Primary Kidney Disease Research Articles

Primary Care-Based Chronic Kidney Disease Management.

Primary Care-Based Chronic Kidney Disease Management.

Primary Care-Based Chronic Kidney Disease Management-Reply.

Primary Care-Based Chronic Kidney Disease Management-Reply.

Hospital admissions for pyoderma gangrenosum in Spain (1999-2021): Epidemiological and clinical characteristics, temporal trends, and factors associated with poor prognosis and higher cost.

Pyoderma gangrenosum (PG) is a neutrophilic inflammatory dermatosis that can be idiopathic or associated with other diseases. The aim was to analyze the epidemiological and clinical characteristics, temporal trends, risk factors for poor prognosis, and admission costs associated with PG in Spain. We conducted a retrospective study, based on the Hospital Discharge Registry of the Spanish National Health System in Spain from 1999 to 2021. Of 82,161,670 admissions during the study period, 4901 were for PG (hospitalization rate of 59.7/1,000,000 admissions). PG hospitalizations increased from 28.8/1,00,000 in 1999 to 91.9/1,000,000 in 2021. PG was a primary cause of admission in 60.5% of cases, and 58.4% of patients were women. The main PG-related comorbidities were inflammatory bowel disease (15.7%) and neoplasms (10%). There was a significant increase over the years in admissions for inflammatory bowel disease, monoclonal gammopathy of undetermined significance, and lymphoma, as well as an increase in diseases unrelated to PG, such as hypertension, diabetes, and chronic kidney disease. The hospital mortality rate was 5.6%. Death was associated with PG being a primary diagnosis, older age, leukemia, neoplasms, diabetes, and chronic kidney disease. The cost of treatment increased over the years and was higher in older people. PG cases in the inpatient setting in Spain over the past 23 years make up a tiny proportion of all hospital admissions, although the rate of hospitalization for PG has increased in the last two decades.

Prevalence and Risk Factors for Secondary Hypertension in Young Adults.

The prevalence of secondary causes of hypertension in young adults is unknown, and therefore, there is no consensus about the indication of screening of secondary hypertension (2HTN) in this population. The objective was to report the prevalence and the causes of 2HTN in young subjects. 2090 patients with confirmed hypertension aged 18 to 40 years with full workup for 2HTN screening were included in this cross-sectional study. We assessed the prevalence of 2HTN and analyzed the factors associated. 619/2090 patients (29.6%) had a 2HTN. The most frequent diagnoses of 2HTN in descending order were primary aldosteronism (n=339; 54.8%), renovascular hypertension (n=114; 18.4%), primary kidney disease (n=80; 12.9%), pheochromocytoma/functional paraganglioma (n=37; 5.9%), hypertension caused by drugs or substances (n=32; 6.0%), and other diagnoses (n=17; 2.7%). Patients with blood pressure <160/100 mm Hg did not have a lower prevalence of 2HTN regardless of the number of treatments. The prevalence of 2HTN was higher in the decade between 30 and 40 years of age than between 18 and 30 years of age (P=0.024). Female sex, hypokalemia, treatment with at least 2 medications, no familial history of hypertension, body mass index <25 kg/m², and diabetes were associated with a higher prevalence of 2HTN. The prevalence of 2HTN is high among young patients with hypertension (29.6% in our cohort), regardless of age and blood pressure level. All patients with hypertension under 40 years of age should be screened for secondary causes.

Egyptian paediatric kidney transplantation pre-transplant guidance highlights on donor and recipient assessment (R. N. 364)

BackgroundKidney transplantation for chronic kidney disease (CKD) in children is the best treatment option. It needs special medical and surgical expertise highly skilled in management of pediatric age group. Our Egyptian profile for causes of end-stage renal failure (ESRF) in transplanted children reflects prevalence of inherited kidney diseases IKD (43%), urologic causes (26%), glomerulonephritis (GN) (17%), and unknown causes (14%). Renal graft availability remains a great challenge.AimWe need pediatric kidney transplantation (PKT) guideline since children have unique causes for ESRF compared to adults. Their transplant team should be skilled in management of children challenges. Recipients may not have one transplant per life. Long-standing immunosuppression will have its toxicity and need regular monitoring. Lots of data are extracted from adult guidelines lacking paediatric background. Young paediatric nephrologists need short version guidelines rich in educational figures for management plans. Children and their families need Arabic orientation booklets and supportive programmes. National Insurance System sponsors should be guided by National Pediatric Guidelines to minimize the centre’s variations.MethodsOur National Pediatric Guidelines are evidence based adapted from international four source guidelines with permissions [KDIGO-2020, RA/BTS 2022-2018, EAU 2018] that were appraised with Agree 2 plus tool using PIPOH format health questions. We followed the ‘adapted ADAPTE’ CPG formal adaptation methodology that consists of three phases and 24 steps and tools. It was registered on the practice guideline registration international guideline registry with a registration number IPGRP-2023-12-27 CN 312.ResultsSummary includes recommendations for assessment of (1) potential living adult donors for age, medical, surgical, immunologic, familial, metabolic, malignancy, and any donor morbidities and (2) transplant recipient assessment for age, weight, nutritional, psychosocial, immunological, infection states, primary native kidney disease, associated morbidities, the presence of genetic, immunologic, infection, and malignancy risks.ConclusionPediatric kidney transplantation guidelines aim for better donor, recipient, and graft survival. Recommendations are tailored as adopted or adapted statements from evidence-based source guidelines to suit our local pediatric CKD profile.

