CKD-EPI Cystatin Research Articles

EVALUATION OF THE FUNCTIONAL STATE OF KIDNEYS IN PATIENTS WITH ACUTE MYOCARDIAL INFARCTION BASED ON THE DETERMINATION OF CREATININE AND CYSTATIN C LEVELS

Aim – to evaluate the functional state of kidneys, glomerular filtration rate based on the determination of creatinine and Cystatin C in STEMI patients undergoing urgent revascularization.Methods and materials. The study included 286 patients with acute myocardial infarction and ST-elevation myocardial infarction (STEMI). Among the examined persons, 202 (70.6%) were men and 84 (29.4%) were women, with an average age of (62.8±9.8) years.Research results. The GFR calculated by the CKD-EPI formula in the examined group of STEMI patients ranged from 15.6 to 87.4 and averaged 51.0±14.3 ml/min∙m2.7. The value of the calculated GFR according to the CKD-EPI Cystatin C formula ranged from 11.1 to 88.1 and averaged 45.7±13.7 ml/min/1.73 m2. The non-parametric Spearman rank correlation analysis showed a high direct correlation between the values of GFR calculated by different formulas (CKD-EPI and CKD-EPI Cystatin C) - R=0.81; p<0.0001. Using the linear regression method, a formula was derived for the conditional calculation of GFR value according to CKD-EPI Cystatin C = 4.15 + GFR value according to CKD-EPI 0.814. Regression coefficient R2 = 0.84 (Fisher's correlation coefficient - F = 728.34 at the proper level = 1.28), p < 0.000001.Conclusions. Determination of GFR based on Cystatin C demonstrates lower rates in both men and women. A decrease in estimated GFR was related to older age and female gender.

#2079 The impact of body composition measures on survival and cardiovascular events in patients with chronic kidney disease

Abstract Background and Aims Multimorbidity, frailty and sarcopenia are increasingly prevalent in people with chronic kidney disease (CKD). Creatinine Muscle Index (CMI) has been proposed as a novel surrogate marker of muscle mass, and lower CMI was associated with frailty and increased mortality in the Atherosclerosis Risk in Community Study [1]. Waist to hip ratio (WHR) has also been proposed as a surrogate marker of visceral adiposity. In order to investigate the impact of body composition on outcomes, we analysed data collected from a large CKD cohort using CMI and WHR as markers of muscle mass and adiposity respectively to examine their effects on 5-year survival and cardiovascular events. Method 1741 people with CKD stage 3 were recruited from 32 primary care practices. Cystatin C was measured using the Abbott c16000 Analyser (Abbott Diagnostics). eGFR cystatin (eGFRcys) was calculated using the CKD-EPI Cystatin C Equation (2012). CMI was calculated as the product of serum creatinine and eGFRcys (CMI [mg/day per 1.73 m2]= eGFRcys [ml/min per 1.73 m2] × serum creatinine [mg/dl] × 1 dl/100 ml × 1440 min/day). Cox proportional hazard model was used to examine if CMI and WHR predicted death or cardiovascular events. Results Mean age of the participants was 72.9 ± 9 years. Mean eGFRCr was 53.5 ± 11.8 ml/min/1.73 m2. Mean eGFRcys was 45.1 ± 16.0 ml/min/1.73 m2. Mean CMI was 766.45 ± 239.2 mg/day/1.73 m2. 300 (17.2%) participants died during 5 years of observation. In a Cox proportional hazards model which included CMI, WHR and age, lower CMI per standard deviation change (B = −0.202, HR 0.817, p = 0.007), higher WHR per standard deviation change (B = 0.313, HR 1.37, p < 0.001) and age at baseline (B = 0.088, HR 1.09, p < 0.001) were independent predictors of mortality at year 5 of follow-up. CMI per standard deviation change also predicted cardiovascular events at 5 years using a univariable cox proportional hazards model, (B = −0.095, HR 0.91, p = 0.03). Conclusion Lower CMI (a surrogate measure of muscle mass) and higher WHR (a surrogate for visceral adiposity) independently predicted 5 year mortality and cardiovascular events in this predominantly elderly population with CKD stage 3. We conclude that body composition has an important impact on mortality and cardiovascular events in patients with CKD and the mechanisms of this merits further investigation. This could inform future interventions that reduce visceral adiposity and improve muscle mass in people with CKD.

#2840 Early tolerance of SGLT2i therapy in patients with ATTR V30M amyloidosis: staging the disease to establish standard of care

Abstract Background and Aims Studies of sodium-glucose co-transporter 2 inhibitors (SGLT2i) therapy on ATTR cardiomyopathy are scarce and focus wild-type and V122I. In ATTRv, namely V30M, SGLT2i introduction to preserve kidney function or improve cardiorenal syndrome is not an outlined practice. Our aim was to assess the clinical evolution and difficulties with SGLT2i therapy in ATTR V30M amyloidosis, a population with neurogenic bladder, dysautonomia and prone to dehydration. Methods Patients with ATTR V30M amyloidosis and criteria for SGLT2i started standard dosages. Gillmore score (GS) for ATTR cardiomyopathy, kidney failure risk equation (KFRE) and the renal system score (RSS) of the FASTEX model (Fabry disease) were calculated. Estimation of heart amyloid load was based on Tc-99-DPD scintigraphy. Results Eight patients were followed on median of 7 months [IQR 5.6-9.4]; 7 treated with dapagliflozin, 1 with empagliflozin. 6 had type-2 diabetes. 4 were treated with tafamidis, 1 inotersen and 1 patisiran. 3/7 had positive DPD scintigraphy. Heart failure decompensation, new arrhythmias and renal adverse events were absent. Neurogenic bladder was present in 4 patients, 2 had urinary tract infections. 1 had symptomatic hypotension, leading to discontinuation of therapy. EGFR and RSS improved in 5 and 3 patients, respectively; NT-proBNP/albuminuria/proteinuria and KFRE at 2 and 5 years decreased. In terms of cardiomyopathy, 1 patient improved to GSI; 2 using CKD-EPI creatinine and none using CKD-EPI cystatin C. 1 progressed to GSII in all equations. Conclusion In this pilot study, we evidenced that ATTR V30M patients meet the criteria for SGLT2i therapy. Dysautonomia and neurogenic bladder were not an impediment for therapy. In addition to disease modifying drugs, SGLT2i may improve kidney and cardiovascular outcomes in ATTR V30M amyloidosis.

