The Influence of Tacrolimus Exposure and Metabolism on the Outcomes of Kidney Transplants.

Tacrolimus (TAC) has a narrow therapeutic window and patient-specific pharmacokinetic variability. In our study, we analyzed the association between TAC exposure, metabolism, and kidney graft outcomes (function, rejection, and histological lesions). TAC trough (C0), coefficient of variation (TAC CV), concentration/dose ratio (C/D), and biomarkers related to kidney injury molecule-1 (KIM-1) and neutrophil gelatinase lipocalin (NGAL) were analyzed. We examined 174 patients who were subjected to a triple immunosuppressive regimen and underwent kidney transplantation between 2017 and 2022. Surveillance biopsies were performed at the time of kidney implantation and at three and twelve months after transplantation. We classified patients based on their Tac C/D ratios, classifying them as fast (C/D ratio < 1.05 ng/mL × 1/mg) or slow (C/D ratio ≥ 1.05 ng/mL × 1/mg) metabolizers. TAC exposure/metabolism did not significantly correlate with interstitial fibrosis/tubular atrophy (IF/TA) progression during the first year after kidney transplantation. TAC CV third tertile was associated with a higher chronicity score at one-year biopsy. TAC C/D ratio at three months and Tac C0 at six months were associated with rejection during the first year after transplantation. A fast TAC metabolism at six months was associated with reduced kidney graft function one year (OR: 2.141, 95% CI: 1.044-4.389, p = 0.038) and two years after transplantation (OR: 4.654, 95% CI: 1.197-18.097, p = 0.026), and TAC CV was associated with reduced eGFR at three years. uNGAL correlated with IF/TA and chronicity scores at three months and negatively correlated with TAC C0 and C/D at three months and one year. Conclusion: Calculating the C/D ratio at three and six months after transplantation may help to identify patients at risk of suffering acute rejection and deterioration of graft function.

Immune Response after Anti-SARS-CoV-2 mRNA Vaccination in Relation to Cellular Immunity, Vitamin D and Comorbidities in Hemodialysis Patients.

In the global threat of SARS-CoV-2, individuals undergoing maintenance dialysis represent a vulnerable population with an increased risk of severe COVID-19 outcomes. Therefore, immunization against SARS-CoV-2 is an essential component of healthcare strategy for these patients. Existing data indicate that they tend to exhibit a reduced immune response to vaccines compared to the general population. Our study aimed to assess both humoral and cellular immune responses following two doses of an anti-SARS-CoV-2 mRNA vaccine, an ability to maintain adequate antibody titers over time, and potential relations with vitamin D, comorbidities and other factors in hemodialysis patients based on a single center experience. A total of 41/45 patients (91.1%) responded to the second dose of the anti-SARS-CoV-2 mRNA vaccine. The titer of anti-SARS-CoV-2 IgG class antibodies and levels of T cells three to four weeks after vaccination were lower in dialysis patients than in healthy controls. Antibodies titer in dialysis patients had a positive correlation with B lymphocytes and was related to cardiovascular diseases. The level of CD4+ cells had a negative correlation with hemodialysis vintage, as did the vitamin D level with post-vaccination seroconversion and decline in anti-SARS-CoV-2 antibodies titer during six months after vaccination. Hemodialysis patients had decreased amounts of CD4+ and CD8+ cells and lower levels of anti-SARS-CoV-2 antibodies than healthy controls. Therefore, chronic hemodialysis could lead to diminished cellular immunity and humoral immune response to the anti-SARS-CoV-2 mRNA vaccination and reduced protection from COVID-19. Comorbidity in cardiovascular diseases was associated with a lower level of specific anti-SARS-CoV-2 antibody titer. Vitamin D may be important in maintaining stable levels of anti-SARS-CoV-2 antibodies, while the duration of dialysis treatment could be one of the factors decreasing anti-SARS-CoV-2 antibody titer and determining lower CD4+ cell counts.

Deceased Kidney Donor Biomarkers: Relationship between Delayed Kidney Function and Graft Function Three Years after Transplantation.