Kidney transplantation in children and adolescents with C3 glomerulopathy or immune complex membranoproliferative glomerulonephritis: a real-world study within the CERTAIN research network

BackgroundComplement 3 glomerulopathy (C3G) and immune complex membranoproliferative glomerulonephritis (IC-MPGN) are ultra-rare chronic kidney diseases with an overall poor prognosis, with approximately 40–50% of patients progressing to kidney failure within 10 years of diagnosis. C3G is characterized by a high rate of disease recurrence in the transplanted kidney. However, there is a lack of published data on clinical outcomes in the pediatric population following transplantation.MethodsIn this multicenter longitudinal cohort study of the Cooperative European Paediatric Renal Transplant Initiative (CERTAIN) registry, we compared the post-transplant outcomes of pediatric patients with C3G (n = 17) or IC-MPGN (n = 3) with a matched case–control group (n = 20).ResultsEleven of 20 children (55%) with C3G or IC-MPGN experienced a recurrence within 5 years post-transplant. Patients with C3G or IC-MPGN had a 5-year graft survival of 61.4%, which was significantly (P = 0.029) lower than the 5-year graft survival of 90% in controls; five patients with C3G or IC-MPGN lost their graft due to recurrence during this observation period. Both the 1-year (20%) and the 5-year (42%) rates of biopsy-proven acute rejection episodes were comparable between patients and controls. Complement-targeted therapy with eculizumab, either as prophylaxis or treatment, did not appear to be effective.ConclusionsThese data in pediatric patients with C3G or IC-MPGN show a high risk of post-transplant disease recurrence (55%) and a significantly lower 5-year graft survival compared to matched controls with other primary kidney diseases. These data underscore the need for post-transplant patients for effective and specific therapies that target the underlying disease mechanism.Graphical abstractA higher resolution version of the Graphical abstract is available as Supplementary information

SGLT-2 inhibitors in chronic peritoneal dialysis patients: a follow-up study

BackgroundSodium-glucose transporter-2 inhibitors (SGLT-2i) are recommended for use in patients with type 2 diabetes comorbid atherosclerotic cardiovascular disease, heart failure, or chronic kidney disease. Limited reports are currently available for their use in dialysis patients. In an observational, retrospective follow-up study, we reported the clinical characteristics of chronic peritoneal dialysis (PD) patients on SGLT-2i.MethodsWe enrolled 50 diabetic chronic PD patients, and 11 continued SGLT-2i after PD treatment. We reported the patients’ ultrafiltration, HbA1c, urinary tract infection episodes, and venous CO2 during follow-up and compared the differences in these factors between patients with and without SGLT-2i.ResultsThe mean age of the patients was 65 ± 15 years, and 16 (32%) patients were female. The age, gender, heart failure, and primary kidney disease were not different between patients with and without SGLT-2i at enrollment. In an average of 31 months follow-up, patients with SGLT-2i had higher ultrafiltration (1322 ± 200 ml/day vs. 985 ± 415 ml/day, p = 0.013), hemoglobin (11.2 ± 1.7 vs. 10.2 ± 1.7 g/dl), white blood cell count (9.2 ± 3.7 vs. 7.4 ± 2.1 109/L), and a lower venous CO2 (p = 0.036). The urine amount, the overall survival, the technical survival, and the chance of UTI were not different between patients with and without SGLT2i.ConclusionSGLT-2i may increase ultrafiltration volume and hemoglobin levels in chronic PD patients. SGLT-2i did not increase urinary tract infection but was linked to subclinical metabolic acidosis.What was knownThe effect of SGLT-2i in chronic PD patients is not clear?This study addsSGLT-2i is associated with increased ultrafiltration, hemoglobin, white blood cell counts, and a decreased CO2 in PD patient.Potential impactSGLT-2i may increase ultrafiltration in PD patients.

Role of Podocyte in Kidney Disease.