Assessment of Circulating Retinol Binding Protein-4 Levels in Patients with Compound Heterozygosity for Hb S and β-Thalassemia

Background: Retinol Binding Protein-4 (RBP-4) is a member of the lipocalin family of proteins and the major transport protein of the hydrophobic molecule retinol, also known as vitamin A, in the circulation. Expression of RBP4 is highest in the liver, where most of the body's vitamin A reserves are stored as retinyl esters. For the mobilization of vitamin A from the liver, retinyl esters are hydrolyzed to retinol, which then binds to RBP-4 in the hepatocyte. After associating with transthyretin (TTR), the retinol/RBP-4/TTR complex is released into the bloodstream and delivers retinol to tissues via binding to specific membrane receptors. While, after its dissociation from TTR and retinol release, retinol-free apo-RBP4 in the circulation is filtrated by the kidney. More than 99% of that is reabsorbed by the proximal renal tubule, which renders urinary RBP-4 a highly sensitive marker for tubular dysfunction. We and other have shown previously that the patients with Sickle Cell Disease (SCD) have deficiencies or suboptimal levels of vitamin A, while recently (Br J Haematol. 2023;doi:10.1111/bjh.18862) higher urine RBP-4 in patients with SCD especially in those with persistent albuminuria but without an association of urine RBP-4 levels with estimated glomerular filtration rate (eGFR). In this context, we aimed to investigate the potential clinical significance of circulating plasma RBP-4 levels and its association with disease features in Caucasian patients with compound heterozygosity for HbS and β-thalassemia (HbS/β thal). Patients and Methods: Ninety Caucasian adult patients with HbS/β thal at steady phase were included in the study, while 22 apparently healthy individuals of similar age and gender served as controls. None of the patients was diabetic and has received any transfusions at least 6-monthes before enrollment in the study. RBP-4 concentration was measured with an immunoturbidimetric assay applied in an automated chemistry analyzer, along with hematologic, and series of blood chemistry parameters reflecting renal, cardiac and endothelial dysfunction. eGFR values were calculated using the CKD-EPI (Cystatin C and/or Creatinine equations). Results: We found that: a) Plasma RBP-4 levels were significantly lower in patients with HbS/β thal compared to controls, 30.5±2.7mg/L (Confidence Intervals (CI): 28.8;32.2mg/mL) vs 36.3±3.6mg/L (CI: 32.7;39.9mg/mL), p<0.003. The patients with β + genotypehave higher RBP-4 levels than those with β 0 genotype (p<0.05), whereas patients treated with hydroxycarbamide(50/90) are more likely to express higher RBP-4 levels, p-trend=0.06; b) RBP-4 levels in patients with HbS/β thal correlated positively with their age, body mass index (BMI) and Hb levels (r=0.264, p=0.012; r=0.334, p=0.001 and r=0.209, p<0.05, respectively; c) RBP-4 levels in patients with HbS/β thal correlated with total bilirubin, total cholesterol, triglycerides and uric acid (r=-0.452, p<0.001; r=0.395, p=0.004; r=0.292, p=0.015 and r=0.435, p<0.001, respectively); d) RBP-4 levels in patients with HbS/β thal correlated negatively with eGFR values rho=-0.360, p=0.003 and hs-CRP concentrations r=-0.309, p=0.004 and e) No correlations were found between RBP-4 levels with markers of cardiac and endothelial dysfunction such as High Sensitivity Troponin T, Growth Differentiation Factor-15, von Willebrand factor antigen, Α Disintegrin and Metalloproteinase with Thrombospondin Type 1 Motif 13 antigen and P-Selectin, as well as with number of vaso-occlusive crisis and mean pulmonary arterial pressure in the patients. Conclusions: These findings demonstrate a multifactorial role of RBP-4 in patients with HbS/β thal as the circulating levels of the protein correlate significantly with markers of erythropoiesis, inflammation and renal function. It is unclear of this study if RBP-4 has any specific functions in patients with HbS/β thal. However, RBP-4 should be more investigated in order to determine its clinical significance and in the case of sickle cell nephropathy both plasma and urine measurements should be considered.