With an increasing number of marginal donors, additional methods for the evaluation of cadaveric kidney quality are required. This study aimed to evaluate pretransplant deceased donor serum (s) and urine (u) biomarkers, including neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), interleukin-18, and C-X-C motif chemokine 10 (CXCL10) for predicting early and late graft function. In total, 43 deceased kidney donors and 76 corresponding recipients were enrolled. Delayed graft function (DGF) occurred in 27.6% of cases. sIL-18, sKIM-1, uNGAL, and uKIM-1 were predictors of DGF. A model incorporating sIL-18, uKIM-1, and clinical factors was developed to predict DGF (AUROC 0.863). Univariate analysis showed a negative association between uKIM and graft eGFR at 6, 12, 24, and 36 months, but this was not confirmed in the multivariate analysis. In conclusion, we report a superior performance of donor biomarkers for predicting DGF and later graft function over serum creatinine. Higher levels of donor sIL-18 and uKIM in conjunction with expanded-criteria donors and longer cold ischemia times predicted DGF. With no renal tubular damage in zero-time donor biopsies, higher pretransplant urine and serum NGAL levels were associated with better allograft function one year after transplantation, and sNGAL with graft function three years after transplantation.

Drugs with a negative impact on cognitive function (Part 1): chronic kidney disease as a risk factor.

People living with chronic kidney disease (CKD) frequently suffer from mild cognitive impairment and/or other neurocognitive disorders. This review in two parts will focus on adverse drug reactions resulting in cognitive impairment as a potentially modifiable risk factor in CKD patients. Many patients with CKD have a substantial burden of comorbidities leading to polypharmacy. A recent study found that patients seen by nephrologists were the most complex to treat because of their high number of comorbidities and medications. Due to polypharmacy, these patients may experience a wide range of adverse drug reactions. Along with CKD progression, the accumulation of uremic toxins may lead to blood-brain barrier (BBB) disruption and pharmacokinetic alterations, increasing the risk of adverse reactions affecting the central nervous system (CNS). In patients on dialysis, the excretion of drugs that depend on kidney function is severely reduced such that adverse and toxic levels of a drug or its metabolites may be reached at relatively low doses, unless dosing is adjusted. This first review will discuss how CKD represents a risk factor for adverse drug reactions affecting the CNS via (i) BBB disruption associated with CKD and (ii) the impact of reduced kidney function and dialysis itself on drug pharmacokinetics.

The Role of Pre- and Post-Transplant Hydration Status in Kidney Graft Recovery and One-Year Function.

Background and Objectives: Early improvements to graft function are crucial for good outcomes in kidney transplantation (kTx). Various factors can influence early graft function. This study aimed to evaluate the pre- and post-transplant hydration statuses of kTx recipients using bioimpedance analysis (BIA) and lung ultrasonography (LUS) and to investigate the hydration status' relationship with the function of the transplanted kidney during the first year after transplantation. Materials and Methods: This observational prospective cohort study included deceased kidney recipients transplanted in the Hospital of the Lithuanian University of Health Sciences between September 2016 and January 2023. BIA and LUS were performed before transplantation, on days 3 and 7, and at discharge. Data on recipient and donor clinical characteristics were collected. Graft function was evaluated according to the serum creatinine reduction ratio and the need for dialysis. Hydration status was evaluated by calculating B-lines (BL) on LUS and the ratio of extracellular/total body water on BIA. Results: Ninety-eight kTx recipients were included in the study. Patients with immediate graft function (IGF) were compared to those with slow or delayed graft function (SGF + DGF). Recipients in the SGF + DGF group had a higher sum of BL on LUS before transplantation. After transplantation in early postoperative follow-up, both groups showed hyperhydration as determined by BIA and LUS. After one year, recipients with no BL before transplantation had better graft function than those with BL. Logistic regression analysis showed that having more than one BL in LUS was associated with a 2.5 times higher risk of SGF or DGF after transplantation. Conclusions: This study found that lung congestion detected by LUS before kTx was associated with slower graft recovery and worse kidney function after 1 year. Meanwhile, the hyperhydration status detected by BIA analysis did not correlate with the function of the transplanted kidney.

