Stage 3b Research Articles

#4457 IONIZED MAGNESIUM LEVELS IN PATIENTS WITH MODERATE-TO-ADVANCED CHRONIC KIDNEY DISEASE: RELATIONSHIP WITH TOTAL MAGNESIUM AND ASSOCIATED FACTORS

Abstract Background and Aims Magnesium (Mg) is involved in a multitude of essential physiological processes. In chronic kidney disease (CKD), the mechanisms compensating for the decrease in glomerular filtration rate (eGFR) become insufficient and Mg excretion tends to decrease, potentially resulting in hypermagnesemia. On the other hand, hypomagnesemia seems also to be common in CKD, due to changes in Mg intake through diet, reduced absorption and drug-induced hypomagnesemia. To date, a few studies have shown an association between increased cardiovascular risk in CKD and either low or high total Mg levels. However, the physiologically active fraction of extracellular Mg is ionized Mg (iMg), which is not routinely measured. In critical ill patients, the correlation between iMg and total Mg has been shown to be poor. Similar data on patients with CKD would be important to future studies aiming at clarifying the link between Mg and outcomes, and ultimately to determine the interest of iMg assay in routine practice. The objectives of this study are i) to study the correlation between total Mg and iMg and ii) to evaluate the relation between serum ionized magnesemia, estimated GFR (eGFR) and demographic and biologic parameters. Method CKD-REIN is a French, prospective, nationally representative cohort study of 3033 CKD patients under nephrology care not receiving maintenance dialysis (stage 3-5: eGFR<60 mL/min/1.73 m² based on 2009 CKD-EPI equation). Baseline iMg and total Mg serum concentrations were respectively centrally measured using the NOVA BIOMEDICAL Stat Profile PRIME ES analyser and with Atellica® CH SIEMENS analyser. Normal range of serum total Mg considered was 0.66 to 1.06 mmol/L (from Atellica®). Mean ± standard deviation (SD) ionized Mg level evaluated in a cohort of 457 healthy volunteers (age = 45 ± 17 years; eGFR = 72.3 ± 13 mL/min/1.73m²) was 0.49 ± 0.05 mmol/L (median [tertile 1 – tertile 3] = 0.49 [0.45-0.52] mmol/L). Correlation between iMg and total Mg was estimated overall. Multivariate linear regressions were performed to identify factors associated with iMg and total Mg levels. Results Among 1741 patients with iMg and total Mg at baseline, the median age was 68 years [59-76], 65% were men, and the mean eGFR was 35 ± 14 mL/min/1.73m². The mean baseline iMg level was 0.48 ± 0.1 mmol/L, 615 patients had an ionized Mg <0.45 mmol/L (Tertile 1), 599 had an iMg between 0.46 and 0.52 mmol/L (Tertile 2), and 527 had an iMg >0.52 mmol/L (Tertile 3). Compared to healthy volunteers, mean iMg levels were significantly lower in CKD patients. However, the difference was small (difference CKD-heatlhy = 0.01 mmol/L). Most of patients were within the total Mg normal range (n = 1522), 12% (n = 208) and 1% (n = 11) presented hypo- and hypermagnesemia, respectively. Correlation between iMg and total Mg was very high (r = 0.88; p<0.001). (Figure). Ionized Mg was weakly inversely correlated with eGFR (r = -0.22; p<0.001). Consequently, the mean iMg level differed according to CKD stages, being more elevated in the advanced stages (0.45 mmol/L in stages 2-3A; 0.47 mmol/L in stage 3B; 0.50 mmol/L in stages 4-5 (p<0.001)). In a fully adjusted linear regression model, iMg concentration was significantly associated with age, decline of eGFR, history of cardiovascular disease and the use of diuretics, and inversely associated with calcium and triglycerides levels, systolic blood pressure, diabetes, and the use of proton pump inhibitors and potassium chelators. The same factors were associated with total Mg. Conclusion Total Mg and iMg were strongly correlated. Decline of kidney function was associated to an increase of iMg in patients with moderate-to-advanced CKD. Additional studies need to compare the difference between total Mg and iMg as a biomarker to predict hard outcomes.

#5868 PREVALENCE AND MANAGEMENT OF CHRONIC COMPLICATIONS IN PATIENTS WITH DIABETES AND ADVANCED CHRONIC KIDNEY DISEASE: A RETROSPECTIVE AUDIT

Abstract Background and Aims Current guidelines recommend that all patients with Chronic Kidney Disease (CKD) stage 3b or higher should be monitored and treated for anaemia, mineral bone disorder (BMD) and metabolic acidosis. We audited the prevalence and management of these complications in a cohort of patients with diabetes and advanced CKD. Method A retrospective audit was undertaken using KDIGO guidelines as standard and necessary approvals were secured from the governance team at University Hospitals Birmingham. We included patients with (a) diabetes (b) eGFR 30 and 15 ml/min/1.73 m2) and (c) attending diabetes clinics as of 30/09/2022. Using electronic patient records, we collected: demographics, co-morbidities, complications, treatments, body weight, BMI, blood pressure and serial biochemistry (creatinine, Hba1c, cholesterol, UAlb/Creat ratio, bicarbonate, haemoglobin, vitamin D, parathyroid hormone (PTH). Following definitions were applied: anaemia as Hb <13 g/dl for men and <12 g/dl for women, BMD as vitamin D <40 nmol/l plus raised PTH, acidosis as bicarbonate <22 meq/l. Data was analysed using SPSS 26. Descriptive statistics (frequencies and cross tabulations) were used to estimate prevalence. Independent means test was used for continuous variables. Comparison between groups was undertaken using the Chi Square test and one way ANOVA test. Results Data for 192 subjects (110 European (EUR), 40 South Asian (SA), 42 African-Caribbean (AFC) /other) was analysed. Mean age (SD) was 73 (+/-11) years. There were no significant differences in general characteristics between the ethnic groups except for albuminuria which was greater in SA and AFC compared to EUR (193 v 133 v 95.5mg/mmol; p=.038). 47% of the cohort had at least one diabetes related complication. 63/192 (32.8%) had cardiovascular disease, 49/192 (25.5%) had retinopathy and 19/192 (9.9%) had neuropathy. Insulin was the most common prescribed glucose lowering agent 105/192 (55%) with proportionately more SA treated with insulin (65%). Anaemia was present in 171/183 (93.4%) of the patients. 82/101 (81.2%) had BMD, and 135/168 (82.8%) of patients had metabolic acidosis. 65/192 (33.9%) of patients had all 3 complications. Only 38/133 (22%) of those with anaemia were receiving treatment out of which only 36.8% were treated adequately with a Hb of >10g/l. Corresponding figures for BMD and metabolic acidosis were: BMD: 39/82 (47.6%) treated and 42% optimally corrected, metabolic acidosis: 54/135 (40%) treated and 53% optimally corrected. There were no significant differences between ethnic groups in prevalence or treatment of these complications. Conclusion The prevalence of CKD related complications is high. The management of these complications however, is suboptimal. Increased emphasis on the management of these complications is required to improve outcomes in patients with advanced CKD.

