Kidney Disease Research Articles

#2308 The effect of Dapagliflozin on albuminuria and biomarkers associated with renal function in patients with β-thalassemia and/or sickle-cell disease

Abstract Background and Aims Patients with β-thalassemia present already from the 1st year of life with serious anemia thus needing regular blood transfusions in order to attain normal hemoglobin levels. Chronic anemia, iron overload and the use of iron chelating agents have been associated with renal dysfunction. In sickle-cell syndromes, which include sickle-cell anemia and sickle-cell trait, patients present with typical kidney functional and structural defects, resulting in urinary concentrating defects, distal nephron dysfunction and albuminuria. Sodium–glucose cotransporter-2 inhibitors (SGLT-2i) have shown beneficial effects on renal outcomes in large clinical trials with the added benefit of a substantial decrease in albuminuria. The aim of this prospective, non randomized open label study is to investigate the effect of Dapagliflozin at a dose of 10 mg daily on albuminuria and the overall progression of CKD in patients with β-thalassemia and/or sickle-cell disease undergoing regular blood transfusions. Method In this study we included adult patients undergoing regular blood transfusions with a baseline albuminuria of ACR>30 mg/gCr (assessed with a spot urine sample) who received treatment with Dapagliflozin, a second group with no albuminuria that did not receive treatment and a group of adults with no kidney disease (Controls). In all patients renal function biomarkers were measured in urine and serum with commercial ELISA kits (NGAL and uPAR in serum, MMP9 and KIM-1 in urine), while in patients that received Dapagliflozin additional measurements of ACR and eGFR (CKD-EPI formula) were performed after 3 months of treatment initiation. Results In this study we included 16 patients (7 males) with β-thalassemia and/or sickle-cell disease with ACR>30 mg/gCr, 35 patients (17 males) with β-thalassemia and/or sickle-cell disease without albuminuria and 20 controls (13 males). Patients that received Dapagliflozin showed a significant reduction in albuminuria three months post-initiation of treatment (ACR: 0.52 ± 1.2 vs. 0.3 ± 0.68 mg/g, p=0.006) while kidney function showed a slight non-significant reduction (eGFR: 99.3 ± 21.7 vs. 94.7 ± 28.9 ml/min/1.73m2, p=0.36). Concerning the urine and serum biomarkers of tubular dysfunction, inflammation and kidney disease progression, all were significantly increased in patients with β-thalassemia and/or sickle-cell disease in comparison to controls (Table 1). In patients that received treatment with Dapagliflozin, NGAL, MMP-9 and suPAR at 3 months post-treatment initiation did not show any significant reduction (Table 2). Conclusion Patients with β-thalassemia and/or sickle-cell disease show increased urine and serum levels of kidney damage biomarkers in comparison to healthy controls. Treatment of these patients with Dapagliflozin for 3 months has a significant effect in albuminuria reduction while it does not alter urine and serum levels of these biomarkers.

#2830 Treatment of primary and secondary distal renal tubular acidosis with a prolonged release formulation of potassium citrate and potassium bicarbonate

Abstract Background and Aims Distal renal tubular acidosis (dRTA) is a rare kidney disease. It can be inherited, i.e. primary (PdRTA), or acquired i.e. secondary (SdRTA). Secondary dRTA is more prevalent in the adult population and is usually caused by underlying autoimmune diseases (e.g. Sjogren syndrome). Both forms of dRTA are characterized by alkaline urine, kidney stone formation, nephrocalcinosis, chronic kidney disease, while metabolic acidosis can be variable. The treatment is based on the substitution of alkali substances. Our clinical study aims to describe a cohort of adult dRTA patients (both PdRTA and SdRTA) treated for 18 months by a prolonged-release alkalizing formulation of potassium citrate and potassium bicarbonate, in terms of electrolyte disbalance correction, metabolic control, nephrolithiasis complications and kidney function. Method Data from seven patients with dRTA (3 with PdRTA and 4 with SdRTA, mean age 44 years, women 71%) taking prolonged-release alkalizing formulation of potassium citrate and potassium bicarbonate in our center, were retrospectively collected and analyzed. The patients were previously treated with alkalizing agents (mostly sodium bicarbonate and potassium citrate). Patients were followed up for up to 18 months after inducing prolonged-release alkalizing formulation of potassium citrate and potassium bicarbonate was introduced. Kidney function, metabolic acidosis control (serum bicarbonate), serum electrolytes, urinary calcium excretion, and urinary citrate were measured. Nephrolithiasis complications and patient compliance were also evaluated. The urine and blood samples were analyzed two weeks after introducing the new drug and every 3 months afterward. Data are presented as mean ± standard error of the mean. Student T-test was used to calculate p values. Results The patients were taking on average 48 mEq of the drug (range 32-72 mEq), the dosage remained the same during the follow-up period (p = 0.365). The average follow-up period was 10 months (range 3-18 months). The metabolic acidosis was well controlled (serum bicarbonate was 24 ± 1.71 mmol/l at baseline, 24.4 ± 1.5 mmol/l at the end of follow-up, p = 0.680). Kidney function remained stable (GFR 73.5 ± 22.67 ml/min/1.73 m2 at baseline, 73 ± 22.69 ml/min/1.73 m2 at the end, p = 0.977). Serum potassium was also well controlled (4.07 ± 0.45 mmol/l at baseline, 4.32 ± 0.40 mmol/l at the end, p = 0.344), as well as calcium in 24-hour urine (2.75 ± 0.59 mmol/24-hour urine at baseline, 2.35 ± 0.12 mmol/24-hour urine at the end, p = 0.222). Urinary citrate levels (calculated as citrate/creatinine ratio) remained in the lower part of the reference range during the follow-up period (103.3 ± 68.3 mmol/mol at baseline, 114.6 ± 64.9 mmol/l at the end, p = 0.775). Two patients had acute renal colic caused by nephrolithiasis, without the need for surgical intervention. Safety and adherence to treatment remained good with no gastrointestinal side effects, one patient discontinued the drug due to headaches. Conclusion Our data show that treatment with a prolonged-release alkalizing formulation of potassium citrate and potassium bicarbonate in adult dRTA patients can achieve good control of metabolic acidosis and electrolyte disbalance with stable kidney function without the need to escalate the dose of the drug during the follow-up period. The adherence to the treatment remained good with no gastrointestinal side effects.