Podocytes are epithelial cells lining the outer surface of the renal glomerular capillaries and they play a pivotal role in maintaining the structural and functional integrity of the glomerular filtration barrier. Podocytes react to injury in various ways and any injury to these highly specialized cells can progress to podocyte dysfunction, resulting in a group of proteinuric renal diseases called podocytopathies. Podocytopathies include a wide spectrum of primary and secondary kidney diseases, including minimal change disease, diffuse mesangial sclerosis, focal segmental glomerulosclerosis, collapsing glomerulopathy, diabetic, membranous and lupus nephropathies. Etiologically, they can be idiopathic, genetic or secondary to infections and drugs, metabolic diseases, hemodynamic factors or associated with various immune and non-immune systemic diseases. This manuscript provides a basic understanding of podocyte structure, causes of podocyte injury, response to the injury and the subsequent progression to podocytopathies. The pathogenesis of these diseases is set around podocytes. The clinical and morphological manifestations, the commonality and heterogeneity of these podocytopathies are also discussed. As our knowledge of podocyte biology improves, so will our treatment avenues with a more podocyte-centric personalized approach.

Cathepsin S (CTSS) in IgA nephropathy: an exploratory study on its role as a potential diagnostic biomarker and therapeutic target.

IgA nephropathy (IgAN), a prevalent form of glomerulonephritis globally, exhibits complex pathogenesis. Cathepsins, cysteine proteases within lysosomes, are implicated in various physiological and pathological processes, including renal conditions. Prior observational studies have suggested a potential link between cathepsins and IgAN, yet the precise causal relationship remains unclear. We conducted a comprehensive bidirectional and multivariable Mendelian randomization (MR) study using publicly available genetic data to explore the causal association between cathepsins and IgAN systematically. Additionally, immunohistochemical (IHC) staining and enzyme-linked immunosorbent assay (ELISA) were employed to evaluate cathepsin expression levels in renal tissues and serum of IgAN patients. We investigated the underlying mechanisms via gene set variation analysis (GSVA), gene set enrichment analysis (GSEA), and immune cell infiltration analysis. Molecular docking and virtual screening were also performed to identify potential drug candidates through drug repositioning. Univariate MR analyses demonstrated a significant link between increased cathepsin S (CTSS) levels and a heightened risk of IgAN. This was evidenced by an odds ratio (OR) of 1.041 (95% CI=1.009-1.073, P=0.012) as estimated using the inverse variance weighting (IVW) method. In multivariable MR analysis, even after adjusting for other cathepsins, elevated CTSS levels continued to show a strong correlation with an increased risk of IgAN (IVW P=0.020, OR=1.037, 95% CI=1.006-1.069). However, reverse MR analyses did not establish a causal relationship between IgAN and various cathepsins. IHC and ELISA findings revealed significant overexpression of CTSS in both renal tissues and serum of IgAN patients compared to controls, and this high expression was unique to IgAN compared with several other primary kidney diseases such as membranous nephropathy, minimal change disease and focal segmental glomerulosclerosis. Investigations into immune cell infiltration, GSEA, and GSVA highlighted the role of CTSS expression in the immune dysregulation observed in IgAN. Molecular docking and virtual screening pinpointed Camostat mesylate, c-Kit-IN-1, and Mocetinostat as the top drug candidates for targeting CTSS. Elevated CTSS levels are associated with an increased risk of IgAN, and this enzyme is notably overexpressed in IgAN patients' serum and renal tissues. CTSS could potentially act as a diagnostic biomarker, providing new avenues for diagnosing and treating IgAN.

#614 Identifying distinct patient phenotypes in patients with chronic kidney disease

