The ERA Registry Annual Report 2021: a summary.

Background: The European Renal Association (ERA) Registry collects data on kidney replacement therapy (KRT) in patients with end-stage kidney disease (ESKD). This paper is a summary of the ERA Registry Annual Report 2021, including a comparison across treatment modalities. Methods: Data was collected from 54 national and regional registries from 36 countries, of which 35 registries from 18 countries contributed individual patient data and 19 registries from 19 countries contributed aggregated data. Using this data, incidence and prevalence of KRT, kidney transplantation rates, survival probabilities and expected remaining lifetimes were calculated. Result: In 2021, 533.2 million people in the general population were covered by the ERA Registry. The incidence of KRT was 145 per million population (pmp). In incident patients, 55% were 65 years or older, 64% were male, and the most common primary renal disease (PRD) was diabetes (22%). The prevalence of KRT was 1040 pmp. In prevalent patients, 47% were 65 years or older, 62% were male, and the most common PRDs were diabetes and glomerulonephritis/sclerosis (both 16%). On 31 December 2021, 56% of patients received haemodialysis, 5% received peritoneal dialysis, and 39% were living with a functioning graft. The kidney transplantation rate in 2021 was 37 pmp, a majority coming from deceased donors (66%). For patients initiating KRT between 2012-2016, 5-year survival probability was 52%. Compared to the general population, life expectancy was 65% and 68% shorter for males and females receiving dialysis, and 40% and 43% shorter for males and females living with a functioning graft.

Risk factors for postoperative acute kidney injury after major abdominal surgery.

AIM: Acute kidney injury (AKI) worsens the outcome in a significant number of hospitalized patients. Risk models mainly address cardiac surgery, while significantly less attention is paid to AKI after major abdominal surgery (MAS). This study aims to evaluate the incidence, along with risk factors, and intrahospital outcomes of AKI after MAS. MATERIAL AND METHODS: Our retrospective study included 200 adult patients treated with MAS (in the same institution). Exclusion criteria were obstructive nephropathy, contrast-induced nephropathy, and dialysis dependence whether due to end-stage renal disease (ESRD) or AKI before MAS. Data on preoperative, intraoperative, as well as postoperative variables were collected from patients' medical history and electronic medical records. RESULTS: AKI was diagnosed in 33 (16.5%) patients, with 2 patients treated with hemodialysis. The multivariate logistic regression model showed that the number of intraoperative blood transfusions (p = 0.01), pneumonia (p < 0.001), and vasoactive drug use (p = 0.02) were independently associated with postoperative AKI. Each blood transfusion administered increased the risk of developing AKI by 1.41, vasoactive drug use by 4.13, and the risk of AKI in those with pneumonia was 15.32 times higher. The lethal outcome was observed significantly more frequently in patients with AKI (39.4 vs. 4.8%, p < 0.001). CONCLUSION: Identification of independent predictors of AKI after MAS such as the number of transfusions during surgery, sepsis, pneumonia, and the need for vasoactive drug therapy could help prevent AKI and lower the probability of lethal outcomes after MAS.

A Study on Mortality Predictors in Hemodialysis Patients Infected with COVID-19: Impact of Vaccination Status.

The global outbreak of COVID-19, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has prompted significant public health concerns. This study focuses on 442 chronic hemodialysis patients diagnosed with COVID-19, emphasizing the impact of vaccination status on clinical outcomes. The study investigates the correlation between vaccination status and laboratory findings, aiming to identify predictive factors for mortality. Results indicate that vaccination status plays a crucial role in outcomes. Full vaccination, evidenced by two or three doses, is associated with better outcomes, including reduced incidence of bilateral pneumonia and lower risks of complications such as hemorrhage and thrombosis. Laboratory analyses reveal significant differences between vaccinated and unvaccinated patients in parameters like C-reactive protein, ferritin, and white blood cell counts. Univariate and multivariate Cox proportional hazards regression analyses identify several factors influencing mortality, including comorbidities, pneumonia development, and various inflammatory markers. In conclusion among hemodialysis patients affected by COVID-19 infection, vaccination with at least three doses emerges as a protective factor against fatal outcomes. Independent predictors of mortality are CRP levels upon admission, maximum CRP values during the illness and cardiovascular comorbidities. Noteworthy lymphocytopenia during infection exhibits a notable level of specificity and sensitivity in predicting mortality.