#2366 Beneficial effects of TRIM33 on myokine-mediated renal function recovery in diabetic and obese mice

Abstract Background and Aims Myokines secreted from myocytes are related to improving metabolic diseases such as diabetes, obesity, and chronic kidney disease (CKD). Patients with diabetic kidney disease (DKD) have lower irisin levels, suggesting that a low level of irisin is a risk factor for the progression of CKD. However, it is not well known how myokines can alleviate metabolic kidney injury. This study aimed to investigate the effect of TRIM33, a negative regulator of TGF-β1 signaling, as a novel strategy to treat multiple metabolic complications simultaneously in the kidneys and muscles of obese db/db mice. Method For the in vivo experiment, five-week-old male db/db mice were assigned to three groups: db/m+, db/db, and db/db with TRIM33 plasmid mice. TRIM33 plasmid (40 μg/mice) was administered intraperitoneally. Serum glucose and myokine levels, urinary albumin excretion, renal and muscle morphology, and myokine expression in muscles were assessed. In vitro, C2C12 cells were cultivated with 2% horse serum and lipid insult in the absence or presence of TRIM33 plasmid and were analyzed for myocyte differentiation and myokines expression or production. Results TRIM33 treatment showed beneficial effects on tubular injury, tubulointerstitial fibrosis, mesangial expansion, renal dysfunction, variations in skeletal muscle fiber size and arrangement, skeletal muscle activity, and serum myokines levels in db/db mice. During the differentiation of C2C12 cells, myokine mRNA and protein expression and secretion were increased in TRIM33-transfected cells. Reduced levels of myokines expression and secretion in C2C12 cells with palmitate were improved by TRIM33 transfection. In coculture with HK-2 and C2C12 cells, increased EMT transition in TGF-b-treated HK-2 cells by coculture with palmitate-treated C2C12 cells was decreased in coculture with palmitate-treated C2C12 cells with TRIM33 transfection. Conclusion This study showed that TRIM33 is involved in the recovery of renal dysfunction via myokine in mice with diabetes and obesity.

#1918 L-NAME accelerates the progression of diabetic kidney disease in mice

Abstract Background and Aims Diabetic kidney disease (DKD) represents one of the major causes of end stage kidney disease worldwide. Despite DN having such a high incidence, mouse models of DN rarely mimic all aspects of the human disease, besides showing very slow progression and sometimes maintenance issues. For this reason, in this project we aimed to develop an accelerated, reproducible and accessible mouse model of DN. Method For our experiments we chose 9-week-old female and male of the leptin receptor knock-out (BKS.Cg-Dock7m +/+ Leprdb/J) mice as type 2 diabetes model. As these mice are still not prone to develop severe kidney injury despite their diabetic condition, we administered the eNOS inhibitor L-NAME for 6 weeks, in order to suppress nitric oxide production and therefore to aggravate kidney damage. Mice were divided in three groups: one vehicle control group, one receiving 40/mg/kg/day of L-NAME and one receiving 80/mg/kg/day of L-NAME dissolved in drinking water. Blood pressure and glomerular filtration rate (GFR) were measured at different time points, together with glycemia and albuminuria. Weight and water intake were also monitored throughout the study. At the end of the experiment, animals were killed and blood and organs collected for further analysis. Results Mice treated with 80 mg/kg/day of L-NAME showed an average increase of 10 mmHg in systolic blood pressure, with a peak of 30 mmHg increase at week 4 of treatment. On the other hand, 40 mg/kg/day of L-NAME did show any effect on blood pressure. Despite the different effect on blood pressure, three weeks of L-NAME administration caused a significant reduction in GFR at both doses, with 5% reduction for the 40 mg-group and 23% for the 80 mg-group. For the 80 mg-group we observed an even further GFR decline after 5 weeks of treatment, with a 28% reduction. No change in GFR was observed in the controls. This decrease in GFR was accompanied by a 10-fold increase in urinary albumin for both experimental groups already after 3 weeks of treatment, which after 4 weeks slightly declined but remained significantly higher than the controls (p < 0.0001). At a histological level, PAS staining of kidney sections revealed that in particular mice treated with 80 mg of L-NAME have enlarged Bowman capsule and glomerular tuft area, besides a reduced glomerular capillary density, coinciding with mesangial expansion. We also stained for overall collagen deposition with picrosirius red staining in order to detect possible fibrosis formation. We then observed that 80 mg of L-NAME accelerates interstitial fibrosis in the cortical area of the kidney, which also overlapped with an increased deposition of collagen I. This increase in collage I was also detected in kidney cortex of mice treated with 40 mg of L-NAME, although their overall collagen deposition and therefore fibrotic tissue did not differ from the control group. The medullar region of kidneys was also analyzed, but none of the two experimental groups revealed significant differences in terms overall collagen or collagen I deposition. Unlike mesangial expansion and fibrosis, L-NAME did not influence microphages infiltration, as revealed by CD68 staining in kidney sections. This suggests that L-NAME treatment does not accelerate kidney damage by triggering or accelerating inflammatory processes. This was also confirmed by qPCR analysis of kidney tissue, where the expression pro-inflammatory markers, such as IL1β, TNFα and MCP-1, did not change in the experimental groups. Conclusion Our results show that L-NAME considerably accelerates the progression of DKD in diabetic mice, with GFR declining and progressive albuminuria already after 3 weeks. Such disfunction is confirmed at 6 weeks by histological analysis, where mesangial expansion and fibrosis were detected. This model can be used to assess the therapeutic potential of novel interventions aimed to slow down DKD.

