Dickkopf 3 (Dkk3) is a WNT/β-catenin signaling pathway regulator secreted by tubular epithelial cells upon the influence of different stressors. Recently Dkk3 was described as a biomarker of tubular cell injury and a tool that may estimate the risk of chronic kidney disease (CKD) progression. The data about Dkk3 concentrations at particular stages of CKD are lacking. The aim of this study was to measure serum and urine Dkk3 levels in patients with different ‘renal status’ and evaluate its role as a biomarker of renal damage. One hundred individuals, aged between 24 and 85 years (mean 53.1 ± 17.1), were enrolled in the study. Five groups of 20 subjects each were recruited based on their kidney function. Serum and urine Dkk3 levels were measured by ELISA. The highest median urinary Dkk3 normalized to urinary creatinine was found in patients with established CKD (7051 pg/mg). It was two times higher in renal transplant patients (5705 pg/mg) than in healthy individuals (2654 pg/mg) and the glomerulonephritis group (2470 pg/mg). Urinary Dkk3 was associated with serum creatinine in participants with established CKD and following transplantation. Our results confirm the potential role of Dkk3 as a biomarker of an ongoing renal injury. Fibrosis and cellular atrophy are well-recognized mechanisms leading to progressive organ failure ,2. If thThe role of WNT/β-catenin pathway in the pathophysiology of CKD is—among other mediators—orchestrated by members of the Dickkopf (Dkk) family proteins. One of them is Dickkopf 3 (Dkk3)—stress-induced glycoprotein secreted by renal tubular epithelial cells. Most Dkk proteins  inhibit the WNT/β-catenin pathway by interaction with two receptors: lipoprotein receptor-related protein (LPR) 5 and LPR6 ,10,11. DMoreover, recent studies suggest that Dkk3 may serve as the clinical biomarker of renal damage and a prognostic tool for estimating the risk of CKD progression. Schunk et al. described urinary Dkk3 as an indicator of tubular injury and predictor of both short-term glomerular filtration rate (GFR) loss as well as the long-term CKD progression, independent from albuminuria or the underlying cause of CKD in humans ,3,5. The2), kidney transplant recipients and patients with end-stage renal disease (ESRD) treated with hemodialysis. The aim of our study was to measure serum and urine Dkk3 in mentioned groups of patients and to evaluate the possible role of this protein as a biomarker of renal injury and cardiovascular risk.To the best of our knowledge no studies are available that would systematically describe the patterns of serum and urine Dkk3 concentrations in patients representing the major groups of ‘kidney’ patients, i.e., those with proteinuria in the course of biopsy-proven glomerular pathology, established CKD  and 46% were female. Five groups of subjects (20 people each) were recruited.2 and normal urine biochemistry and sediment, served as a control group. None of them was previously diagnosed with any chronic disease, including arterial hypertension (AHT) and diabetes (DM).Group 1 (G1) of healthy individuals with normal kidney function, i.e., eGFR ≥ 60 mL/min/1.73 m2 and urinary albumin-to-creatinine ratio (UACR) > 0.5 g/g and/or abnormal urine sediment. All patients diagnosed with DM, a history of cardiovascular event, or prior immunosuppressive treatment were excluded . Biopsy-based diagnoses were as follows: IgA nephropathy , anti-PLA2R antibody-positive membranous nephropathy , primary focal/segmental glomerulosclerosis , type IV collagen disease , minimal change disease and C3 nephropathy with membrano-proliferative pattern of injury .Group 2 (G2) consisted of patients with preserved kidney function who were admitted to our department to perform a kidney biopsy. Enrollment criteria included eGFR ≥ 60 mL/min/1.73 mGroup 3 (G3) comprised patients with established CKD G3-5 . Mean time since CKD diagnosis equaled 3.5 ± 7.8 years. All patients were recruited from our outpatient department. Four patients in this group (20%) had a history of a cardiovascular event, none of them suffered from diabetes nor received immunosuppressive agents at the time of assessment. Causes of CKD were as follows: CKD attributed to cardio-renal syndrome or ischemic/hypertensive nephropathy , chronic glomerulonephritis , nephrolithiasis, autosomal dominant polycystic kidney disease (ADPKD), CKD following chronic pyelonephritis (1 patient or 5% each).Individuals included in group 4 (G4) were treated in our dialysis center . All of them were dialyzed 3 times a week for 4.0–4.5 h using High Flux biocompatible FX-class dialyzers . Six patients had a history of cardiovascular events, none of them was treated with immunosuppressive drugs at the time of assessment. End-stage renal disease (ESRD) resulted from glomerulonephritis in 11 patients (55%), ischemic/hypertensive nephropathy in 4 (20%), and ADPKD in 1 (5%). In the case of 4 patients (20%) origin of ESRD remained unknown.2 (mean time following KTx 3.7 ± 5.4 years and mean time on RRT before KTx 2.6 ± 1.5 years). Only one (5%) had a history of prior cardiovascular events. Immunosuppressive regimens were as follows: steroids/mycophenolate mofetil/tacrolimus (70%), steroids/mycophenolate mofetil/cyclosporine (25%), steroids/mycophenolate sodium/tacrolimus (5%).Group 5 (G5) comprised kidney transplant recipients (KTx) with eGFR ≥ 60 mL/min/1.73 mBlood samples were collected from all participants. Morning (first void) urine samples were not collected only from G4 patients because of anuria or negligible urine volume. Biochemical parameters were analyzed at the certified laboratory using Cobas 6000 analyzer . Urine albumin used to calculate UACR was measured using immunoturbidimetric assay by the same analyzer. Blood pressure (BP) and heart rate (HR) were measured using the Omron M3 device  according to the ESH/ESC Guidelines. Pulse wave velocity (PWV) was measured with a Sphygmocor X-cell device .g for 15 to 30 min. All serum and urine samples were stored at −80 °C. Then material was thawed at −20 °C for 24 h, 6 °C for the next 24 h, and finally at room temperature for 30 min prior to mixing by a vortex shaker. Dkk3 level was assayed using Human Dickkopf 3 ELISA kit . All measurements were repeated twice for each sample with a coefficient of variation (CV) of 0.84%. The CV was calculated as the ratio of the standard deviation to the mean multiplied by 100. We normalized urinary Dkk3 (uDkk3) concentrations to urinary creatinine levels to correct urine volume (uDkk3/creat.).Fasting blood for assessing Dkk3 and other parameters was centrifuged immediately after sampling at 4 °C with a speed of 1000× Body mass index (BMI) was calculated as weight in kilograms divided by the square of height in meters. Arterial hypertension (AHT) was defined as a systolic blood pressure (SBP) ≥ 140 mmHg and/or diastolic blood pressure ≥ 90 mmHg and/or any anti-hypertensive therapy, according to 2019 ESH/ESC Guidelines. The estimated glomerular filtration rate (eGFR) was calculated using creatinine-based abbreviated MDRD formula. Cardiovascular event was defined as: the history of myocardial infarction and/or stroke, transient ischaemic attack and/or peripheral vascular disease, and/or diagnosis of heart failure . Chronic kidney disease (CKD) was diagnosed and staged according to the KDIGO criteria.t-test with Bonferroni correction was applied. A comparison of differences among 5 independent groups was conducted using the Kruskal–Wallis test. Spearman’s correlation coefficients were calculated to determine the association between Dkk3 and biochemical parameters. Serum and urine Dkk3 protein amounts were presented as the median and interquartile range (IQR). Values of p < 0.05 were considered statistically significant.All statistical analyses were performed using the SciPy library (version 1.7.1) in Python language . Data distribution was checked with the Shapiro–Wilk test. To compare differences between 2 independent groups, Student’s t-test with Bonferroni correction. They were significant only for G2 vs. G4  (p = 0.02).The distribution of serum Dkk3 (sDkk3) values was normal only in G1, i.e., healthy individuals. In other groups it was non-normal. The highest median sDkk3 concentration was found in subjects from G1 . In G2, i.e., a proteinuric group with normal renal function, it was the lowest  and 57% lower than in G1. In order to reduce the false positive results, differences between the two groups were checked by Student’s p = 0.002 and p = 0.04, respectively). p = 0.016 and p < 0.001, respectively), but not for uDkk3/creat. (p = 0.38).In case of uDkk3/creat. concentrations, data distribution was non-normal in all groups. The highest median uDkk3/creat. value was found in G3 patients (established CKD) . It was two times higher in G5 (transplant patients)  than in G1  and in G2  . Differep = 0.042) (p = 0.008) (p = 0.028). In G2 patients, the group characterized by proteinuria and normal renal function, uDkk3 and uDkk3/creat. correlated inversely with UACR  (p = 0.001) (p = 0.009) (p = 0.043) (p = 0.004).To verify an association between parameters, Spearman’s correlation analysis was performed. We found a correlation between uDkk3 vs. troponin T  A and CK-= 0.008) B in G1, ctively) C. We als= 0.001) D. Intere= 0.009) E and G5 = 0.043) F, i.e., 2). uDkk3/creat. levels in patients with eGFR ≥ 60 mL/min/1.73 m2  were much lower, which is in agreement with the above-mentioned hypothesis and with results published previously by other research groups. In the study conducted by Zewinger et al. median uDkk3/creat. value was also higher in the CKD cohort than in the general population (431 versus 33 pg/mg). Moreover, they observed that urinary Dkk3/creat. level above 4000 pg/mg was independently associated with a mean annual decline in eGFR of 7.6% over 12 months [Recently published data suggest that urinary Dkk3 is a sensitive indicator of ongoing tubular injury independent of eGFR and albuminuria ,3. Susta2 months ). Of notUACR is a marker of endothelial dysfunction, commonly used in everyday practice ,18. SchuPiek et al. described sDkk3 as the predictor of a new-onset CKD in patients with low urinary albumin excretion (<6.6 mg/24 h) . In our Our study suffers from several limitations. One of them is a cross-sectional nature of observation with a lack of follow-up. Cardiovascular status assessment was based only on cardiac biomarkers and PWV, with only a few patients with echocardiography assessment available. The size of each subgroup  is low, nevertheless, to the best of our knowledge, this is the first study that comprehensively addressed the value of serum and urine Dkk3 as novel biomarker in patients within the whole spectrum of renal disease. It is also important that in all patients from the G2 group we established an exact (biopsy-based) diagnosis of CKD (and we did so for most of the G5 group subjects).Urinary Dkk3 level was the highest in participants with advanced CKD and correlated with serum creatinine level and eGFR only in individuals with CKD and those with functioning kidney grafts. Our results confirm the potential role of Dkk3 as a biomarker of an ongoing renal injury. Future studies are needed to assess the utility of this protein in the short and long-term prognosis of CKD progression.