#4162 COMPARISON OF EGFR CYSTATIN C AND EGFR CREATININE IN RECENTLY HOSPITALISED INDIVIDUALS

Abstract Background and Aims Creatinine and cystatin C are endogenous biomarkers that can be used to estimate glomerular filtration rate (GFR). Cystatin C may be less dependent on age, gender and muscle mass. The comparative performance of these markers in patients recently hospitalised patients with acute kidney injury (AKI), who may have experienced changes in body composition, is unclear. Method Two matched cohorts of hospitalised individuals who had survived to 90 days after admission were recruited. The cohorts consisted of people who had sustained AKI during hospital admission and those who had not, and were matched 1:1 for age, baseline eGFR stage and diabetes. Serum creatine and serum cystatin C were measured at 3 months after hospitalisation and eGFR calculated using CKD EPI creatinine (eGFRcr) and CKD EPI cystatin C (eGFRcys) equations. Difference between the measures (eGFRdiff) was calculated as eGFRcys-eGFRcr and percentage difference (eGFR%diff) was relative to the mean of both eGFR measures. Primary outcome was mortality after 5 years of prospective follow up. Univariable survival analyses were conducted with the Kaplan Meier method and comparisons were performed with the log rank test, and a fully adjusted multivariable analysis performed with Cox proportional hazards model. Results 854 individuals were recruited, matched, and had paired creatinine and cystatin C measurements. 427 (50%) had sustained AKI. Median eGFRcys was lower than eGFRcr (53.5ml/min/1.73 m2 [34.4-85.4] vs 68.4ml/min/1.73 m2 [52.6-84.7], p<0.001). eGFRcys and eGFRcr were correlated (r = 0.486, p<0.001) but Bland Altman analysis showed variable bias across the eGFR range. More individuals had an eGFR <60ml/min using eGFRcys (57%) compared with eGFRcr (35.6%). There was a graded relationship between eGFR%diff and outcome, with a shorter survival time (Figure 1) and higher proportion of deaths at 5 years (Q1 64 (30.0%), Q2 54 (25.4%), Q3 41 (19.2%), Q4 (31 (14.6%), p<0.001) in the first quartile. Cox proportional hazards analysis showed that eGFR%diff was an independent predictor of 5-year mortality after adjustment for age, Charlson index score and albuminuria (adjusted OR 0.995 [0.992-0.998], p = 0.002). Conclusion Cystatin C eGFR measures were lower than creatinine eGFR measures in recently hospitalised individuals. Lower eGFRcys relative to eGFRcr was independently associated with increased mortality. A larger difference between eGFRcys and eGFRcr may reflect loss of muscle mass (resulting in relatively lower serum creatinine) in somebody who has recently had an acute illness. Further, these results confirm how eGFRcr may over-estimate kidney function and potentially miss patients with failed renal recovery at 3-months after AKI. The difference between eGFRcys and eGFRcr may be helpful in identifying people at greater risk of early mortality after an acute illness.

#2948 β-2-MICROGLOBULIN AND β-TRACE-PROTEIN DO NOT IMPROVE ESTIMATION OF GFR IN KIDNEY TRANSPLANT RECIPIENTS COMPARED TO CREATININE AND CYSTATIN C

Abstract Background and Aims Precise estimates of glomerular filtration rate (eGFR) are important in kidney transplant recipients (KTRs). Current eGFR formulas based on plasma creatinine and/or cystatin C are associated with significant bias. We investigated whether race free formulas based on plasma values of β-trace-protein and β-2-microglobulin performed better than formulas based on creatinine and cystatin C in a Scandinavian cohort of KTRs. Method We included samples and data from the randomised, controlled trial CONTEXT. GFR was measured by plasma clearance of 51Cr-EDTA or iodothalamate. eGFR was calculated using the new race-free CKD-EPI eGFR-creatinine and/or cystatin C(2021) formulas as well as the CKD-EPI eGFR-β-trace-protein and/or eGFR-β-2-microglobulin formulas. GFR estimates were evaluated at 3 (n = 82) and 12 (n = 64) months post-transplant using mean bias, precision, and accuracy. Also, formulas were analysed for their ability to correctly classify changes in measured GFR from 3 to 12 months. Results At 12 months eGFR-creatinine-cystatin C performed best according to mean bias (−4.54 ml/min/1.73 m2), precision (SD = 8.18 ml/min/1.73 m2) and accuracy (P10 = 47%) among creatinine and cystatin C based formulas (Table 1). Among the β-trace-protein and β-2-microglobulin based formulas, eGFR-β-trace-protein-β-2-microglobulin performed best according to precision (SD = 7.64 ml/min/1.73 m2) and accuracy (P10 = 36%) (Table 1). eGFR-β-trace-protein-β-2-microglobulin and eGFR-creatinine-cystatin C performed similar when comparing residuals (p = 0.481). eGFR-β-trace-protein, eGFR-β-trace-protein-β-2-microglobulin and eGFR-creatinine-cystatin C performed best in correctly classifying changes in mGFR from 3 to 12 months. Conclusion β-trace-protein and β-2-microglobulin do not improve the measurement of GFR compared to creatinine and cystatin C based formulas in KTRs.

Comparison of glomerular filtration rate estimating equations in Indian geriatric patients with cancer.

e24025 Background: Accurate estimation of glomerular filtration rate (eGFR) is essential for dose calculation of certain anticancer drugs. It is particularly important in older cancer patients because of age-related compromise in renal function. 99mTc-DTPA plasma clearance for GFR measurement poses practical difficulties in the elderly and is expensive. Therefore, we investigated the predictive accuracy of eight commonly used eGFR equations against 99mTc-DTPA plasma clearance as the gold standard in Indian geriatric oncology population. Methods: A cross-sectional study was conducted in the geriatric oncology clinic of Tata Memorial Hospital, India, from June 2021 to November 2022. Age, sex, weight, BUN and serum creatinine were obtained from the hospital records. Serum cystatin C was estimated using sandwich ELISA (Sigma, Germany). GFR was estimated using Cockcroft-Gault (CG); 6 variable MDRD; 4 variable MDRD; CKD-EPI creatinine; CKD-EPI cystatin; CKD-EPI creatinine-cystatin; BIS 1; and BIS 2 equations. GFR was also measured by 99mTc-DTPA plasma technique (Gates’ method). The agreement between different eGFR methods and the measured GFR was analyzed using Bland-Altman test. Results: Out of 311 enrolled patients, 276 patients having full covariate data required for estimation of eGFR by all eight equations were included in the analysis. Majority were males (N = 214). Median age (range) of the patients was 68 (60 – 88) years. Median of measured GFR using 99mTc-DTPA was 71 (17 – 141) ml/min. The performance i.e., bias and 95% Limit of Agreement (LoA) of eGFR equations against measured GFR is shown in table 1. Overall, the BIS 2 equation with least bias of 0.854 and narrowest 95% LoA (-31.23 to 32.94) had the highest agreement with ‘gold standard’. In fact, BIS 2 performed consistently well across age (60-70, 71-80, 81-90) and BMI (≤18.5, 18.6-24.9, ≥25) groups (data not shown). BIS 2 was followed by CKD-EPIcr-cys and CKD-EPIcys with best estimates of bias and 95% LoA (Table 1). Interestingly, all three equations have cystatin C as a covariate. 4vMDRD had the highest bias (-24.08) and least agreement with DTPA (-86.52 – 38.36). Post hoc analysis showed that 59/115 (51.3%) patients who were cisplatin-ineligible (GFR < 60) based on CG were cisplatin-eligible based on BIS 2, while 19/161 (11.8%) patients who were cisplatin-eligible based on CG were actually ineligible as per BIS 2. Conclusions: Equations derived using cystatin C in general, and BIS 2 in particular, have highest predictive accuracy for GFR estimation in older cancer patients. [Table: see text]