#395 Gut dysbiosis in ADPKD patients: a controlled pilot study

Abstract Background and Aims Gut dysbiosis has been associated with chronic kidney disease (CKD) and nephrolithiasis and may thus be a factor explaining variability of outcome in autosomal dominant polycystic kidney disease (ADPKD). However, beside a single pilot study the gut microbiome has not been studied in ADPKD. Due to the implications of microbiota in inflammation and crystal formation, we hypothesized that gut dysbiosis could also negatively affect PKD. For this reason, we aimed to characterize the intestinal microbiome in a controlled pilot study of PKD patients and explore the potential impact of dysbiosis on PKD disease progression. Method This study was designed as an observational, cross-sectional controlled pilot study. 25 ADPKD patients were recruited from the AD(H)PKD patient cohort. 12 healthy control subjects were age- and sex matched. Patients with chronic bowel disease were excluded. Serum parameters including eGFR were analyzed around the timepoint of stool collection. The gut microbiome was analyzed by 16S rRNA gene profiling of stool samples. The sequencing data was processed using the DADA2 pipeline and QIIME version 2. Differentially abundant features were identified using linear discriminant analysis (LDA) effect size (LEfSe) analysis. Bacteria-derived serum uremic toxins (total and free Trimethylaminoxid, Indoxylsulfate, p-Cresyl-Sulfate) were measured using liquid chromatography coupled to tandem mass spectrometry (LC- MS/MS). Microbiome data was then correlated with age, kidney function, and markers of PKD disease progression like Mayo classification and early onset of arterial hypertension or urologic complications (<35 years of age). Results Healthy control subjects revealed a significantly higher abundance Actinobacteria (LEfSe LDA score = 3.9, p = 0.025) including probiotic Bifidobacteriaceae (LEfSe LDA score = 3.9, p = 0.021). ADPKD patients displayed a significantly increased abundance of potentially dysbiotic Enterobacteriaceae (LEfSe LDA score = 3.6, p = 0.009). Those findings were independent of kidney function. Most notably, the abundance of Streptococcaceae were significantly overrepresented in PKD patients with Mayo Classes 1D and 1E compared to 1A-1C (p = 0.011). Additionally, early onset of hypertension (< 35 years of age) was associated with an increased abundance of potentially dysbiotic Proteobacteria and a decreased abundance of potentially probiotic Tannerelleaceae. Furthermore, ADPKD patients revealed increased abundance of Peptococcaceae with increasing age and declining kidney function. Finally, serum uremic toxins were significantly increased in ADPKD patients and highly correlated with eGFR. Serum uremic toxins revealed a tendency of positive correlation with the abundance of Peptococcaceae which did not reach statistical significance. Conclusion This controlled pilot study confirms alterations of specific OTUs in PKD patients showing an increase of Enterobacteriaceae and decrease of probiotic Bifidobacteriaceae upon PKD. This suggests a potential shift towards gut dysbiosis. Most notably, the abundance of specific OTUs were observed to be associated with markers of rapid disease progression like Mayo classification 1D and 1E, as well as early onset of arterial hypertension. This suggests for the first time, that gut dysbiosis could affect PKD disease progression. However, it still remains unknown whether gut dysbiosis is caused by ADPKD itself or is a consequence of secondary circumstances such as antibiotic treatment which is common in ADPKD due to frequent urinary tract or cyst infections. Thus, further investigation in larger cohorts is warranted to elucidate the impact of gut microbiota on ADPKD.

#1086 Blood-brain barrier permeability in patients with end-stage kidney disease: results from the BREIN study

Abstract Background and Aims Chronic kidney disease (CKD) is associated with an increased risk of cognitive impairment. In several models of CKD in rodents, we highlighted that CKD was associated with cognitive impairment and increased blood-brain barrier (BBB) permeability, quantified using 99mTc-DTPA scintigraphy imaging (SPECT/CT). BBB permeability was both correlated with cognitive impairment and with indoxyl sulfate (IS) levels. Inactivation of Aryl Hydrocarbon Receptor (AhR), receptor of the IS, protected the CKD mouse from the IS-induced BBB permeability. The objective of the BREIN study is to confirm the existence of an increased BBB permeability in humans with CKD. Method The prospective cohort study BREIN (NCT04328415) prospectively included patients with end-stage kidney disease (ESKD), and healthy volunteers (Ctrl) matched in age (±5 years), gender, and educational level to a patient. In patients and volunteers, BBB permeability was quantified by brain 99mTc-DTPA SPECT/CT performed by a senior nuclear physician and as percentage of injected activity (%IA). A battery of neuro-cognitive tests was performed, serum uremic toxins accumulation and AhR activation were assessed in all participants. Results 15 ESKD patients and 14 healthy volunteers were included. In ESKD patients had higher BBB permeability compared to controls: 0.29 0.07 vs. 0.14 0.06%IA, p < 0.0001. ESKD patients displayed lower MoCA score: 22.0 ± 5.0 vs. 27.3 ± 2.8, p = 0.008, impaired short-term memory (doors test): 12.5 ± 3.4 vs. 16.5 ± 3.4, p = 0.009, higher Beck depression score 8.1 ± 9.1 vs. 2.7 ± 3.4, p = 0.046, and slightly more daily cognitive complaints: 42.5 ± 29.3 vs. 29.8 ± 14.0 p = 0.153. ESKD patients displayed higher IS levels (2.8 ± 2.3 mmol/L vs. 0.9 ± 0.7 mmol/L, p = 0.006) and AhR activation (37.5 ± 17.8% vs. 24.7 ± 10.4%, p = 0.027). In ESKD patients, no significant correlation was found between BBB permeability and scores in cognitive tests, or serum uremic toxins levels. Conclusion This study confirms that ESKD patients display an increased BBB permeability compared to matched healthy volunteers, as well as cognitive and impairment. Association with uremic toxins and cognitive impairment needs to be assessed in larger cohorts.

Sixty years of European Renal Association (ERA) Registry data on kidney disease: visualizing differences in clinical practice.

Sixty years of European Renal Association (ERA) Registry data on kidney disease: visualizing differences in clinical practice.

#2090 Kidney Biopsy by Nephrologists in Patients with Severe Renal Impairment: Complications and histological Spectrum

Abstract Background and Aims Kidney biopsy is the gold standard test for assessing kidney disease and offers pivotal insights into the diagnosis, prognosis, and treatment of kidney disorders. However, its application in patients with a diminished glomerular filtration rate (GFR) poses a heightened risk of complications. In this study, we explored the safety and utility of kidney biopsy in patients with an estimated GFR <15 ml/min/1.73 m2. Method In this prospective study, we enrolled consecutive adult patients with an eGFR below 15 ml/min/1.73 m2 who underwent a kidney biopsy and provided informed consent. Exclusions comprised patients with solitary or transplanted kidneys or acute kidney injury. All biopsies were performed under ultrasound guidance. Following the procedure, patients were observed for 24 hours to monitor complications, and an analysis of their associated risk factors was done. Results Among the 88 patients included in the study, 60% were male, 20% had diabetes, and 30% were hypertensive. Chronic glomerulonephritis (45%), with IGA nephropathy being the most prevalent), chronic tubulointerstitial disease (43%), and diabetic kidney disease (12%) were the predominant histological diagnoses in kidney biopsies. Peri-renal hematomas ≥2 cm were observed in 9 patients, with three requiring blood transfusions. A major complication necessitating angioembolization occurred in one patient. The biopsy sample was deemed adequate in 80% of patients (n = 70). The requirement of blood transfusion (p < 0.04) and hemodialysis before biopsy (p = 0.05) was associated with an increased risk of complications. This study suggests the safety and necessity of kidney biopsy in CKD patients, underscoring its importance for accurate diagnosis and the initiation of appropriate therapeutic measures, irrespective of GFR Conclusion This study suggests the safety and necessity of kidney biopsy in CKD patients, underscoring its importance for accurate diagnosis and the initiation of appropriate therapeutic measures, irrespective of GFR

#2832 Lean tissue mass is associated with mortality across different stages of chronic kidney disease: a systematic review and meta-analysis