Chronic kidney disease (CKD) is a major health problem worldwide. The general objective of this study is to identify the joint factors of serum creatinine (SCr) and time to end stage of renal disease (ESRD) for CKD patients under treatment at University of Gondar Referral Hospital (UOGRH).A retrospective cohort study was conducted. The collected information was secondary data type obtained from 311 CKD patient's medical charts in the UOGRH from September 2019 to January 2022 G.C. Joint modeling analysis contained a linear mixed model for SCr and the Cox‐PH model for time to ESRD of CKD patients under treatment was used.p = < 0.001), diabetes mellitus , chronic heart disease , HIV , hypertension , and hepatitis  have a significant effect on the variable ESRD. On the basis of the result of the joint model, the variable anemia, diabetes mellitus, chronic heart disease, hypertension, and hepatitis were common significant factors.From the total of 311 patients, 104 (33.4%) patients were developed the ESRD, while the other 207 (66.6%) were censored patients. In the longitudinal submodel, the variable sex, age, electrolyte, visit time, anemia, diabetes mellitus, chronic heart disease, hypertension, and hepatitis have a significant effect on the variable SCr. In survival process, anemia  of CKD patients were censored. On the basis of the smaller information criteria value and the significance association value, the joint model better fits the data. In the joint model, the variable anemia, diabetes mellitus, chronic heart disease, hypertension, and hepatitis were common factors of two responses, and also concluded that the rate of progression of longitudinal measure SCr decreased over time. AICAkaki Information CriteriaBICBayesian Information CriteriaBMIBody Mass IndexCKDchronic kidney diseaseESRDend stage of renal diseaseGFRglomerular filtration rateHDhemodialysisNDTNeuro Developmental TechniquePHproportional hazardRRTrenal replacement therapySCrserum creatinineUOGRHUniversity of Gondar Referral HospitalWHOWorld Health Organization1Chronic kidney disease (CKD) is a significant health problem that can result in the end stage of renal disease (ESRD).Globally, CKD has been identified as a major public health issue in the world. The number of people with ESRD who need renal replacement therapy is expected to be between 4.902 and 7.083 million. The expected incidence of CKD was 13.4% (11.7%–15.1%). Global burden of disease and death is directly impacted by CKD through its effect on cardiovascular risk and ESRD.In sub‐Saharan Africa (SSA), adults are estimated to have a 13.9% prevalence of CKD. Hypertension, diabetes mellitus, glomerulonephritis, and HIV infection are the main causes of CKD in Africa. The prevalence of CKD ranges from 5.6% to 27.3% in those with HIV infection, from 14.1% to 32.6% in those with diabetes mellitus, and from 15% to 48% in those with hypertension. Glomerulonephritis affects up to 33% of African individuals with ESRD. Glomerulonephritis and congenital abnormalities of the kidneys and urinary tract are the key sources of CKD in kids in Africa. The estimated prevalence of ESRD attributable to diabetes and hypertension in SSA is 239 per million people, although only 1.5% of patients receive renal replacement treatment.In Ethiopia, a study was done on the prevalence of CKD and its contributing factors. Thorough investigation and meta‐analysis patients with CKD had a notably high prevalence of the chronic renal disease. A substantial correlation exists between CKD and hypertension. In Ethiopia, the prevalence of CKD is estimated to be 21.71% . Among patients with chronic illnesses, Oromia had the highest frequency of CKD . Compared with people with no hypertension, people with hypertension have an increased risk of developing CKD.In Northwest Amara, the study was conducted to evaluate the incidence of CKD and its risk variables among adult hypertension patients. Between July and August 2020, 581 adult hypertension patients in a chronic follow‐up clinic at referral hospitals in Northwest Amara Ethiopia were the subjects of a facility‐based cross‐sectional study. The sample in the study was chosen by systematic random sampling. A total of 17.6% of patients with hypertension were found to have CKD. Regarding contributing causes, dyslipidemia, proteinuria, concomitant illness, serum creatinine (SCr) greater than 0.9 mg/dL, hypertension lasting longer than 10 years, and diastolic blood pressure more than 90 mmHg are all connected to the development of CKD in hypertensive individuals.A separate analysis of longitudinal and survival data, linear mixed effects models for longitudinal data, and semiparametric models for survival data was performed. However, their separate analysis is inappropriate when the longitudinal variable is correlated with time to event. Joint models of longitudinal and survival data and include complete evidence at the same time and provide effective and efficient conclusions. However, by separate modeling, the associations between the two outcomes cannot be studied. SCr is measured at dissimilar times for every patient, the SCr changes from time to time for every patient, and also there was a considerable difference in the SCr fluctuations variability among subjects. The general objective of this study is to identify the joint factors of SCr and time to ESRD for CKD patients under treatment at University of Gondar Referral Hospital (UOGRH).The study enables the government to fulfill the necessary materials and infrastructures for the hospitalization of CKD patients until recovery from the ESRD. It also enables health professionals to give special attention to the patients who recorded very high SCr. It also enables clinicians to increase the responsiveness of society about influences that increase the chance of risk of ESRD from the treatment of CKD patients. The outcome of this study also provides evidence for public health practitioners and stakeholders who are working in the areas of giving attention, care, and handling CKD patients by modeling disease evolution to understand CKD prognosis.22.1A secondary data collection process was used by reviewing the patient's chart and follow‐up cards on a CKD patient, who was treated in the medical ward section at UOGRH from September 2019 to January 2022. The data were collected from the medical chart of CKD patients at UOGRH from which necessary attributes have been obtained to identify the most important determinants of SCr CKD patients. Laboratory tests would be performed every 2 months, and both the longitudinal and survival data were extracted from the patient's chart which contains sociodemographic and clinical data of all renal failure patients who met the inclusion criteria. Thus, in this study, we have used secondary data obtained from CKD patients' follow‐up charts at UOGRH.2.2This study was conducted at UOGRH, Amhara Region, and Northern Ethiopia on CKD patients who started treatment on kidney dialysis from September 2019 to January 2022.2.3In this study, we have got information through a retrospective cohort study design where mainly joint longitudinal and survival modeling have considered identifying novel predictors.2.4All CKD patients whose ages were 16 years and above were treated on kidney dialysis follow‐up from September 2019 up to January 2022 at UOGRH.2.52.5.1The study population includes all CKD patients who attended three follow‐up visits and above in the time interval of September 2019–January 2022 G.C. at the UOGRH.2.5.2CKD patients whose follow‐up time is less than three in the time interval of September 2019–January 2022 G.C., incomplete medical records, and all CKD patients who start their treatment before September 2019 and after January 2022 G.C. at UOGRH is excluded from this investigation.2.62.6.1The continuous longitudinal SCr and time up to the complication of ESKD in patients would be the two response variables considered in this study. The continuous longitudinal outcome variable SCr was measured in mg/dL. SCr is the concentration of a compound known as creatinine in the blood or urine.2.6.2In this study, predictor variables expected to be associated with repeated measures of SCr and time to ESRD of CKD patients were either sociodemographic variables, such as sex, age, residence, weight behavioral variable smoking status, and clinical variables, such as HIV, diabetes mellitus, hypertension, anemia, chronic heart disease, urine output, hepatitis, respiratory rate, and electrolyte (potassium).2.7In descriptive statistics, a frequency distribution table would be used to summarize the distribution of outcomes by different levels of covariates and response variables, graphs were used for Kaplan–Meier (KM) survival, and a longitudinal distribution chart would be used to summarize the distribution of SCr level frequency in each response variable category. Various socioeconomic variables and clinical factors of CKD were considered and analyzed using descriptive statistics through a considerate and detailed univariate description of the data. This contains exploratory data analysis to use an appropriate statistical model for the data. Hence, individual profile plot, mean profile plot, the KM curve, and normal Q–Q plot were performed.In this study, we considered three different models, which mean that the linear mixed effect model (LMM) for the longitudinal SCr, the Cox proportional hazard (PH) model for time to ESRD, and a joint model for SCr and time to ESRD of CKD patients linked by shared random effects.2.8LMM is commonly used in which random effects include between‐subject variations and within‐subject relationships in the data. In marginal models, the mean structure and the correlation structure are modeled separately without distribution assumptions for the data while in the transitional models, the within‐subject relationship is modeled via Markov structures. Mixed models extend classical linear regression models by containing random or subject‐specific effects next to the fixed effects in the structure for the mean. The random effects not only determine the correlation structure between observations on the same subject, but they also take account of heterogeneity among subjects, due to unobserved characteristics.2.9The basic model for survival data is the PH model, planned by Cox. This is used to determine