Abstract Background and Aims Patients with chronic kidney disease (CKD) are heterogeneous in terms of age, causes of CKD, and comorbidities. Although individual risk factors greatly influence patients’ risk of clinical outcomes, this heterogeneity is rarely used to guide clinical decision-making. In this study we aimed to derive phenotypes in patients with CKD based on characteristics commonly available in routine clinical practice and evaluated whether these phenotypes were associated with clinical outcomes. Method Patients from the Utrecht Patient Oriented Database (UPOD) who were 18 years or older with CKD (defined as an eGFR &amp;lt;60 ml/min/1.73 m2 or an UACR &amp;gt; 3 mg/mmol present for &amp;gt;3 months) and visited one of the cardiovascular outpatient clinics of the University Medical Center Utrecht between 2012 and 2019 were included. Patient phenotypes were derived with latent class analyses based on age, sex, CKD stage, cause of kidney disease, and (cardiovascular) comorbidities. The incidence rate/100 person years (IR/100PY) for all-cause mortality and kidney failure (defined as initiation of kidney replacement therapy or a sustained eGFR &amp;lt;15) and 95% confidence interval (95% CI) was calculated for each phenotype. Results Overall 9005 patients were included (mean age 65 ± 14 years, 42% women, mean estimated glomerular filtration rate (eGFR) 49 ± 17 ml/min/1.73 m2). The median follow-up was 3.8 years [interquartile range 1.8–6.4]. Latent class analysis identified 7 phenotypes with the following characteristics: phenotype 1 were young patients with primary kidney disease (10%); phenotype 2 were patients with diabetes and a preserved eGFR (9%); phenotype 3 were patients with low comorbidity and inflammation (28%); phenotype 4 were older patients with a history of cardiovascular disease (27%); phenotype 5 were older patients with a history of cardiovascular disease and severe CKD (16%); phenotype 6 were younger patients with a kidney transplant and low comorbidity (6%); and phenotype 7 were older patients with a kidney transplant and cardiovascular disease (6%). The risk of all-cause mortality and kidney failure differed significantly between the identified phenotypes. The phenotypes of younger kidney transplant recipients, younger patients with primary kidney disease, and diabetes with preserved eGFR had the lowest risk for all-cause mortality (for all, IR/100 PY &amp;lt;5) (Fig. 1). The phenotypes with an intermediate incidence rate for all-cause mortality were the low comorbidity and inflammation phenotype (IR/100PY 7.4, 95% CI 6.9–8.0), the phenotype of older patients with cardiovascular disease (IR/100PY 7.2, 95% CI 6.7–7.8), and the phenotype of older patients with a kidney transplant and cardiovascular disease (IR/100PY 6.5, 95% CI 5.5–7.6). The phenotypes with highest incidence rate for all-cause mortality was the phenotype of older patients with cardiovascular disease and severe CKD (IR/100PY 12.5, 95% CI11.5–13.4). The phenotypes with the lowest risk for kidney failure were the diabetes phenotype, the low comorbidity and inflammation phenotype, and the phenotype of older patients with cardiovascular disease (all IR/100 PY &amp;lt;1). The phenotype of older patients with cardiovascular disease and severe CKD also had the highest risk to develop kidney failure (IR/100PY 5.8, 95% CI 5.1–6.6), followed by the phenotype of patients with primary kidney disease (IR/100PY 4.4, 95% CI 3.7 −5.5). Conclusion We identified 7 different phenotypes of patients with CKD including 2 phenotypes of patients with a kidney transplant with different clinical characteristics and prognosis. The differences in risk of all-cause mortality and kidney failure warrants a different monitoring and follow-up across the different phenotypes within the setting of CKD. Future studies should invest In evaluating the implementation of our identified phenotypes in routine clinical practice or clinical trial design with respect to differences in treatments.

#150 Effect of dapagliflozin in patients with CKD depending on primary kidney disease

Abstract Background and Aims Multiple trials have reported that SGLT2 inhibitors reduce the risk of its primary composite outcome of kidney disease progression or cardiovascular death in a wide range of patients with CKD. Our aim was to compare effects on kidney outcomes among the different types of kidney diseases. Method Eligible patients with eGFRs ≥30-45, or ≥45-90 ml/min/1.73 m2 with a urinary albumin-to-creatinine ratio of ≥300 mg/g, and receiving renin angiotensin system inhibitor, where indicated and tolerated were randomized to dapagliflozin 10 mg once daily vs placebo. Kidney disease progression was defined as a sustained ≥30% eGFR decline from randomization or to &amp;lt;10 mL/min/1.73 m2, start of maintenance dialysis or receipt of a kidney transplant, or renal death, and the effects of dapagliflozin were analyzed using a pre-specified Cox model. Testing for heterogeneity of effect between pre-specified kidney disease subgroups was performed, including exploratory analyses by specific glomerular disease etiologies. Results 362 participants were followed for a median of 2.0 years. 90 (24.8%) had diabetic kidney disease, 126 (34.8%) had glomerular disease, 94 (26%) had hypertensive or renovascular disease, and 52 (14.4%) had other or unknown causes. Overall, dapagliflozin reduced the risk of kidney disease progression by 34% (dapagliflozin 29/178 vs placebo 48/184; hazard ratio 0.62, 95% CI 0.51-0.78). This relative risk reduction appeared broadly similar in subgroup analyses by primary cause of kidney disease and by different types of glomerular disease. Conclusion Our study with a few numbers of patients with diabetic and non-diabetic causes of CKD showed that dapagliflozin reduced risk of kidney disease progression with relative risk reductions that were broadly similar across the different CKD etiologies.

#1439 Risk factors and significance of a reduction of serum albumin after start of PD

Abstract Background and Aims A reduction in the serum level of albumin following the initiation of peritoneal dialysis (PD) has been reported to associate with impaired survival. Our aim was to identify pre-PD risk factors of drop of serum albumin, and to estimate how a decrease in albumin level affects PD patients’ survival prognosis. Method We included all adult patients who had been on PD for at least half a year in the Helsinki area in Finland during the years 2004 to 2019. Patients who had a dialysis history longer than 1 year before transferal to PD were excluded. We analysed the serum albumin level at start of PD and the last available albumin level before 6 months after start of PD. A 20% reduction of serum albumin was considered significant. Logistic regression was used to assess the association between risk factors (age, sex, primary kidney disease, comorbidities, laboratory variables) and a 20% drop of serum albumin. Cox regression was employed to study the effect of albumin drop on survival with adjustment for confounders. Results Of 379 patients, 80 (21%) showed a reduction of serum albumin of at least 20% after start of PD. High age, high albumin level at start of PD, high level of HDL cholesterol and low level of ionized calcium all associated independently with the risk of an albumin drop in the logistic regression analysis. The albumin level at start (hazard ratio 0.94 per one g/l increment, 95% CI 0.89-0.98) and a 20% or larger drop of albumin level (HR 2.3, 95% CI 1.4-3.9) were connected to impaired survival irrespective of each other. Other independent predictors of worse survival were high age, peripheral vascular disease, a history of stroke, and diabetes. Conclusion A drop of serum albumin after start of PD is frequent and associates with impaired survival. Drop of albumin is more common among elderly patients and those with high values HDL cholesterol or low levels of ionized calcium.