Abstract Background and Aims Loss of lean tissue mass (LLTM) commonly occurs in multiple long-term conditions (LTC), including chronic kidney disease (CKD), and is thought to be associated with adverse outcomes including mortality, frailty surrogates and poor quality of life. It remains unclear whether LLTM is directly associated with mortality in CKD after adjusting for the severity of CKD or the degree of multimorbidity, and whether such associations remain in other LTC with similar levels of multimorbidity, such as heart failure (HF). Method A systematic review was conducted in adult CKD [kidney transplant (KT), CKDG3-5 or dialysis treated kidney failure (D-KF)] and HF patients who had whole body bioimpedance defined lean tissue mass (BI-LTM). The primary outcome was mortality, with secondary outcomes including hospitalisation and health related quality of life (HRQoL). The review was registered with PROSPERO (CRD42021240688) and was conducted according to PRISMA guidelines. Electronic database searches of MEDLINE, EMBASE, AMED, CINAHL, PsychInfo, Web of Science, CENTRAL, ICTRP and ISRCTN were searched from inception until June 2023. Data extraction and risk of bias assessments, using the Quality in Prognosis Studies (QUIPS) tool, was performed by two independent reviewers. Random effects meta-analysis was conducted using STATA SE16.2 using restricted maximum likelihood (REML) estimation. Results From 10,024 citations, 126 studies were identified (100 D-KF, 12 CKDG3-5, 2 KT, 3 mixed CKD and 9 HF) reporting outcomes on 143,053 D-KF, 15,164 CKDG3-5, 346 KTR and 3716 HF patients respectively. There were 1,227 deaths (over 2-5 years) in the HF studies and 16,471 deaths (over 1-20 years) in the CKD studies. The weighted mean eGFRCreat was 54 and 42 ml/min/1.73 m2 in the KT and CKDG3-5 studies, with only 3 HF studies reporting any measure of renal function (all using categorical cut offs). In 87 studies survival analyses of all-cause mortality (ACM) showed that BI-LTM was associated with mortality in 67%, 100%, 85% and 74% of the HF, KT, CKDG3-5 and D-KF studies respectively after adjusting for age, sex, diabetic status, comorbidity score, CRP / IL-6, albumin and bioimpedance defined fluid measures in 93%, 77%, 64%, 17%, 32%, 59% and 24% of analyses. Meta-analysis within D-KF studies reporting MVA revealed a 1-degree decrease in phase angle (pooled HR 1.82, 95% CI 1.50-2.20: Fig. 1A) and lean tissue index <10th percentile (pooled HR 1.48, 95% CI 1.31-1.66: Fig. 1B) was associated with ACM. Leave one out meta-analysis and sensitivity analyses removing studies at high-risk of statistical analysis and study confounding bias confirmed these pooled estimates were robust. Of the studies reporting secondary outcomes including hospitalisation and HRQoL (including the Short Form-36 and Kidney Disease Quality of Life Instrument), 67% showed associations with BI-LTM. Conclusion LLTM is associated with mortality across all stages of CKD and in heart failure. Furthermore, LLTM is associated with adverse outcomes such as hospitalisation and poor quality of life. This study confirms that LLTM potentially has an important role in the explanatory pathway for adverse outcomes in patients with LTCs, including CKD. Using BI-LTM may provide a way to identify early LLTM and target interventions to reduce the risk of adverse outcomes in these multimorbid cohorts.

#2155 Evaluating the health-related quality of life of patients undergoing haemodialysis: highlights from a multicentric nationwide study

Abstract Background and Aims Haemodialysis (HD) represents the most common renal replacement therapy for end-stage renal disease worldwide. Despite recent advances in HD the health-related quality of life (HRQoL) should be monitored in conjunction with clinical variables to optimize a comprehensive treatment. Method From June to July 2022, all patients from 47 clinics were included. Among other key relevant clinical variables, HRQoL was assessed by using the Kidney Disease Quality of Life Short Form (KDQOL-SF™ 1.3).It`s generic part is summarised in the physical component summary (PCS) and mental component summary (MCS). The specific part evaluates 11 domains: symptom/problem list; effects of kidney disease on daily life; burden of kidney disease; work status; cognitive function; quality of social interactions; sexual function; sleep; social support; dialysis staff encouragement; and patient satisfaction. All scores range from 0 (worst) to 100 (best). To ensure comparability of results, mean ± SD values are outlined, even though non-parametric tests were used to test associations. Results A total of 3,595 patients (67.3% male) completed the KDQOL (out of 4259 HD patients treated during study period). Most of them (67.18%) were over 60yo of age, and 65.67% had a severe comorbidity index score. In addition, 50.54% had a native AV fistula and only 3.92% were incident HD. PCS scores reported were higher in over 75yo (47.68 ± 10.63) rather than normative population (40.16 ± 11.62), indicating an overall good physical function. However, MCS values (33.17 ± 9.36) were indicative of substantial impact. Gender differences were noted across almost all disease-specific and generic domains (all p < 0.05). Severe comorbidity scores were associated with lower scores in certain renal specific domains and MCS. Finally, incident HD patients reported lower satisfaction and poorer perceived overall health (p-values = 0.001). Conclusion Although PCS scores reported were reasonable, a remarkable impact on mental health was found. Moreover, a differential impact of patient's HRQoL was captured based on gender and other variables highlighting the need of individualised evaluation and management of HD patients.

#3008 Very low protein diet with ketoanalogues supplementation could start haemodialysis with AVF without additional CVCs insertion