Abstract P430: Role of Cystatin C-based Estimated Glomerular Filtration Rate for Direct Oral Anticoagulant Dosing in Patients With Atrial Fibrillation

Introduction: Renal dose adjustment is imperative to appropriate direct oral anticoagulant (DOAC) prescribing among patients with atrial fibrillation (AF). Serum creatinine is routinely used to estimate GFR (eGFRcr) in clinical practice, but eGFRcr may be less accurate in certain settings. It is unknown whether other kidney function biomarkers, like cystatin C, is helpful to guide DOAC dosing. Hypothesis: Appropriate DOAC dosing by eGFRcr but supratherapeutic dosing by cystatin C-based eGFR (eGFRcys) is associated with bleeding, compared to appropriate dosing by both eGFRcr and eGFRcys. Methods: We conducted observational study from the SCREAM project, a healthcare utilization cohort of Stockholm, Sweden, during 2006-2018. We identified patients with AF on DOACs who had creatinine and cystatin C measured on the same day. We calculated eGFRcr with the 2021 Chronic Kidney Disease (CKD)-EPI and eGFRcys with 2012 CKD-EPI cystatin C equations. We estimated defined daily dose consumed per day and considered <0.8 as a reduced dose. We separately classified supratherapeutic, subtherapeutic, and appropriate dosing by eGFRcr and eGFRcys, and examined the bleeding risk using Cox regression. Results: Among 5427 AF patients on DOACs, mean age (SD) was 76 (9) years and 43% were women. Compared to eGFRcr, eGFRcys identified more patients with CKD (61% for eGFRcys <60 ml/min/1.73 m 2 vs. 35% for eGFRcr <60 ml/min/1.73 m 2 ), as well as more patients with supratherapeutic dosing (7.9 vs. 2.4%). Among 3064 patients who were classified as appropriate dosing by eGFRcr, 312 (10.2%) were reclassified as supratherapeutic dosing by eGFRcys and had a higher risk of bleeding (hazard ratio=1.58, 95% CI: 1.03-2.42), compared with those who were classified as appropriate dosing by both eGFRcr and eGFRcys ( Table ). Conclusions: Appropriate DOAC dosing by eGFRcr but supratherapeutic dosing by eGFRcys was associated with a higher risk of bleeding. The findings suggest that eGFRcys may inform decisions on DOAC dosing.

Whole and cortical kidney volume predict 5-year post-nephrectomy eGFR in Indian living kidney donors.

To study the additional utility of pre-nephrectomy whole and cortical kidney volumes (WKV, CKV) in predicting long-term post-nephrectomy kidney function in Indian living kidney donors (LKDs). This retrospective cohort study included all LKDs who underwent nephrectomy between 1 January 2006 and 31 December 2015 at our centre, had pre-nephrectomy height, weight and computed tomography (CT) angiography with arterial and nephrographic phase documented, and 5-year post-nephrectomy creatinine values measured. Correlation between body surface area (BSA) adjusted pre-nephrectomy total CKV, WKV and pre-nephrectomy CKD EPI eGFR; BSA-adjusted remnant pre-nephrectomy CKV (rCKV), WKV (rWKV) and 5-year post-nephrectomy CKD EPI creatinine eGFR (5yeGFRCr ); predictors of 5yeGFRCr < 70% of pre-nephrectomy CKD EPI creatinine eGFR (pre-eGFRCr ), and an equation to predict 5yeGFRCr from pre-nephrectomy variables were calculated. A total of 196 LKDs (74% female, mean age 41.7 ± 11.0 years) were included in the study. Total WKV showed higher correlation with pre-nephrectomy eGFR than CKV, the highest with CKD EPI cystatin eGFR. Remnant WKV showed higher correlation than rCKV with post-nephrectomy eGFRCr and this increased over time. Older age, lower rWKV or rCKV, higher BSA, and higher pre-eGFRCr identified LKDs with 5yeGFRCr < 70% of pre-eGFRCr , with rCKV identifying a higher proportion (4.5%) of such LKDs. A model including rWKV or rCKV predicted 5yeGFRCr better than one including age, gender, BSA and pre-eGFRCr alone. Inclusion of pre-nephrectomy remnant CKV and WKV into models for 5yeGFRCr and sub-optimal post-nephrectomy adaptation in Indian LKDs improves their accuracy. CKD EPI cystatin eGFR correlates better with functional renal mass.

Abnormal Free Light Chains in Individuals with African Ancestry Screened for Monoclonal Gammopathy: Definition of New Reference Range Accounting for Renal Function and Race