First-year mortality in incident dialysis patients: results of the Peridialysis study.

BACKGROUND: Controversy surrounds which factors are important for predicting early mortality after dialysis initiation (DI). We investigated associations of predialysis course and circumstances affecting planning and execution of DI with mortality following DI. METHODS: Among 1580 patients participating in the Peridialysis study, a study of causes and timing of DI, we registered features of predialysis course, clinical and biochemical data at DI, incidence of unplanned suboptimal DI, contraindications to peritoneal dialysis (PD) or hemodialysis (HD), and modality preference, actual choice, and cause of modality choice. Patients were followed for 12 months or until transplantation. A flexible parametric model was used to identify independent factors associated with all-cause mortality. RESULTS: First-year mortality was 19.33%. Independent factors predicting death were high age, comorbidity, clinical contraindications to PD or HD, suboptimal DI, high eGFR, low serum albumin, hyperphosphatemia, high C-reactive protein, signs of overhydration and cerebral symptoms at DI. Among 1061 (67.2%) patients who could select dialysis modality based on personal choice, 654 (61.6%) chose PD, 368 (34.7%) center HD and 39 (3.7%) home HD. The 12-months survival did not differ significantly between patients receiving PD and in-center HD. CONCLUSIONS: First-year mortality in incident dialysis patients was in addition to high age and comorbidity, associated with clinical contraindications to PD or HD, clinical symptoms, hyperphosphatemia, inflammation, and suboptimal DI. In patients with a "free" choice of dialysis modality based on their personal preferences, PD and in-center HD led to broadly similar short-term outcomes.

Immune Response after SARS-CoV-2 Vaccination in Kidney Transplant Patients.

Background and Objectives: The prospective study was conducted to evaluate humoral and cellular immune responses after two doses of BNT162b2 (Pfizer-BioNTech) vaccine and possible relation with other factors (medication, etc.) in kidney transplant patients. Materials and Methods: Out of 167 vaccinated patients, 136 agreed to a follow-up visit three to six weeks after vaccination. Results: Only 39 patients (29%) developed antibody response against SARS-CoV-2 (≥35.2 binding antibody units (BAU)/mL) after full vaccination. Multivariate binary logistic regression analysis showed that predictive factors for good antibody response to the COVID-19 vaccine were better kidney function, higher hemoglobin level, and no use of mycophenolate mofetil for immunosuppression. For seropositive kidney transplant patients there was a significant negative correlation between anti-SARS-CoV-2 antibody titer and CD4/CD8 ratio (Spearman's correlation coefficient -0.4, p = 0.02), percentage of CD19+ cells (r = -0.37, p = 0.02), and a positive correlation with percentage of CD8+ cells (r = 0.4, p = 0.01). There was an increase of total leucocyte count after vaccination in the total studied population, and in the group of responders. Conclusions: Only one third of kidney transplant patients develop sufficient antibody responses after full COVID-19 vaccination with Pfizer-BioNTech. Better kidney function, higher hemoglobin level, and no use of mycophenolate mofetil for immunosuppression increases the adequacy of response. The antibody titers correlated positively with relative number of CD8+ cells and negatively with CD4/CD8 ratio in responders.

Cognitive disorders in patients with chronic kidney disease: specificities of clinical assessment.

Neurocognitive disorders are frequent among chronic kidney disease (CKD) patients. Identifying and characterizing cognitive impairment (CI) can help to assess the ability of adherence to CKD risk reduction strategy, identify potentially reversible causes of cognitive decline, modify pharmacotherapy, educate the patient and caregiver and provide appropriate patient and caregiver support. Numerous factors are associated with the development and progression of CI in CKD patients and various conditions can influence the results of cognitive assessment in these patients. Here we review clinical warning signs that should lead to cognitive screening; conditions frequent in CKD at risk to interfere with cognitive testing or performance, including specificities of cognitive assessment in dialysis patients or after kidney transplantation; and available tests for screening and observed cognitive patterns in CKD patients.