Abstract Background and Aims Nutritional interventions and a low-protein diet (LPD) are a critical point in the management of chronic kidney disease (CKD). Several protein-restricted dietary regimens have been proposed in patients with end stage kidney disease: a typical LPD provides around 0.6–0.7 g·kg meanwhile a very low-protein diet (VLPD) provides around 0.3–0.4 g·kg and it is basically a vegetarian diet which has to be supplemented with essential amino acids (EAA) to satisfy the body nitrogen need and with nitrogen-free ketoanalogues (KA) to recirculate the endogenous urea, whose serum levels are elevated in patients with CKD. KA and EAA reduce the rate of progression of chronic kidney disease and improve the inflammatory state; they reduce the absorption of phosphates and can maintain a good state of nutrition even if associated with diets with very low protein content. On the contrary, an excessively restrictive and inadequate diet in terms of EAA or calorie intake induces a negative nitrogen balance, therefore cachexia. The recommended vascular access to start dialysis treatment is represented by the arteriovenous fistula (AVF). An early referral to the vascular surgeon for vascular access creation is pivotal for deciding on a patient-specific strategy for planning access. Guidelines advise referral at least 3–6 months before the expected start of HD, because time is needed for AVF maturation and possible repeat interventions when it is impaired. An early referral results in more autologous AVFs, which have a better long-term patency, whereas late referral, results in a greater risk of AVF non-maturation and failure and therefore the need for additional central venous catheters (CVCs) to initiate dialysis. Recent studies have shown that pre-dialysis patients who undergo a VLDP + KA require less emergency dialysis access and have better elasticity of the arterial wall, better maturation rates and duration of the AVF and sometimes a reduction in the uremic toxins responsible of endothelial dysfunction. The aim of the study was to evaluate if patients could start haemodialysis with fistula cannulation, without central venous catheter insertion. Method 10 patients, late referral end stage renal disease were enrolled in a prospective, single arm study starting very low protein diet supplemented with ketoanalogues after arteriovenous fistula creation; they were followed with periodically assessment of renal function, uremic toxin, and acid-base balance until they need to start haemodialysis. It was evaluated AVF maturation and needs to additional CVC insertion. Results Patients (3 females, 7 males) mean age was 71.2 years; before AVF creation, baseline mean value was: sCr: 6.46 mg/dl, sUrea: 150 mg/dl, phosphorus: 4.45 mg/dl, bicarbonates: 19.8 mmol/l, eGFR: 8,37 ml/min. After 3 months of VLPD supplemented with KA, eGFR and sCr was stable to 8.25 ml/min and 6.69 respectively, sUrea and phosphorus reduced to 115 mg/dl and 3.8 mg/dl, and bicarbonate increased to 22.4 mmol/l. All 10 patients achieved AVF maturation within 3 months, no one needed CVC insertion. Conclusion In this small group we see how late referral ESRD patients, undergone AVF surgery, after 3 months of VLPD supplemented with KA, had stability of renal function, with reduction of urea and phosphorus, improvement of acid-base balance and achievement of AVF maturation, without needing of CVC insertion. For these reasons VLPD + KA could be useful in delaying haemodialysis start in late referral ESRD patients who have created AVF, without emergency placement of a central venous catheter.

#541 Secular trends in CKD and ESKD mortality rates in the United States, 2011–2021

Abstract Background and Aims Patients with chronic kidney disease (CKD) and end-stage kidney disease (ESKD) have a considerably higher mortality than the general population. Nevertheless, in the United States, mortality rates in the CKD and ESKD populations have declined steadily over the last decade until the onset of the COVID-19 pandemic [1]. Through a quantitative analysis of the age- and time-dependence of mortality rates in renal patient populations in the US, we aimed at quantifying trends in life expectancy between 2011 and 2021. Method We analysed CKD and ESKD mortality rates as reported in the US Renal Data System's (USRDS) Annual Data Report 2023 for the years 2011–2021 [1]. There, CKD mortality rates were determined from a Medicare 5% random sample (CKD stages 4 and 5) for patients aged 65 and above (“CKD 65+”). ESKD mortality rates were obtained from the USRDS database; we analysed data for patients aged 45 and above (“ESKD 45+”). We used fits of analytical functions to the data to hosphorzed their dependence on age and time. This technique enables us to extract quantitative trends in time by tracking fit parameters. Results We found that for each year between 2011 and 2021, mortality rates in the adult CKD and ESKD populations in the US largely conformed to an exponential dependence on patient age, $m = {{m}_0}( t ){{2}^{a/{{\Delta }}a}}$, that is, mortality rates doubled over constant age increments ${{\Delta }}a$. While overall, mortality rates were declining between 2011 and 2019, the age increments over which mortality rates doubled were nearly identical for each year (CKD 65+: ${{\Delta }}a$ = 10.5 ± 0.4 y, ESKD 45+: ${{\Delta }}a$ = 15.1 ± 0.9 y; mean ± SD). Exploiting this simple relationship, we found that the changes in mortality rates over time could largely be reduced to a steady right-shift of an otherwise unchanged mortality curve over time (shown for the ESKD 45+ group in Fig. 1a). By quantifying this right-shift over time, we estimated the gain in 1-year survival probability for different ages (Fig. 1b,c). This gain in survival does not necessarily imply a prolonged time on renal replacement therapy (RRT), e.g., when patients concomitantly start RRT at a later age. The onset of the COVID-19 pandemic in 2020 coincides with an abrupt cessation of these positive trends, reflected by a setback of mortality curves close to those in the year 2016 for the CKD population and to before 2011 for the ESKD population. Conclusion Public health data on CKD and ESKD show systematic dependencies of mortality rates on age and time, which can be revealed using analytical parameterisations of the data. Using this technique, we can capture trends in mortality rates and 1-year survival probability in adult kidney patient populations in the US during the years 2011–2019 and can quantify the abrupt cessation of these trends during the onset of the COVID-19 pandemic. In the CKD population we observed a setback of mortality rates close to those in the year 2016 with the onset of the pandemic. Changes in mortality rates in the ESKD population were more distinct. Specifically in elderly patients (aged 65 and above) 1-year survival dropped abruptly to levels lower than those observed in the previous decade.

#1091 Quantifying the potential contribution of drugs to the occurrence of acute kidney injury in patients with chronic kidney disease

Abstract Background and Aims Patients with CKD have high risk of AKI. Quantifying the contribution of drugs to the occurrence of AKI in this population and assessing its risk factors is important to design preventive interventions. We sought to comprehensively describe drug-related components associated with AKI in patients with CKD. We documented the incidence of drug-related AKI, the proportion of preventable AKI, identified the various drugs potentially associated with it, explored the risk factors, and assessed the one-year incidences of the recurrence of drug-related AKI, kidney failure, and death. Method The CKD-REIN study is a national prospective cohort of 3,033 nephrology outpatients with a confirmed diagnosis of CKD (eGFR <60 mL/min/1.73 m²) in France. AKIs and adverse drug reactions (ADRs) were prospectively identified from hospital charts, medical records, and patient interviews. Nephrologists used the Kidney Disease: Improving Global Outcomes criteria to adjudicate all stages of AKI, and expert pharmacologists used validated tools to adjudicate ADRs (including drug-related AKIs). A drug-related AKI was considered serious when the outcome is death, a life-threatening situation, hospital admission, disability, permanent damage, or another important medical event. We used cause-specific Cox proportional hazard models to investigate the patients’ baseline clinical characteristics associated with the risk of drug-related AKI. Results Over a median [interquartile range] period of 4.9 [3.4-5.1] years, 832 cases of AKI were reported in 639 (21%) of the 3,033 study participants. Over a quarter of the AKI events were drug-related (n = 236, 28%); from those, 47% were hospital- and 53% community-acquired AKI. From the 168 serious drug-related AKI events, 28% were considered preventable or potentially preventable. The three most frequently implicated drug classes were diuretics, renin-angiotensin system inhibitors, and contrast agents. At least two concomitant medications were implicated in more than half of the AKIs with a drug-related component, RASis and diuretics, two diuretics, and diuretics and antibiotics were the 3 most frequent associations (Figure). A history of cardiovascular events, and the presence of diabetes, lower levels of hemoglobin and eGFR, poor medication adherence, and ≥5 drugs being taken daily were associated with a greater risk of drug-related AKI. The one-year cumulative incidences of recurrent drug-related AKI, kidney replacement therapy, and death were 7%, 15%, and 11%, respectively, after the first drug-related AKI. Conclusion Drug-related AKI is prevalent among patients with CKD. Further training in drug management for both CKD patients and healthcare professionals involved in their care might mitigate the incidence of drug-related AKI.