Introduction Serum free light chain (sFLC) are important for diagnosis and prognosis of plasma cell dyscrasias and are known to be affected by kidney function and inflammatory conditions. However, African Americans (AA) have been reported to have significantly higher Kappa (κ) and Lambda (λ) sFLC levels than European Americans (EA) in a biobanked population, even after adjusting for kidney function (El-Khoury et al., Lancet Haem 2022). Data on race-adjusted reference ranges for sFLC and sFLC ratio (sFLCr) remain limited. We hypothesize that an adjustment in sFLC reference ranges for individuals of African and European ancestry is needed. Methods We analyzed serum samples from 738 healthy Black South African (SA) and 3402 US individuals (AA+EA) as part of an international study screening for individuals at high risk of multiple myeloma (MM) and precursor conditions. Self-identification as Black or having family history of hematologic cancer or MM precursor were key eligible criteria. sFLC levels were measured using the Optilite® Freelite assay (The Biding Site). All participants were screened for Monoclonal Gammopathy of Undetermined Significance (MGUS; M protein concentration ≥ 0.2 g/L) by matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry. Serum Cystatin C (Optilite®) was used to calculate estimated Glomerular Filtration Rate (eGFR) with CKD-EPI Cystatin C Equation (2012) formula for 752 individuals (568 SA, 184 AA). Clinical data was collected using validated questionnaires at study enrollment. Group medians were compared with Wilcoxon tests. Abnormal sFLCr was defined as any value outside the normal reference range with the involved sFLC above the manufacturer's normal reference range. We used 95% central interval (CI) values to compute new sFLCr reference values for each group. Results After excluding individuals with Heavy Chain-MGUS, our study population consisted of 654 SA, 326 AA, and 2,551 EA. Median age was 52 (IQR 46-59), 56 (IQR 50-65, and 58 (IQR 50-64) for the three groups, respectively. There was a female predominance in the AA (74%) and EA (73%) groups compared to SA (52%). Chronic kidney disease (CKD) was self-reported in 0.2%, 1% and 1% of the three groups, respectively. Calculated median eGFR was 118 ml/min (IQR 106-134) for SA and 112 (IQR 98-123) for AA. HIV positivity was higher (23%) in SA than the other groups (<1%) and 99% were under treatment (Tenofovir 92%, which is known to be nephrotoxic). The median free κ was higher in SA (32 mg/l, IQR 24.8-46) than AA (18.1 mg/l, IQR 14.4-23, +80%, p<0.01) and EA (13.7 mg/l, IQR 10.8 - 17.1, +133%, p<0.01). Similarly, median free λ was higher in SA (24.6 mg/l, IQR 18.8-33.4) than AA (15 mg/l, IQR 11.7-19.3, +64%, p<0.01) and EA (11.9, mg/l IQR 9.1-15.5, +106%, p<0.01). 92% of SA, 43% of AA, and 16% of EA had κ values above the normal range. Similarly, 43% of SA, 10% of AA, and 3% of EA had λ values outside the normal range. Median sFLCr was higher in SA (1.34, IQR 1.13-1.65) than AA (1.25, IQR 1.03-1.48, p<0.01), and EA (1.18, IQR 0.99-1.39, p<0.01) (Fig 1). Using the standard manufacturer ranges, 25% of SA, 11% of AA and 3% of EA had abnormal sFLCr and involved FLC. Decreasing eGFR, increasing age, HIV positivity, and the cohort (SA, AA, or EA) were all significant predictors of changes in sFLCr in univariate analysis. In multivariate logistic regression, increasing age, HIV positivity, and decreasing eGFR were independent predictors of abnormal sFLCr (Table 1) for SA or AA compared to EA. In SA with normal renal function (eGFR >60 ml/min), excluding those with free κ and λ outside the 95% CI, we identified a new reference (95% CI) for FLCr of 0.80-2.38. Conclusions This is the first report of sFLC measurements in an African population screened for MG and compared to AA and EA. We observe a significantly higher sFLC for Black (SA and AA) than White individuals (EA), independent of renal function. This difference could be due to genetic background and socioeconomic and environmental factors (e.g., HIV epidemiology). In contrast with previous reports (Zemlin, et al, J Clin Pathol 2015), HIV was associated with higher FLCr, maybe with a possible role of nephrotoxic HIV drugs. Here, standard reference ranges do not apply to SA participants. While further validation is needed, we propose to use a different sFLC range for African ancestry populations with normal renal function. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

The relationship between nonalcoholic fatty liver disease with visceral fat depots of other localization, metabolic parameters and markers of renal dysfunction in patients with obesity

Background and Aims : To assess the relationship between non-alcoholic fatty liver disease (NAFLD) with visceral fat, metabolic parameters, markers of renal dysfunction in patients with obesity.Methods: The study included 105 people aged 44.8±6.4 years. The group №1-patients with NAFLD, BMI 36.1±3.2kg/m2. The group №2- without NAFLD with BMI 35.5±3.9kg/m2. The TNF, β2 microglobulin, ACRU, IL 6, MCP-1, leptin, resistin and cystatin C was determined by ELISA. GFR was calculated by CKD-EPI formula and cystatin C. The examination of visceral adipose tissue: VAT- measurement at the level of the navel from the inner surface of the rectus abdominis to the posterior wall of the aorta and L4; the thickness of the posterior perirenal fatty tissue and perirenal fatty tissue on both sides.Conclusions: In patients with NAFLD, the parameters of the lipid profile and renal dysfunction deteriorate, which can contribute to the development of atherosclerosis. Background and Aims : To assess the relationship between non-alcoholic fatty liver disease (NAFLD) with visceral fat, metabolic parameters, markers of renal dysfunction in patients with obesity. Methods: The study included 105 people aged 44.8±6.4 years. The group №1-patients with NAFLD, BMI 36.1±3.2kg/m2. The group №2- without NAFLD with BMI 35.5±3.9kg/m2. The TNF, β2 microglobulin, ACRU, IL 6, MCP-1, leptin, resistin and cystatin C was determined by ELISA. GFR was calculated by CKD-EPI formula and cystatin C. The examination of visceral adipose tissue: VAT- measurement at the level of the navel from the inner surface of the rectus abdominis to the posterior wall of the aorta and L4; the thickness of the posterior perirenal fatty tissue and perirenal fatty tissue on both sides. Conclusions: In patients with NAFLD, the parameters of the lipid profile and renal dysfunction deteriorate, which can contribute to the development of atherosclerosis.