Assessment of Fluid Status by Bioimpedance Analysis and Central Venous Pressure Measurement and Their Association with the Outcomes of Severe Acute Kidney Injury.

Background and Objectives: Fluid disbalance is associated with adverse outcomes in critically ill patients with acute kidney injury (AKI). In this study, we intended to assess fluid status using bioimpedance analysis (BIA) and central venous pressure (CVP) measurement and to evaluate the association between hyperhydration and hypervolemia with the outcomes of severe AKI. Materials and Methods: A prospective study was conducted in the Hospital of the Lithuanian University of Health Sciences Kauno Klinikos. Forty-seven patients treated at the Intensive Care Unit (ICU) with severe AKI and a need for renal replacement therapy (RRT) were examined. The hydration level was evaluated according to the ratio of extracellular water to total body water (ECW/TBW) of bioimpedance analysis and volemia was measured according to CVP. All of the patients were tested before the first hemodialysis (HD) procedure. Hyperhydration was defined as ECW/TBW > 0.39 and hypervolemia as CVP > 12 cm H2O. Results: According to bioimpedance analysis, 72.3% (n = 34) of patients were hyperhydrated. According to CVP, only 51.1% (n = 24) of the patients were hypervolemic. Interestingly, 69.6% of hypovolemic/normovolemic patients were also hyperhydrated. Of all study patients, 57.4% (n = 27) died, in 29.8% (n = 14) the kidney function improved, and in 12.8% (n = 6) the demand for RRT remained after in-patient treatment. A tendency of higher mortality in hyperhydrated patients was observed, but no association between hypervolemia and outcomes of severe AKI was established. Conclusions: Three-fourths of the patients with severe AKI were hyperhydrated based on bioimpedance analysis. However, according to CVP, only half of these patients were hypervolemic. A tendency of higher mortality in hyperhydrated patients was observed.

Molecular Characterization and Seroprevalence of Hepatitis E Virus in Inflammatory Bowel Disease Patients and Solid Organ Transplant Recipients.

Seroprevalence rates and molecular characterization of hepatitis E virus (HEV) prevalent in the Lithuanian human population has not yet been evaluated. Immunosuppressed individuals have been recognized as a risk group for chronic hepatitis due to HEV genotype 3 (HEV-3) infections. The objectives of the present study were to determine prevalence rates of anti-HEV antibodies among inflammatory bowel disease (IBD) patients and solid organ transplant (SOT) recipients, to isolate and characterize HEV strain present in the Lithuanian human population, and to investigate its capacity to infect non-human primate (MARC-145 and Vero), swine (PK-15) and murine (Neuro-2a) cells in vitro. In the present study, the significant difference of anti-HEV IgG prevalence between healthy (3.0% (95% CI 0-6.3)) and immunosuppressed individuals (12.0% [95% CI 8.1-15.9]) was described. Moreover, our findings showed that anti-HEV IgG seropositivity can be significantly predicted by increasing age (OR = 1.032, p < 0.01), diagnosis of IBD (OR = 4.541, p < 0.01) and reception of SOT (OR = 4.042, <0.05). Locally isolated HEV strain clustered within genotype 3i subtype of genotype 3 and was capable of infecting MARC-145 cells. This study demonstrates higher HEV seroprevalence in the risk group compared to healthy control individuals without confidence interval overlap. The high level of genetic homology between human and animal strains in Lithuania and the capacity of locally isolated strains to infect cells of non-human origin suggests its potential for zoonotic transmission.

Suboptimal dialysis initiation is associated with comorbidities and uraemia progression rate but not with estimated glomerular filtration rate.

