% of patients had a sodium urinary excretion below 100 mmol/24 h. As alkalinizing agent, 87.2% of patients received potassium citrate, 16.3% sodium bicarbonate and 9.1% potassium bicarbonate. As cystine binding drug, 71 patients (26.7%) were treated with Tiopronin and 3 experienced serious adverse events (hematological, cutaneous, proteinuria). 15 (5.6%) were treated with D-Penicillamine and 2 had adverse events (proteinuria and gastrointestinal). In adults, mean eGFR at inclusion was 82.1 ml/min/1.73 m² (26.3): 40.9% of patients were at chronic kidney disease (CKD) stage 1, 40.1% at CKD2, 16.7% at CKD3, 0.7% at CKD 4 and 1.5% at CKD5. Conclusion The EUROCYS registry shows real life data on cystinuria patients followed in European centers. Despite alkalinizing treatment, most patients do not reach the recommended urinary pH level and only one third have an adequate urinary volume. This registry will allow analyzing the impact of adhesion to recommendations on disease activity.

#2191 Platelet function in chronic kidney disease; can flow cytometry guide in the difficult balance between risk for bleeding versus thrombotic events?

Abstract Background and Aims Increased risk of bleeding is a well-known complication of chronic kidney disease (CKD). However, these patients also have an increased risk of thrombotic events. Several studies have implicated both impaired and enhanced platelet function in patients with chronic kidney disease, but results vary between different studies and methods. Flow cytometry has emerged as a new method to study platelet function. Our aim was to investigate platelet function using flow cytometry in patients with chronic kidney disease. Method 20 patients were included between February and May 2023. Pre-dialytic patients with an eGFR between 8-20 mL/min/1,73 m2 were included, mean eGFR 14.7 mL/min/1,73 m2. Patients with platelet levels >100 × 109/L were included. Medication in the form of anticoagulants, NSAIDs, platelet inhibitors or SSRIs were used as exclusion criteria. Platelet activation assay was performed with flow cytometry. The expression of activation markers PAC-1 (activated GPIIb/IIIa), CD62P (P-selectin) and CD63 (dense granules) were analysed before and after activation with ADP, CRP-XL (collagen stimulating peptide, activates GPVI) or TRAP-6 (stimulates platelet activating receptor 1, PAR1). Platelets from 20 healthy control subjects were analysed for comparison. Results The level and size of platelets (MPV) were comparable in both groups. There were significantly higher levels of D-dimer in the CKD group vs healthy controls (1,17 mg/L FEU vs 0,27 mg/L FEU). Except for the decreased expression of activated GPIIb-IIIa receptor after activation with ADP and CRP-XL in one patient, the platelet activation did not significantly differ between CKD patients and healthy controls. Conclusion No significant differences in the activation of platelets were observed between the CKD population and the healthy controls when analysed by flow cytometry. Elevated levels of D-dimer in CKD patients have previously been described and are believed to be due to increased fibrin formation, lysis and decreased renal clearance. Further studies in a larger patient population, including thrombocytopenic patients are planned, with greater focus to be placed on dense granula quantities which may correlate with decreased levels in the CKD population.

#1891 Evaluating the safety and effectiveness of Tolvaptan for management of adult Korean ADPKD patients (ESSENTIAL study): final report

Abstract Background and Aims Tolvaptan, a selective vasopressin V2 receptor antagonist, was first approved by Korean FDA in 2015 as a treatment option in autosomal dominant polycystic kidney disease (ADPKD). In order to prescribe Tolvaptan safely and effectively, we designed the phase 4 clinical trial among Korean ADPKD patients with chronic kidney disease (CKD) stage 1-3. Method Korean patients aged 19 to 50 with rapidly progressing ADPKD were enrolled in the study. The dose titration was performed every one week for a total of 4 weeks. The patient was prescribed Tolvaptan with the maximum tolerable dose up to 120 mg per day. A total duration of Tolvaptan prescription was 24 months. The primary outcome was the incidence of treatment emergent adverse events (TEAE) including drug-induced liver injury (DILI). The secondary outcomes were the annual mean percent change of total kidney volume (TKV) and the annual mean change of estimated glomerular filtration rate (eGFR). Results A total of 117 patients were included in the analysis. Mean age was 38.7 ± 8.4 years old and male were predominant (58.1%). The average TKV was 2066 ± 1094 mL and mean eGFR was 79.7 ± 27.7 mL/min/1.73 m2. Mean duration of Tolvaptan exposure was 1.7 ± 0.6 years and the average daily dose of Tolvaptan was 94.4 ± 24.1 mg/day. A total of 489 treatment-emergent adverse events (TEAE) occurred in 106 (90.6%) patients during study duration. The drug-induced liver injury and aquaresis-related adverse events were two most common adverse events. A total of 17 DILI cases (14.5%) occurred during the study period and mostly within 18-month period. However, liver enzymes were normalized after drug discontinuation The patients with previous history of liver disease as well as those who were prescribed higher dose of Tolvaptan demonstrated higher frequency of DILI. Mean growth rate of TKV after Tolvaptan treatment was 4.5 ± 0.5% and mean eGFR decline rate was -3.0 ± 0.39 mL/min/1.73 m2/year. Comparing with the predicted value from calculation, Tolvaptan attenuated both TKV growth and eGFR decline rate. Conclusion This study is the first post-marketing survey assessing the safety and efficacy of Tolvaptan in Korean ADPKD patients. The incidence of DILI was higher than the previous studies and especially in those with liver disease and higher Tolvaptan prescription dose. While Tolvaptan can effectively reduce TKV and attenuate eGFR decline, the clinicians should be aware of higher frequency of DILI among Korean population.