#741 Gender differences in vascular access for prevalent dialysis patients

Abstract Background Gender disparities of some aspects of vascular access (VA) for hemodialysis (HD) have been reported. Aim To analyze the VA profile of prevalent HD patients (pts) according to gender in Catalonia Method Data from the Catalan Renal Registry of end-stage kidney disease (ESKD) pts over 18 years of age treated by HD on 31 December were examined from 1997 to 2021. Results The total cumulative number of follow-ups registered for prevalent ESKD pts treated by HD was 95 575 out of 25 130 pts; we have VA information for most of the follow-ups (93.1%, 88 980/95 575). The number of prevalent HD pts increased from 3104 in 1997 to 4270 in 2021. The characteristics of prevalent HD pts in 2021 (n = 4270) were different for male (n = 2731) vs female (n = 1539) regarding mean age (69.1 ± 14.6 vs 70.9 ± 14.3 years), age bracket &amp;gt;74 years (42.4% vs 48.3%), median time on HD [24.0 (9.8−48.2) vs 27.6 (10.5−59.1) ], aetiology of ESKD as polycystic kidney disease (4.4% vs 7.2%), normal functional status (38.0% vs 28.4%), cardiovascular disease (76.3% vs 71.1%) and obesity rate (body mass index BMI&amp;gt;30 kg/m2: 17.4% vs 27.2%) (for all comparisons, p &amp;lt; 0.001). The distribution of the VA used for performing HD in 2021 was also different in men vs women: fistula AVF (58.1%, n = 1465 vs 45.6%, n = 657), graft (1.8%, n = 45 vs 3.5%, n = 51) and tunnelled catheter (35.8%, n = 903 vs 45.8%, n = 660) (for all comparisons, p &amp;lt; 0.001) ; there were no differences for non-tunnelled catheter (4.3%, n = 107 vs 5.0%, n = 72) (p = 0.15). In addition, the type of AVF was different in men vs women: radiocephalic AVF (53.9% vs 40.9%) and brachial artery-based AVF (46.1% vs 59.1%) (p &amp;lt; 0.001). The percentage of pts who required at least one hospital admission or outpatient procedure for any VA pathology in 2021 was similar when comparing men [7.3% (n = 180) and 19.6% (n = 456), respectively] and women [8.6% (n = 122) and 19.3% (260), respectively] (p = 0.34 and p = 0.38, respectively). Regarding the total cumulative number of VA used for HD, the percentage of pts who used only one VA was higher for men (50.4%, n = 1265) than women (47.1%, n = 663); however, this difference is reversed when the percentage of pts who used ≥4 VA was calculated: 11.5% (n = 289) vs 14.4% (n = 203) (for all comparisons, p = 0.001). The percentage of pts who have been dialyzed through AVF at some point over time was higher for men (69.2%, n = 1889) than women (62.6%, n = 964) (p &amp;lt; 0.001) The probability of performing HD through AVF in 2021was independently associated with male gender (odds ratio 1.58 [95% confidence interval: 1.36–1.82], p &amp;lt; 0.001) after adjusting for age, time on HD, primary kidney disease, cardiovascular disease, functional status and BMI (multivariate logistic regression analysis). The percentage of both men and women on HD through AVF decreased progressively from 1997 (89.1% and 81.3%, respectively) to 2021 (58.1% and 45.6%, respectively) (for both comparisons, p &amp;lt; 0.001). The percentage of prevalent men on HD with AVF was always higher over time than that of women from 1997 (89.1% vs 58.1%) to 2021 (81.3% vs 45.6%) (for both comparisons, p &amp;lt; 0.001). Conclusions 1) AVF was the main type of VA used for prevalent men on HD, but AVF and tunnelled catheter shared this ranking in women. 2) Male gender was an independent factor associated with a 58% greater probability of performing HD through AVF than female. 3) The percentage of prevalent HD pts dialyzed through AVF progressively decreased over time in both sexes but it was always higher in men than women. 4) The type of AVF mainly used was different depending on gender: radiocephalic AVF for men and brachial artery-based AVF for women.