BACKGROUND: Despite early referral of uraemic patients to nephrological care, suboptimal dialysis initiation (SDI) remains a common problem associated with increased morbimortality. We hypothesized that SDI is related to pre-dialysis care. METHODS: In the 'Peridialysis' study, time and reasons for dialysis initiation (DI), clinical and biochemical data and centre characteristics were registered during the pre- and peri-dialytic period for 1583 end-stage kidney disease patients starting dialysis over a 3-year period at 15 nephrology departments in the Nordic and Baltic countries to identify factors associated with SDI. RESULTS: SDI occurred in 42%. Risk factors for SDI were late referral, cachexia, comorbidity (particularly cardiovascular), hypoalbuminaemia and rapid uraemia progression. Patients with polycystic renal disease had a lower incidence of SDI. High urea and C-reactive protein levels, acidosis and other electrolyte disorders were markers of SDI, independently of estimated glomerular filtration rate (eGFR). SDI patients had higher eGFR than non-SDI patients during the pre-dialysis period, but lower eGFR at DI. eGFR as such did not predict SDI. Patients with comorbidities had higher eGFR at DI. Centre practice and policy did not associate with the incidence of SDI. CONCLUSIONS: SDI occurred in 42% of all DIs. SDI was associated with hypoalbuminaemia, comorbidity and rate of eGFR loss, but not with the degree of renal failure as assessed by eGFR.

A roadmap for optimizing chronic kidney disease patient care and patient-oriented research in the Eastern European nephrology community.

Chronic kidney disease (CKD) is a major health problem because of its high prevalence, associated complications and high treatment costs. Several aspects of CKD differ significantly in the Eastern European nephrology community compared with Western Europe because of different geographic, socio-economic, infrastructure, cultural and educational features. The two most frequent aetiologies of CKD, DM and hypertension, and many other predisposing factors, are more frequent in the Eastern region, resulting in more prevalent CKD Stages 3-5. Interventions may minimize the potential drawbacks of the high prevalence of CKD in Eastern Europe, which include several options at various stages of the disease, such as raising public, medical personnel and healthcare authorities awareness; early detection by screening high-risk populations; preventing progression and CKD-related complications by training health professionals and patients; promoting transplantation or home dialysis as the preferred modality; disseminating and implementing guidelines and guided therapy and encouraging/supporting country-specific observational research as well as international collaborative projects. Specific ways to significantly impact CKD-related problems in every region of Europe through education, science and networking are collaboration with non-nephrology European societies who have a common interest in CKD and its associated complications, representation through an advisory role within nephrology via national nephrology societies, contributing to the training of local nephrologists and stimulating patient-oriented research. The latter is mandatory to identify country-specific kidney disease-related priorities. Active involvement of patients in this research via collaboration with the European Kidney Patient Federation or national patient federations is imperative to ensure that projects reflect specific patient needs.

Factors influencing renal graft survival: 7-Year experience of a single center.

BACKGROUND AND OBJECTIVE: The demand for kidney transplants exceeds the existing supply. This leads to a recently growing interest of research in the area of factors that could prolong graft long-term outcomes and survival. In Lithuania, approximately 90% of kidney transplantations are from deceased donors. Donor organs are received and shared only inside the country territory in Lithuania; therefore, donor data is accurate and precise. This study was performed to present particularities of kidney transplantation data in Lithuania and to identify the effect of donor and recipient factors and histologic findings on renal graft outcomes. The aim of this study was to identify the effect of donor and recipient factors and histologic findings on renal graft outcomes. MATERIALS AND METHODS: We analyzed the influence of deceased donor and recipient factors and histological findings on the graft function in 186 renal transplant patients. Graft survival was estimated within the first year after transplantation. RESULTS: The donors and recipients were older in worse eGFR group 1 year after transplantation. Dissimilarity of degree of glomerulosclerosis (GS), interstitial fibrosis (IF) and arteriolar hyalinosis (AH) were significant in inferior and superior renal function groups (GS >20% 11.4 vs. 0%, P=0.017; IF 9.3 vs. 0%, P=0.034; AH 69 vs. 26.2%, P<0.001). Nine independent variables were significantly associated with a worse renal transplant function 1 year posttransplantation: AH (OR=6.287, P<0.001), an episode of urinary tract infection (OR=2.769, P=0.020), acute graft rejection (OR=3.605, P=0.037), expanded criteria (OR=4.987, P=0.001), female gender donors (OR=3.00, P=0.014), cerebrovascular disease caused donor brain death (OR=5.00, P=0.001), donor's age (OR=1.07, P<0.001), and recipient's age (OR=1.047, P=0.022). Worse renal graft survival 1 year posttransplantation was associated with a delayed graft function and a higher level of glomerulosclerosis in time-zero biopsy. CONCLUSIONS: Donor factors, such as age, female gender, brain death of cerebrovascular cause and expanded criteria donor status had a significant negative impact on the renal graft function 1 year after transplantation. Recipients' age, urinary tract infection and acute graft rejection episodes after transplantation were associated with a worse kidney function 1 year after transplantation. Lower 1-year graft survival was related to a delayed graft function (DGF) and a higher degree of glomerulosclerosis.