#2348 Paradoxical association of pre-donation estimated glomerular filtration rate with kidney function decline in living kidney donors

Abstract Background and Aims Living kidney donors (LKD) are at risk for chronic kidney disease (CKD). Whether differences in pre-donation estimated glomerular filtration rates (eGFR) are associated with differences in the rate of post-donation eGFR decline is unclear. We aim to examine the association between pre-donation eGFR and the risk of kidney function decline post-donation. Method A retrospective cohort study using the Organ Procurement and Transplantation Network (OPTN) and Scientific Registry of Transplant Recipients (SRTR) database included LKD with pre- and early post-donation eGFR as well as eGFR at 6, 12, and 24 months after donation. The association between the quartile (Q) of pre-donation eGFR and time to ≥35% decline in post-donation eGFR compared to pre-donation eGFR was examined by competing-risks survival regression with death serving as a competing risk variable. Results Of 129,943 LKD ≥18 years old undergoing donation between October 1987 and September 2022, mean ± SD age was 42 ± 12 years and 61% were female. Mean overall pre-donation eGFR was 95.76 ± 29.80 mL/min/1.732 and mean pre-donation eGFR of LKD in Q1, 2, 3, and 4 were 63.50 ± 8.86, 83.05 ± 4.53, 100.30 ± 5.72, and 136.22 ± 23.69 mL/min.1.73 m2, respectively (Ptrend <0.001). Compared to pre-donation eGFR, the mean eGFR at early post-donation was significantly decreased to 53.56 ± 39.81 mL/min.1.73 m2 (mean eGFRpost-pre −43.38 mL/min.1.73 m2; P < 0.001), but mean post-donation eGFR at 6, 12, and 24 months continued trending up to 57.58 ± 45.37, 59.28 ± 43.25, and 61.05 ± 42.51 mL/min.1.73 m2, respectively which were significantly greater than early post-donation eGFR (mean eGFR 6mo-post 4.28, eGFR12mo-post 6.01, and eGFR24mo-post 7.82 mL/min.1.73 m2; P < 0.001; Fig. 1). Median survival for ≥35% decline in post-donation eGFR was 6.43 months (5.50, 11.30) with an incidence rate of 0.08 person-months. Among 75,220 LKD with follow-up data, 58,985 (78%) had the event and 15 (0.02%) died. Compared to LKD with pre-donation eGFR in Q1, LKD in other Q had a significantly higher risk for ≥35% decline in post-donation eGFR with a positively graded association (HR (95% CI)Q2 1.28 (1.23, 1.32); HRQ3 1.41 (1.36, 1.46); and HRQ4 1.60 (1.55, 1.65)). After adjusting for age, gender, race, body mass index, history of hypertension, diabetes, U.S. citizen status, education, and the interaction term between the quartile pre-donation eGFR and race, the magnitude of the association increased but the direction remained (HR (95%C I)Q2 1.41 (1.36, 1.47) HRQ3 1.72 (1.65, 1.79), and HRQ4 2.11 (2.02, 2.20). In addition, race was identified as an effect modifier with an increased risk for ≥35% decline in post-donation eGFR observed in Hispanic/Latino LKD (Pinteraction Q 2, Q3, Q4 0.025, 0.005, and <0.001). Conclusion Higher pre-donation eGFR is associated with a greater risk for post-donation eGFR decline especially among Hispanic/Latino LKD. Candidacy for living kidney donation should not be declined based only on eGFR; while some racial-ethnic minorities may be at greater risk even having higher pre-donation eGFR.