#2848 Persistent albuminuria is a marker of persistent congestion in patients with chronic heart failure

Abstract Background and Aims Albuminuria is prevalent in patients with heart failure (HF) and associated with poor prognosis. Initial reports indicate albuminuria as a congestion marker in HF. Frequency and associations of persistent albuminuria with kidney function, NT-proBNP and venous congestion in this population are not clearly understood. We aimed to evaluate the dynamics of albuminuria and its relationship with congestion and renal function in patients with chronic HF (CHF). Method The study included patients ≥18 years, observed in an outpatient HF center, who signed an informed consent. Patients receiving renal replacement therapy, with cancer or primary kidney diseases were excluded. The visits were carried out with an interval of 3 months. During each visit we performed routine physical examination, laboratory tests (NT-proBNP, urine albumin/creatinine ration (uACR), and serum creatinine) and pulse-wave Dopplerography to assess renal venous blood flow. Persistent albuminuria was defined as maintaining an uACR &amp;gt; 30 mg/g on two visits. Albuminuria level was assessed according to KDIGO guidelines 2012 (A1, A2, A3). The absence of venous congestion was defined as continuous renal blood flow, while venous congestion - as intermittent (biphasic or monophasic) blood flow. A P value &amp;lt;0.05 was considered statistically significant. We prospectively included 103 patients with CHF (46% male, mean age - 70 (61;75) Me (IQR) years, 53% with reduced ejection fraction (EF), mean EF 45(34;53)%, 92% hypertensive, 60% with atrial fibrillation, 34% with diabetes mellitus type 2, 51% with chronic kidney disease (CKD), 43% with coronary heart disease). Results Mean uACR values at the 1st visit was 18(8;56) mg/g, at the 2nd visit - 11(0;35) mg/g. The frequency of albuminuria levels at the 1st visit were A1-66%, A2-26%, A3-8%; at the 2nd visit – A1-73%, A2-23%, A3-4%. Persistent albuminuria was detected in 37 patients (36%). The mean values of albuminuria were higher in the persistent albuminuria group on the 1st visit (76(39;222) vs 10.5(0;19.5) for patients with and without persistent albuminuria, p&amp;lt;0.001) and on the 2nd visit (94(44;176) vs 7(0;13), p &amp;lt; 0.001). The patient groups were comparable in gender, age, frequency of comorbidities, EF. The administration of disease-modifying therapy was the same in the groups, however, the dose of loop diuretic was higher in the group of persistent albuminuria (20 (10;75) vs 10(5;20) mg respectively, p = 0.024 (doses in terms of furosemide)). Serum creatinine level was 95(79;121) mmol/l; GFR (CKD-EPI 2021)- 69(52;88) mL/min/ 1.73 m2 at the 1st visit. Kidney function did not statistically differ in the groups with and without persistent albuminuria (at the 1st visit eGFE - 63(52;87) vs 70 (50;90) mL/min/1.73 m2, p = 0.52 and the 2nd visit eGFR- 68(48;85) vs 66 (48;89) mL/min/1.73, p = 0.65 respectively). The level of NT-proBNP was higher in patients with persistent albuminuria during the 1st (926 (472;1820) vs 550(260;919), pg/ml p = 0.04) and the 2nd visit (1244(987;2000) vs 593(264;1405), pg/ml, p = 0.0008). Intermittent renal veins blood flow on the 2nd visit was observed in 26 patients (25%). In patients with persistent albuminuria persistence of intermittent venous renal blood flow was more frequently than in patients without it (43% vs 7%, p = 0.017, respectively). Figs. 1 and 2 demonstrate that renal venous congestion was more severe in group of persistent albuminuria on visit 1st and 2nd respectively. Conclusion Persistent albuminuria over 3 mounts in patients with stable chronic heart failure is associated with persisting congestion (higher NT-proBNP levels and higher incidence and severity of renal venous congestion). There was no association between changes in albuminuria and changes in renal function.

#2049 Prognosis of decreased renal function in patients with arterial hypertension

Abstract Background and Aims Chronic kidney disease and hypertension are closely related in cause and effect. As the glomerular filtration rate decreases, the frequency and severity of arterial hypertension increases. In addition, the risk of morbidity and mortality from cardiovascular diseases increases significantly with comorbidity of arterial hypertension and chronic kidney disease. The purpose of this study was to identify predictors of a decrease in GFR below 60 ml/min in patients with arterial hypertension. Method The cross-sectional study included 43 patients with arterial hypertension (average age 56.7 (10.6) years). Exclusion criteria were age over 80 years, primary kidney disease, diabetes mellitus, cancer, heart failure, stage III arterial hypertension. All patients underwent determination of cystatin C in the blood, the composition of the body was studied using the bioimpedance method and 24-hour blood pressure monitoring. To identify predictors of kidney damage, we used regression analysis with ROC curve estimation using MedCalc software. Results The optimal value (cut-off point) of the content of total adipose tissue, which allows the most accurate prediction of a decrease in GFR &amp;lt; 60 ml/min in patients with hypertension, was 26.1% (sensitivity −100%, specificity—77.8%), and the content of total muscle tissue—35.9% (sensitivity −100%, specificity—44.4%). The optimal value (cut-off point) of cystatin C was 1.13 (sensitivity −100%, specificity—53.9%), AUC—0.73 (0.46; 0.92). At the same time, when this predictor was included once in multiple logistic regression, the statistical significance decreased (p = 0.5). Among individual predictors of decreased renal function, indicators of 24-hour blood pressure monitoring were studied. The optimal value (cut-off point) of the ambulatory arterial stiffness index, which allows the most accurate prediction of a decrease in GFR &amp;lt; 60 ml/min in patients with arterial hypertension, was 0.36 (sensitivity −100%, specificity—71.4%), an indicator of an increase in the rate of increase in diastolic blood pressure. blood pressure—0.27%, AUC 0.74 (0.48; 0.91)) and the rate of increase in nighttime decrease in systolic blood pressure—8.1%, AUC 0.71 (0.47; 0.89). Conclusion Increase in total adipose tissue &amp;gt; 26.1%, decrease in total lean tissue &amp;lt;35.9%, increase in ambulatory arterial stiffness index &amp;gt;0.36, increase in rate of increase in diastolic blood pressure &amp;gt;0.27%, and increased nocturnal decrease in systolic blood pressure &amp;gt; 8.1% were identified as significant predictors of a decrease in GFR below 60 ml/min in hypertension.