which combination of the combination independent variables affects the form of the hazard of event and also to get an estimation of the hazard function itself for different. From this, an evaluation of the survivor functions and from now the median survival time can be got. While the model is based on the assumption of PHs, no specific form of the probability distribution is assumed for the survival times. The model is therefore referred to as a semiparametric model.2.10p value less than or equal to 0.25 predictors were included in the multivariable model.In the joint model of longitudinal and survival data effect of the longitudinal outcome (SCr) on time to ESRD for CKD patients, predictors that affect the two responses simultaneously and the association between longitudinal (SCr) and time to event (time to ESRD) were identified. The result of the joint model would be obtained by joining the selected random intercept and slope effect from the linear mixed model and the Cox‐PH model. If the test for the univariable analysis has a 33.1In this study, sociodemographic, behavioral, and clinical variables were included that were recorded from 311 CKD at UOGRH during the period of September 2019–January 2022. The study considered two response variables: these are longitudinal measures of SCr and survival time to ESRD. The longitudinal response is the number of SCr in mg/dL of CKD patients, which were measured approximately every 2 months; at the first entry, and again at 2‐, 4‐, 6‐, 8‐, 10‐, 12‐, 14‐, 16‐, 18‐, 20‐, 22‐, and 24‐month visits.The survival interest of the study was time to ESRD. Thus, based on the data obtained from UOGRH, out of 311 patients, 104 (33.4%) patients developed ESRD, while the other 207 (66.6%) were censored patients.Table The average baseline age of CKD patients was 48.82 with a standard deviation of 18.36. The average baseline weight of CKD patients was 56.73 with a standard deviation of 8.956. The average baseline respiratory rate of CKD patients was 19.16 with a standard deviation of 13.99. Similarly, the average baseline urine output and electrolyte of CKD patients were 65.09 and 5.18 with a standard deviation of 8.58 and 1.04, respectively. The minimum and maximum baseline weights of CKD patients were 32 and 80 kg, respectively. The minimum and maximum baseline ages of CKD patients were 16 and 85 years, respectively.3.2Figure The KM survival curve indicates whether there is a difference in survival time to ESRD between different categories of the variables. Figure 3.3p value less than or equal to 0.25, predictors were included in the multivariable model. On the basis of the univariable result variables baseline weight of patients, the presence of hypertension, HIV status, diabetes mellitus, anemia status, hepatitis, and chronic heart diseases was included for building a multivariable Cox model.The univariable Cox‐PH regression models were fitted for every predictor to check predictors affecting time to ESRD of patients before proceeding to multivariable models. If the test for the univariable analysis has a From Table 3.4On the basis of univariable analysis of the linear mixed model, the variable visit time of patient, sex, age, diabetes mellitus, chronic heart disease, status of anemia, hypertension, hepatitis, and electrolyte were significant candidate variables for multivariable analysis of the linear mixed model at a 0.25 level of significance.The above Table α) indicates the association between the longitudinal measurement and the survival parts of the data. There is a relationship between longitudinal and survival outcome since the estimated parameter (α) in the survival submodel under joint model analysis was significant and different from zero.The result of Table 3.5From Tables p < 0.001).Table p < 0.0043) compared with the patient who had no hepatitis by keeping all other variables constant. In this study, visit time had a significant negative effect on SCr from the longitudinal process. If the patients visit time increased by a unit, the average SCr of CKD patients is reduced by 0.0978 (p < 0.0024) keeping all other variables constant. This implies that the patients with more visit time made a particular decrease in SCr. The average SCr of CKD patients who had hypertension was significantly higher by 0.722 mg/dL (p = 0.010) compared with the patients who had no hypertension by keeping all other variables constant.The average SCr of CKD patients who had hepatitis was significantly increased by 2.134 mg/dL (p = 0.037) compared with the patients who had no chronic heart disease by keeping all other variables constant. The mean SCr of CKD patients who had diabetes mellitus was significantly higher by 0.7559 mg/dL (p = 0.029) compared with the patients who had no diabetes mellitus by keeping all other variables constant. The average SCr of CKD patients who had anemia was significantly higher by 0.6687 mg/dL (p = 0.014) compared with the patients who had no anemia by keeping all other variables constant.The mean SCr of CKD patients who had chronic heart disease was significantly higher by 0.8288 mg/dL (p = 0.032) by keeping all other variables constant. For a unit increase in electrolyte, the mean SCr of CKD patients was significantly increased by 0.0904 mg/dL by keeping all other variables constant by keeping all other variables constant. Similarly, the average SCr of CKD patients decreased by 1.829 mg/dL for females as compared with male patients by keeping all other variables constant.For a unit increased in age the mean SCr of CKD patients was significantly increased by 0.0316 mg/dL (3.6The proportion of (unexplained) variation in the dependent variable due to subjects is 71%.p = < 0.001) This indicates that the hazard of ESRD for CKD patients with hepatitis was 2.23 times higher as compared with no hepatitis CKD patients, keeping all other variables constant. The estimated hazard ratio of ESRD for CKD patients with HIV was HR = 1.4141, p = < 0.022) This indicates that the hazard of ESRD for CKD patients with HIV was 1.4141 times higher as compared with no HIV CKD patients, keeping all other variables constant.In the survival submodel, the estimated hazard ratio of ESRD for CKD patients with hepatitis was HR = 2.228, p = < 0.001. This indicates that the hazard of ESRD for CKD patients with hypertension was 1.5225 times higher as compared with no hypertension CKD patients, keeping all other variables constant. The calculated hazard proportion of ESRD for CKD patients with chronic heart disease was HR = 1.3938, p = < 0.015. This indicates that the hazard of ESRD for CKD patients with chronic heart disease was 1.3938 times higher as compared with no chronic heart disease CKD patients, keeping all other variables constant.The calculated hazard proportion of ESRD for CKD patients with hypertension was HR = 1.5225, p = < 0.010. This indicates that the hazard of ESRD for CKD patients with diabetes mellitus was 1.3349 times higher as compared with no diabetes mellitus CKD patients, keeping all other variables constant. The calculated hazard proportion of ESRD for CKD patients with anemia was HR = 1.2791, p = < 0.017. This indicates that the hazard of ESRD for CKD patients with anemia was 1.2791 times higher as compared with no anemia CKD patients, keeping all other variables constant.The calculated hazard proportion of ESRD for CKD patients with diabetes mellitus was HR = 1.3349, α) = 0.13 (p = < 001) shows that there is an indication of a positive relationship between SCr and risk of ESRD for CKD patients, which means a unit increase of SCr the risk of ESRD increased by HR = 1.1388, the result showed that the higher value of SCr was associated with the higher risk of ESRD for CKD patients in UOGRH.The estimation of the association parameter  have a negative association with SCr, while the remaining age, electrolyte, anemia, diabetes mellitus, hepatitis, chronic heart disease, and hypertension have a positive significant effect on the variable SCr. In the survival process, anemia, diabetes mellitus, chronic heart disease, HIV, hypertension, and hepatitis have a significant and positive association effect on the variable risk of ESRD at a 5% level of significance.On the basis of the result of the joint model, the variable anemia, diabetes mellitus, chronic heart disease, hypertension, and hepatitis were common factors for a longitudinal measure of SCr and time to ESRD. The variable longitudinal measure of SCr has an association with time to ESRD; hence the association parameter is different from zero. The rate of progression of SCr decreases over time hence visit time had a negative association with SCr in the longitudinal model. The mean profile plot indicated that the average SCr decreased as the visit time increased the rate of progression of SCr decreased over time.The main challenge of the study was limited information on important predictors. Since the data were a secondary data type extracted from the patient medical chart basic sociodemographic and behavioral variables such as marital status, religion, family history of CKD, physical exercise, education level, and alcohol use were unable to obtain from the medical chart. Thus, the variables are not included in the study. The other limitation of the study was the lack of enough literature in our country as well as the study area related to the study, therefore the reference is more to other country outcomes.Samson Belay: Formal analysis; investigation; methodology; software; validation; visualization. Dessie Melese: Formal analysis; software; supervision; validation; visualization; writing—original draft; writing—review and editing. Kasim Muhammed: Conceptualization; supervision; validation.The authors declare no conflict of interest.The ethical clearance approval letter was obtained from the Ethical Approval Committee of the University of Gondar, College of Natural and Computational Science. According to the rules and principles of the ethical approval of the University of Gondar, the name of the subject will not be extracted to insure the privacy of the patients, and confidentiality was maintained through the data collection and analysis process. To collect the data permission was obtained from UOGRH.The lead author Dessie Melese affirms that this manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned  have been explained.