#4051 FGF-23 IN CHRONIC KIDNEY DISEASE: CORRELATION WITH BONE AND CARDIOVASCULAR PARAMETERS – A PRELIMINARY STUDY

Abstract Background and Aims The FGF-23/Klotho ratio increases from early stages of chronic kidney disease (CKD) in parallel with kidney function declined. In some cases, serum FGF-23 levels increase is unbalanced, causing organ damage and increasing cardiovascular risk. The aim of our study was to evaluate the intact FGF-23 (iFGF-23) levels in a cohort of CKD patients and to establish its correlation with cardiovascular and bone mineral metabolism parameters. Method A prospective observational study in 59 adult normophosphatemic patients with CKD stage 2-4, was performed. Clinical and analytical variables (serum calcium, phosporus, intact parathyroid hormone (iPTH), iFGF-23, calcidiol and calcitriol) were evaluated. Basal transthoracic echocardiogram, bone densitometry (Lunar prodigy, GE iDXA), software trabecular bone score (TBS), iNsight clinical data analyzer and carotid Doppler ultrasound were performed. We excluded patients with background of primary hyperparathyroidism, hepatorenal polycystic disease, kidney transplant, tumoral nephrectomy, active neoplasm, tubulopathies or treatment with active vitamin D or calcimimetics. For statistical analysis, we use SPSS software (T Student, Xi2, Fisher test, ANOVA test, U-Mann Whitney test and correlations of Pearson and Spearman) Results Mean age was 62,7±10,5 years, 82,5% were men; 17,7% have CKD stage 2, 28,8% stage 3a, 42,3% stage 3b and 9,6% stage 4. The main CKD etiology was vascular (25%) and diabetes (22%). Previous cardiovascular disease was observed in 11% (ischemic heart disease 6,3%, cerebrovascular disease 3,2% and descompensated heart failure with hospitalization 1,6%). Mean iFGF-23 levels in CKD stage 2 were 80,4±38 ng/l (38-170, median 71 ng/l), in CKD stage 3a 95,5±39,7 ng/l (46-178,9 ng/l, median 85,5 ng/l), in CKD stage 3b 118,8±55,06 (35,5-285 ng/l, median 124,6 ng/l) and in stage 4 134,8±50,9 ng/l (65,25-216,5 ng/l, median 136,1 ng/l). We found correlation between iFGF-23 levels and glomerular filtration rate (Rho:-0,390, p: 0,003), as well as with CKD stages (ANOVA test, p: 0,057). We performed 48 carotid doppler ultrasound and observed mild carotid atheromatosis in 58,7%, mainly bilateral, and intima-media thickness >0,9 mm in 7,9%. In patients with atheromatosis, 38,9% showed iFGF-23 levels in second tertil and 36% in the third. We observed left ventricular hypertrophy (LVH) in 46% of patients, mostly mild degree. In bone densitometry, we found mean femoral neck T-Score of -1±1,1 and lumbar spine T-Score of -0,07±1,5, mean mineral bone density (DMO) in femoral neck of 0,89±0,25 g/cm2 and 1,17±0,20 g/cm2 in lumbar spine. Only 40% of patients had normal TBS score. We found correlation between serum iFGF-23 levels and phosphorus tubular reabsorption (r:-0,396, p: 0,002), calcidiol (Rho: 0,264, p:0,047), calcitriol (r: -0,412, p:0,002), iPTH (Rho: 0,296, p:0,025), lumbar T-Score (r: -0,320 p:0,022), lumbar DMO (r:-0,267, p:0,049) and TBS (r: -0,396, p:0,005). Conclusion We confirm an association between a glomerular filtration rate decline and an increase in serum iFGF-23 levels. The inverse correlation observed between iFGF-23 serum levels and lumbar T-Score, lumbar DMO and trabecular microarchitecture suggests a negative effect of iFGF-23 in bone mineralization.

#4674 CLINICAL PROFILE OF PATIENTS WITH DIABETIC KIDNEY DISEASE ATTENDING NEPHROLOGY CLINICS IN A LOW-MIDDLE INCOME COUNTRY

Abstract Background and Aims Chronic kidney disease secondary to diabetes is a significant contributor to the global burden of disease, both financially and through a marked deterioration in the quality of life. Diabetic kidney disease (DKD) increases the likelihood of adverse outcomes such as infirmity, cardiovascular events, progressive multi-organ damage, impaired quality of life and reduced life expectancy. Pakistan, a low-middle income country, is ranked among the top 10 countries for absolute diabetes prevalence. Over 19 million Pakistani adults have diabetes, which amounts to 17.1% of the adult population in the country. There is a dearth of literature examining the quality of care of diabetic kidney disease (DKD) patients in Pakistan. The aim of the current study is to evaluate the clinical profile and the quality of care delivered to patients with DKD attending nephrology clinics at a large tertiary care hospital in Karachi, Pakistan. Method It was a cross-sectional observational study at Aga Khan University Hospital (AKUH), a private tertiary-care facility located in Karachi, Pakistan. The data used in the study was acquired from the Diabetic Kidney Disease outpatient-database, a registry of patients managed by AKUH. It was used to identify a cohort of patients, with DKD presenting to the nephrology clinic at AKUH from December 2018-January 2021 (n = 553). Results Mean age of the study participants was 61.7 + 11.0 years and 60.9% of the study participants were male. 80.5% (n = 445) were non-smokers and over three-quarters (n = 400) had a body mass index (BMI) > 25 which according to the Asian-Pacific BMI cut-offs classified them as obese. These patients had been living with diabetes for an average of 15 years (median IQR = 10-21) and 99% had type 2 diabetes mellitus. A total of 519 study participants (93.9%) had hypertension while 34.2% and 30.9% had dyslipidemia and ischemic heart disease (IHD), respectively. Almost two third of the participants (68.4%) had advanced CKD (stages 3b, 4and 5) at the time of presentation. Less than half of the study population (43.6%) had HbA1c < 7.0 percentage and only 34.9% attained systolic blood pressure (BP) target <130mm Hg while optimal diastolic BP (<80 mmHg) targets were achieved in 72.7%. Almost 70% of the study population were on insulin while 49.7% were receiving oral anti-diabetics. The most prescribed oral anti-diabetic was DPP4 followed by metformin and two thirds were on statins. Calcium channel blockers and beta-blockers were the most used antihypertensive drugs 53.5% and 52.6% respectively; half of the population was on diuretics, while 47.4% were taking Renin-angiotensin system (RAAS) blockers. Those who had eGFR> 60, only 60% of them were receiving RAAS blockade therapy. Women were more likely to be obese and to have higher systolic BP compared to men. Diastolic BP and HbA1c were similar in men and women. The use of statins was higher in men and use of calcium channel blockers and RAAS blockers was significantly higher in women. Conclusion The basis for DKD management is multifactorial risk factor reduction which is achieved by optimizing care through modifiable risk factors. In our study we identified potential gaps in the quality of care related to risk factor control, optimal glycemic and/or blood pressure targets and pharmacotherapy to delay the progression of DKD and minimize cardiovascular events. This highlights a major treatment gap in DKD prevention and management calling for greater quality improvement effort in Pakistan, which now has the third highest number of people living with diabetes in the world.

#5047 DIABETES AND CHRONIC KIDNEY DISEASE IN TURKEY (DIAKIT): THE STUDY ON CHRONIC KIDNEY DISEASE IN DIABETES MELLITUS PATIENTS IN THE CAPPADOCIA COHORT