#1469 Predicting mortality risk in incident dialysis patients using clinical predictors and patient-reported predictors

Abstract Background and Aims Prognostic prediction models can be used to identify dialysis patients that are at high risk of dying. By doing so, vulnerable patients can be monitored more closely and treatment can be intensified where needed. In addition, individualized predictions can help inform patients about their prognosis. Traditionally, prognostic models primarily rely on known clinical predictors such as age, comorbidities and laboratory markers. Although it is still unchartered territory in the field of nephrology, studies in other fields have shown that patient-reported predictors, like pain and fatigue, can be of use as predictors of survival. Predictive performance of current prognostic models for mortality risk amongst dialysis patients is subpar and we hypothesized that the addition of patient-reported predictors may improve predictions. Therefore, we aimed to develop a novel prognostic model for the prediction of two-year mortality in patients starting dialysis using both clinical predictors and patient-reported predictors. Method Data from the Netherlands Cooperative Study on the Adequacy of Dialysis (NECOSAD) were used to develop two prognostic models for the prediction of 2-year all-cause mortality in incident dialysis patients: a base model consisting of clinical predictors and an updated model containing additional patient-reported predictors. Missing data were handled using a tenfold multiple imputation with fully conditional specification. The imputation model included all candidate predictors as well as the outcome variable of 2-year mortality. Predictors for the base model were selected based on existing mortality models and clinical expertise. Patient-reported predictors to add to the base model were chosen based on availability in NECOSAD, clinical expertise and literature describing patient-reported predictors. The models were developed using multivariate logistic regression and their discriminative abilities were assessed by calculating the area under the curve (AUC). Results A total of 1956 patients from NECOSAD were used for the analyses. Of these, 447 (22.9%) died within two years after baseline (3 months after dialysis initiation). The base model contained the following predictors: age, sex, serum albumin, C-reactive protein, diabetes mellitus, hemoglobin, residual kidney function (GFR at 3 months), body mass index, cardiovascular disease, dialysis modality, malignancy and primary kidney disease. The discriminative abilities of the base model were moderate with a AUC of 0.79 (95% CI: 0.77-0.82). The base model was updated using the following patient-reported predictors: mental component score, physical component score, general health perception, number of symptoms, symptom burden (measured with the KDQOL instrument) depressive symptoms, fatigue and pain. The addition of the patient-reported predictors marginally improved the predictive performance of the model achieving an AUC of 0.81 (95% CI: 0.79-0.84). Conclusion The base model including clinical predictors was enhanced slightly by the addition of patient-reported predictors.

#2913 The malignancy in transplant recipients exposed to immunosuppressive therapy prior kidney transplantation

Abstract Background and Aims Post-transplant malignancy has a negative effect on morbidity and mortality of kidney transplant recipients (KTR). Pre-transplant exposure to immunosuppression (PTI) might increase the risk for post-transplant malignancy. Method In a single-center, retrospective study of 3874 KTR transplanted between January 2000 and December 2019 with follow-up until 2020 the cancer incidence and outcome were compared between KTR with glomerulonephritis as primary kidney disease treated with PTI (GN group) and KTR with polycystic kidney disease as non-PTI-receiving controls (PKD group). Results In both groups, the average time from transplantation to cancer manifestation was similar (p=0.947) as well as from cancer diagnosis to death (p=0.856). Depending on cancer type we observed no difference between time of onset (p=0.351) but in incidence rate for death. The worst survival probability was in lung (0.041 years, 95% confidence interval (CI) [0.014-0.301]) and gastrointestinal (0.350 years, 95% CI [0.022-1.558]) cancer. The risk of cancer increased with age (hazard ratio (HR)=1.05, 95% CI [1.03, 1.07], p&amp;lt;0.001). After adjustment, GN increased the risk for post-transplant cancer (HR=1.72, 95% CI [1.12, 2.63], p=0.013). PTI exposure had adjusted increase of risk of cancer (HR=1.76, 95% CI [1.07, 2.89], p=0.027). Posttransplant malignancy was associated with higher risk of death (HR=8.29, 95% CI [5.46, 12.59], p&amp;lt;0.001) together with patient's age at the time of transplant surgery (HR=1.09, 95% CI [1.06, 1.11], p&amp;lt;0.001) while neither gender (p=0.633) nor PTI (=0.0639). Patient's adjusted probability of remaining cancer-free posttransplant had decreasing tendency over time. Conclusion Patients with GN exposed to PTI showed higher adjusted risk of development of post-transplant malignancy.