Background: Asthma is a clinical syndrome characterized by recurrent episodes of airway obstruction, bronchial hyperresponsiveness and airway inflammation. Most patients with asthma present a “type 2” (TH2) inflammation. ILC2 and TH2 cells release cytokines IL4, IL-13 and IL-5. CRSwNP is a condition characterized by hyposmia or anosmia, nasal congestion, nasal discharge, and face pain or pressure that last for at least 12 weeks in a row without relief. Both asthma and CRSwNP are often characterized by a type 2 inflammation endotype and are often present in the same patient. Dupilumab is a fully human monoclonal antibody targeting the interleukin-4 receptor α (IL-4Rα) subunit, blocking IL4/IL-4Rα binding and IL13. It has been labelled for the treatment of moderate to severe asthma in patients from the age of 12 years with an eosinophilic phenotype, and it has demonstrated efficacy and acceptable safety. Our study aims to investigate the effects of dupilumab on type 2 inflammatory biomarkers, such as eosinophils and eosinophil cationic protein (ECP). ECP is an eosinophil-derived substance contained in granules that are released during inflammation and causes various biological effects, including tissue damage in asthmatic airways. Methods: ECP, Eosinophil counts (EOS), and total immunoglobulin E (IgE) levels were longitudinally measured using immunoassays in the serum of 21 patients affected by CRSwNP, of which 17 had asthma as a comorbidity, receiving 300 mg dupilumab every two weeks. Results: The EOS and ECP, after a first phase of significant increase due to the intrinsic characteristic of the block of IL-4 and IL-13, returned to the baseline 10 months after the initial administration of dupilumab. Fractional exhaled nitric oxide (FeNO) and serum total IgE decreased significantly after 9 months. Asthma Control Test (ACT) scores improved after dupilumab treatment. FEV1% and FEV1 absolute registered a significant improvement at 10 months. Conclusions: Patients who received 300 milligrams of dupilumab every two weeks first experienced a temporary increase in eosinophils (EOS) and eosinophil cationic protein (ECP), then exhibited a gradual decline in these variables with a subsequent return to the initial baseline levels. When compared to the baseline, we observed that the levels of IgE and FeNO decreased over time, while there was an increase in both FEV1 and FEV1%. Asthma is a clinical syndrome characterized by recurrent episodes of airway obstruction, bronchial hyperresponsiveness and airway inflammation. Among the most frequent symptoms are shortness of breath, cough, wheezing, and chest tightness . Asthma Chronic rhinosinusitis with nasal polyps (CRSwNP) is a medical condition characterized by a significant decline in quality of life, impacting approximately ten percent of the adult population in the United States and Europe. CRSwNP is an abbreviation denoting the medical condition known as chronic rhinosinusitis with nasal polyps. This condition is defined by the manifestation of symptoms such as hyposmia or anosmia, nasal congestion, nasal discharge, and facial pain or pressure that persist for a minimum duration of 12 consecutive weeks without relief. Furthermore, this disorder is distinguished by the manifestation of symptoms such as anosmia or hyposmia . IndividThe JESREC study’s primary objective is to develop a set of clinical diagnostic criteria for the condition known as eosinophilic chronic rhinosinusitis (ECRS). In this study, a scoring system is developed that takes into consideration a variety of parameters, including the affected side of the disease, the existence of nasal polyps, the findings from facial CT scans, and the peripheral eosinophil count . In addiBased on the results of two studies involving Japanese individuals, it was observed that the presence of comorbid asthma was commonly associated with eosinophilic chronic rhinosinusitis (CRS), regardless of the presence of polyps ,8.Both asthma and CRSwNP are marked by a defect of the epithelial barrier, and they frequently have the same type 2 immunopathogenesis. It has been demonstrated that CRSwNP patients who also have asthma have an upregulation of type 2 cytokines as well as an IgE-mediated release of immune mediators in both the upper and lower airways. Patients who have type 2 CRSwNP typically have a more severe form of the disease, characterized by a high polyp recurrence rate and asthma that is difficult to treat. CRSwNP that is associated with asthma is characterized by eosinophilia and a high local IgE level . Recent Dupilumab is a monoclonal antibody that targets the interleukin-4 receptor (IL-4R) subunit specifically. As a result of its action, it has the effect of inhibiting the binding of IL4/IL-4R and IL-13. This drug has been approved for the treatment of severe asthma in individuals who are at least 12 years old, and who have an eosinophilic phenotype or are in need of oral corticosteroid therapy. Individuals must meet both of these criteria in order to take the medication. In pivotal trials, the efficacy of Dupilumab in mitigating severe asthma exacerbations and boosting lung function was proven through the measurement of spirometric outcomes (particularly FVC and FEV1), as well as assessments of asthma control and quality of life scores. This indicated that dupilumab is effective in mitigating severe asthma exacerbations and enhancing lung function . The effEosinophil cationic protein (ECP) is a granule-bound eosinophil-derived peptide that damages asthmatic airway tissue when released during inflammation . ECP is The serum levels of ECP have been linked to the degree of eosinophilic inflammation, suggesting that it could be an indirect marker of eosinophilic activity . The levThe utility of any assay that quantifies eosinophils and/or assesses eosinophil activation is entirely contingent upon the specificity of the biomarker for eosinophils . DespiteThe observational study employed a real-world methodology, wherein physicians faced the proven efficacy of the treatment derived from randomized control trials with the complex factors present in the real-life setting, in order to provide data on the treatment effectiveness and safety .This prospective real-life observational study enrolled patients diagnosed with asthma grades 3-4-5 according to GINA , and CRSDupilumab was administered every 2 weeks for 54 weeks, and the levels of various biomarkers were serially analyzed. We scheduled a baseline Visit V0 and a follow-up visit at 3 and 10 months after baseline. At the baseline visit, for all the patients, study and control group, we collected information about bio-anthropometric features, comorbidities and medications. At the baseline and each other visit, patients were assessed for their Asthma Control Test (ACT) score , Sino-NaEosinophil count was assessed using a whole-blood sample collected in a specimen containing Ethylenediaminetetraacetic acid (EDTA), then analyzed using Fluorescence Flow Cytometry with a DASITXN 1500 Total IgE was assessed using ImmunoCAP and Phadia 250 system , a fully quantitative assay that determines circulating IgE levels over a measurement range from 2 to 5000 kU/L.Pulmonary function testing was obtained using a Vyaire Medical Vyntus™ BODY Plethysmograph ; this, and the measurement of fractional exhaled nitric oxide (FeNO), using NIOX VERO , were performed before starting dupilumab  and after 3 (T3m) and 10 (T10m) months. The first endpoint was to describe the course of ECP and eosinophils at 3 and 10 months after the first dupilumab dose and compare it with the baseline.A Bartlett test was carried out in order to evaluate the differences that were observed between the samples. The Mann–Whitney U test was applied in order to investigate the disparities that could be observed between the two groups. The Spearman correlation coefficient was applied so that we could study the link that existed between the biomarkers. Following the completion of a two-way analysis of variance, the Dunnett multiple comparisons test was used to the clinical index and biomarkers at each time point.We included adult patients with eosinophilic asthma of grades 3-4-5 (according to GINA) and CRSwNP, who had previously undergone OCS or surgery. A total of 21 patients initiated dupilumab treatment: 11 were female and 10 were male, and the median age was 45 y (IQR 27.3) .All patients were affected by CRSwNP and asthma, 11 were atopic, and 10 were non-atopic. At baseline, the ACT median score of those with asthma was 21 (IQR 6.4), the median FeNO was 48 ppb (IQR 32.3), the median IgE was 170 (IQR 353), the median EOS was 500 (IQR 366.7) and the median ECP was 120 (IQR 128). Dupilumab was administered every 2 weeks by subcutaneous injections; two patients had an indication for asthma, so they were administered an initial dose of 600 mg once.p = 0.35)  group ( = 0.35) .3 (IQR 233) and then significantly increased at 3 months up to a median of 860 cell/mm3 (IQR 1079) (p = 0.013), and later returned to a median of 300 cell/mm3 (IQR 833) at 10 months (p = 0.93 vs. baseline) (p = 0.03), and at 10 months we observed a reduction versus baseline to a median of 36.5 U/mL (IQR 155) (p = 0.90)  a (Table  = 0.90) b. Overalme point .No patient showed symptoms or clinical events that were attributable to hypereosinophilia.p = 0.05) (p = 0.01) at T3m, and to a median of 104 (IQR 16) at T10m (p = 0.03) (p = 0.002), and the reduction was maintained at 10 months (p = 0.01). Similarly, the FeNO decreased significantly at 3 months (p = 0.04) and the reduction was maintained at 10 months (p = 0.015). SNOT-22 greatly improved after 3 months from a baseline of 66.5 (IQR 34) to 42 (IQR 46.2) (p = 0.01), and then the improvement continued at 10 months to 27 (IQR 44) (p = 0.02) (p = 0.09) between T0 and T10m, mainly because most patients were non-severe asthmatics with CRSwNP and often had a normal baseline ACT . Similarly, we did not observe significant changes for FEV1, FEV1%, FeNO, total IgE or SNOT22 according to the baseline EOS or ECP value in our study.We also evaluated spirometry, FeNO, serum IgE, the Asthma Control Test (ACT) questionnaire and the Sino-Nasal Outcome Test 22 (SNOT22) . At 10 m = 0.05) c. Simila = 0.03) d. FeNO a = 0.02) . The gailine ACT . As a reIn patients with allergic rhinitis or allergic asthma, the eosinophil mediators have the potential to induce inflammation in the adjacent tissues, specifically the nasal mucosa and the tracheal/bronchial mucosa. In individuals who have been diagnosed with chronic rhinosinusitis (CRS), it has been observed that specific procedures can potentially induce eosinophilic infiltration. The measurement of ECP has also indicated its potential as a biomarker for the diagnostic purposes of Chronic Eosinophilic Rhinosinusitis (ECRS), as it is thought more accurately reflect active eosinophilic inflammation compared to alternative biomarkers . FurtherWe assessed how the ECP levels and the peripheral blood eosinophil counts changed over time during the first course of dupilumab in CRSwNP asthmatic patients. We first analyzed the precise time course of ECP levels in the setting of a real-world observational study. Our analysis showed that at the third month of treatment with dupilumab, there is a significant transient increase in EOS counts in 52% of patients and of ECP levels in 43.5% of patients, which is consistent with a previous report of an RCT . The obsIn contrast to IL-5, IL-4 and IL-13 have a relatively minor direct impact on the number of eosinophils that are produced by the bone marrow. In contrast, the principal effect that is anticipated to result from the administration of dupilumab, which works by inhibiting the IL-4 and IL-13 pathways, is the disruption of the migration of eosinophils, which makes it possible for the number of circulating cells to increase . To promThe trials LIBERTY NP SINUS-24 and LIBERTY NP SINUS-52 indicated that the levels of ECP in nasal lavage fluid were lowered at 24 weeks after the beginning of therapy with dupilumab . Our resIt is important to note that over the course of the study duration, we documented neither serious adverse events (SAEs) nor asthma exacerbations. Furthermore, our findings confirm, in real life, the effectiveness of dupilumab in patients with CRSwNP in terms of quality of life (SNOT22) and in terms of FeNO and total IgE, in contrast with mepolizumab and benralizumab therapy that do not affect these two biomarkers ,17. In pIL-4 and IL-13 control the expression of inducible NO synthase, which generates NO . FeNO anWe did not find a correlation between nasal symptom improvement (SNOT22) and eosinophil count or ECP levels. The results of our investigation are in line with the findings of the SINUS 52 clinical trial, showing that dupilumab is effective in reducing the severity of symptoms associated with severe chronic rhinosinusitis with nasal polyps (CRSwNP) in patients who have either eosinophilic chronic rhinosinusitis (ECRS) or chronic rhinosinusitis that is not caused by eosinophils (non-ECRS). This study also shows that eosinophils are not a relevant biomarker for monitoring the efficacy of dupilumab in subjects who suffer from CRSwNP . In agreIn contrast to anti-IL-5/5R mAbs approved for severe asthma, which showed a consistent and significant drop in ECP during treatment, we found a statistically significant increase in ECP after 3 months in 43.5% of subjects treated with dupilumab, which was followed by a decline towards baseline at 10 months in our cohort. Because of the limitations of the current study, more research with a larger sample size is required to replicate our findings and to investigate the possibility that the chosen biomarkers can serve as predictive indicators of efficacy.The results of our study show that data collected in real life are comparable to those that were formerly documented in pivotal RCTs of dupilumab. Close to those studies, in addition to a significant improvement in clinical status, we also observed an increase in ECP and EOS during the first three months with dupilumab, which subsequently returned to normal levels. This occurred despite the fact that there was a significant improvement in clinical status. In terms of adverse events or lung function, greater ECP levels or EOS does not have a clinical impact.