#1521 EZH2 promotes cyst growth in autosomal dominant polycystic kidney disease

Abstract Background and Aims Autosomal dominant polycystic kidney disease (ADPKD) is the leading hereditary kidney disease worldwide. Epigenetic modulations of genes and proteins play important roles in ADPKD pathogenesis. In this study, the role of enhancer of zeste homolog 2 (EZH2), a histone lysine methyltransferase, was investigated in ADPKD. Method To elucidate the role of EZH2 in ADPKD pathogenesis, we employed inducible knockout models, specifically targeting Pkd1 alone (Pkd1fl/fl) or both Pkd1 and EZH2 (Pkd1fl/fl: Ezh2fl/fl) in mouse models. Molecular analyses included assessing EZH2 expression levels and H3K27 trimethylation in Pkd1 knockout cells, kidney tissues from Pkd1 knockout mice, and samples from ADPKD patients. Functional investigations involved the use of EZH2-specific inhibitors, GSK126 and EPZ-6438, to inhibit EZH2 activity. Additionally, Ezh2 knockdown was employed to assess its impact on cystogenesis in MDCK cells. The embryonic kidney cyst model was utilized to evaluate the effects of GSK126 and EPZ-6438 on cyst growth. Results We found that EZH2 expression and the trimethylation of lysine 27 on histone H3 (H3K27) were upregulated in Pkd1 knockout cells and kidney tissues of Pkd1 knockout mice and ADPKD patients. Using EZH2-specific inhibitors GSK126/EPZ-6438 and knockdown of Ezh2 both suppressed cystogenesis in MDCK cells. GSK126 and EPZ-6438 delayed cyst growth in the embryonic kidney cyst model. Double knockout of Pkd1 and Ezh2 significantly decreased the kidney volume, cyst indexes, H3K27 methylation level, and the proliferation of renal cystic epithelial cells compared with Pkd1 knockout mice. Moreover, GSK126 delayed cyst growth and protected renal function in both early- and late-onset Pkd1 conditional knockout mice. EZH2 promoted the proliferation of renal cystic epithelial cells by activating STAT3 through H3K27 methylation. Conclusion Inhibiting EZH2 emerged as a promising strategy to impede cyst growth and attenuate disease progression across various PKD models. These findings establish a molecular foundation for the potential use of EZH2-specific inhibitors in delaying ADPKD cyst growth in the future.

#1614 Fenofibrates and chronic kidney disease – Is there anything to worry about?

Abstract Background and Aims Chronic Kidney Disease (CKD) patients have increased risk of cardiovascular disease and dyslipidemia is a frequent comorbidity. Many patients are medicated with anti-lipidemic agents to reduce atherosclerotic disease and coronary vascular events. Fenofibrates are lipid-lowering agents used to treat mixed dyslipidemia and hypertriglyceridemia and are widely used by primary care physicians. Many studies described reversible increase in serum creatinine (SCr) associated with fenofibrates use, but the underlying mechanism is poorly understood. Whether hypercreatinemia is secondary to alterations in creatinine metabolism, tubular handling, or reflects a true impairment in kidney function remains unknown. This phenomenon is also fairly unknown to many primary care providers and, as a result, patients with a SCr rise while on fenofibrates are often referred to nephrology consultation. In this study, we have analyzed the effect of fenofibrate withdrawal on SCr, eGFR and hemoglobin (Hb) in patients referred to nephrology consultation for CKD or decrease of eGFR. Our aim was to understand the impact of fenofibrates withdrawal on kidney function and to look for factors that might influence the risk of fenofibrate nephrotoxicity. Methods We conducted a retrospective observational study, reviewed electronic medical records and collected data of all adult patients discontinued on fenofibrates at first nephrology consultation, between January 2022 and October 2023. Ninety patients were included, of which four were excluded due to simultaneous suspension of antihypertensive drugs. Patients were subsequently evaluated for clinical reasons from 2 to 6 months after the first appointment, with new laboratory data collected, including Hb, SCr and lipid profile. eGFR was calculated using MDRD 4 formula. Continuous variables were compared by t-test and categorical variables were compared by chi-square test. A p value of < 0.05 was considered statistically significant. All data was analyzed using Stata software. Results A total of eighty-six patients were included in this study, 65% (n=56) were male, mean age of 71.2 ± 11.4 years old; all patients were medicated with fenofibrates due to dyslipidemia and 77% (n=66) were also on statins; 94% (n=81) had hypertension, 60% (n=52) had type 2 diabetes mellitus, and 20% (n=17) had ischemic cardiopathy. Ninety-two percent (n=79) were taking renin-angiotensin system inhibitors (RASi). Nearly half the patients (49% n = 42) had stage 4 CKD and 45% (n = 39) had stage 3 CKD; Main causes of CKD were presumed diabetic kidney disease (34% n = 29) and ischemic nephropathy (15% n = 13), 30% (n = 26) of patients had undetermined etiology. Upon fibrate discontinuation, mean SCr was 2.1 ± 0.6 mg/dL and mean eGFR was 31.3 ± 10.9 mL/min/1.73 m2. Mean Hb was 12.5 ± 2.0 g/dL. After fenofibrate discontinuation, eGFR significantly improved in mean 15.2 mL/min/1.73 m2 (31.3 vs 46.5 mL/min/1.73 m2, p < 0.0001) with a mean reduction of SCr of 0.6 mg/dL (2.1 vs 1.5 mg/dL, p < 0.0001). Mean Hb increased 0.4 g/dL (12.4 vs 12.7 g/dL, p = 0.112). Mean total cholesterol was 168.4 ± 56.4 mg/dL and mean triglycerides was 234.8 ± 285.3 mg/dL. Only one patient was restarted on fenofibrate due to severe hypertriglyceridemia. Fenofibrate discontinuation effect on eGFR improvement remained statistically significant when adjusted for diabetes, hypertension, CKD etiology and RASi use. Conclusion Our study reports a consistent increase in eGFR and SCr decrease following discontinuation of fenofibrate, as other reports before. A true effect on eGFR could be supported by the Hb rise, though it did not reach statistical significance. The exact mechanism by which fenofibrates increase SCr remains to be clarified. Cardiovascular disease is the main cause of death amongst CKD population and the potential benefits of fenofibrates should not be disregarded. Our results suggest that patients started on fenofibrates should be carefully selected, specially if CKD is present, and kidney function monitoring should be considered. A drop in eGFR should prompt physicians to weigh on the strict indications for fenofibrates use.