Influence of Pretransplant Factors on Posttransplant Anemia Recovery Rate in Primary Deceased Donor Kidney Transplant Recipients.

OBJECTIVES: Our objective was to evaluate the influence of pretransplant risk factors on posttransplant anemia recovery. MATERIALS AND METHODS: This single-center observational retrospective study included 80 deceased donor kidney transplant recipients who had been followed up to 16 months after kidney transplant. Time point of posttransplant anemia recovery was considered the time when hemoglobin of 11.0 g/dL was achieved and maintained for 3 consecutive monthly visits. We collected donor/transplant characteristics (age, sex, hypertension history, cause of death, donor kidney function, expanded criteria donor status, deceased donor score, HLA mismatch, and cold ischemia time) and recipient data (pretransplant hemoglobin, parathyroid hormone, kidney graft function, delayed graft function, acute rejection, infections, surgical bleeding, posttransplant parathyroid hormone, iron stores, and C-reactive protein and tacrolimus levels). We used univariate and multivariate Cox proportional hazards analyses and Kaplan-Meier plots to determine associations between variables and posttransplant anemia recovery rate. P < .05 was considered significant. RESULTS: We identified 62 deceased donors (33 male; mean age 50 ± 15.1 years) and 80 kidney transplant recipients (52 male; mean age 47.0 ± 10.6 years). Mean pretransplant hemoglobin was 11.4 ± 1.5 g/dL. Donor age, deceased donor score, pretransplant parathyroid hormone, posttransplant transferrin saturation (all P < .05), and tacrolimus level (P < .01) were significantly related to posttransplant anemia recovery. Kaplan-Meier curve identified that recipients of deceased donors below 60 years old achieved hemoglobin of 11.0 g/dL more frequently and earlier than recipients of deceased donors above 60 years old (P < .05). CONCLUSIONS: Deceased donor age, deceased donor score, pretransplant serum parathyroid hormone, posttransplant transferrin saturation, and tacrolimus level were significantly associated with posttransplant anemia recovery rate in deceased donor kidney transplant recipients. Anemia recovery was more frequent and earlier in recipients of deceased donors below 60 years than in recipients of donors 60 years old and above.

Serum Resistin, Adenylate Cyclase-Associated Protein 1 Gene Expression, and Carotid Intima-Media Thickness in Patients with End-Stage Renal Disease and Healthy Controls.

BACKGROUND: Human resistin is a proinflammatory cytokine with significant proatherogenic effects which acts through adenylyl cyclase-associated protein 1 (CAP1). Chronic kidney disease (CKD) and end-stage renal disease (ESRD) patients have increased cardiovascular risk and resistin levels. Previous studies indicated resistin significance as a predictor of mortality in CKD. AIMS: We sought to investigate plasma resistin levels, peripheral blood mononuclear cell (PBMC) resistin mRNA, and for the first time CAP1 mRNA levels in ESRD patients and healthy controls. We also sought to investigate the relation of resistin and CAP1 to carotid intima media thickness (CIMT), CD36 gene expression, and matrix metalloproteinase 9 (MMP-9) circulating levels in ESRD patients and healthy controls. METHODS: This study included 33 patients with ESRD and 27 healthy controls. Resistin and MMP-9 levels were measured by ELISA. Resistin, CAP1, and CD36 PBMC mRNA were measured by quantitative PCR. RESULTS: Our study showed that ESRD patients have significantly higher levels of circulatory resistin compared to healthy controls (p < 0.001), while there was no significant difference in resistin mRNA. A significant upregulation of CAP1 and CD36 was observed in the ESRD group (p < 0.001; p < 0.001). Resistin concentration correlated with CIMT in healthy controls (r = 0.512, p = 0.036), and with MMP-9 concentration in ESRD (r = 0.353, p = 0.044) and healthy controls (r = 0.463, p = 0.026). CAP1 correlated positively with CIMT (r = 0.464, p = 0.008) in ESRD, and with CD36 in healthy controls (r = 0.447, p = 0.022) and ESRD (r = 0.824, p < 0.001). CONCLUSION: The obtained data suggest that high levels of circulating resistin acting upon cells with an upregulated CAP1 gene could contribute to the increased inflammation and accelerated atherosclerosis seen in CKD patients.