To compare perioperative and oncologic surgical outcomes during laparoscopic partial nephrectomy (LPN) performed by standard carbon dioxide insufflation, with those from surgeries in which the AirSeal® intelligent insufflation system was used for renal tumors.A total of 27 patients with renal tumor were identified, 14 underwent LPN with AirSeal® (group A) and 13 LPN with standard insufflator (group B), respectively. Demographic baseline characteristics were similar in the two groups.The size of the tumor was largest in group B (29.64 vs. 32.1 mm). The mean operative time was shorter in the AirSeal® group . Positive margin rates were absent in the two groups. Estimated blood loss presented a difference in the perioperative period . Time to ischemia was found to be shorter in group A with a median of 18 min compared to a median of 20 min in group B. No subcutaneous emphysema, pneumothorax, and pneumomediastinum cases occurred in either group. A postoperative complication developed in one patient requiring superselective embolization.In selected patients, our preliminary surgical experience has shown that the LPN procedure performed with the aid of the AirSeal® intelligent insufflation system can be used to treat even medium-/high-complexity kidney lesions, with a reduction in operating times, lower rates of complications, and perioperative blood loss.AirSealV1. Homeostasis can be negatively affected by the increase in intra-abdominal pressure, consequent to the insufflation of CO2, causing significant changes in the cardiovascular and respiratory systems  , has significant advantages over conventional insufflation systems. The AirSeal® mode is designed to provide CO2 insufflation that ensures stable pneumoperitoneum and continuous suction of surgical vapors during laparoscopic procedures. This feature is very useful during procedures where numerous monopolar instrumentations are used. The objective of our study was to compare the surgical outcomes of laparoscopic partial nephrectomy (LPN) procedures performed using the standard CO2 insufflation with those of procedures in which the AirSeal® intelligent insufflation system was used.Renal cell carcinoma (RCC) accounts for 2%–3% of all malignancies , with a  and RN) , 7. In a and RN) , 9 and a and RN) –12. Ther and RN) . Even in and RN) . Complic systems , 16. Con2.2.1.2 insufflation at 12 mmHg. Anatomopathological evaluation of the treated renal lesions was performed by a pathologist with experience in urological surgery, using the latest criteria (2016) of the WHO . Between January 2019 and December 2019, 27 patients with localized RCC, treated with LPN, were enrolled. Exclusion criteria were, age under 18 years, metastatic disease at presentation, absence of a normal contralateral kidney , and missing data on preoperative studies. The patients’ enrollment process was shown in  the WHO  and thos the WHO .2.2.p < 0.20 were included in the multivariate models. Subsequently, the results were expressed as adjusted odds ratios (ORs), 95% confidence intervals (CI), and p-values. Final models were selected by backward elimination of non-significant variables based on the likelihood-ratio test . In the final multivariate regression models, results with p < 0.05 were considered significant. The following variables were tested: use of AirSeal® technique , portion of kidney treated surgically , blood transfusion after surgery , type of surgical approach , ASA index , changes of hemoglobin values before and after surgery, the time needed for the surgery, the size of the lesion, and RENAL score. All analyses were performed using Stata v. 17 software . All data were anonymously processed.Descriptive analysis was performed using frequencies and percentages for categorical variables and means, standard deviations, medians, and interquartile ranges (IQR) for continuous variables. The latter were also tested for normality using the Shapiro–Wilk test. Continuous and categorical variables were compared using the Mann–Whitney test and Fisher's exact test or chi-square test, respectively. Second, multivariate logistic regression analysis was performed to build three regression models using three different outcomes. To evaluate the operative time and use it in a regression model, the first regression model was used to test the outcome of quick surgery by taking the lower quartile of the operative time and using it as a cutoff for a binary variable which distinguishes fast operations from average or slow operations . A second regression model was constructed to test the outcomes of ischemia. To evaluate the presence of ischemia during surgery, a binary variable was created using the variable warm ischemia time, considering patients with no ischemia time as patients without ischemia. On the other hand, every value of >1 was considered a patient with ischemia. A third regression model was built to test for the occurrence of transfusions. Univariate analysis was performed out to identify all possible covariates to be included in the models. Variables with 3.The two groups of patients had similar preoperative characteristics. The mean age was 61.3 years  for group A and 65.9 years  for group B, respectively. The mean lesion size, as assessed by contrast-enhanced CT, was 29.6 mm  and 32.1 mm , respectively. The observed RENAL nephrometry score . No SCE 4.2 insufflation systems often respond. In fact, conventional insufflators typically switch from CO2 insufflation for approximately 3 s to a pause of 1 s and then measure the pressure and cyclically reinflate to maintain the set pressure. Therefore, conventional mechanical insufflators cause cyclic oscillation of the pressure inside the abdomen  without any other influencing factors. Regarding ischemia, a significant negative association has been found with surgery in the polar medial region of the kidney . Furthermore, a longer intervention time was associated with an increased risk of ischemia   . There w00–1.13) , highlig5.Although not comparable with studies with a larger number of patients undergoing minimally invasive PN surgery, our preliminary experience has shown that the LPN procedure performed with the aid of the AirSeal® intelligent insufflation system can be used to treat even medium-/high-complexity renal lesions, with a reduction in operating time, “warm ischemia” time, and perioperative blood loss. However, the uniqueness of our study is represented by the fact that for the first time, the advantages of this system were investigated only in the field of laparoscopic partial nephrectomy in renal cell carcinoma. Furthermore, our data investigated the feasibility and safety of an LPN approach using a smart insufflation system.


Alterations in skin blood flow is a marker of inadequate tissue perfusion in critically ill patients after initial resuscitation. The effects of red blood cell transfusions (RBCT) on skin perfusion are not described in this setting. We evaluated the effects of red blood cell transfusions on skin tissue perfusion in critically ill patients without acute bleeding after initial resuscitation.BT), together with mean arterial pressure (MAP), heart rate (HR), hemoglobin (Hb), central venous pressure (CVP), lactate, and central or mixed venous oxygen saturation before and 1 h after RBCT. SBF responders were those with a 20% increase in SBFBT after RBCT.A prospective observational study included 175 non-bleeding adult patients after fluid resuscitation requiring red blood cell transfusions. Using laser Doppler, we measured finger skin blood flow (SBF) at skin basal temperature (SBFBT did not significantly change after RBCT . A relative increase equal to or more than 20% in SBFBT after RBCT (SBF responders) was observed in 77/175 of RBCT (44%). SBF responders had significantly lower SBFBT , mixed or central venous oxygen saturation  and CVP  at baseline than non-responders. SBFBT increased in responders , and decreased in the non-responders  after RBCT. Pre-transfusion SBFBT was independently associated with a 20% increase in SBFBT after RBCT. Baseline SBFBT had an area under receiver operator characteristic of 0.73  to predict SBFBT increase; A SBFBT of 73.0 perfusion units (PU) had a sensitivity of 71.4% and a specificity of 70.4% to predict SBFBT increase after RBCT. No significant differences in SBFBT were observed after RBCT in different subgroup analyses.Overall, SBFBT at baseline was associated with a relative increase in skin tissue perfusion after RBCT.The skin blood flow is globally unaltered by red blood cell transfusions in non-bleeding critically ill patients after initial resuscitation. However, a lower SBF Anemia is a prevalent issue in critically ill patients , 2. DespCurrent guidelines recommend a restrictive RBCT strategy with a hemoglobin (Hb) threshold of 7 g/dL for considering transfusions in non-bleeding ICU patients . HoweverSome studies have indicated that RBCT have heterogeneous effects on sublingual microcirculation, with either improved or altered microvascular density, in critically ill patients , 13. SimThe aim of this study was therefore to evaluate the effects of RBCT on SBF and to identify predictors of skin blood flow response to RBCT in non-bleeding critically ill patients after initial resuscitation.This prospective observational study was conducted at the Department of Intensive Care at Erasme Hospital (Belgium) from September 2018 to April 2021. The Ethics Committee approved the study (protocol number P2018/588), and all patients and/or their next of kin provided informed consent.Consecutive adult patients (>18 years of age) admitted to the 34-bed ICU during the study period who did not have evidence of active bleeding and who were considered euvolemic and for whom the attending physicians decided to administer RBCT were eligible for inclusion. Exclusion criteria were pregnancy, RBCT transfusion within the preceding 24 h, the presence of any skin lesion that prevented the use of SLD, and mechanical assist devices or renal support.The decision to transfuse the patient was made by the responsible physician following a local transfusion policy that considers a hemoglobin level below 7–8 g/dL as an indication for transfusion. Packed red blood cells (RBCs) units were obtained from the blood bank at the Erasme Hospital Belgian Red Cross and were transfused in the ICU. All RBC units underwent leukocyte reduction through filtration before storage. A storage solution consisting of saline-adenine-glucose-mannitol was added to the RBCs before storage, and the maximum allowed storage period was 42 days.2 or SvO2), arterial lactate levels, arterial and venous blood gas analyses , body temperature , hematocrit (Htc) and Hb were collected for all patients before RBCT. All measurements, including SBF, were repeated at the end of RBCT. The survival status was recorded 28 days after RBCT. The use of vasopressors, sedatives, or mechanical ventilation on the study day was also documented. If two units were transfused on the same day, data were collected and measurements were obtained only after the first transfusion. Hemodynamic, Hb, and SBF variables were measured immediately before and 1 h after RBCT. During the measurements, the patient’s position was kept constant. Measurements were classified as “interference” when the dose of vasopressor/inotropic and sedative/analgesic agents was not maintained at a constant level over time, as determined by the responsible physician.Demographic data, disease severity, and the main diagnosis were collected from all patients. The Acute Physiology and Chronic Health Evaluation II (APACHE II) score  was calcBT) was recorded for 3 min. Subsequently, the skin probe temperature was then immediately increased to 37°C, and the SBF (SBF37) was again recorded after 3 min. The thermal challenge test (TCT) at a skin temperature of 37°C was calculated using the following formula: SBF37–SBFBT/37-BT . The measurements were obtained using the same device in all patients, and the skin probe was