Mortality Prediction in Patients with Severe Acute Kidney Injury Requiring Renal Replacement Therapy.

Background and Objective: Acute kidney injury (AKI) remains a serious health condition around the world, and is related to high morbidity, mortality, longer hospitalization duration and worse long-term outcomes. The aim of our study was to estimate the significant related factors for poor outcomes of patients with severe AKI requiring renal replacement therapy (RRT). Materials and Methods: We retrospectively analyzed data from patients (n = 573) with severe AKI requiring RRT within a 5-year period and analyzed the outcomes on discharge from the hospital. We also compared the clinical data of the surviving and non-surviving patients and examined possible related factors for poor patient outcomes. Logistic regression was used to analyze the odds ratio for patient mortality and its related factors. Results: In 32.5% (n = 186) of the patients, the renal function improved and RRT was stopped, 51.7% (n = 296) of the patients died, and 15.9% (n = 91) of the patients remained dialysis-dependent on the day of discharge from the hospital. During the period of 5 years, the outcomes of the investigated patients did not change statistically significantly. Administration of vasopressors, aminoglycosides, sepsis, pulmonary edema, oliguria, artificial pulmonary ventilation (APV), patient age ≥ 65 y, renal cause of AKI, AKI after cardiac surgery, a combination of two or more RRT methods, dysfunction of three or more organs, systolic blood pressure (BP) ≤ 120 mmHg, diastolic BP ≤ 65 mmHg, and Sequential Organ Failure Assessment (SOFA) score on the day of the first RRT procedure ≥ 7.5 were related factors for lethal patient outcome. Conclusions: The mortality rate among patients with severe AKI requiring RRT is very high-52%. Patient death was significantly predicted by the causes of AKI (sepsis, cardiac surgery), clinical course (oliguria, pulmonary edema, hypotension, acidosis, lesion of other organs) and the need for a continuous renal replacement therapy.

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.

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.

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.

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.

Risk factors for cardiovascular hospitalization in hemodialysis patients.

UNLABELLED: The aim of this study was to evaluate the risk factors for cardiovascular hospitalization in hemodialysis patients. MATERIALS AND METHODS: A cross-sectional cohort analysis of risk factors during one census month (November) and one-year follow-up for cardiovascular hospitalization rates during 5 consecutive years (2002-2006) in all end-stage renal disease patients hemodialyzed in Kaunas region was carried out. During the census month, we collected data on patient's age and sex, disability status, comorbidities, anemia control, malnutrition and inflammation, calcium-phosphorus metabolism, and patient's compliance with prescribed medications. We analyzed 559 patients during 1163 patient-years of observation. Patients were considered as new patients every year (1520 cases). Kaplan-Meier method and Cox regression analysis were used to evaluate time to first hospitalization. RESULTS: The mean number of cardiovascular hospitalizations was 0.31 per patient-year at risk, the total days of cardiovascular hospitalizations per patient-year at risk were 3.93, and the mean length of one hospitalization was 13.2±12.9 days. Cardiovascular diseases were the most frequent cause of hospitalization (25% of all hospitalizations). The relative risk of cardiovascular hospitalization increased by 1.03 for every year of age, by 1.7 for worse disability status, by 1.4 for nonadherence to medications, by 1.1 for every additional medication prescribed to the patient. Cardiovascular hospitalization risk was decreased by 0.99 with a 1-g/L rise in hemoglobin level. CONCLUSIONS: Older age, worse disability status, patient's noncompliance with medications, and higher number of medications used were associated with a higher risk for cardiovascular hospitalization. Higher hemoglobin level was associated with a lower risk for cardiovascular hospitalization.

Ten-year experience of kidney transplantation at the Hospital of Kaunas University of Medicine: demography, complications, graft and patient survival.