Abstract Background and Aims Diabetes mellitus (DM) is the most common cause of chronic kidney disease (CKD) [1]. The prevalence of CKD is therefore increasing worldwide with increasing prevalence of DM [1]. Among those with DM, CKD prevalence varies widely between countries. The actual prevalence of CKD in patients with DM in Turkey is unknown. This study aimed to determine frequency of CKD among diabetic patients of Cappadocia cohort and patients’ awareness about the disease. Method A total of 1591 diabetic patients from the Cappadocia cohort were invited to this cross-sectional study. A trained study team administered a questionnaire for patients’ medical history, knowledge, attitudes, and awareness of the disease and measured patients’ blood pressures (BPs) at least three times using an automated device. Serum creatinine was measured and spot urine albumin/creatinine ratio (ACR) measurements were performed for three consecutive days. A diagnosis of CKD was established if glomerular filtration rate (GFR)is <60 mL/min or ACR is >30 mg/g. Results The mean age of the patients was 63±10 years. Overall, 60.9% patients were obese (body mass index ≥30 kg/m2), and 70% patients were hypertensive. HbA1c was analyzed in 98.2% of the patients; HbA1c was <7% in 27.4%, ≥7%-≤8% in 20.8%, >8%-≤9% in 17.7%, and >9% in 34.1% of the patients. of 1535 patients with blood and urine analyses, 231 of 1008 (22.9%) females and 154 of 527 (29.2%) males had CKD (P = .007). Among patients with GFR values, 11.4% had a GFR of <60 mL/min and 88.6% had a GFR of ≥60 mL/min. Among 1544 patients with ACR measurements, 18.2% had values ≥30 mg/g and 4.4% had values ≥300 mg/g. CKD was detected in 385 (25.1%) of 1535 patients with both GFR and ACR values (Figure 1). of these patients, 28.1% had Stage 1, 25.7% had Stage 2, 32.5% had Stage 3A, 11.2% had Stage 3B and 2.6% had Stage 4 or 5 CKD. Excluding two patients with missing data, 36 of 383 CKD patients (9.4%) knew that they had CKD. In the logistic regression analysis, old age (OR=1.05, 95% CI 1.03-1.07; p<0.001), male sex (OR=2.11, 95% CI 1.43-3.12; p<0.001), duration of DM (OR=1.03, 95% CI 1.00-1.05; P = .022), morbid obesity (OR=3.58, 95% CI 1.28-10.03, P = .015), a CRP level of >5 mg/L (OR=1.60, 95% CI 1.12-2.27; P = .009), a triglyceride level of ≥150 mg/L (OR=1.74, 95% CI 1.24-2.45; P = .002), and grade 3 hypertension (OR=2.13, 95% CI 1.02-4.44; P = .043) were found to be significantly associated with an increased risk of CKD in patients with DM. Conclusion In the present study, CKD prevalence among diabetic patients in Turkey was 25.1%. Overall, 53.8% of the patients with CKD had a GFR of ≥60 mL/min although they had an ACR of ≥30 mg/day; that is, if albuminuria was not studied, this subgroup of patients would have been considered to have normal kidney function according to GFR. The awareness of CKD was found to be quite low in the patients. Therefore, periodic screening of diabetic patients should always include urinalysis, particularly ACR, as well as serum creatinine, fasting blood glucose and HbA1c.

#2845 TOLVAPTAN TREATMENT FOR THREE YEARS SIGNIFICANTLY IMPROVED RENAL PROGNOSIS IN AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE (ADPKD) PATIENTS

Abstract Background and Aims Vasopressin receptor antagonist, tolvaptan, is the first specific treatment approved for ADPKD. Long-term real clinical results with this drug are not yet available. We present the results regarding renal function, cyst-kidney volume and renal prognosis in patients with rapidly progressive disease after three years of tolvaptan treatment. Method Forty-one ADPKD patients who remained in tolvaptan treatment, without adverse reactions for 3 years, were included in the study. Total kidney volume (TKV) was measured using Magnetic Resonance Imaging (MRI), before and after three years of treatment. The Mayo Clinic Imagining Category (MCIC) and the prediction of End Stage Renal Disease (ESRD) based on the Mayo Clinic formula (Irazabal MV et al, JASN, 2015) were also calculated for all patients, before and 3 years post treatment. Using the same formula the expected estimated-glomerular filtration rate (e-GFR) at 3 years without treatment was calculated and compared to the e-GFR found after three years of treatment. The expected TKV increment at 3 years was calculated (5.3% increment per year) and was compared to the TKV measured in the second MRI. Finally, the expected renal prognosis at the time of treatment initiation (i.e. minus 3 years at the end of the study) was compared to the prognosis calculated based on real patients’ data found after 3 years of treatment. The dose of tolvaptan was adjusted according to the urine osmolarity (< 200 mOsm/Kg). In the third year of treatment, 15, 13 and 13 patients were treated with 90/30, 60/30, and 45/15 mg/day of tolvaptan respectively Paired t-test and Wilcoxon signed-rank test were used for statistical analysis. Results Forty-one patients (18 females, 23 males), mean (SD) age 42.5 (8.6) years old were treated with tolvaptan for 3 years. According to MCIC, 41% of the patients were classified as 1C, 44% as 1D, and 15% as 1E. Pre-treatment mean (SD) e-GFR was 61.8 (24.6) ml/min while 15% of the patients were on stage 1 of Chronic Kidney Disease, 42% on stage 2, 12% on stage 3a, 24% on stage 3b, and 7% on stage 4 (>25 ml/min). The expected mean (SD) TKV at 3 years without treatment was 2717 (1839) ml, while the measured TKV found after 3 years of treatment was 2773.3 (2086.9) ml (p = 0.44). The expected e-GFR at 3 years without treatment was calculated at 51.1(25.2) ml/min while the measured e-GFR after 3 years of treatment was 57.3 (30.2) ml/min (p = 0.001). Finally, while the expected mean (SD) ESRD prediction at the time of treatment initiation was 10 (6.9) years, the calculated ESRD prediction after 3 years of tolvaptan treatment was 12 (8) years (p<0.001). Conclusion Tolvaptan treatment for three years slowed down the clinical course of ADPKD in terms of renal function decline and ESRD prediction, but had no impact on total kidney volume.

#4703 IMPACT OF THE EARLY STAGES OF CKD WITH AND WITHOUT PROTEINURIA ON CARDIOVASCULAR OUTCOMES IN THE UK BIOBANK COHORT

Abstract Background and Aims Chronic kidney disease (CKD) is an established predictor of cardiovascular disease. However, the relationship between cardiovascular disease and the early stages of CKD defined as stage 1 (eGFR > 90 mL/min per 1.73 m2 + albuminuria) and stage 2 (eGFR 60–89 mL/min per 1.73 m2) with and without proteinuria, is lacking. In this study, we explored the incidence of major adverse cardiovascular events (MACE), heart failure (HF) and all-cause mortality of participants with early stages of CKD in the UK Biobank population. Method 456,015 participants from the UK Biobank were categorised into CKD stages. We calculated eGFR using the CKD-EPI 2021 equation and proteinuria was ascertained by the urinary protein creatinine ratio (defined as > 30mg/ mmol). We demonstrated the survival probability of adverse outcomes using unadjusted Kaplan-Meier curves and performed an adjusted Cox proportional hazard analysis to include MACE, HF, MACE and HF and all-cause mortality across CKD stages. Results Among the participants (mean age ± standard deviation, 56.5 ± 8.1 years) 282,121 (61.9%) had normal kidney function, 33,582 (7.4%) stage 1 CKD, 121,358 (26.6%) stage 2 CKD without proteinuria, 10,788 (2.4%) stage 2 CKD with proteinuria, 4,654 (1.0%) CKD stage 3A (eGFR 59-45mL/min per 1.73 m2) without proteinuria, 1034 (0.2%) stage 3A with proteinuria and 1,478 (0.3%) with more advanced CKD defined as stages 3B and above. Using Cox regression setting normal kidney function as the reference group, with the exception of stage 2 CKD without proteinuria; there was a progressive increase in the hazard ratio (HR) in all other stages of CKD with respect to MACE, HF, MACE and HF (Figure 1). Significantly, stage 2 CKD without proteinuria was associated with a lower incidence of adverse events than stage 1 CKD and had a comparable prognosis to normal renal function. There was a statistically significant association between stage 2 with proteinuria and MACE (HR 1.33, CI: 1.26 – 1.41), which was comparable to stage 3A without proteinuria (HR 1.32, CI: 1.22 – 1.42). Preliminary analysis of the ongoing cardiac magnetic resonance imaging (cMRI) data from this cohort shows similar progressive changes, apart from stage 2 CKD without proteinuria. Conclusion The presence of proteinuria in patients with mild CKD is a significant risk factor for MACE, HF, cMRI changes and all-cause mortality independent of age, sex, ethnicity, height, BMI, hypertension, diabetes, smoking status, and hyperlipidaemia. We recommend that in order to better risk stratify patients for prognostication and early treatment, stage 2 CKD should be considered as a significant cardiovascular risk only in the presence of proteinuria.