placed on the same studied area during all SBF measurements. Patients were instructed not to move their hands or change the bed’s position during SBF measurements and the transfusion period.SBF was measured using the SLD device Periflux System 5000  at the same time points. The thermostatic probe was positioned on the tip of the index finger, and the SBF at skin basal temperature /SBFBT baseline) × 100%. RBCT was considered “early” if administered within 3 days of ICU admission. Sepsis was diagnosed according to standard criteria. Acute neurological disease (AND) was defined as patients admitted with one of the following conditions: acute brain injury , acute ischemic stroke, or meningoencephalitis. Chronic anemia was defined based on a known history of anemia/or decreased hematocrit (Hct) and Hb concentration on previous laboratory tests , we estimated that a sample size of 95 patients was needed to have a power of 80% with an alpha error of 5% to test the study hypothesis.Based on the hypothesis of a relative increase greater than or equal to 20% in SBFU-test or Unpaired Student’s tests were used for data with non-normal and normal distribution, respectively. Multivariable logistic regression models were performed to investigate predictors of tissue response to RBCT, which included as covariates in the model all variables with value of p <0.2 at univariate analysis. A generalized mixed model (GMM) with logit link and covariance matrix with the first-order autoregressive structure was used to identify baseline variables that were independently associated with a significant SBFBT increase of all included RBCT ; variables with a value of p less than 0.2 in the univariate analysis were included. The odds ratio with their 95% CI was computed for all variables. The independence of errors and the presence of collinearity were also checked. The area under the receiving operator curve (AUROC) was computed to assess the predictive value of pre-transfusion SBFBT for tissue response to RBCT; the optimal predictive cut-off score was determined using Youden’s index. All considered tests were two-tailed and a value of p <0.05 was considered to be statistically significant. Statistical analyses were performed using SPSS Statistics for Windows, version 27.0 .Normality distribution was evaluated using the Kolmogorov–Smirnov test for each parameter. Data are presented as median (25th–75th percentiles) or mean with standard deviation, as appropriate. Categorical variables were described and counted (%) and differences between groups were assessed using the chi-square test or Fisher’s exact test as required. A Wilcoxon’s test or Paired Student’s tests were used to compare the pre-transfusion and post-transfusion values, as appropriate. Mann–Whitney n = 6), refused consent (n = 2), start ultrafiltration at the moment of RBCT (n = 5), concomitant fluid challenge (n = 3), interruption of transfusion due to adverse effects (n = 1), other procedures , need for imaging tests (n = 3), isolation because of multi-resistant bacteria (n = 1), end-of-life procedure (n = 1), acute bleeding (n = 1), and skin lesions (n = 1). As such, 175 patients receiving 175 RBCT were included in the final analysis for the primary and secondary outcomes. Also, 175 patients receiving 226 RBCT were included in the sensitivity analysis of the primary outcome . RBCT were given after a median of 4 (0–42) days after ICU admission; 6 (3.4%) RBCT had interference. Twenty-nine patients (16.6%) died 28 days after the study inclusion.The characteristics of the study cohort  are shown in BT was 79.8 (4.3–479.4) PU , Htc , mean arterial pressure  and venous oxygen saturation  PU . There wter RBCT ; Table 2BT after RBCT (responders). The clinical characteristics of SBF responders and non-responders are shown in BT were significantly lower in SBF responders than in non-responders , whereas it significantly decreased in non-responders  patients had their first RBCT resulting in a significant increase in SBFsponders . Also, bBT, older age, and the absence of an acute neurological disease were independently associated with SBF response to RBCT . The optimal baseline SBFBT to predict skin blood flow response to RBCT was 73.0 PU, with 71.4% sensibility and 70.4% specificity (n = 226 RBCT), lower baseline SBFBT, older age, and the absence of an acute neurological disease were independently associated with skin blood flow response to RBCT  between the early and the late groups  between groups (BT (BT after RBCT was observed between groups (Sixty-three out of 175 (36%) patients had sepsis ; there wn groups . There woups , tissue perfusion, oxygenation, or cellular metabolic needs  , and artlar flow . Our finlar flow , 28, 55.lar flow . These fAnother important finding in our study is that a significant reduction in the SBF was observed after RBCT in an important proportion of patients . Other clinical studies have also reported a decrease in the microvascular sublingual perfusion and tissue oxygenation when an RBCT was administered to patients who already have normal baseline tissue perfusion , 28. OneOur study has several limitations. First, it was a single-center study, which limits its external validity. Second, during the intervention period, some interventions other than RBCT were ongoing , and we cannot rule out the possibility that these changes may have influenced the final results, but they were a minority around 3.4%. Third, we did not collect other potential variables of interest, such as cardiac output, as it was not monitored in all our patients. This analysis would be informative to detect some incoherence between the microcirculatory and global systemic variables, as previously reported , 61–63. In conclusion, the present study shows that RBCT results in variable tissue perfusion changes during critical illness. Altered skin tissue perfusion at baseline had a higher probability to improve after RBCT. Skin tissue perfusion monitoring might help to individualize transfusion strategies in this setting.elaine_meduece@yahoo.com.br.Due to ethical restrictions, the datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request. Requests to access the datasets should be directed to EC, The studies involving humans were approved by Erasme Hospital Ethical Committee. The studies were conducted in accordance with the local legislation and institutional requirements. The participants provided their written informed consent to participate in this study.EC and FT conceived the study. EC, PB, and DO selected the population and collected the data. EC and FT conducted the statistical analysis and wrote the first draft of the article. PB, DO, J-LV, and JC revised the text for intellectual content. All authors contributed to the article and approved the submitted version.


Pulmonary arterial hypertension (PAH) is defined as an elevated mean pulmonary artery pressure (mPAP) of >20 mmHg together with a pulmonary arterial wedge pressure (PAWP) of ≤15 mmHg and pulmonary vascular resistance (PVR) of>2 Wood units (WU). Although the total mortality of pregnant women with PAH has decreased significantly in recent years and is reported to be around 12% in some databases, total mortality is still at an unacceptably high percentage. Moreover, some subgroups, such as patients with Eisenmenger’s syndrome, have a particularly high mortality rate of up to 36%. Pregnancy in patients with PAH is contraindicated; its appearance is an indication for a planned termination. Education of patients with PAH, including counseling on effective contraception, is essential. During pregnancy, blood volume, heart rate, and cardiac output increase, while PVR and systemic vascular resistance decrease. The hemostatic balance is shifted towards hypercoagulability. Among PAH-specific drugs, the use of inhaled or intravenous prostacyclins, phosphodiesterase inhibitors, and calcium channel blockers (in patients with preserved vasoreactivity) is acceptable. Endothelin receptor antagonists and riociguat are contraindicated. Childbirth can take place through either vaginal delivery or caesarean section; similarly, neuraxial and general anesthesia have proven indications. In a situation where all pharmacological options have been used in pregnant or postpartum patients in a serious condition, veno-arterial ECMO is a useful therapeutic option. For PAH patients who want to become mothers, an option that does not endanger their lives is adoption. According to the 2022 European Society of Cardiology/European Respiratory Society (ESC/ERS) guidelines for the diagnosis and treatment of pulmonary hypertension (PH), it is defined as an elevated mean pulmonary artery pressure (mPAP) of >20 mmHg, and the definition of pulmonary arterial hypertension (PAH) also implies an pulmonary arterial wedge pressure (PAWP) of ≤15 mmHg and pulmonary vascular resistance (PVR) of >2 Wood units (WU). Anew clinical classification of PH has also been presented  [1]. PAHThe main causes of death, according to the order of occurrence, are right ventricle failure, cardiac arrest, pulmonary hypertension crisis, preeclampsia, and sepsis ,5.There are still situations where it is necessary to manage pregnancy in patients with PAH or even the diagnosis of PAH during pregnancy. These circumstances require a well-planned, multidisciplinary approach with detailed monitoring during gestation and after delivery. The aim of this review is to present the current state of knowledge on pregnancy in patients with PAH, and additionally, we would like to share the experience of our center regarding the issue of motherhood in such patients.2) of >15 mL/min/kg, ventilatory equivalents for carbon dioxide (VE/VCO2 slope) of <36, and among the laboratory parameters, with the concentration of brain natriuretic peptide (BNP) of <50 ng/L or N-terminal pro-brain natriuretic peptide (NT-proBNP) of <300 ng/L. The echocardiographic parameters of a good prognosis are the right atrium (RA) area of <18 cm2, no pericardial effusion, tricuspid annular plane systolic excursion/systolic pulmonary arterial pressure index (TAPSE/sPAP) of >0.32 mm/mmHg, and among the MRI parameters, belong the right ventricular ejection fraction (RVEF) of >54%, SVI > 40 mL/m2 and right ventricular end-systolic volume index (RVESVI) of >42 mL/m2. The hemodynamic markers of low risk of death are right atrial pressure (RAP) of <8 mmHg, cardiac index (CI) of ≥2.5 L/min/m2, mixed venous oxygen saturation (SvO2) of >65%, and stroke volume index (SVI) of >38 mL/m2 (1). In addition to generally recognized risk factors, a woman’s first pregnancy, general anesthesia, and elevated PVR (but without a clear cut-off point) have been identified as risk factors for the mother [In the case of PAH patients, not only during pregnancy, but it is also optimal to achieve and maintain the lowest possible risk profile. In accordance with the current ESC recommendations, the determinants of good PAH control include no clinical signs of right heart failure, no progression of symptoms, no syncope, a I or II WHO functional class, and 6min walking distance of >440 m. Among the parameters of cardiopulmonary exercise testing, the low risk of death is associated with peak oxygen consumption  and low birth weight (83.7%) were observed; however, in most cases, it did not affect the development of the newborns as compared to their peers [In the case of pregnancy in patients with PAH, it should also be remembered that children may inherit mutations that increase the risk of PAH. Mutations responsible for the development of the disease have been found in idiopathic and familial PAH, anorexigen-associated PAH, pulmonary veno-occlusive disease pulmonary capillary hemangiomatosis (PVOD/PCH), and PAH associated with congenital heart disease. If a mutation in PAH is identified, it should be classified as hereditary PAH (HPAH), and the available data show that around 25–30% of IPAH cases should be classified into this group .Recommendations against becoming pregnant may lead