Mortality prediction in patients with acute kidney injury requiring renal replacement therapy after cardiac surgery.

BACKGROUND AND OBJECTIVE: Acute kidney injury (AKI) is a common and potentially serious postoperative complication after cardiac surgery, and it remains a cause of major morbidity and mortality. The aim of our study was to assess the prognostic illness severity score and to estimate the significant risk factors for poor outcome of patients with AKI requiring renal replacement therapy (RRT) after cardiac surgery. MATERIALS AND METHODS: We retrospectively analyzed data of adult (>18 years) patients (n=111) who underwent open heart surgery and had developed AKI with need for RRT. Prognostic illness severity scores were calculated and perioperative risk factors of lethal outcome were assessed at the RRT initiation time. We defined three illness severity scores: Acute Physiology and Chronic Health Evaluation (APACHE II) as a general score, Sequential Organ Failure Assessment (SOFA) as an organ failure score, and Liano score as a kidney-specific disease severity score. Logistic regression was also used for the multivariate analysis of mortality risk factors. RESULTS: Hospital mortality was 76.5%. More than 7% of patients remained dialysis-dependent after their discharge from the hospital. The prognostic abilities of the scores were assessed for their discriminatory power. The area under the receiver-operating characteristic (ROC) curve of SOFA score was 0.719 (95% CI, 0.598-0.841), of Liano was 0.661 (95% CI, 0.535-0.787) and 0.668 (95% CI, 0.550-0.785) of APACHE II scores. From 16 variables analyzed for model selection, we reached a final logistic regression model, which demonstrated four variables significantly associated with patients' mortality. Glasgow coma score<14 points (OR=3.304; 95% CI, 1.130-9.662; P=0.003), mean arterial blood pressure (MAP)<63.5mmHg (OR=3.872; 95% CI, 1.011-13.616; P=0.035), serum creatinine>108.5µmol/L (OR=0.347; 95% CI, 0.123-0.998; P=0.046) and platelet count<115×109/L (OR=3.731; 95% CI, 1.259-11.054; P=0.018) were independent risk factors for poor patient outcome. CONCLUSIONS: Our study demonstrated that SOFA score estimation is the most accurate to predict the fatal outcome in patients with AKI requiring RRT after cardiac surgery. Lethal patient outcome is related to Glasgow coma score, mean arterial blood pressure, preoperative serum creatinine and postoperative platelet count.

Hepcidin serum levels and resistance to recombinant human erythropoietin therapy in hemodialysis patients.