#6045 TWO-YEAR INPATIENT ACTIVITY OF A DEDICATED ONCONEPHROLOGY DEPARTMENT

Abstract Background and Aims Onconephrology is a rapidly evolving nephrology subspecialty that focuses on the interaction between cancer and the kidney. Our aim was to describe the clinical activity of a Nephrology Department in a cancer care center, in a 2-year period. Method We retrospectively analyzed the patients observed by the Nephrology Department at our center between 2021 and 2022. Demographic, clinical and laboratory data were collected. The statistical analysis was performed with SPSS software. Results During the 2-year period, there were 26,015 admissions, 636 of which required a Nephrology observation. Sixty-two per cent were female; the mean age was 68 years (SD ±12.4) with a median Charlson Comorbidity Index of 7. Most cancers were from gastrointestinal (24.1%, n = 153) or urologic origins (22.3%, n = 142), 37% had metastatic disease. Hematologic malignancies accounted for 12.1% of patients (n = 77). Nearly 44.5% of patients (n = 283) had chronic kidney disease (CKD), 20.8% (n = 59) of which were on hemodialysis (HD). Urinary tract obstruction (23.3%), cardiovascular risk factors (17.3%) and nephron loss (10.6%) were the most common causes of CKD. The main reasons for admission were renal dysfunction (23.7%; n = 151), infectious complications (23.3%, n = 148) and elective surgery (20.3%; n = 129). Of the patients observed, 40.7% (n = 259) had acute kidney injury (AKI), 23.3% (n = 148) acute-on-chronic kidney disease and 11.8% (n = 75) hydro-electrolytic disorders. Ten patients (1.6%) were evaluated for nephrotic syndrome (NS) or rapidly progressive renal failure (RPRF). Among AKI patients, intrinsic causes were the most prevalent (48.7% of all cases), with sepsis and ischemic and toxic acute tubular necrosis being the most frequent. Pre-renal and post-renal etiologies occurred in 29.7% and 21.6% of cases, respectively. Gynaecological and prostate tumours were the main neoplastic cause of post-renal AKI. There were 5 TMA cases in allogenic stem cell transplanted patients or treated with gemcitabine and six cases of acute interstitial nephritis, the majority immune check-point inhibitors-related. Over 54% (n = 142) of patients presented with AKI stage 3. About 13% (n = 34) needed renal replacement therapy (RRT), mainly continuous or hybrid techniques (58.8%; n = 20), and only 38% (n = 13) recovered renal function. The group of acute-on-chronic CKD patients included mostly stage 3b and 4 CKD. Most of them (54.1%; n = 80) had an intrinsic cause for kidney dysfunction. There was an equal distribution between stages of AKI severity. About 5% (n = 8) needed RRT and only two of those recovered. Hyponatremia was the most common electrolyte disturbance (56%; n = 42), followed by hypercalcemia (17.3%; n = 13). Over 40% of all cases of hyponatremia occurred in patients with metastatic lung cancer, probably related with the high prevalence of SIADH in this population. All but two patients with NS or RPRF underwent kidney biopsy. Among the patients with NS, its etiologies were: focal and segmental glomerulosclerosis secondary to pamidronate (n = 2), podocytopathy related to pazopanib (n = 1), paraneoplastic membranous nephropathy (n = 1), AL amyloidosis (n = 1) and TMA secondary to gemcitabine (n = 1). The causes of RPRF were ANCA-negative small vessel vasculitis, crescentic glomerulonephritis (GN) related to pembrolizumab and TMA. We also followed two patients with acute kidney disease, one with ATN secondary to bisphosphonates therapy and other with paraneoplastic fibrillary glomerulopathy. The median duration of hospitalization was 10 days (IQR 7.0 – 20.8), with median Nephrology follow-up time of 5.5 days (IQR 3.0 – 9.0). The overall mortality rate was 21.5%, and it was even higher on the subgroup with AKI (27.4%; p = 0.03). About 44% (n = 219) of patients were referred to outpatient Nephrology follow-up, at discharge. Conclusion Our data provides a picture of the rich inward activity developed at our cancer center by the nephrology team. The complexity of these patients highlights the importance of a multidisciplinary approach in their management. No surprisingly, there was a high mortality rate, which was even higher in the AKI-patients subset.

#5123 EFFICACY AND SAFETY OF PATIROMER IN THE TREATMENT OF CHRONIC HYPERKALEMIA IN ASTURIAS: THE K-ASTUR STUDY

Abstract Background and Aims Hyperkalemia is a frequent problem in patients with chronic kidney disease (CKD), especially in those on hemodialysis (HD) and confers increased morbidity and mortality. It is common to carry out urgent HD sessions or increase the number of weekly sessions due to toxic hyperkalemia. Hyperkalemia also prevents the administration or adequate titration of drugs such as renin-angiotensin-aldosterone system (RAAS) inhibitors despite the evidence of their cardiovascular benefits and on the progression of CKD. New drugs have recently entered the market that can help treat chronic hyperkalemia. The aim of the present study was to analyse the efficacy and safety of Patiromer in patients with CKD Method Multicenter, prospective, clinical practice study in patients with CKD stages 3-5. Patiromer was administered with the indication of chronic hyperkalemia. Epidemiological and clinical data were analyzed; the evolution of serum potassium and elements involved in bone and mineral metabolism were taken into account. Results Finally, 52 patients (71±12 years old, 75% male, 63% diabetic, 54% with heart failure, and 42% receiving RAAS inhibitors) were included in the study. Regarding CKD, 17% were in stage 3b, 31% in stage 4, 38% in stage 5 (not on dialysis) and 13% were on HD. Of the 52 patients included, 46 reached 6 months of follow-up, 2 died, 2 underwent a kidney transplant and 2 were transferred to another center. The initial dose of Patiromer was in all cases 8.4 g administered orally in a single dose. Only one patient required doubling the dose because the therapeutic objectives were not achieved. Taking Patiromer was associated with a decrease in the levels of serum potassium of 27% (5.9 vs 4.6 mEq/L; P<0.001), a decrease that was more pronounced in the first month of treatment. There were no changes in the concentration of serum calcium and magnesium. We did find a decrease of 18% in serum phosphorus (5.1 vs 4.2 mg/dl; P 0.022), with no changes in dieto r phosphate binders. Patiromer was well tolerated and only 2 patients reported mild constipation; none discontinued the medication due to adverse effects. Conclusion Patiromer is effective and safe in reducing serum potassium concentrations. Due to its calcium content, it is possible that it favors the reduction in phosphoremia due to a decrease in the intestinal absorption of phosphorus. The use of this drug can help us control potassium levels in patients with CKD, properly titrate the use of ISRAAs, and even reduce the number of HD sessions or dialysis emergencies in some patients.

#5974 CLINICAL AND HISTOPATHOLOGICAL CHARACTERISTICS OF THE ONCONEPHROLOGICAL POPULATION: A MULTICENTRE PROSPECTIVE OBSERVATIONAL STUDY