Association Between Superoxide Dismutase Isoenzyme Gene Expression and Total Antioxidant Status in Patients with an End-Stage Renal Disease

Background: Chronic renal failure, particularly end-stage renal disease, is a serious health problem associated with a high mortality rate. Uremic syndrome leads to increased oxidative stress, inflammation, and dyslipidemia. Aims: To examine superoxide dismutase isoenzyme gene expression in peripheral blood mononuclear cells of patients on hemodialysis and to determine the associations between superoxide dismutase isoenzyme gene expression, oxidative stress, and non-enzymatic antioxidative protection. Study Design: Case control study. Methods: This study included 33 patients on hemodialysis (age, 55.33±15.31 years old) and 33 apparently healthy controls (age, 45.37±8.92 years old). Superoxide dismutase isoenzyme messenger ribonucleic acid levels were determined by real-time polymerase chain reaction. General biochemical parameters, high sensitivity C-reactive protein, total antioxidant status, thiobarbituric acid-reactive substances, and the superoxide anion radical were also determined. Results: Normalized Cu/Zn superoxide dismutase and Mn superoxide dismutase messenger ribonucleic acid levels were significantly higher in patients than controls (p<0.001 and p=0.011). A significant negative correlation was detected between normalized Cu/Zn superoxide dismutase messenger ribonucleic acid levels and total protein, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and total antioxidant status. Normalized Mn superoxide dismutase messenger ribonucleic acid levels were negatively correlated with total protein and total antioxidant status. A multiple regression analysis revealed independent associations between total antioxidant status and normalized Cu/Zn superoxide dismutase (p=0.038) and between total antioxidant status and normalized Mn superoxide dismutase messenger ribonucleic acid levels (p=0.038 and p=0.018, respectively). Conclusion: The superoxide dismutase isoenzyme gene is expressed at a higher rate in patients with end-stage renal failure, probably due to increased oxidative stress and attenuated antioxidative defense. The plasma total antioxidant status is an independent predictor of normalized superoxide dismutase isoenzyme messenger ribonucleic acid levels.

Cytokine Gene Polymorphism Profiles in Kidney Transplant Patients - Association of +1188A/C RS3212227 SNP in the IL12B Gene Prevents Delayed Graft Function.

BACKGROUND AND AIMS: Transplantation is the best treatment option for end stage kidney disease. The most common early complications in post-transplant period are acute rejection (AR) of the graft and delayed graft function (DGF). The underlying mechanisms in these events are heterogeneous and at least in part involve cytokine genes which regulate immune response to allograft. We have investigated whether functional single nucleotide polymorphisms (SNP) in the genes encoding IFN-γ (IFNG), TNF (TNFA), IL-10 (IL10) and p40 subunit of IL-12/IL-23 (IL12B) could predict risk of AR and DGF in kidney allograft recipients. METHODS: Our study involved 152 kidney transplant recipients on standard immunosuppressive regimen which included calcineurin inhibitors, mycophenolic acid derivatives and corticosteroids. Genotyping of IFNG, TNFA, IL10 and IL12B was performed using commercial TaqMan assays. RESULTS: We found association between the carriers of AA genotype of IL12B +1188A/C polymorphism (rs3212227) and a lower rate of DGF (p = 0.037, OR = 0.45, 95% CI = 0.21-0.96), implying protective role of A allele in the pathogenesis of DGF in kidney transplant recipients, whereas no such association was observed with AR. None of the analyzed SNPs in TNFA (-308G/A), IFNG (+874T/A), IL10 (-1082G/A, -819T/C, -592C/A) were associated with AR or DGF in our patients. CONCLUSIONS: Our study shows a preliminary evidence that the AA genotype of rs3212227 SNP in the IL12B gene might be associated with a lower risk for DGF after kidney transplantation. In the future, additional well-designed large studies are required for the validation of our results.