UNLABELLED: During 10 years, 163 cadaveric kidney transplantations were performed at the Hospital of Kaunas University of Medicine. The aim of this study was to analyze the first 10-year experience in kidney transplantation and to evaluate the most frequent early and late complications after transplantation, graft and patient survival, and impact of delayed graft function on graft survival. MATERIAL AND METHODS: A total of 159 patients were included into the study. Graft and patient survival was calculated at 1, 3, and 5 years after transplantation using the Kaplan-Meier method; graft function was also analyzed. RESULTS: Fifty-three patients (33.3%) in the early period and 72 (55.4%) in the late period had at least one episode of urinary tract infection. Less than half (47.2%) of patients had complications related to immunosuppressive treatment, mostly cytomegalovirus infection, in the late period. The risk of CMV reactivation was 3.98 times higher among recipients who received prophylaxis only with intravenous ganciclovir as compared to patients who received valganciclovir after a brief course of ganciclovir (OR, 3.98; 95% CI, 1.48-8.19; P=0.003). Delayed graft function was observed in 53 cases (33.3%); 37 (23.3%) grafts were lost. Graft and patient survival at 1, 3, and 5 years after transplantation was 85%, 82%, and 71% and 97%, 94%, and 94%, respectively. Graft survival at 1, 3, and 5 years was worse among patients with delayed graft function as compared to patients with good graft function (69%, 69%, 50% vs. 93%, 86%, 84%, respectively; P<0.05). CONCLUSIONS: Urinary tract infection was the most frequent complication after kidney transplantation. Reactivation of cytomegalovirus infection was present only in a quarter of our patients. The administration of valganciclovir was associated with a significantly lower incidence of CMV infection/disease. Graft and patient survival was sufficiently good. Delayed graft function was an independent risk factor for worse graft survival.

[Infection-related hospitalization of hemodialysis patients]. / Hemodializuojamu ligoniu hospitalizavimas del infekcijos.

Infection is an important cause of morbidity and mortality in hemodialysis patients. These patients are frequently hospitalized for infections. The objective of our study was to evaluate hospitalization rate for infections and to determine risk factors for infection-related hospitalizations of hemodialysis patients in Kaunas region, Lithuania. Ambulatory case records of 533 patients with end-stage renal disease, dialyzed in all hemodialysis centers in Kaunas region during the period of 2001-2004, were analyzed. Data on patient's condition and routine laboratory tests were collected in November of 2001, 2002, and 2003. These patients then were followed up for the next 12 months in order to evaluate infection-related hospitalization rate. All patients were considered new patients every year, and general analysis of three-year data was performed. Statistical analyses were carried out using SPSS (Statistical Package for Social Sciences) and STATISTICA. Univariate statistical analysis was performed comparing the groups of patients that were hospitalized because of infections and were not hospitalized. Relative risk of infection-related hospitalization was estimated using Cox regression evaluating the time to first infection-related hospitalization. The unadjusted infection-related hospitalization rate was 0.2 per patient a year (18% of all hospitalizations). The median length of hospital stay for infections was 11 days. Univariate statistical analysis showed a statistically significant association between infection-related hospitalizations and diabetes (P=0.02); lower hemoglobin (P<0.0001), creatinine (P=0.045), and albumin (P=0.01) concentrations; higher interdialytic weight gain (P=0.01). Multivariate Cox regression analysis revealed that only hemoglobin concentration (P<0.001, RR=0.96), interdialytic weight gain (P=0.002, RR=1.38), and creatinine level (P=0.02, RR=0.99) were important risk factors for infection-related hospitalization. Relative risk of infection-related hospitalization was 4.4 times greater when hemoglobin concentration was less than 100 g/L (P<0.001) and 1.9 times greater when interdialytic weight gain was more than 4% of body weight (P=0.008). CONCLUSION. In Kaunas region, infection-related hospitalizations accounted for 18% of all hospitalizations. Anemia, creatinine level, and interdialytic weight gain were important risk factors for infection-related hospitalization of hemodialysis patients.

[Estimated average yearly treatment expenditures for hemodialysis patients (data of Kaunas University of Medicine Hospital in the year 2005)]. / Hemodializuojamu ligoniu vidutines apskaiciuotos metines gydymo islaidos (Kauno medicinos universiteto kliniku 2005 metu duomenys).