Abstract Background and Aims Onconephrology is a recently developed discipline aimed at diagnosing and managing renal disease in cancer patients. Few data are available regarding clinical and histological aspects concerning the whole population referred to an onconephrology clinic. Our study aimed to describe the clinical and histopathological characteristics of these patients and to evaluate indices of renal function recovery, renal damage progression, and mortality; a specific aim was to determine in our cohort the prevalence of acute kidney injury (AKI), chronic kidney disease (CKD) and acute kidney disease (AKD) which included all patients meeting KDIGO criteria for AKD but not for AKI. Secondary aims were the analysis of the immunotherapy subgroup and to determine the rate of immune-related adverse events (IRAEs). Method In this prospective observational study, we consecutively enrolled 84 patients for the clinical analysis and 10 patients in two centres for the histopathological study. Clinical assessment in the former group were performed at the first visit (T0), 1 month (T1), 3 months (T2) and 1 year (T3) and compared with a pre-determined baseline. Complete oncological and nephrological assessments were performed. For kidney biopsies, histopathological findings were expressed with quantitative and semi-quantitative parameters. Outcomes were: AKI or AKD complete or partial recovery of renal function (respectively defined as: return to baseline; sCr reduction ≥ 0.3 mg/dl or ≥ 25% or improvement to a lower stage of AKI); a composite of events (MAKE) based on CKD development or progression or death (only at T3). Results Our population was predominantly elderly, hypertensive, in metastatic phase (64.2%), M>F; other factors associated with increased cardiovascular risk were: previous AKI (18.8%), diagnosis of type 2 diabetes (25.9%), history of former/current smoker (55.4% and 19.6%), hyperuricemia (mean uric acid 7 mg/dl), previous/current cisplatin treatment (15.5% and 3.6%). The estimated prevalence in our cohort was: AKI 30.1%; CKD 27.7%; AKI on CKD 25.7%; AKD 9.6%. Regarding AKI, 68.4% were stage 1; for CKD, most patients were stage 3A and 3B (28.2% and 46.2%). More than 1/3 of the patients presented with suspended anticancer treatment; complete therapy resume rates were modest. Complete and partial AKI recovery rates at T2 were both ∼33%. Renal function was fully recovered in 50% of the AKD patients. During the follow-up, a new episode of AKI was observed in 15.5% of the patients, more frequently in the first 3 months. Patients receiving immunotherapy showed worse renal function (sCr 2.02 vs 1.51 mg/dl at T0, p<.001) and higher mortality (4 vs 0, p<.05); patients with IRAEs (25.8%) presented more frequently with discontinued therapy (Table 1). Of 36 patients with data available at 1 year, 21 (58.3%) presented the outcome MAKE; 11 patients died, 4 in the first three months. No nephrological conditions were found to predict MAKEs; presence of metastasis and female sex were the only predictors with Cox regression. Patients who underwent renal biopsy showed marked heterogeneity in the diagnoses (4 Membranous nephropathy, 1 drug-induced podocyte damage, 1 extracapillary GN after SARSCoV2 vaccination, 1 Light/Heavy Chain Deposition Disease, 1 Chronic Tubulointerstitial Nephritis, 1 sclerohyalinosis, 1 nonspecific); histopathological data was unremarkable. Conclusion AKI and CKD occur frequently in the onconephrological population. These patients are susceptible to new AKI episodes. The absence of AKI recovery and anticancer therapy withdrawal are common, potentially holding negative prognostic value. Particular attention should be paid to patients undergoing immunotherapy, especially when associated with IRAE. A larger number of patients is needed to estimate the impact of nephrological factors in the extended follow-up.

#5705 EFFICACY AND SAFETY OF SACUBITRIL/VALSARTAN IN PATIENTS WITH STAGE 3B-5 CKD AND HYPERTENSION

Abstract Background and Aims Sacubitril/valsartan (SV) plays a key role in improving left ventricular remodeling and prognosis in patients with heart failure. However its effects on kidney function in people with moderate to severe chronic kidney disease (CKD3b-5) are unknown. The present study was designed to assess the efficacy and safety of sacubitril-valsartan in patients with stage 3b-5 CKD and hypertension. Method In this randomized, double-blind, 3-month trial, patients with stage 3b-5 CKD and hypertension were randomly assigned to sacubitril/valsartan treatment group (n = 44, the doses of SV were up-titrated to sacubitril/valsartan 400 mg), and conventional antihyperensive treatment group (n = 40). The primary outcome was reduction in GFR from baseline at week 12. Results In total, 44 participants were assigned to sacubitril/valsartan group and 40 to crontol group (conventional antihyperensive group). Baseline measured GFR was 29.94±11.83, 27.86±10.14 mL/min/1.73 m2, respectively. There was no difference in measured GFR (P = 0.064). At week 12, there was a reduction in measured GFR in control group: 27.86±9.15 versus 22.03±11.41, but there was no significant difference (P = 0.155). Sacubitril/ valsartan could improve eGFR: 29.94±11.83 versus 32.05±14.57 (P = 0.018). We also observed that, compared with control group, sacubitril/valsartan decreased albuminuria: reductions in urinary albumin:creatinine ratio (ACR) in sacubitril/valsartan group was 89.5mg/g and reductions in urinary ACR in control group was -44.55mg/g. At week 12, Sacubitril/valsartan provided a significantly greater reduction in office mean sitting (ms) systolic BP (msSBP) than control group (20.75mmHg vs 12.88mmHg, P = 0.046). There was no serious adverse events in both groups. The incidence of hyperkalemia (potassium≥5.5 mmol/L) was 4.5% in SV group and 7.5% in control group. Conclusion The present data suggested that, in patients with stage 3b-5 CKD and hypertension, Sacubitril-valsartan could improve kidney function and decrease albuminuria, and was generally safe and well tolerated.

#3156 REAL WORLD CHARACTERISTICS, SYMPTOM BURDEN AND TREATMENT PATTERNS OF ANAEMIA OF CKD IN EGYPT, SAUDI ARABIA, SOUTH AFRICA, AND TURKEY

Abstract Background and aims Patients with chronic kidney disease (CKD) often have comorbid anaemia [1]. Real-world data on patient characteristics, disease burden, and treatment management for people with anaemia of CKD in the Middle East and Africa are limited. Methods SATISFY (Survey on treatment patterns in Anemia of CKD, patient Treatment satISFaction and perspectives as reported by patients with phYsicians) was a real-world survey conducted between 01 June to 01 September 2022 in Egypt, Saudi Arabia, South Africa, and Turkey. Physician and patient perceptions of treatment were captured via cross-sectional surveys; patients’ clinical characteristics were recorded by physicians in electronic case report forms via retrospective review of medical records. Eligible physicians were nephrologists with ≥1 years’ experience who managed ≥12 patients with anaemia of CKD per month and with drug management experience for anaemia of CKD. Physicians collected data on the first 7–10 patients seen in routine clinical practice during the study period. Eligible patients were ≥18 years with CKD stage 3b, 4, or 5 at the time of anaemia of CKD diagnosis and with ≥2 years’ follow-up data from diagnosis to time of survey. Patients with functioning kidney transplants or acute kidney injury were excluded. Primary outcomes were to describe clinical and demographic characteristics, monitoring test results, treatment patterns of patients with anaemia of CKD, physicians’ reasons for not treating anaemia of CKD, and physicians’ and patients’ reasons for therapy choice. Data were analysed descriptively. Results A total of 1788 patients and 217 physicians were included; 1138 patients (64%) were non-dialysis dependent (NDD) and 611 (34%) were dialysis dependent (DD) at the time of data extraction (n = 39 [2%] data missing). Mean (standard deviation [SD]) age was 46 (14) years, mean (SD) body mass index was 24.1 (3.1) kg/m2, 56% (n = 1004) were male, and median (interquartile range [IQR]) follow-up from diagnosis of anaemia of CKD was 2.6 (2.5–3.2) years. The most common comorbidities were hypertension (n = 858, 48%) and diabetes (n = 324, 18%). Symptom burden was high, with lack of energy and fatigue being among the most commonly reported symptoms by physicians and patients across both NDD and DD groups (Figure 1). Differences were seen between physician and patient symptom reporting and between NDD and DD groups. Patients’ self-reported symptom burden was greater than that reported by physicians, particularly for NDD patients. The median (IQR) times per year physicians reported testing CKD patients for anaemia was 4 (4–6) for NDD patients and 12 (10–12) for DD patients. Median test levels for haemoglobin at which patients were diagnosed were lower than those reported by physicians as being used for diagnosis; similar results were seen for thresholds used to initiate treatment (Table 1). Median (IQR) days from diagnosis to first treatment was 61 (0–419). Of those who received treatment, the most common first treatment option was erythropoietin-stimulating agents + intravenous iron for both patients with NDD and DD anaemia of CKD at diagnosis (NDD n = 291/736, 40%; DD n = 170/316, 54%). A large proportion of patients never received treatment for anaemia of CKD (n = 701, 39%). The most important reasons to not initiate treatment from a physician perspective were patient refusal (n = 172, 79%) and risk of adverse reactions (n = 168, 77%); for patients, top reasons were that their symptoms were not severe (n = 168, 22%) and their physicians’ concerns about adherence (n = 116, 15%). Similar reasons were seen for both the Middle East and Africa regions. Conclusion Symptom burden is high in patients with anaemia of CKD in the Middle East and Africa, particularly lack of energy and fatigue. Differences were seen between physician and patient perceptions of symptom burden and between NDD and DD groups. Substantial treatment inertia exists. Physicians rated patient refusal and risk of adverse reactions as main reasons for not treating patients, while patients attributed this to a belief that their symptoms were not severe.