Chronic kidney disease (CKD) and chronic kidney insufficiency (CKI) diagnosing equation in cirrhotic patients.

estimated GFR (CKD-EPI creatinine and cystatin equations) were recorded in 175 adult stable patients suffering from cirrhosis, and these patients were classified as presenting or not CKD and CKI after evaluation by two independent nephrologists. Based on these data, the variables with the significant discriminating capability to identify CKD and CKI (based on creatinine and cystatin) were detected by applying the Student's t-test for two independent groups, later confirmed by the lambda test of Wilks, in order to obtain the renal function equations. CKD equation (creatinine)=7.094238-0.043104 × CKD-EPI creatinine - 0.057537 × haematocrit. CKD equation (cystatin)=8.375074-0.117218 × CKD-EPI cystatin. CKI equation (creatinine)=0.428389-0.043214 × CKD-EPI creatinine +0.183051 × Child-Pugh score + 0.050162 × age (in years). CKI equation (cystatin)=9.169579-0.139319 × CKD-EPI cystatin. Simple and reliable equations have been obtained for screening chronic kidney disease and chronic kidney insufficiency in cirrhotic patients.

A comparison of four established GFR formulas to estimate measured GFR and changes in GFR in adult kidney transplant recipients

The accurate assessment of glomerular filtration rate (GFR) is important in the follow-up of kidney transplant recipients in order to identify graft dysfunction. A number of formulas have been proposed to calculate GFR from endogenous plasma markers such as creatinine or cystatin C since measuring GFR using exogenous markers is troublesome. This study compares and evaluates the ability of four different GFR formulas to estimate kidney graft function and to detect changes in GFR in kidney transplant recipients. The study included patients from the prospective, multicenter CONTEXT trial in kidney transplant recipients. GFR was measured using plasma clearance of 51Cr-EDTA and estimated using the MDRD, CKD-EPI Creatinine, CKD-EPI Cystatin C and CKD-EPI Cystatin C + Creatinine equations at three (n = 83) and twelve (n = 65) months post-transplantation. For each formula mean bias, precision, and accuracy were evaluated. The MDRD equation had the lowest mean bias (0.2 ml/min/1.73 m2), whereas the CKD-EPI Cystatin C + Creatinine equation had the highest precision (8 ml/min/1.73 m2). Accuracy at three months were similar for all equations (P30 > 80%) except for the CKD-EPI Cystatin C equation, which performed poorer (P30 = 55%). None of the formulas evaluated avoided misclassification of changes in GFR. The most optimal combination of precision and accuracy suggests the use of CKD-EPI Creatinine + Cystatin C equation in kidney transplant recipients.

MO321: The Critical Role of Cytokine Dysregulation in Acute Kidney Injury Development in Patients With COVID-19

BACKGROUND AND AIMSOne of the complications described in critically ill patients in intensive care units with severe COVID-19 was acute kidney injury (AKI). The pathophysiology of AKI in patients with COVID-19 is multifactorial. In addition to the direct virulence of SARS-CoV-2 in renal cells, the tissue inflammation and local immune cell infiltration, cytokine storm, secondary infections and nephrotoxicity associated drugs may contribute to AKI [1]. Mounting evidence throughout the pandemic suggests that patients with severe COVID-19 may have a cytokine storm syndrome, one of the possible causes of AKI in these patients [2]. The present prospective cohort study analysed the correlation between circulating cytokine profile and estimated glomerular filtration rate (eGFR) in patients with COVID-19.METHODAfter signing the informed consent, patients positive for SARS-CoV-2 infection (n = 74) had blood samples (n = 139) collected at hospital admission until the day of the outcome. ELISA measured the cytokines IL-10, IL-4, L-6, TNF-α and IFN-γ, and the eGFR was calculated by the CKD-EPI Cystatin C equation. Statistics description: Continuous variables were checked for normality and presented as mean ± standard deviation or median and interquartile range. The association between continuous variables is shown in scatterplots, and a predicted response with 95% confidence interval (95% CI) is plotted using fractional polynomials. For linear correlations, we obtained P-values using Pearson's correlation coefficient.RESULTSThere is a more significant distribution of eGFR below 90 mL/min in the population studied, associated with older patients. Glomerular filtration rates were negatively correlated with age as expected (–0.60; P < 0.0001). Lower eGFR was correlated with levels of proinflammatory cytokines such as IL-6 (–0.33; P < .0007) and TNF- α (–0.21; P < .03); but without positive correlation with IL-10 (0.04; P < 0.68) or IFN-γ (–0.14; P < .16), even though higher IFN-γ levels have been linked to a worse prognosis in patients with severe COVID-19 [3]. Curiously, a positive correlation was observed between lower eGFR and IL-4 levels.CONCLUSIONThese results demonstrate that a shift in the immune response profile, cytokines with a Th2 profile such as IL-4, and cytokines with systemic functions such as IL-6 and TNF-α can be related to renal failure. The elucidation of the potential pathophysiological mechanisms of AKI associated with COVID-19 as well as monitoring of cytokine levels can (a) help to identify patients with severe COVID-19 at risk of loss of renal function, (b) provide information on specific therapeutic strategies.

Renal Autologous Cell Therapy to Stabilize Function in Diabetes-Related Chronic Kidney Disease: Corroboration of Mechanistic Action With Cell Marker Analysis

IntroductionChronic kidney disease (CKD) is a worldwide disease without cure. Selected renal cells (SRCs) can augment kidney function in animal models. This study correlates the phenotypical characteristics of autologous homologous SRCs (formulated product called Renal Autologous Cell Therapy [REACT]) injected into patients’ kidneys with advanced type 2 diabetes-related CKD (D-CKD) to clinical and laboratory findings.MethodsA total of 22 adults with type 2 D-CKD underwent a kidney biopsy followed by 2 subcortical injections of SRCs, 7 ± 3 months apart. There were 2 patients who had only 1 injection. We compared annualized estimated glomerular filtration rate (eGFR) slopes pre- and post-REACT injection using the 2009 CKD-EPI formula for serum creatinine (sCr) and the 2012 CKD-EPI Creatinine-Cystatin C equation and report clinical/laboratory changes. Fluorescent Activated Cell Sorting (FACS) Analysis for renal progenitor lineages in REACT and donor vascular endothelial growth factor A (VEGF-A) analysis were performed. Longitudinal parameter changes were analyzed with longitudinal linear mixed effects model.ResultsAt baseline, the mean diabetes duration was 18.4 ± 8.80 years, glycated hemoglobin (Hgb) was 7.0 ± 1.05, and eGFR was 40.3 ± 9.35 ml/min per 1.73 m2 using the 2012 CKD-EPI cystatin C and sCr formulas. The annualized eGFR slope (2012 CKD-EPI) was −4.63 ml/min per 1.73 m2 per year pre-injection and improved to −1.69 ml/min per 1.73 m2 per year post-injection (P = 0.015). There were 7 patients who had an eGFR slope of >0 ml/min per 1.73 m2 postinjection. SRCs were found to have cell markers of ureteric bud, mesenchyme cap, and podocyte sources and positive VEGF. There were 2 patients who had remote fatal adverse events determined as unrelated with the biopsies/injections or the REACT product.ConclusionOur cell marker analysis suggests that SRCs may enable REACT to stabilize and improve kidney function, possibly halting type 2 D-CKD progression.