#2592 Tubular cell polyploidy is involved in kidney compensatory hypertrophy

Abstract Background and Aims Chronic kidney disease (CKD) affects more than 10% of the population and it is associated with high risk of death for cardiovascular causes or progression towards end stage kidney disease (ESKD) requiring dialysis or kidney transplantation. CKD is characterized by progressive loss of nephrons, with consequent structural degeneration and fibrosis. Nephron number is established during prenatal kidney development and cannot increase. Consequently, following a reduction in kidney mass or in condition of altered metabolic demands, the remaining nephrons undergo compensatory hypertrophy. Compensatory hypertrophy results in increased functional output and has been observed in the absence of direct tissue injury after nephrectomy. Recently, we have identified a previously unknown mechanism of cellular adaptation: polyploidization of tubular epithelial cells (TC), and demonstrated that this is the essential mediator of kidney hypertrophy after acute kidney injury (AKI). Here, we hypothesize that TC polyploidy is involved in compensatory hypertrophy following nephrectomy. Method Polyploid TC are characterized by an increased DNA content in the absence of cell division. To discriminate polyploid cells from actively proliferating cells, we employed a series of in vitro and in vivo transgenic models based on the Fluorescence Ubiquitin Cell Cycle Indicator (FUCCI2aR) technology. Nephrectomy was performed by removing the left kidney and mice were sacrificed at different days after uni- Nephrectomy (Nfx). Cytofluorimetric techniques were employed to characterize a subpopulation of polyploid TC and histology investigation was employed analyze fibrosis development. These results were further corroborated by single cell RNA-sequencing (scRNA-seq) analyses in vitro and in vivo. Results Employing mice that express the FUCCI2aR reported under the Pax8 promoter (which marks all TC), we found that TC polyploidy increases immediately after uni-Nfx. This was accompanied by an increased kidney to body mass ratio with a maximum peaks 3 days afterwards. Importantly, after uni-Nfx, YAP1 expression and nuclei localization (i.e., implying pathway activation) was exponentially increased, suggesting that the same mechanism that drives TC polyploidy after AKI controls TC polyploidization response after uni-Nfx. However, unlike in AKI, polyploidy after nephrectomy was not accompanied by structural alterations as shown by PAS and Masson's trichrome staining. Conversely, after uni-Nfx YAP1 knock-out mice, that are unable to undergo rapid polyploidization, displayed an impaired kidney function in the long term, characterized by extensive tubular dilations. Conclusion Polyploidization of TC mediates compensatory hypertrophy following nephrectomy via YAP1 activation

#1910 Echocardiographic findings in patients with advanced diabetic kidney disease and obstructive sleep apnea

Abstract Background and Aims Obstructive sleep apnea (OSA) is associated with accelerated development of cardiovascular disease. The prevalence of OSA is increased in both type 2 diabetes (DM2) and in chronic kidney disease, and is very high in patients with diabetic kidney disease. However, the contribution of OSA to alterations in cardiac structure and function in diabetic kidney disease remains unknown. We therefore compared cardiac structure and function in diabetic kidney disease patients with or without OSA. Method In a cross-sectional study, 120 patients with DM2, a urine albumin-creatinine ratio (UACR) > 30 mg/g and an estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m2 were tested for OSA. OSA severity was quantified by the apnea-hypopnea-index (AHI). Patients without OSA (AHI < 5 events/hour) were compared to patients with moderate (AHI 15-29 events/hour) or severe OSA (AHI ≥30 events/hour). Transthoracic echocardiography was conducted in all patients to evaluate cardiac structure and function. Linear regression analyses were used to assess the associations between OSA and echocardiographic parameters. Results AHI-data were available for 114 patients; 43 had no OSA, 33 had mild OSA and 38 had moderate-severe OSA. A total of 74 patients (73% men), 39 with no OSA and 35 with moderate-severe OSA, had complete data for both echocardiography and OSA. Their mean age was 71.5 ± 9.4 years, mean eGFR was 32.2 ± 12.3 mL/min/1.73 m2 and the median UACR of 533 (192–1707) mg/g. Age, smoking status, diabetes duration, eGFR, blood pressure, antihypertensive medicine, chronic obstructive pulmonary disease and atrial fibrillation were not significantly different between patients with and without OSA. Patients with moderate-severe OSA had significantly larger left atrial volume index (LAVI) (39.0 ± 19.6 vs. 28.1 ± 10.5 mL/m2, P = 0.0035), left ventricular mass index (LVMI) (49.2 ± 12.0 vs. 41.8 ± 9.7, g/m2, P = 0.0043), and right ventricular diameter (34.3 ± 5.8 vs. 28.4 ± 4.4 mm, P < 0.0001) compared to those without OSA (Fig. 1). Global longitudinal strain (GLS) was significantly reduced in OSA patients (−14.9 ± 3.1 vs. −16.6 ± 2.8, P = 0.0196), while no difference was observed in LV ejection fraction (54.4 ± 8.1 vs. 56.5 ± 6.2, p = 0.21). The association between OSA and LAVI, LVMI, right ventricular diameter and GLS remained significant after adjustment for age, sex, eGFR and mean arterial pressure. Conclusion Moderate-severe OSA is independently associated with alterations in cardiac structure and function in patients with diabetic kidney disease and reduced renal function. OSA could be an independent contributor to the development of heart failure in patients with diabetic kidney disease.