#5529 RED BLOOD CELL TRANSFUSION RATES IN THE INTERNATIONAL DOPPS PROGRAM (2012–2022): HEMODIALYSIS, PERITONEAL DIALYSIS, AND NON-DIALYSIS CKD POPULATIONS

Abstract Background and Aims Anemia is a common complication of chronic kidney disease (CKD), and affects the majority of patients on hemodialysis (HD) and peritoneal dialysis (PD). Consequences of anemia include lower quality of life, increased healthcare utilization, and greater mortality risk. Current international guidelines recommend treating patients with iron and erythropoiesis-stimulating agents (ESAs) to a target hemoglobin (Hb) range, and avoiding red blood cell transfusions (RBCT) when possible, given the associated short- and long-term adverse consequences including hyperkalemia and allosensitization. A description of contemporary RBCT rates – after the 2012 KDIGO guideline changes – across the spectrum of CKD and different geographies is lacking. In this analysis, we estimated RBCT rates in non-dialysis CKD (ND-CKD), PD, and HD patients in a multinational setting, overall and stratified by Hb levels. Method We used data from 3 ongoing prospective cohort studies from the Dialysis Outcomes and Practice Patterns Study (DOPPS) Program: 2443 Stage 3–4 ND-CKD patients from 2 countries in CKDopps phases 1–2 (2013–2022), 3557 PD patients from 6 countries in PDOPPS phase 1 (2014–2018), and 22,771 HD patients from 20 countries in DOPPS phases 5–7 (2012–2022). Within each study, patients were randomly selected from stratified national samples of clinics, representative of a snapshot in time at study entry. Prospective information on RBCT receipt (yes/no) was captured at the patient-month level; thus, multiple events per patient were considered in the rate calculation, if they occurred in different months. RBCT rates were calculated as a count of the total patient-months with an RBCT event divided by the total patient-months with RBCT data available. Rates (per patient-month) were converted to per 100 patient-years, with 95% confidence intervals estimated by Poisson regression. RBCT rates are presented in each population (ND-CKD, PD, HD) across strata of interest, including CKD stage, country/region, and baseline Hb levels. Results Mean age (years) of the cohort was 68.6 for ND-CKD, 59.1 for PD, and 63.2 for HD. Mean (std dev) baseline Hb levels (g/dL) were 12.1 (1.9) in ND-CKD compared to 10.9 (1.7) in PD and 10.9 (1.5) in HD. Median [IQR] months of follow up (with RBCT data available) was 17 [6, 27] for ND-CKD, 16 [9, 20] for PD, and 8 [4, 19] for HD. Table 1 shows crude RBCT rates (per 100 patient-years) in the ND-CKD, PD, and HD populations, overall, by CKD stage and country/region. For ND-CKD, the RBCT rate was 6.7 (95% CI: 5.9, 7.6) overall, including 7.0 in the US and 5.5 in Brazil. RBCT rates increased with ND-CKD stage, from 2.2 in Stage 3a to 4.5 in Stage 3b to 8.5 in Stage 4. For PD, the RBCT rate was 20.3 (95% CI: 19.1, 21.6), higher than in ND-CKD, with substantial variation across countries, from 7.3 in the UK to 45.6 in Thailand. For HD, the RBCT rate was 23.9 (95% CI: 23.3, 24.5), also higher than in ND-CKD, with international variation observed. In the HD cohort, RBCT rates were lower in China (6.3) compared to the US (21.9), Canada (34.4), and the Gulf Cooperation Council region (34.8). Within HD-Europe, RBCT rates were highest in Belgium (48.1) and Sweden (42.4), and lowest in Germany (15.4), France (19.0), and Italy (20.4). Table 2 shows crude RBCT rates by baseline Hb levels. In all 3 cohorts (ND-CKD, PD, HD), RBCT rates appeared higher among patients with lower versus higher baseline Hb levels. In the PD and HD populations, patients with baseline Hb <8 g/dL had RBCT rates >100. Conclusion Our multinational study used uniform and standardized data collection tools, procedures, and processes to estimate RBCT rates in the post-2012 era following the revision of international guidelines. As expected, we observed higher RBCT rates in the PD and HD (vs. ND-CKD) populations, and higher RBCT rates among patients with lower baseline Hb levels. Interestingly, we also observed substantial international variation in RBCT rates in all 3 cohorts (ND-CKD, PD, HD). Further research is needed to better understand the reasons why RBCT use is higher or lower in certain countries, and to investigate predisposing and modifiable risk factors for RBCT. Funding: GSK (study 218930)

#4609 ASSOCIATION BETWEEN THE SERUM CREATININE-TO-CYSTATIN-C RATIO AND RAPID PROGRESSION OF CHRONIC KIDNEY DISEASE

Abstract Background and Aims Chronic Kidney Disease (CKD) is a common and progressive condition that affects a significant portion of the global population. It is a leading cause of death and requires timely evaluation and monitoring to ensure proper management. Cystatin C has been shown to be an effective marker of kidney function and a predictive marker of CKD progression. However, there is limited research evaluating the relationship between the serum creatinine-to-cystatin-C (Cr/cysC) ratio and the rapid progression of CKD. This study aims to investigate the effectiveness of the Cr/cysC ratio in predicting rapid progression of CKD. Method A retrospective study was conducted on 1,104 patients with CKD who were treated at the Nephrology Outpatient Clinic of Hanyang University Guri Hospital between December 2020 and November 2022. Eligible patients had at least two simultaneous measurements of serum creatinine and cystatin C, with a minimum interval of 6 months. The definition of rapid progression of CKD was a decrease in creatinine-based estimated glomerular filtration rate (eGFR) of more than 4 mL/min/1.73 m2 over a 1-year period or initiation of renal replacement therapy (RRT). In addition, considering the short duration of the study, initiation of RRT was considered as a secondary outcome only in CKD stages 3b, 4, and 5. Results The study population consisted of patients with CKD stages 1 to 5, with a mean age of 69.7 years and 57.7% of the population being male. The mean baseline body mass index was 25.8 kg/ m2, and the mean initial eGFR was 46.7 mL/min/1.73 m2. 38.4% of the total patients showed rapid progression of CKD. The analysis showed that a lower Cr/cysC ratio was significantly associated with an increased risk of rapid progression of CKD (OR: 0.812, 95% CI: 0.761-0.867, p<0.001). After adjusting for age, sex, body mass index, and initial eGFR, a lower Cr/cysC ratio remained a significant risk factor for rapid progression of CKD (OR: 0.760, 95% CI: 0.685-0.844, p<0.001). The initiation of RRT increased with the advancement of CKD stage, with 11 patients with CKD stage 3b, 30 patients with CKD stage 4, and 41 patients with CKD stage 5 initiating dialysis treatment. After adjusting for all variables, the OR was 0.774 (95% CI: 0.667-0.898, p = 0.001), indicating that as the Cr/cysC ratio increased, the progression of dialysis significantly decreased by 22.6%. Conclusion In this study, a lower Cr/cysC ratio was significantly associated with an increased risk of rapid progression of CKD and initiation of RRT. The results of this study suggest that monitoring the Cr/cysC ratio may provide valuable information for the management of CKD patients.