OBJECTIVE: The aim of this study was to analyze the factors that are associated with the response to erythropoiesis-stimulating agents (ESAs) and its association with hospitalization and mortality rates; to evaluate the serum hepcidin level and its associations with iron profile, inflammatory markers, ESA responsiveness, and mortality; and to determine independent factors affecting ERI and hepcidin. MATERIALS AND METHODS: To evaluate a dose-response effect of ESAs we used the erythropoietin resistance index (ERI). Patients were stratified in two groups: nonresponders and responders (ERI>15, n=20, and ERI ≤15U/kg/week/g per 100mL, n=153, respectively). Hematological data, hepcidin levels, iron parameters, inflammatory markers, hospitalization and mortality rates were compared between the groups. Multiple regression analysis was used to determine independent factors affecting ERI and hepcidin. RESULTS: C-reactive protein (CRP) (ß=0.078, P=0.007), albumin (ß=-0.436, P=0.004), body mass index (ß=-0.374, P<0.001), and hospitalization rate per year (ß=3.017, P<0.001) were found to be significant determinants of ERI in maintenance hemodialysis (MHD) patients. Inadequate dialysis was associated with higher ERI. Patients with concomitant oncological diseases had higher ERI (31.2±12.4 vs 9.7±8.1U/kg/week/g per 100mL, P=0.002). The hepcidin level was 158.51±162.57 and 120.65±67.28ng/mL in nonresponders and responders, respectively (P=0.33). Hepcidin correlated directly with ERI, dose of ESAs, ferritin and inversely with Hb, transferrin saturation, and albumin. ERI (ß=4.869, P=0.002) and ferritin (ß=0.242, P=0.003) were found to be significant determinants of hepcidin in MHD patients. The hospitalization rate per year was 2.35±1.8 and 1.04±1.04 in nonresponders and responders, respectively (P=0.011). The mean length of one hospitalization was 25.12±21.26 and 10.82±17.25 days, respectively (P=0.012). Death occurred in 30% of the patients from the responders' group and in 50% from the nonresponders' group (P=0.289). The mean hepcidin concentration of patients who died was 141.9±129.62ng/mL and who survived, 132.98±109.27ng/mL (P=0.797). CONCLUSIONS: CRP, albumin, BMI, and hospitalization rate per year were found to be significant determinants of ERI in MHD patients. Inadequate dialysis was associated with higher epoetin requirements. There were no difference in patient mortality by ERI, but a significant difference in hospitalization rates and mean length of one hospitalization was revealed. A significant positive relation between hepcidin and ERI was revealed. ERI and ferritin were found to be significant determinants of hepcidin in MHD patients. Hepcidin was not related to mortality.

Association between vascular calcification assessed by simple radiography and non-fatal cardiovascular events in hemodialysis patients.

BACKGROUND: Vascular calcification (VC) is one of the factors associated with cardiovascular mortality in hemodialysis (HD) patients. Recommendations concerning screening for VC differ. Possible ability to prevent and reversibility of VC are major subjects on debate whether screening for VC could improve outcomes of renal patients. The objective of the study was to evaluate the significance of simple vascular calcification score (SVCS) based on plane radiographic films and to test its association with non-fatal cardiovascular events in patients on chronic HD. METHODS: A study population consisted of 95 prevalent HD patients in the HD unit of Hospital of Lithuanian University of Health sciences Kaunas Clinics. Clinical data and laboratory tests information were collected from medical records. SVCS was evaluated as it is described by Adragao et al. After measurement of VC, HD patients were observed for novel non-fatal cardiovascular events. RESULTS: Patients were divided into two groups: SVCS≥3 (57 patients [60%]) and <3 (38 patients [40%]). The Kaplan-Meier survival curves show a significant difference in non-fatal cardiovascular events in the group with SVCS≥3 vs. <3 group (26.3% vs. 7.8%; log rank 5,49; P=0.018). Multivariate Cox regression analysis confirmed a negative impact of VC, hyperphosphatemia, and lower ejection fraction on cardiovascular events. No statistically significant differences were observed comparing parameters of Ca-P metabolism disorders between groups with different SVCS. On separate analysis, the presence of VC in hands was also associated with higher rate of novel cardiovascular events (score 0 goup-5 events [10.6%] vs. score≥1 group-13 events [27%], log rank P=0.035). CONCLUSION: VC assessed by simple and inexpensive radiological method was an independent predictor of novel non-fatal cardiovascular events in HD patients.

Changes of etiology, incidence and outcomes of severe acute kidney injury during a 12-year period (2001-2012) in large university hospital.