With increasing number of hemodialysis patients, expenditures for the treatment of hemodialysis patients are rising every year. The objective of our study was to collect and analyze the data on estimated average treatment expenditures, which were covered by State Patients' Fund, for patients undergoing hemodialysis in Kaunas University of Medicine Hospital in 2005 and the costs of medications paid by patient and to compare with the analogical data of the year 2001. We analyzed ambulatory case records of all 106 patients with end-stage renal disease who were hemodialyzed in Kaunas University of Medicine Hospital from November 1, 2004, to October 31, 2005. Data on medications used and number of hemodialysis procedures and hospitalizations were collected. On average, 2.8+/-0.4 hemodialysis procedures per patient a week were carried out. Expenditures for hemodialysis procedures were 38 094.12+/-5003.17 litas (11,041 euros) per patient per year, and this accounted for 63% of all expenditures for hemodialysis patient. Hospitalization rate was 1.4+/-1.8 per patient a year; expenditures for hospitalizations were 1538.4+/-1941 litas (446 euros) per patient a year (3% of all expenditures for hemodialysis patients). The mean number of drugs prescribed per patient monthly was 7.7+/-2.17 including 2.12+/-1.6 antihypertensive medications. The total costs of drugs reimbursed by State Patients' Fund were 20,639.82+/-15,439.3 litas (5983 euros) per patient per year, of which 92% was spent on erythropoietin and intravenous iron. The average expenditures for health insurance of hemodialysis patients were 60,272.35+/-16,624.18 litas (17,470 euros) per patient a year. One patient had to pay 1.9+/-1.6 litas for medications per day and 699.71+/-583.6 litas (203 euros) per year. The comparison of the data gathered in 2001 and 2005 revealed an increase in the total expenditures for hemodialysis patients due to increase in the expenditures for hemodialysis procedures and medications.

[Reactivation of cytomegalovirus infection after kidney transplantation in Kaunas University of Medicine Hospital during the period of 2000-2006]. / Citomegalovirusines infekcijos reaktyvavimasis po inkstu persodinimo Kauno medicinos universiteto klinikose (2000-2006).

Cytomegalovirus infection has been associated with increased morbidity and mortality after transplantation and with diminished graft survival. After transplantation, more than 75% of solid organ transplant patients are newly infected with cytomegalovirus, or latent cytomegalovirus infection may be reactivated. The objective of our study was to evaluate reactivation rate of cytomegalovirus infection after kidney transplantation in Kaunas University of Medicine Hospital and its relation to anticytomegalovirus prophylaxis. A retrospective review of all kidney transplants performed between May 2000 and December 2006 was conducted. We analyzed the prevalence of cytomegalovirus in the groups of donors and recipients, and risk categories were defined for cytomegalovirus infection/disease in transplant patients. During this period, a total of 93 transplantations were performed in 56 men (60.2%) and 37 women (39.8%). The mean age of recipients was 41.04+/-12.74 years. There were 33 (68.7%) men and 15 (31.3%) women in the group of donors; their mean age was 39.49+/-14.81 years. Patients at high risk for the development of cytomegalovirus infection/disease were defined as those who had donor-positive/recipient-negative serostatus (D+/R-), and they made up 5.4% of all patients. Intermediate-risk patients with cytomegalovirus infection (D+/R+ and D-/R+) accounted for 73.1% and 15.1% of all recipients, respectively; 6.4% of patients were at low risk (D-/R-). Anti-cytomegalovirus prophylaxis with i/v ganciclovir was given during the period of hospitalization in all cases, except when there was a D-/R- combination, or when the transplant was removed in the early period after transplantation. The reactivation of cytomegalovirus infection was observed in 23 patients (24.7%). We have observed 41 episodes of cytomegalovirus infection, but during this period, no patient developed cytomegalovirus disease that might cause lethal outcome.