to the disruption in the emotional well-being of patients with PAH, with the recommendation being a source of frustration resulting from limitations that cannot be overcome . More paEffective contraception should be used by all PAH patients of childbearing age. Based on the Centers for Disease Control and Prevention recommendations on the effectiveness of different methods of contraception, tier I methods  with failure rates of less than 1% per year are recommended for all patients for whom pregnancy is contraindicated (WHO pregnancy risk group IV) and they can be used as a single form of contraception. Tier II methods  with failure rates of 6–12% per year do not have such recommendations; therefore, two methods should be used simultaneously, e.g., hormonal and barrier methods or two barrier methods ,14,15. IPatients with PAH who become pregnant should receive comprehensive counseling regarding their condition, pregnancy-related risks to the mother and fetus, and treatment options, including the termination of pregnancy. If the termination of pregnancy is an accepted therapeutic option, it should be performed as early as possible. Taking into account all methods of termination of pregnancy in patients with pulmonary hypertension (PH-1 and PH-2), i.e., laparoscopic, open, or transvaginal, the total periprocedural mortality rate is estimated at 4–6% . Data avThe growing uterus and its metabolic requirements as well as fluctuations in hormone levels that appear at the onset of pregnancy and last until the postpartum period affect the function of the entire body. During pregnancy, blood volume increases by about 50% compared to the period before pregnancy, which increases the burden on the circulatory system and also causes a decrease in the blood concentration of the drugs used so far. The red blood cell (RBC) volume increases, but not to the same extent as the plasma volume, which can lead to dilutional anemia . Heart rAn important element influencing an individual’s health condition in pregnancy is also an increase in the tendency to suffer from supraventricular and ventricular arrhythmias . Blood pIn patients with a normal pregnancy, in order to reduce the risk of hemorrhagic complications during childbirth, the hemostatic balance is shifted towards hypercoagulability. There is a decrease in the concentration of free protein S—a blood coagulation inhibitor—as well as acquired activated protein C resistance, and an increase in coagulation factors and fibrinogen. Together, they may lead to an increased risk of thromboembolic complications. The hemostatic changes in pregnancy usually normalize within 4 to 6 weeks after delivery . ChangesThe physiologic cardiovascular adaptations of pregnancy and labor appear in the vast majority of women without circulatory decompensation, but increased plasma volume and increased CO often cannot be handled by a failed right ventricle which may lead to right ventricular failure in patients with PAH.The risk of cardiovascular decompensation for patients with PAH is particularly high in the perinatal period, which is associated with rapid hemodynamic changes that occur during this period. It is influenced by many factors, including uterine contractions, pain, anxiety, bleeding, or anesthesia. During labor, each uterine contraction causes the transfer of about 500 mL of blood into the mother’s bloodstream, which increases CO and systemic pressure . CardiacThe standard medications for the treatment of PAH are calcium channel blockers , endothelin receptor antagonists , phosphodiesterase type 5 inhibitors , guanylate cyclase stimulators (riociguat), prostacyclin analogues , and prostacyclin receptor agonists (selexipag). Based on the Food and Drug Administration recommendations for the use of the above-mentioned drugs in pregnancy, Endothelin receptor antagonists  and guanylate cyclase stimulators (riociguat) are contraindicated in pregnancy due to their teratogenic properties. Prostacyclins  and phosphodiesterase inhibitors  are among the basic medications recommended in pregnancy for patients with PAH and have been proven effective in reducing mortality. Responders (patients with preserved vasoreactivity) may benefit from the use of calcium channel blockers. Another therapeutic option is also inhaled NO, which, through its local action, improves ventilation/perfusion mismatch and oxygenation without reducing system pressure . SymptomDue to the hypercoagulability state in pregnancy and possible thromboembolic complications, which in patients with PAH may additionally strain their already low cardiovascular reserves, the use of low-molecular-weight heparins is recommended .Data on breastfeeding in patients using PAH therapy are limited; there are no clear recommendations, although there are reports in which there are patients undergoing PAH-targeted therapy with PDE5 inhibitors or parenteral prostacyclins breastfeeding without any known complications . The conPregnant patients with PAH should be under the care of an experienced, multidisciplinary team and undergo regular check-ups—initially at least once a month and even weekly in the last trimester . The optNatural childbirth entails a lower risk of complications—lower blood loss and thus lower hemodynamic fluctuations, as well as a lower risk of thromboembolic complications and local infection; on the other hand, prolonged labor puts additional strain on the already small capacity reserves in patients with PAH and carries risks associated with the Valsalva maneuver during labor and vasovagal response, resulting in the risk of decreased venous return ,56,57. TRegional neuraxial anesthesia rather than general anesthesia is recommended and selected during labor. Spinal epidural or epidural anesthesia with a slow titration of an agent is usually recommended because single bolus epidural anesthesia can cause hypotension . Data onThe greatest risk of death for mothers is within 30 days postpartum and is associated with RV failure ,63,64. IPatients in whom the above-mentioned pharmacotherapy is ineffective are candidates for mechanical circulatory support in the form of an intra-aortic balloon pump (IABP), right ventricular assist device (RVAD), or extracorporeal membrane oxygenation (ECMO).The first two solutions may be beneficial in a situation where the dominant problem is hypotension and circulatory failure, with good blood oxygenation maintained. However, in the case of patients with PAH, we usually deal with low blood saturation; hence, the use of ECMO is much more beneficial . Veno-arAmong PAH patients under the care of the 2nd Department of Cardiology, Faculty of Medical Sciences in Zabrze, Silesian Medical University in Katowice, all pregnancies occurred before the diagnosis of PAH was made. The diagnosis of PAH is a particularly difficult period for patients in which they have to face the consciousness of being ill with an incurable, progressive disease and change many life plans, including those regarding motherhood. It is important to educate patients, including emphasizing the contraindications of pregnancy in PAH and the fact that even a well-controlled disease can have an unpredictable course. The solution for patients who want to be mothers is adoption, and two of our patients chose this option. Case 1. Patient 1, born in 1983, with PH after correction of the common atrium by age 5. The diagnosis of PH was confirmed in 2006 during right heart catheterization (RHC) with an inhaled NO (iNO) reversibility test. The patient’s pulmonary artery (PA) pressure was 65.6/28.2 (mean 40.7 mmHg) and 58.8/29.8 (mean 39.5 mmHg) during NO inhalation and their PVR was 584.3 and 496.6 dyna, respectively. The patient was treated with sildenafil (20mg three times a day) from 2008, and in 2021, the therapy was extended with the addition of ARB—bosentan, after RHC where the patient’s PA pressure was 109/39 mmHg (mean 62 mmHg) and their PVR was 11.5 WU. The first NT-proBNP concentration determined in 2008 was 182 pg/mL, with small fluctuations and progression over the years to 471.30 pg/mL in 2022. The patient remains in WHO functional class II; however, extending therapy to include prostanoids is currently being discussed.Case 2.Patient 2, born in 1980, with IPAH diagnosed in 1997 and confirmed during RHC with an iNO reversibility test in 2003. The patient’s PA pressure was 90.0/48.0 (mean 62 mmHg) with a reduction to 50.0/28.4 (mean 35.3 mmHg) during NO inhalation, and following pretreatment with sildenafil, their PVR was 1607 and 905.4 dyna, respectively. Sildenafil was introduced as the permanent treatment and its beneficial hemodynamic effect was confirmed after 4 weeks; the value of PA pressure in RHC was 67.5/28.4 (mean 38.4 mmHg) and the PVR was 736 dyna. The patient has remained clinically stable over the years, with the measurement values obtained in the RHC at a comparable level, stable WHO functional class I/II, and NT-proBNP concentration levels below <200 pg/mL. Because of a continuously persistent vasodilatation reserve during NO inhalation, therapy of PAH was switched from sildenafil to riociguat (2.5 mg three times a day) which allowed for additional reduction in mPAP from 40.5 mmHg in 2020 to 31 mmHg in 2020 and a reduction in PVR from 6.2 WU to 4.05 WU. In accordance with Polish law, non-incapacitated adults who have appropriate moral and health capacities and a stable financial situation as well as having obtained the qualified opinion of an adoption center and a certificate of completion of training organized by the center may apply for adoption. Current PAH therapy, which in Poland is fully financed by the government, allows good disease control in most cases, which results in maintaining daily life activity and in some cases, even the opportunity to complete light professional work. The examples of PAH patients presented above who have adopted children concern patients with a stable form of the disease, with little progression over the years of follow-up and good control, giving a chance of survival that will allow them to raise their children. Only in this situation can adoption be considered. It is a difficult and complex problem; on the one hand, it provides PAH patients with the opportunity to become mothers without exposing them to the risks associated with pregnancy, improves their mental condition, and provides abandoned children or orphans with the chance to grow up outside of an orphanage in a loving family; on the other hand, it is the institution’s responsibility to prevent situations in which the adopted children may lose their foster parent and family again.Based on data from available registries, the improvement in maternal and infant prognosis among pregnant patients with PAH is significant, but total mortality rates are still unacceptably high. Rapid diagnosis of PAH is essential to avoid situations in which the disease is diagnosed during pregnancy, as well as adequate education of patients regarding having children so that it is possible for all decisions to be made with full awareness. Case reports on successful pregnancies and deliveries have been frequently published in the literature, which may give the impression of a good prognosis. Successful completion of pregnancy in PAH patients does not mean that after giving birth, the patient’s condition will return to what it was before pregnancy. There is a high burden on the mother’s circulatory system due to reaching the gestational point that will allow the birth of a child who has a chance of survival, but it is the perinatal period in which we have to deal with the highest mortality rates. It is also important to remember the long-term consequences and risks of PAH progression, as well as any consequences for the child resulting from premature birth and being born with a low birth weight. The available literature data on successful pregnancies in patients with well-controlled PAH do not provide sufficient evidence to recommend pregnancy in such patients . Despite