BACKGROUND: Despite improvement in the quality of critical care, the incidence and mortality of acute kidney injury (AKI) continues to rise. The aim of our study was to analyze the changes during a 12-year period in etiology, incidence and outcomes of severe AKI, which required dialysis, in a large single centre. METHODS: We performed retrospective analysis of all the patients (n=3215) with severe AKI hospitalized and dialysed in the hospital of Lithuanian university of health sciences Kauno Klinikos (HLUHS KK) during the period of 2001-2012. RESULTS: During a 12-year period, the incidence of severe AKI increased from 154 to 597 cases/p.m.p. The mean age of the patients increased from 58.2±19.2 years in 2001 to 65.7±17 years in 2012 (P<0.001). The number of men (n=2012; 62.6%) was significantly higher than that of women (n=1201; 37.4%; P<0.001). The causes of severe AKI were renal (n=1128; 35.1%), prerenal (n=642; 20%), obstructive (n=310; 9.6%) and in 12.7% of the patients-multifactorial. Overall, the most frequent cause of AKI was acute tubular necrosis (n=1069; 33.2%). The renal replacement therapy (RRT) was discontinued due to improved kidney function in 45.3% of cases. 8.1% of the patients remained dialysis dependent. The mortality rate was 44%. CONCLUSIONS: During a 12-year period, the number of the patients with severe AKI increased three times with the predominance of men and elderly people. There was an observed increase in multifactorial causes of severe AKI; however, ATN remained dominant over the decade. The mortality rate remained high, almost half of the patients died, less than 10% remained dialysis dependent, the rest had the improvement of renal function.

Nationwide renal biopsy data in Lithuania 1994-2012.

BACKGROUND: Our aim was to evaluate the incidence of biopsy-proven kidney diseases in Lithuania and to compare their changes in three different time intervals. All Lithuanian kidney biopsies were performed in the National Center of Pathology, enabling analysis at the national level. METHODS: The native kidney biopsy data were reviewed, and incidence of renal disorders and patient demographics were compared during three time intervals: 1994-1999, 2000-2006, and 2007-2012. RESULTS: A total of 5,368 kidney biopsies were performed, including 3,640 native kidney and 1,728 kidney transplant biopsies; 59.5% (2,165) of the native kidney biopsies were classified as primary glomerulopathies. The most common entity was IgA nephropathy (737; 34.0%), followed by focal segmental glomerulosclerosis (285; 13.2%) and membranoproliferative glomerulonephritis (256; 11.8%). Prominent decrease in incidence of membranoproliferative glomerulonephritis (16.8 to 8.7% from the first to third time interval) and increase in (mainly, pauci-immune) crescentic glomerulonephritis (6.2 to 15.3%) were noted over the study period. In a subgroup of 427 pediatric native kidney biopsies, IgAN accounted for 24.9% of biopsies. The incidence of MCNS increased dramatically from the first to third time interval (6.3 to 25.4%), while the number of MPGN increased in the second time interval (from 7.2 to 8.9%) but decreased in the third one (to 4.4%). CONCLUSIONS: Decrease in relative incidence of membranoproliferative glomerulonephritis, most likely, reflects improvement in socioeconomic conditions, while relative increase in crescentic glomerulonephritis is interpreted as improved diagnostics of the disease.

Renal anemia control in Lithuania: influence of local conditions and local guidelines.

Erythropoietin stimulating agents had a long haul in Lithuania--we had no epoetin till 1994 and there was no intravenous iron in 2001-2004. The aim of this study was to assess the changes of renal anemia control in hemodialysis patients from early independence of Lithuania till nowadays and to evaluate the link of anemia with hospitalization rates and survival and hemoglobin variability in association with mortality. In December of each year since 1996 all hemodialysis centers have been visited and data has been collected using special questionnaires. The history of renal anemia control in Lithuania was complicated; however, a significant improvement was achieved: 54.7% of hemodialysis patients reached the target hemoglobin; all patients have a possibility of treatment with epoetin and intravenous iron. The involuntary experiment with an intravenous iron occurred in Lithuania because of economic reasons and confirmed the significant role of intravenous iron in the management of renal anemia. Hemoglobin below 100 g/L was associated with a 2.5-fold increase in relative risk of death and 1.7-fold increase in relative risk of hospitalization in Lithuanian hemodialysis patients. Although hemoglobin variability was common in Lithuanian hemodialysis patients, we did not find the association between hemoglobin variability and all-cause mortality in our study.