The relationship between visceral fat depots and markers of renal dysfunction in patients with borderline arterial hypertension and obesity

Abstract Introduction Obesity is a potent risk factor for the development of kidney disease (CKD). The localization of adipose tissue and its hormonal activity plays an important role in the formation of the cardiorenal relationship. Purpose of work To assess the relationship between visceral fat stores with hormonal activity of adipose tissue, metabolic parameters and markers of renal dysfunction in patients with borderline arterial hypertension (AH) and obesity. Materials and methods The study included 100 people aged 44.8±6.4 years. Group 1 – patients with borderline hypertension – SBP 134.1±4.7 mm Hg; DBP – 84.3±5.9 mm Hg, BMI 36.1±3.2kg/m2. Group 2 was patients with BMI 35.5±3.9 kg/m2, SBP level 120.6±10.1 mm Hg and DBP 70.1±8.4 mm Hg. Albumin/creatinine ratio urine (ACRU), β2 microglobulin, tumor necrosis factor (TNF), interleukin 6 (IL6), monocytechemoattractant protein (MCP-1) was determined in a single portion of morning urine, the level of leptin, resistin and cystatin C was determined by ELISA. Glomerular filtration rate (GFR) was calculated using the CKD-EPI formula and cystatin C (Hoek's formula). The examination of visceral adipose tissue (VAT) was using an ultrasound method of investigation: the epi- and pericardial fat depots were assessed; VAT 1 – measurement at the level of the navel from the inner surface of the rectus abdominis to the posterior wall of the aorta and L4; VAT 2 – measurement at the level of the navel from the inner surface of the rectus abdominis to L4; the thickness of the posterior perirenal VAT on the right and left and the area of perirenal fat on both sides. Result The amount of fat depots in the groups is shown in Table 1. Indicators of hormonal activity of adipose tissue and renal markers are presented in Table 2. In the group with borderline hypertension the relationship between VAT 1 and 2 with ALT levels (r=0.40) and (r=0.42) was established, AST (r=0.52) and (r=0.47); HDL (r=−0.67) and (r=−0.70), TG (r=0.38) and (r=0, 39), HOMA index (r=0.45) and (r=0.39), MCP-1 (r=0.28) and (r=0.36). Perineal fat depot located to the right and left is correlated with LDL (r=0.40) and (r=0.37), glucose (r=0.49) and (r=0.50), ACRU (r=0.43) and (r=0.57), urinary excretion of cystatin C (r=0.28) and (r=0, 39). The connection with the optimal blood pressure level in control group was established between the perineal adipose tissue on the right and the left with the level of TG (r=0.35) and (r=0.29), GFR according to Hoek (r=0.29) and (r=0, 38), MCP-1 (r=0.36) and (r=0.29). Findings The increase of perinephral adipose tissue in obese patients is associated with an increase in cytokine excretion in the urine, an increase in VAT is accompanied by a deterioration in metabolic parameters. Funding Acknowledgement Type of funding sources: None.

P-154: Cytatin C: a new biomarker in Multiple Myeloma?

<h3>Background</h3> Renal impairment in patients with multiple myeloma (MM), according with the International Myeloma Working Group (IMWG), is based on serum creatinine (sCrea) ≥ 2mg/dL or creatinine clearance < 40 ml/minute. The aim of this study was to determine whether the different equations used for the evaluation of glomerular filtration rate estimation (GFRe) could also define kidney disease in MM. We also compared the equations with a single parameter (CKD-EPI crea, CKD-EPI cystatin C (CC) and CAPA equation) against the reference method that includes the two parameters (CKD-EPI crea-CC) to know the most sensitive equation for detection of kidney disease and to identify patients with more risk factors. <h3>Methods</h3> In this epidemiologic cross-sectional study, 61 consecutives newly diagnosed MM patients (24 women/37 men) from December 2018 to April 2021 were included. In order to compare CKD-EPI and CAPA equations, Cohen's Kappa statistic was employed. Mann-Whitney T-test and chi-square or Fischer's exact test were used to evaluate parameters associated to decreased eGFR according to Crea o CC (statistical significance p-value <0.05). Correlation between GFRe CC and GFRe Crea and poor prognosis factors was determined by univariate and multivariate analysis. Statistical analysis were performed using Med.Calc v9.2.1.0 y SPSS v.24 (Armony,NY). <h3>Results</h3> A total of 61 newly diagnosed patients with MM (24 women/37 men) with a mean age of 68 years (±11) were included. According to IMWG criteria, kidney disease with increased sCrea was found on 20% of patients (1 woman/11 men), compared to 26% (3 women/13 men) or 39% (7 women/17 men) when CKD-EPI Crea or CKD-EPI CC equations were used, respectively. The degree of agreement between the different equations and the reference method was very good for the CKD-EPI crea equation (Kappa: 0.958 (0.88 - 1.00, 95% CI) and good for the CKD-EPI CC and CAPA equations (Kappa: 0.747 (0.577- 0.917, 95% CI), Kappa: 0.779 (0.619 - 0.939, 95% CI). Patients with decreased GFRe CC showed higher risk factors in comparison with those identified by GFRe Crea, including: age, β2-microglobulin, serum urate, increased monoclonal component in urine, 24 hours urine proteinuria and decreased hemoglobin and albumin. Importantly, GFRe CC methods detected more patients with renal impairment and worse prognosis according to R-ISS-3 criteria by univariate and multivariate analysis (Exp (B) 14,73; rango 1,78- 122,23; 95%CI, P=0,013). <h3>Conclusions</h3> IMWG criteria may underestimate kidney disease in patients with MM, mostly in women, which could affect to the dose received as well as to its toxicity. Altogether, our data suggest that equations that include CC (CKD-EPI and CAPA) are more accurate to detect hidden kidney disease as well as patients with more and worse prognostic factors.