The accuracy of the measurement of renal function in potential living kidney donors (PLKD) is essential. The direct measurement of glomerular filtration rate (mGFR) has been considered the “gold standard.” The estimated GFR (eGFR) with 24-hour urinary creatinine clearance (CrCl) is frequently used because of its availability. We aim to evaluate the correlation and agreement of eGFR using serum-based creatinine formulas  and the eGFR based on 24-hour urinary CrCl to evaluate kidney function in PLKD.  We evaluated the kidney function in 799 PLKD using 24-hour urinary CrCl method and compared the correlation and agreement with the eGFR based on creatinine formulas . We calculated the mean bias (difference), precision (SD of this difference), accuracy, and performed Bland–Altman plots.  A total of 799 PLKD were analyzed. The age of the PLKD ranged from 18 to 73 years. Weak to mild correlation was observed between 24-hour urinary CrCl and all formulas (ranged from 0.31 to 0.49). The three equations underestimated the GFR. Using the Bland–Altman graphic, we observed that the CKD-EPI was the least scattered and most precise; however, mean bias and the interval range (limits of agreement) of all formulas were too big to assume equivalence between 24-hour urinary CrCl method and eGFR based on creatinine. Results of mean bias were similar when comparing the three equations in patients with CrCl GFR <60. However, the accuracy of all formulas was better for the female group and the youngest individuals (≤40 years old).  In this PLKD cohort, of all the three equations, the CKD-EPI was the least scattered and most precise. However, the correlation and the level of agreement between the three equations and 24-hour urinary CrCl were too low to assume the equivalence. The glomerular filtration rate (GFR) has been considered the best method to calculate global kidney function . The inuThe eGFR such as Cockcroft–Gault (CG), modification of diet in renal disease (MDRD), and chronic kidney disease epidemiology collaboration (CKD-EPI) are useful to calculate GFR and kidney function stratification –8. OtherIn kidney transplantation, the selection of potential living kidney donors (PLKD) must be a rigorous process where the eGFR is one of the main factors to determine PLKD eligibility . GFR is In this study, we aimed at comparing the different eGFR with 24 hours urine CrCl in PLKD to determine their accuracy, bias, and agreement and how it may influence PLKD eligibility.This retrospective study was carried out with PLKD evaluated in Colombiana de Trasplantes from October 2008 to October 2020. Colombiana de Trasplantes is a transplant network in Colombia with 4 centers within the country that performs around 21% of the annual national kidney transplant activity. Inclusion criteria included patients older than 18 years old who were screened as potential donors. The potential donors were all the patients that submitted themselves to become living donors and were approved by our mental health team. The mental health team did a semistructured interview to assess the psychosocial status, disapproving the patients who had compromised legal requirements , ethical principles , or psychological considerations . Exclusion criteria for the study included 24 hours urine CrCl >180 mg/dl. Comorbidities were not considered exclusion criteria in the study but were a relevant factor for selecting effective donors. We studied all the PLKD, regardless of whether they became effective donors. We reviewed a total of 829 medical records. In case of implausibility or inconsistency, medical records and laboratory registers were reviewed for correction/verification. The final study population comprised 799 PLKD after applying the exclusion criteria. Data collection included demographic data, age, sex, race, weight, height, body mass index (BMI), and serum creatinine, and eGFR was estimated by the three equations  and 24-hour urine creatinine clearance.2), Cockcroft–Gault (CG), and CKD-EPI (ml/min/1.73 m2) formulas. Definitions of estimation methods are shown in Based on the recommendations made by the kidney disease improving global outcomes (KDIGO)  and Orga2 are not accepted for donation. Live kidney donors should have GFR (24 h urine creatinine clearance) equal to or higher than 90 ml/min/1.73 m2, donors with GFR between 60–89 ml/min/1.73 m2 will be assessed depends on age, demographics, and risk factors [The policy of our center is that individuals who had a history of a primary renal or systemic disease known to affect kidney's function and GFR lower than 60 ml/min/1.73 m factors .Numerical data were expressed as medians or means and ranges or standard deviation according to distribution, and the categorical variables as numbers and percentages. To examine the correlation between 24 h urine CrCl and estimated GFR  the Lin's concordance correlation coefficient was used (ranges from −1.0 to +1.0). The closer the coefficients are to +1.0 or −1.0, the greater the strength of the linear relationship is. Correlation degree was defined as weak 0.20–0.39, moderate 0.40–0.59, strong 0.60–0.79, and very strong 0.80–1.00.X-axis represented the average ((K1 + K2)/2) and the Y-axis represented the difference (K1 − K2) of two measurements. After the graph is drawn, the mean bias (mean of the K1 − K2) and its confidence limits (limits of agreement) are quantified [To assess the agreement between the two measurement methods (24 h urine CrCl and estimated GFR with the three equations) we performed the Bland–Altman analysis. Bland and Altman quantified the difference between measurements using a graphical method. Furthermore, this method evaluates a bias between the mean differences, and it estimates an agreement interval, encompassing 95% of the differences observed in the second method when compared to the first method. Then, we drew a scatterplot in which the antified .Performance of each eGFR equation was assessed in terms of accuracy (bias), precision, and agreement. Bias was defined as the mean difference between measured (24 h urine CrCl) and estimated GFR  and the standard deviation (SD) of this difference was defined as precision. Accuracy and precision were also evaluated separately for age groups , BMI , and gender.These statistical limits were calculated by using the mean and the SD of the differences between the two measurements.The difference between 24-hour urinary CrCl and eGFR was plotted against the mean of 24-hour urinary CrCl and eGFR. Bias and the 95% limits of agreement which were calculated as the mean difference ±1.96 times the precision were examined. Statistical Analysis Software R 4.0.3 was used for all analyses.This study was approved by the Institutional Research Committee, acting in concordance with national regulations, and International Regulations, such as the Declaration of Helsinki  and the 2, 106 ml/min/1.73 m2, and 102 ml/min/1.73 m2 for CG, CKD-EPI, and MDRD equations, respectively. No significant differences were found in the mean of CKD-EPI or MDRD in Afro-American population. Demographics of the entire study cohort are described in A total of 799 PLKD were analyzed. Median age was 38.1 (range 18–73), 443 subjects were female, median of 24-hour urinary CrCl was 116 mg/dl (range 38.3–180 mg/dl), mean of eGFR was 110 ml/min/1.73 mrMDRD = 0.31 (95% CI 0.2659–0.3681), rCKD-EPI = 0.32 (95% CI 0.2744–0.3798), and rCG = 0.49 (95% CI 0.4449–0.5469). Lin's concordance correlation coefficient did not show significant differences in terms of race (Black vs others) by the eGFR equations (CKD-EPI rCKD-EPI = 0.32 and MDRD rMDRD = 0.31).After calculating the Lin's concordance correlation coefficient, weak to moderate correlation was observed between 24-hour urinary CrCl and all formulas with coefficients of After calculating the mean difference (bias) between measurements (24-hour urinary CrCl and each equation), these results showed that there was a positive difference for each equation , revealing that all of three equations tended to underestimate GFR.CG gave the lowest bias of the three equations , whereas CKD-EPI was the least scattered and most precise : 97.5 compared to 98.5 and 99.3 for the CG and MDRD, respectively).Analyzing individuals by gender, BMI, and age groups separately, highest accuracy was found for the female and the youngest group for the three equations, whereas individuals with BMI >25 performance of CG and CKD-EPI was better compared to MDRD. The Afro-American race was analyzed by the eGFR equations that consider race (CKD-EPI and MDRD) in its estimation variables without any significant difference in bias  or Bland–Altman plots analysis.The Bland–Altman plots of the measured and estimated renal function with bias and 95% limits of agreement for each equation showed the smallest mean bias for the CG compared to the CKD-EPI, CG, and MDRD equations compared with 24-hour urinary CrCl .A crucial point in living kidney donation is the accurate evaluation of renal function in terms of ensuring donor safety and the best recipient outcomes. Many transplant centers evaluate the renal function of potential donors from CrCl. However, the clinical practice guidelines are not clear about the ideal method to estimate the GFR in PLKD.The present study aimed to analyze the performance of the MDRD, CKD-EPI, and CG equations to estimate renal function among a cohort of PLKD by comparing estimates to GFR based on 24-hour urinary CrCl. Results of our study showed a weak to moderate correlation between 24-hour urinary CrCl and eGFR for all formulas. Moreover, all of them underestimated the GFR, while the CG provided a least biased estimate with the highest accuracy in the entire cohort. This was also true when the subjects were divided into subgroups , whereas the CKD-EPI was the least scattered and most precise. The interval range (limits of agreement) of all formulas was too big to assume equivalence between 24-hour urinary CrCl method and eGFR based on creatinine .p  <  0.001) [Our study did not find significant differences in terms of race by the eGFR equations (CKD-EPI and MDRD). In a systematic review with 1064 studies, CKD-EPI had equal accuracy between white, black, or other races . Kong et  0.001) .Other studies looking at the performance of these equations have found inconsistent results. In a study from India on 173 kidney donors, Mahajan et al.  reportedIn our study, we found that the accuracy of all formulas was better for the female group and the highest accuracy was for the CG and the CKD-EPI formulas, being the CKD-EPI the most precise. Arreola–Guerra et al.  found th2.Hafeez et al.  assessedChaurasia et al.  from NepThere are some weaknesses of this study. First, we studied a single Colombian population of PLKD and it is unlikely that a single equation will work well in all populations. Second, there were few participants older than 70 years of age or racial minorities and the study population is not representative of the general population. Furthermore, this is a cohort of PLKD that were generally healthy, and these findings could not be generalized to the general population. Finally, comparison between measurements do not overcome limitations of serum creatinine as an endogenous filtration marker. Strengths included that to the best of our knowledge, ours is the first study that validate these equations in a Colombian cohort of PLKD.in this PLKD cohort, of all the three equations, CKD-EPI was the least scattered and most precise. However, the three equations underestimated the GFR. These may misclassify the healthy individuals into chronic kidney disease population. The correlation and the level of agreement between the three equations and 24-hour urinary CrCl were too low to assume equivalence. Therefore, the use of the three equations in the evaluation of renal function among living kidney donor candidates must be performed with caution. The accuracy of all formulas was better for the female group and the youngest individuals (≤40 years old).We conclude that