#4893 THE INCIDENCE, RISK FACTORS AND OUTCOMES OF ACUTE KIDNEY INJURY AFTER MINOR LOWER LIMB AMPUTATIONS

Abstract Background and Aims Minor lower limb amputations (toe amputations and/or amputations distal to or through the tarsometatarsal joint), are limb and potentially lifesaving procedures. However, they are associated with serious adverse events including acute kidney injury (AKI). The aim of this study was to determine the incidence of AKI after such interventions, identify potential risk factors and assess impact on patient survival. Method This was a single centre retrospective study involving patients who underwent minor lower limb amputations at Mater Dei Hospital Malta between January and December 2019. Patient and procedure details were obtained from hospital records. Estimated glomerular filtration rate (eGFR) was calculated using the Modification of Diet in Renal Disease formula. Chronic kidney disease (CKD) was defined as per Kidney Disease: Improving Global Outcomes (KDIGO) criteria. AKI was defined using Acute Kidney Injury Network (AKIN) criteria or KDIGO criteria if day 7 serum creatinine was available. Statistical analysis was performed using SPSS Statistics for Windows v21.0 (IBM Corp.). Results A total of 201 patients were included; males 69.7%, mean age 70.4 ±11.5 years, 87.1% had diabetes mellitus, 71.1% hypertension and 26.4% had ischemic heart disease. Pre-existing CKD was identified in 35.8%; 16.4% CKD stage 3a, 13.4% CKD stage 3b, 5.5% CKD 4 and 1 patient CKD 5. The majority (76.1%) underwent single toe amputations. Surgery was performed under loco-regional anaesthesia in 90% of patients, mostly in view of lower limb ulcers (64.7%) or gangrene (29.4%). A cohort of 54 (26.9%) patients received iodine based contrast within 7 days of procedure, including those who underwent bypass surgery (8%) and endarterectomy (4%). The incidence of AKI after minor lower limb amputations using AKIN criteria was 18.9%. An additional 12 patients were identified using KDIGO criteria (24.9%), however KDIGO criteria could only be applied for 123 patients as the rest did not have a day 7 serum creatinine. Most developed stage 1 AKI (18.4%), one patient developed stage 2 AKI and none developed stage 3 AKI using AKIN criteria. Only 1 patient needed temporary haemodialysis having developed AKI after day 3 post-operatively fulfilling KDIGO but not AKIN criteria. Recovery of kidney function occurred in all patients. All-cause mortality at 30 days, 60 days and 18 months (end of follow-up) was 2.0%, 5.5% and 19.9% respectively. None of the deaths were directly related to the AKI-amputation event. Patients who developed AKI, compared to those who did not, were more likely to have an eGFR <45ml/min/1.73 m2 at the time of procedure (39.5% vs. 14.7%, p = 0.001). They were significantly older (73.0 ±10.4 vs. 68.5 ±11.8 years, p = 0.033), and more likely to have underlying chronic obstructive pulmonary disease (COPD) (28.9% vs. 13.5% p = 0.028). Use of loop and/or thiazide diuretics (68.4% vs. 49.1%, p = 0.049), fluoroquinolones (71.1% vs. 52.8% p = 0.047) and/or carbapenems (10.5% vs. 2.5%, p = 0.043) was also more frequent in this group. Use of iodine based contrast within 7 days of procedure did not effect incidence of AKI. Hospital length of stay and all-cause mortality were not significantly higher in patients with AKI. An eGFR <45ml/min/1.73 m2 was established as a strong independent predictor for the development of AKI (odds ratio [OR] 3.24, confidence interval [CI]: 1.40–7.52, p = 0.006), as were use of fluoroquinolones (OR: 3.19, CI: 1.30–7.82, p = 0.012) and day 1 C-reactive protein (CRP) (OR: 1.01, CI: 1.00–1.01, p = 0.009). Cumulative survival censored at the end of follow-up was not significantly lower in patients who developed AKI (log rank: 0.45, p = 0.50). Conclusion In our study, 18.9% of patients developed AKI after minor lower limb amputations using AKIN criteria. One patient required acute haemodialysis. Age, COPD, diuretics, fluoroquinolones and carbapenems were associated with increased incidence of AKI. An eGFR <45ml/min/1.73 m2, day 1 CRP and fluoroquinolone use were independent risk factors for the development of AKI. In this small patient cohort, AKI was not associated with higher all-cause mortality, and none of the deaths were directly related to the AKI-amputation event.

#4735 USEFULNESS OF CYSTATIN C IN MEASURING RENAL FUNCTION AND PREDICTING METHOTREXATE ASSOCIATED TOXICITIES IN PATIENTS WITH RHEUMATOID ARTHRITIS

Abstract Background and Aims Rheumatoid arthritis (RA) is a representative chronic disease accompanied by muscle loss, and cystatin C may be more useful than traditional creatinine (Cr) when measuring renal function. RA is affected not only by drug dose but also by side effects of treatment according to renal function. Therefore, we tried to compare the estimated glomerular filtrate rate (eGFR) using cystatin C and Cr and analyze the methotrexate (MTX) associated toxicities after treatment. Method A total of 436 RA patients was enrolled in this study. The eGFR was calculated using the Chronic kidney Disease Epidemiology Collaboration (CKD-EPI) equation based on cystatin C and serum Cr. According to eGFR, CKD stages and drug dosing stages were classified and MTX associated toxicities were evaluated. Results Mean eGFR using the CKD-EPI cr and CKD-EPI cystatin C equations were 95.36 and 89.44 mL/min. In the CKD-EPIcr group, there were 11 patients with eGFR less than 50 mL/min that required dosing reduction, and 38 patients in the CKD-EPI cystatin C group, showing a statistically significant difference (Table 1A). In addition, CKD stage 3B and 4 patients were also higher in the CKD-EPI cystatin C group compared to those in CKD-EPI cr group (Table 1B), and anemia and nephrotoxicity were high in the MTX related toxicity stage upgraded group. Conclusion Our study showed that eGFR by CKD-EPI Cr can be overestimated than that by CKD-EPI cystatin C, and also demonstrated higher MTX associated toxicities in the group, which the stage was changed upward. Therefore, this study suggests that cystatin C is useful predictor in measuring renal function and predicting MTX associated toxicities in RA patients

#5924 LATE DIAGNOSIS OF IGA NEPHROPATHY IN LOWER SAXONY (GERMANY) – CLINICAL AND HISTOPATHOLOGICAL DATA FROM 246 PATIENTS AT TIME OF INITIAL RENAL BIOPSY

Abstract Background and Aims IgA Nephropathy (IgAN) is the most frequent glomerulonephritis and contributes significantly to the burden of dialysis dependence. If not detected in the context of screening health examinations e.g. for the military service, decline in renal function is usually unnoticed due to the lack of specific symptoms. After decades of limited pharmacological options, the advent of new therapies provides opportunities for early intervention. Age and renal function as well as proteinuria at the time of renal biopsy varies depending on healthcare systems but might influence the use of novel interventions. Publications from outside Germany report that eGFR at the time of first renal biopsy in IgAN varies between 73.8 and 94.9ml/min/1,73 m2. The age at the time of diagnosis is between 27 and 40 years. The aim of our study was to investigate renal function, degree of proteinuria as well as histological parameters at the time of first renal biopsy in patients with IgA nephropathy. Method This retrospective study evaluated data from two different tertiary care hospitals in Germany that that sent their renal biopsies to the Nephropathology Department at the Hannover Medical School from January 2012 – October 2022. Only initial biopsies from native kidneys were included. Histopathological parameters and clinical as well as laboratory parameters at the month of biopsy were obtained. eGFR was calculated according to the CKD-EPI formula. Results First time diagnosis of IgA nephropathy was made in 246 patients at a median age at of 45 (range 4–79) years, 76.8% were male. The median serum creatinine level was 1.44mg/dl, corresponding to a median eGFR of 43.0 (3.8–132) ml/min/1.73 m2. Surprisingly 49.5% of all patients were at CKD KDIGO GFR stage 3B or higher at the time of first biopsy (Figure 1). Median proteinuria was 1.84 (0.08 – 16.5) g/d in those patients where 24h urine collection was performed. 156 of 246 patients had microhematuria at the time of biopsy. Based on the Oxford classification >50% had hypercellularity. Endocapillary hypercellularity was present in 24%. Segmental glomerulosclerosis was almost evenly distributed (S0:116 | S1:112). Tubular atrophy and interstitial fibrosis were visible in most biopsies in 0-25% of cortical area (T0:153 | T1:59 | T2:16). In 27.2% the C-score was analyzed, showing cellular and/or fibrocellular crescent in 26.8% of those patients. Thrombosis and necrosis were rather uncommon in initial biopsies of IgA Nephropathy. Conclusion The study shows that an IgA Nephropathy shows severe renal impairment at the time of diagnosis i.e. first renal biopsy, suggesting that patients are referred rather late for this diagnostic procedure. These regional data have to be validated in larger cohorts. If confirmed, measures for earlier screening and referral should be implemented to allow timely intervention thus lowering need for renal replacement therapy.