#2056 Epigenetic profiles differ by level of kidney function in idiopathic nephrotic syndrome

Abstract Background and Aims DNA methylation (DNAm) is an epigenetic mechanism which can therefore induce changes in gene expression without any change to the underlying DNA sequence. Although generally quite stable, DNAm patterns in whole blood do vary across individuals, with DNAm levels associating with age and responding to environmental factors. We aimed to investigate whether peripheral blood cell DNAm associates with level of kidney function in patients with Idiopathic Nephrotic Syndrome (INS). Method Peripheral blood cell DNAm values were generated using the Illumina MethylationEPIC Beadchip (>850,000 CpG sites) for 293 INS patients recruited to the National Unified Renal Translational Research Enterprise–National Study of INS (NURTuRE- INS and NephroS). All patients were younger than 30 years old at INS diagnosis. An Epigenome Wide Association Study (EWAS) was performed using generalised linear models to evaluate associations between DNAm sites and estimated glomerular filtration rate (eGFR). Regions of differentially methylated sites were identified using the ‘dmrff’ R package. Sex chromosomes were excluded from the analyses and all analyses were adjusted for estimated cell type proportions, age, sex and technical variation. A Bonferroni adjusted p value of 5.88 × 10−8 was used as a significance threshold to adjust for multiple tests. Results Of the selected 293 INS patients, 173 (59%) were male, 213 (73%) were white and the median age at INS diagnosis was 4 years old (IQR 2-10). One hundred and forty-three (48%) patients were steroid responsive at diagnosis and the remainder were steroid resistant. Sixty-eight of the steroid resistant patients had pathogenic NS variants. We identified 6 CpG sites associated with eGFR (p < 5.88 × 10−8) in this cohort of INS patients, one replicating a previously reported association. We identified 3 differentially methylated regions, one coinciding with the transcriptional start site of an RNA binding protein which regulates alternative splicing, and another located in the body of a transcription factor regulator containing genetic variants associated with chronic kidney disease. Conclusion We have demonstrated variation in peripheral blood DNAm by level of kidney function in children and young adults with INS. Associations between DNAm and eGFR have previously been demonstrated in diabetic kidney disease and heterogenous chronic kidney disease cohorts, including one of the sites which we have identified in our study. Further work is underway to determine if these differences in DNAm are likely to be a cause or consequence of reduced kidney function, which will help to determine their potential clinical utility.

#426 “Predict-PD”: a machine learning tool to predict patient survival in peritoneal dialysis patients

Abstract Background and Aims With the rising prevalence of chronic kidney disease (CKD), particularly among the elderly, the need for effective renal replacement therapy has become increasingly crucial. Peritoneal dialysis (PD), recognized as a gentler alternative to haemodialysis, offers advantages in cognitive preservation and overall quality of life. Patient survival on PD, a tangible outcome measure, gains particular importance, especially in an aging demographic confronting end-stage kidney disease. Predicting survival thus becomes vital in facilitating individualized treatment planning and has implications on resource allocation and patient counseling. Method Our study analysed data from the UK Renal Registry and included 22 711 incident dialysis patients choosing PD between 2007 and 2022. Our objective was to employ Artificial Intelligence (AI) algorithms in developing an advanced risk stratification indicator with high predictive capabilities, specifically tailored for use in the United Kingdom's transplant selection procedure. We conducted experiments using three distinct machine learning models and evaluated their performance in terms of calibration and discrimination, utilizing metrics such as the integrated Brier score (IBS) and Harrell's concordance index. We assessed the potential clinical utility using decision curve analysis. Results The XGBoost model demonstrated excellent predictive efficacy for patient survival, with a concordance of 0.78. Further scrutiny revealed AUC values at 1 year (0.81), 3 years (0.78), and 5 years (0.77). The integrated Brier score, a comprehensive measure of predictive accuracy, was 0.09. There was no statistical difference between the actual and predicted survival probabilities (P = 0.72). Decision curve analysis accentuated the model's clinical applicability. Conclusion This study illustrates the potential of machine learning in prognosticating patient survival in PD, offering a pathway towards individualized patient-centric management in nephrology. The findings advocate for the integration of data-driven methodologies in clinical decision-making, paving the way for enhanced personalized care in CKD management and can serve as a guide for future research.

#205 Features of chronic kidney disease in patients with obesity and arterial hypertension

Abstract Background and Aims to assess the indicators of composite body composition in patients with obesity and chronic kidney disease with arterial hypertension. Method 59 patients with obesity and arterial hypertension were examined. When selecting patients, inclusion criteria were taken into account: men and women aged 25 to 55 years, obesity (BMI more than 30 kg/m²; waist circumference (WC) more than 80 cm in women and more than 94 cm in men), presence of hypertension I– Stage II, grade 1–2, absence of renal pathology (history of kidney disease, structural changes in the parenchyma and vessels of the kidneys during ultrasound examination, changes in urinary sediment and urine density, proteinuria, decreased GFR less than 60 ml/min/1.73 m² ), signed informed consent. Metabolically complicated obesity was defined as the presence of abdominal obesity, a BMI of more than 30 kg/m2 in combination with hypertension and ≥ 2 cardiometabolic abnormalities. A metabolically healthy obesity phenotype was considered to be the presence of obesity without hypertension, dyslipidemia, or hyperglycemia. The results obtained during the study were compared with the indicators of a control group formed from 30 practically healthy individuals aged 25–55 years without obesity or overweight. Differences in age, gender, duration of hypertension and obesity were not established. Metabolic activity of adipose tissue was assessed by the level of leptin, soluble leptin receptors (sLR), adiponectin, resistin, free leptin index (FLI), leptin/adiponectin index (L/A). Renal function: GFR (CKD EPI and Hoek), serum and urine cystatin C, albuminuria. The composite composition of the body was studied using bioimpedance analysis using an ABC-01 Medass analyzer of body composition and balance of water sectors of the body. Results In a comparative analysis of the parameters of the composite body composition in the obese groups, the highest values ​​of fat mass (42.8 ± 6.8 and 35 ± 4.2 kg) and total fluid (40.2 ± 5.0 and 36.0 ± 2.8 kg) with a reduced proportion of 17 active cell mass (ACM) (53.0 ± 3.2 and 56.1 ± 3.4%) were detected in patients with complicated obesity (p < 0.05). Regardless of the obesity phenotype, correlations were established: between the level of diastolic blood pressure (DBP) and the volume of total (r1 = 0.42; r2 = 0.52) and extracellular fluid (r1 = 0.50; r2 = 0.60); level of DBP and urinary excretion of cystatin C (r1 = 0.51; r2 = 0.61) (p < 0.01). A decrease in the proportion of ACM in obese groups was associated with an increase in resistin levels (r1 = −0.56; r2 = −0.31). In obese groups, regardless of phenotype, fat mass was associated with leptin levels (r1 = 0.52; r2 = 0.42) and free leptin index (FLI) (r1 = 0.75; r2 = 0.46 ) (p < 0.05). In group 1, a positive correlation was additionally established for the volume of fat mass with systolic blood pressure (SBP) (r1 = 0.70) and DBP (r1 = 0.65), with the level of uric acid (r1 = 0.57), cholesterol LDL (r1 = 0.52), cystatin C in urine (r1 = 0.75) and insulin resistance index (HOMA-IR) (r1 = 0.65) (p < 0.01). Conclusion Body mass index does not determine the obesity phenotype. In patients with complicated obesity, the proportion of fat mass is higher than in metabolically healthy obesity and is associated with increased levels of glucose and uric acid. All obese patients are characterized by an increase in the percentage of total and extracellular fluid, associated with the level of blood pressure and urinary excretion of markers of tubular dysfunction.