The importance of MDR1 gene polymorphisms for tacrolimus dosage.

Polymorphisms of the multi drug resistance (MDR1) gene cause variability in P-glycoprotein mediated metabolism of tacrolimus. The aim of this study was to examine the relationship between MDR1 gene single nucleotide polymorphisms (SNPs) and their haplotypes with dosage of tacrolimus in kidney transplant recipients who were cytochrome (CYP) 3A5*3 homozygotes. This study included 91 kidney transplant recipients followed two years after transplantation. Detection and analysis of MDR1 gene polymorphisms in positions C1236T, G2677T/A and C3435T were performed using PCR method. Patients with variant alleles for SNPs G2677T/A and C3435T required higher doses of tacrolimus and had a lower level/dose (L/D) ratio than patients with wild alleles or heterozygotes. That difference was the most obvious for SNP G2677T/A where TT homozygotes required significantly higher doses of tacrolimus during whole follow-up. Their L/D was significantly lower in the first month after transplantation. Recipients with CTT/TTT haplotype also had lower L/D than those with CGC/TTT and CGC/CGC, significantly in the 10th and 20th days after transplantation respectively (p<0.05). Our results demonstrate that TT homozygotes at positions G2677T/A and C3435T required a higher tacrolimus dose than those with wild alleles or heterozygotes. It may be helpful in the prevention of tacrolimus nephrotoxicity early after transplantation.

Downregulation of AdipoR1 is Associated with increased Circulating Adiponectin Levels in Serbian Chronic Kidney Disease Patients.

BACKGROUND: Since the rise in plasma adiponectin levels in chronic kidney disease (CKD) patients has not yet been elucidated, we sought to investigate if patients on hemodialysis (HD) have altered expression of adiponectin receptors in peripheral blood mononuclear cells (PBMCs) compared to healthy subjects. METHODS: This study included 31 patients with chronic kidney disease on HD and 33 healthy subjects (CG). Circulating adiponectin levels were measured by ELISA while AdipoR1 and AdipoR2 mRNA levels in PBMCs were determined by real-time PCR. RESULTS: Plasma adiponectin levels were significantly higher in patients compared to control group (P=0.036). After adjustment for age, BMI and creatinine, this difference became even more significant (P=0.004). In both groups adiponectin correlated with creatinine (CG: r=-0.472, P=0.006; HD: r=-0.375, P=0.038), triglycerides (CG: r=- 0.490, P=0.004; HD: r=-0.488, P=0.005), insulin (CG: r=-0.386, P=0.038; HD: r=-0.506, P=0.012) and high density lipoprotein cholesterol (HDL-C) (CG: r=-0.672, P<0.001; HD: r=-0.584, P=0.001). Significantly lower expression of PBMCs AdipoR1 mRNA was found in patients compared to CG (P=0.034), while AdipoR2 mRNA levels were similarly expressed in PBMCs in both groups. CONCLUSIONS: Complex pathological processes in CKD cause downregulation of AdipoR1 which could ultimately influence AdipoR1 protein levels leading to a state of ≫adiponectin resistance≪.

[High rate of native arteriovenous fistulas: how to reach this goal?].