#5417 EARLY MARKERS AND VASCULAR IMPAIRMENT IN THE PROGRESSION OF CHRONIC KIDNEY DISEASE (CKD)

Abstract Background and Aims Soluble Klotho (sKlotho) is thought to decrease early in CKD, but its use as biomarker of the CKD progression is controversial. In addition, the use of newnon-invasive techniques to diagnose incipient vascular damage in CKD would be of clinical interest. The aims of this study were: to assess the utility of serum and urinary sKlotho as a useful biomarker of kidney impairment and; to analyse the value of carotid adventitial neovascularization and aortic stiffness in the course of CKD. Method Forty-three CKD patients were classified according to their estimated glomerular filtration rate (eGFR) into 4 groups (CKD-2/3a, CKD-3b, CKD-4 and CKD-5) and 38 sex and age matched controls were studied. Carotid and femoral adventitial neovascularization was assessed by ultrasensitive ultrasonography without contrast (Superb microvascular image, SMI). Aortic pulse wave velocity (PWV) was measured to determine stiffness. Results No differences in age and body mass index between control group and the four CKD stages were observed. The eGFR showed a significant and progressive decrease (Table 1). Serum PTH, FGF23 and proteinuria were significantly higher and serum calcitriol lower in CKD stages 3b to 5 (Table 1). No changes were observed in serum Ca and serum P increased only in CKD-5 (Table 1). Serum sKlotho displayed a progressive decrease from CKD-2/3a to CKD-5, before other CKD parameters, such as FGF23 and PTH changed. A significant correlation between serum sKlotho and serum creatinine was observed (r = -0.394, p = 0.0003). Urinary sKlotho increased in CKD-2/3a stage and remained similar up to CKD-5 (Table 1). The carotid artery of CKD patients stages 4 and 5 showed a higher number of adventitial vasa vasorum (CKD-4 = 2.09±2.26, p = 0.002; CKD-5 = 1.56±1.67, control = 0.90±2.37, p = 0.019) and a greater area of adventitial neovascularization (CKD-4 = 3.52±3.49, p = 0.0008; CKD-5 = 4.51±7.75, control = 0.84±2.18, p = 0.009) compared to controls. No differences in femoral neovascularization were found. PWV was significantly higher only in CKD-5 (CKD-5 = 12.91, control = 10.81, p = 0.045). A significant correlation was observed between PWV and the area of adventitial neovascularization (r = 0.360, p = 0.001) and the number of adventitial vasa vasorum in the carotid artery (r = 0.246, p = 0.028). Conclusion Serum sKlotho decreased before FGF23 levels begun to rise, indicating the sKlotho decrease as the earliest marker of CKD-MBD, although it remains with no changes throughout the CKD progression. Carotid adventitial neovascularization by SMI and PWV increased in advanced CKD stages, suggesting that they have a limited clinical utility as early markers of vascular damage in CKD.

CEREBRAL OXYGENATION DURING EXERCISE DETERIORATES WITH ADVANCING CHRONIC KIDNEY DISEASE

Objective: Cognitive impairment and exercise intolerance are common in CKD. Cerebral perfusion and oxygenation play a major role in both cognitive function and exercise execution. This study aimed to examine cerebral oxygenation during a mild physical stress in patients at different CKD stages and controls without CKD. Design and method: Ninety-participants (18 per CKD-stage 2,3a,3b,4 and 18 controls) underwent a 3-min intermittent-handgrip-exercise at 35% of their maximal-voluntary-contraction(MVC). During exercise, cerebral oxygenation (oxyhemoglobin-O2Hb, deoxyhemoglobin-HHb, total-hemoglobin-tHb) was assessed by near-infrared-spectroscopy. Indices of microvascular (muscle-hyperemic-response) and macrovascular function (cIMT and PWV), cognitive and physical activity status were also evaluated. Results: No differences in age, sex and BMI were detected among-groups. The MMSE score was significantly reduced with advancing CKD stages (Controls: 29.2±1.2 Stage 2: 28.7±1.0 Stage 3a: 27.8±1.9 Stage 3b: 28.0±1.8 Stage 4: 27.6±1.5; p = 0.019). Similar trends were observed for physical activity levels and handgrip strength. The average response in cerebral oxygenation during exercise was lower with advancing CKD stages (O2Hb: Controls: 2.50±1.54, Stage-2: 1.30±1.05, Stage-3a: 1.24±0.93, Stage-3b: 1.11±0.89, Stage-4: 0.97±0.80micromol/l; p<0.001)). The average tHb response(index of regional-blood-volume) showed a similar decreasing trend (p = 0.003); no differences in HHb among groups were detected. In univariate linear analysis older age, lower eGFR, Hb, microvascular hyperemic response, and increased PWV were associated with poor O2Hb response during exercise; in the multiple model, eGFR was the only parameter independently associated with the O2Hb response. Conclusions: Brain activation during a mild physical task appears to decrease with advancing CKD as suggested by the smaller rise in cerebral oxygenation. This may contribute both to impaired cognitive function and reduced exercise tolerance with advancing CKD.

CARDIOVASCULAR EVENTS IN TYPE 2 DIABETIC PATIENTS

Objective: Cardiovascular diseases represent the first cause of death of patients with type 2 diabetes. The aim of our work is to identify the prevalence of cardiovascular disease in type 2 diabetes. Design and method: This is a retrospective descriptive study conducted over a period of three years (January 2013- January 2016) including type 2 diabetic patients followed up at the nephrology consultation of Mongi slim hospital. Clearance was calculated according to the MDRD formula. The stage of chronic kidney disease (CKD) was defined according to the KDIGO 2012 classification. Results: Our study included 42 patients with diabetic kidney disease followed at our nephrology consultation. The mean age was 63.3 [31-80] with a sex ratio M/F = 1.47. Eighty-eight percent of our patients had hypertension. At the first consultation our patients already had macrovascular disease: 4 patients were suffering from peripheral artery disease, 4 patients had heart failure, a history of ischemic stroke was found in 4 patients and acute coronary syndrome in 11 patients. Regarding cardiovascular risk factors, obesity was found in 13 patients, 6 patients were smokers and 25 patients (59.5%) had dyslipidemia with a mean cholesterol level of 4.48 +/- 1.09 mmol/l. The mean fasting blood glucose level was 10.5 +/-5.23 mmol/l and a mean glycated hemoglobin was 8.24 +/-2.22%. The renal impact was as follows: chronic kidney disease stage 3A in 12 patients (28.6%), stage 3B in 14 patients (33.3%), stage 4 in 6 patients (14.3%) and stage 5 in 2 patients. During the course of the study, 7 patients had an acute coronary syndrome and 1 patient had an ischemic stroke. Conclusions: Diabetes is a cardiovascular risk factor in itself. Although nothing can be done about the non-modifiable risk factors (heredity, age, gender), it is possible to act early and effectively on the other modifiable factors.