Diagnostic Accuracy of Serum Cystatin C for Early Recognition of Nephropathy in Type 2 Diabetes Mellitus.

Objectives Diabetic nephropathy is one of the major complications that develop over time in type 2 diabetes mellitus (T2DM). This prospective study was conducted to assess the diagnostic accuracy of serum cystatin C in detecting diabetic nephropathy at earlier stages. Materials and Methods This study was undertaken on 50 cases of T2DM and 50 healthy subjects as controls. Demographic and anthropometric data and blood and urine samples were collected. The concentration of serum cystatin C (index test) and traditional markers of diabetic nephropathy, serum creatinine, and urinary microalbumin (the reference standard) were estimated. Similarly, blood glucose, glycated haemoglobin (HbA1c), triglycerides, total cholesterol, high-density lipoprotein (HDL) cholesterol, and urinary creatine were measured. Results The mean ± SD serum cystatin C was significantly higher in T2DM as compared to control (1.07 ± 0.38 and 0.86 ± 0.12 mg/dl, respectively, p < 0.001). The mean ± SD bodyweight, BMI, W : H ratio, pulse, SBP, and DBP were 66.4 ± 12.6 kg, 26.2 ± 5.6 kg/m2, 1.03 ± 0.09, 78 ± 7, 125 ± 16 mm of Hg, and 77 ± 9 mm of Hg, respectively, in cases. A significant difference in HDL cholesterol (p=0.018) and serum cystatin C (p < 0.001) was observed among different grades of nephropathy. Cystatin C had a significant positive correlation with age (r = 0.323, p=0.022), duration of T2DM (r = 0.326, p=0.021), and UACR (r = 0.528, p < 0.001) and a significant negative correlation with eGFR CKD-EPI cystatin C (r = −0.925, p < 0.001). The area under ROC curve for serum cystatin C (0.611, 95% CI: 0.450–0.772) was greater than for serum creatinine (0.429, 95% CI: 0.265–0.593) though nonsignificant. Conclusion Serum cystatin C concentration increases with the progression of nephropathy and duration of diabetes in Nepalese T2DM patients suggesting cystatin C as a potential marker of renal impairment in T2DM patients.

COMPARISON BETWEEN SERUM CREATININE AND SERUM CYSTATIN C LEVEL IN DIAGNOSING EARLY DIABETIC NEPHROPATHY IN NEWLY DIAGNOSED TYPE 2 DIABETES MELLITUS

Background: This study was done to evaluate clinical usefulness of cystatin C levels of serum and urine in predicting renal impairment in normoalbuminuric patients with type 2 diabetes and to evaluate the association between albuminuria and serum/urine cystatin C. Cockroft-Gault equation was previously used for GFR calculation. The most recently advocated formula for calculating the GFR are The modification of diet in renal disease study group ,CKD-EPI equation(2009),CKD-EPI cystatin C(2012), CKD-EPI creatinine –cystatin C(2012). The cystatin C levels of serum and urine could be useful markers for renal dysfunction in type 2 diabetic patients with normoalbuminuria.&#x0D; Conclusion; This finding has major implications for clinical research and early intervention to prevent development of chronic kidney disease in patients with type 2 Diabetes mellitus.&#x0D; Keywords: Cystatin C, Diabetic Nephropathies, Albuminuria

POS-687 DONOR CYSTATIN C eGFR> 100 ml/min/1.73m2 IS AN INDEPENDENT PREDICTOR OF GRAFT SURVIVAL IN INDIAN KIDNEY TRANSPLANT RECIPIENTS

India is currently facing an explosion of lifestyle related non-communicable disease, a fact that has major implications for its kidney transplant programme, which is predominantly living kidney donor driven. In this scenario, careful donor selection is required in order to maximise benefit to the recipient and minimise harm to the donor. This study aimed to determine the effect of demographic and metabolic donor characteristics on recipient graft outcome. This single centre, retrospective cohort study included all living donor kidney transplants taking place at a tertiary care centre in southern India from July 2009 – June 2018. Data concerning donor demographic characteristics (age at donation, gender, relationship to the recipient, parity), metabolic risk factors (glycemic status, BMI, non-alcoholic fatty liver disease, dyslipidemia, smoking history, abdominal aortic calcification, hypertension), and kidney function and structure (CKD EPI cystatin C eGFR, CKD EPI creatinine eGFR, presence of cysts or scars in the kidney) were collected from transplant records and the hospital information system and analysed to determine their effect on recipient graft survival A total of 706 living kidney donor transplants took place during the study period. Mean donor age was 43.1 ± 10.8years, 69.1% were female and 62.7% were first degree relations of the recipient. On multivariate Cox proportional hazards analysis, only donor pre-donation CKD EPI cystatin C eGFR> 100 ml/min/1.73 m2 (p = 0.037, HR 0.485, 95% CI 0.246 – 0.957 ), was independently associated with better graft survival, even after adjustment for induction agent, native kidney disease, HLA mismatches, prior sensitization, rejections and symptomatic UTIs. A pre-donation CKD EPI cystatin C eGFR> 100 ml/min/1.73m2 is associated with better graft survival, and may be a useful indicator of adequate donor nephron endowment in South Asian kidney donors which needs to be validated in prospective studies.