#634 Prognosis is still poor in patients with posttransplant C3 glomerulopathy: a multicenter cohort

Abstract Background and Aims Data on patients with posttransplant recurrent or de novo C3 glomerulopathy (C3G) are limited. We therefore aimed to analyze features and outcomes of patients developed posttransplant C3G. Method In this retrospective multicenter study conducted across 3 centers, we collected the data of kidney transplant recipients (KTRs) who were diagnosed with posttransplant recurrent or de novo C3G between 2014-2023 and followed for at least 3 months after the diagnosis. Demographic, clinical, laboratory and histopathological characteristics of patients were retrieved from the databases of participating centers. Primary outcome was defined as death-censored graft loss necessitating dialysis or re-transplantation, and secondary outcome was complete (CR) or partial remission (PR). CR was the recovery of baseline eGFR and proteinuria of &amp;lt;0.5 g/g. PR was ≥50% reduction of proteinuria (and to &amp;lt;3 g/g in patients with nephrotic-range proteinuria at baseline) plus stabilization or improvement in kidney function. Results Eleven patients were identified, and 10 with follow-up data were included. Detailed features of patients were shown in the Table. Five (50%) were male, and mean age at the time of transplantation (KTx) was 33.2 ± 8.5 years. Nine KTRs (90%) were diagnosed with recurrent C3G and the etiology of primary kidney disease was not known in one patient. Majority of KTx were performed from living donors (9.90%). One patient had a history of T-cell mediated rejection before posttransplant C3G, which had showed good response to anti-rejection treatment. Posttransplant C3G was diagnosed after a median of 26 (3-85) months after KTx, and mean age was 36.8 ± 9.1 years. Mean hemoglobin, serum creatinine, serum albumin, and proteinuria at the time of diagnosis were 10.5 ± 1.8 g/dl, 1.9 ± 0.7 mg/dl, 4.1 ± 0.5 g/dl, and 1.1 ± 0.9 g/g, respectively. Monoclonal disorders were excluded by using serum and urine electrophoresis and serum free light chain assays in all KTRs. Serum C3 was low (67.1 ± 29.7 mg/dl, ref: 90-180 mg/dl) in 7 of 8 KTRs with available data (87.5%). Further immunosuppressive treatment was administered in 9 cases. Eculizumab was used in 8, and 1 patient was treated with pulse steroids and therapeutic plasma exchange. Median duration of treatment was 14.5 (3-24.3) months. Four patients (44.4%) who were treated with eculizumab showed CR. After a median of 32 (9.5-82) months, 5 KTRs (50%) experienced graft loss despite eculizumab use in 3 of them. No adverse events attributed to treatment were observed. Conclusion Prognosis is still quite dismal in patients with posttransplant C3G despite the use of eculizumab. Better treatment options are urgently needed.

#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) &amp;lt;60 ml/min/1.73 m2 or an urinary albumin creatinine ratio (UACR) &amp;gt;3 mg/mmol present for &amp;gt;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.

Group2 innate lymphoid cells ameliorate renal fibrosis and dysfunction associated with adenine-induced CKD

Renal fibrosis is a common pathway of chronic kidney disease (CKD) progression involving primary kidney injury and kidney diseases. Group 2 innate lymphoid cells (ILC2s) mediate type 2 immune responses irrespective of antigen presentation and play a reno-protective role in kidney injury and disease. In the present study, we observed a decrease in kidney-resident ILC2s in CKD and found that enrichment of ILC2s in the kidney ameliorates renal fibrosis. In CKD kidney, ILC2s preferentially produced IL-13 over IL-5 in response to IL-33 stimulation, regardless of ST2L expression. Moreover, GATA3 expression was decreased in ILC2s, and T-bet+ ILC1s and RORγt+ ILC3s were increased in CKD kidney. Adoptive transfer of kidney ILC2s into adenine-induced CKD model mouse improved renal function and fibrosis. Renal fibroblasts cultured with IL33-activated kidney ILC2s suppressed myofibroblast trans-differentiation through Acta2 and Fn-1 regulation. These results suggest that kidney ILC2s prevent CKD progression via improvement of renal fibrosis. Our findings also suggest that ILC2s may contribute to the development of new therapeutic agents and strategies for tissue fibroses.