The types of vascular accesses for hemodialysis (HD) include the native arteriovenous fistula (AVF), arteriovenous graft (AVG) and central venous catheter (CVC). Adequately matured native AVF is the best choice for HD patients and a high percentage of its presence is the goal of every nephrologist and vascular surgeon. This paper analyses the number and type of vascular accesses for HD performed over a 10-year period at the Clinical Center of Serbia, and presents the factors of importance for the creation of such a high number of successful native AVF (over 80%). Such a result is, inter alia, the consequence of the appointment of the Vascular Access Coordinator, whose task was to improve the quality of care of blood vessels in the predialysis period as well as of functional vascular accesses, and to promote the cooperation among different specialists within the field. Vascular access is the "lifeline"for HD patients. Thus, its successful planning, creation and monitoring of vascular access is a continuous process that requires the collaboration and cooperation of the patient, nephrologist, vascular surgeon, radiologist and medical personnel.

Association of small, dense low-density lipoprotein cholesterol and galectin-3 in patients with chronic kidney disease.

BACKGROUND: Dyslipidemia is a common feature of chronic kidney disease (CKD). Although it has been observed that the pattern of lipid abnormalities can vary according to the stage of CKD, there is lack of data concerning the distribution of lipoprotein subclasses at various stages of the disease. In addition, association of proatherogenic small, dense low-density lipoprotein (sdLDL) subclasses with markers of inflammation, such is galectin-3, is not sufficiently explored. The aim of this study was to analyze concentrations and relative proportions of sdLDL-cholesterol (sdLDL-C) and galectin-3 in patients with CKD, with respect to the stage of the disease. Also, we sought possible independent associations of galectin-3 and sdLDL-C. METHODS: The study involved 100 hemodialysis (HD) and 50 pre-dialysis patients, together with 94 healthy individuals. SdLDL-C was measured by heparin-magnesium precipitation method. Galectin-3 was measured by ELISA technique. RESULTS: Galectin-3 levels were higher in pre-dialysis and HD patients than in the control group (p < 0.01). The concentration of sdLDL-C was highest in the pre-dialysis group and lowest in HD patients (p < 0.01). CKD patients with increased galectin-3 concentrations had significantly higher relative proportions of cholesterol in sdLDL (% sdLDL-C) than their counterparts with lower galectin-3 levels (p < 0.05). Relative proportion of sdLDL-C was shown to be an independent determinant of galectin-3 concentration. CONCLUSIONS: Our results demonstrated alterations in concentrations and proportions of sdLDL-C according to the stages of CKD. The observed independent associations of % sdLDL-C and galectin-3 provide further insight into their complex interaction during the progression of atherosclerosis in CKD.

Risk factors associated with coronary artery calcification should be examined before kidney transplantation.

The best treatment for end stage renal disease (ESRD) patients is kidney transplantation, but the renal transplant recipients still have a higher incidence of cardiovascular events compared with general population. Cardiovascular risk factors were imposed long before ESRD, as the majority of patients starting dialysis or kidney transplantation already have signs of advanced atherosclerosis. Artery calcification is an organized, regulated process similar to bone formation. Coronary artery calcification (CAC) is found frequently in advanced atherosclerotic lesions and could be a useful marker of them. We evaluated the prevalence of CAC in 49 stable renal transplant recipients and in 48 age- and gender-matched patients with chronic kidney disease (CKD) in stages 2-5 not requiring dialysis to assess risk factors associated with CAC. Computed tomography was used for CAC detection and quantification (CAC score). The prevalence of CAC was 43.8% in transplant recipients and 16.7% in CKD patients (p < 0.001). Transplant recipients with CAC were significantly older and had longer duration of CKD and/or dialysis than recipients without CAC. In contrast, the serum levels of fetuin A (an inhibitor of vascular calcification) and albumin were significantly lower in CKD patients with CAC than those without CAC. During the observation period (30 months), 30 patients, including 23 CKD patients, began dialysis, and 4 transplant recipients and 2 CKD patients died. Independent predictors of mortality were age, serum amyloid A and the CAC score. In conclusion, the examination and prevention of risk factors associated with atherosclerosis should be started at the beginning of renal failure.