Treatment of acute kidney injury with continuous renal replacement therapy and cytokine adsorber (CytoSorb®) in critically ill patients with COVID-19.

INTRODUCTION: This retrospective study aimed to evaluate the 30 and 60-day survival of critically ill patients with COVID-19 and AKI. METHODS: Inflammatory and biochemical biomarkers, length of intensive care unit (ICU) stay and mortality at Day 30 and Day 60 after ICU admission were analyzed. A total of 44 patients treated with continuous renal replacement therapy (CRRT) with cytokine adsorber (CA group) were compared to 58 patients treated with CRRT alone (non-CA group). RESULTS: Patients in CA group were younger, had better preserved kidney function prior to the beginning of CRRT and had higher levels of interleukin-6. There were no statistically significant differences in their comorbidities and in other measured biomarkers between the two groups. The number of patients who died 60 days after ICU admission was statistically significantly higher in non-CA group (p = 0.029). CONCLUSION: Treatment with CRRT and cytokine adsorber may have positively influenced 60-day survival in our COVID-19 ICU patients with AKI.

Serum zinc values, ankle brachial index and mortality in hemodialysis patients.

INTRODUCTION: The atherosclerotic state of haemodialysis (HD) patients may be influenced by heavy metals. The purpose of our study was to assess the relationship between serum zinc (Zn) ankle brachial index (ABI) as a non-invasive diagnostic tool for atherosclerosis, and mortality in chronic haemodialysis (HD) patients. METHODS: Sixty one HD patients were included (mean age 61.2 ± 13.8 years). The ABI was measured with an automated measuring device (ABPI MD, MESI®, Slovenia). Two groups of patients were formed based on the median value of Zn (14.1 mcmol/l). The average observation time was 2.8 years. Comorbidities (arterial hypertension (AH), diabetes mellitus (DM), dyslipidaemia), smoking and oral nutritional supplements (ONS) consumption were noted. Survival rates were analysed by Kaplan-Meier and Cox regression was used to determine the influence of Zn, ABI, AH, DM, dyslipidaemia, smoking and ONS. RESULTS: Zn values were between 9.2 and 23.5 mcmol/l (14.4 ± 2.34), ABI values ranged from 0.8 to 1.4 (1.14 ± 0.12). Patients with lower Zn values had lower ABI (p = 0.036). Mean survival time of patients with higher Zn values was 985 days ± 277 days and with lower Zn values 1055 ± 143 days. Six (19.4%) patients with lower Zn and five (16.7%) patients with higher Zn died. We found statistically insignificant lower survival in patients with higher Zn. We failed to find any predictor of all-cause mortality, except for ONS consumption (95% CI 1.6-33.3; p = 0.012). CONCLUSIONS: Lower Zn is associated with lower ABI in HD patients, but we found no impact of Zn on patient survival.

Polypharmacy and Mental Health Issues in the Senior Hemodialysis Patient.

Hemodialysis (HD) is the most common method of chronic kidney failure (CKF) treatment, with 65% of European patients with CKF receiving HD in 2018. Regular two to three HD sessions weekly severely lower their quality of life, resulting in a higher incidence of depression and anxiety, which is present in one third to one half of these patients. Additionally, the age of patients receiving HD is increasing with better treatment and care, resulting in more cognitive impairment being uncovered. Lastly, patients with other mental health issues can also develop CKF during their life with need for kidney replacement therapy (KRT). All these conditions need to receive adequate care, which often means prescribing psychotropic medications. Importantly, many of these drugs are eliminated through the kidneys, which results in altered pharmacokinetics when patients receive KRT. This narrative review will focus on common issues and medications of CKF patients, their comorbidities, mental health issues, use of psychotropic medications and their altered pharmacokinetics when used in HD, polypharmacy, and drug interactions, as well as deprescribing algorithms developed for these patients.

The effect of high-flux hemodialysis and post-dilution hemodiafiltration on platelet closure time in patients with end stage renal disease.

INTRODUCTION: We aimed to compare prospectively the effect of high-flux hemodialysis and post-dilution hemodiafiltration on platelets. METHODS: Twenty-two hemodialysis patients were treated with one high-flux hemodialysis and one post-dilution hemodiafiltration procedure. PFA-100 closure times (collagen/epinephrine-CEPI and collagen/adenosine diphosphate-CADP) were measured before and after the procedure, as well as platelet count, hemoglobin, hematocrit, and red blood cell count. All pre-dialysis and post-dialysis samples were taken from the afferent line. FINDINGS: The platelet count after vs. before hemodialysis did not change significantly (229.3 ± 55.0 x109 /L vs. 233.6 ± 55.8 × 109 /L; P = 0.269), but was significantly lower after post-dilution hemodiafiltration (215.5 ± 51.7 × 109 /L vs. 245.3 ± 59.9 × 109 /L; P < 0.0001). CEPI after vs. before hemodialysis was not significantly prolonged (192.9 ± 60.8 s vs. 173.4 ± 52.5 s; P = 0.147), and the same applied to CADP (143.6 ± 40.3 s vs. 142.6 ± 38.4 s; P = 0.897). CEPI after vs. before post-dilution hemodiafiltration was significantly prolonged (268.3 ± 41.3 s vs. 176.4 ± 54.0 s; P < 0.0001) as was CADP (221.0 ± 53.9 s vs.133.9 ± 31.1 s; P < 0.0001). DISCUSSION: Only after post-dilution hemodiafiltration, we found a lower platelet count and prolonged platelet closure times.

Cystatin C as a predictor of mortality in elderly patients with chronic kidney disease.

BACKGROUND: The prevalence of chronic kidney disease (CKD) in the elderly is high. Serum cystatin C is an accurate marker of kidney function and it also has prognostic utility in CKD patients. The aim of our study was to determine the prediction of serum cystatin C and other markers of kidney function on long-term survival in elderly CKD patients. METHODS: Fifty eight adult Caucasian patients, older than 65 years, without known malignancy, thyroid disease and/or not on steroid therapy were enrolled in the study. In each patient, 51CrEDTA clearance, serum creatinine, serum cystatin C, and estimated glomerular filtration rate using different equations were determined on the same day and patients were then followed for 11 years or until their death. RESULTS: The means are as follows: 51CrEDTA clearance 53.3 ± 17.4 ml/min/1.73 m2, serum creatinine 1.62 ± 0.5 mg/dl, serum cystatin C 1.79 ± 0.5 mg/l, Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation 40.1 ± 14 ml/min/1.73 m2, Berlin Initiative Study 2 (BIS2) equation 38.9 ± 10.7 ml/min/1.73 m2, full age spectrum (FAS) creatinine equation 43.8 ± 13.8 ml/min/1.73 m2, FAS cystatin C equation 40.1 ± 11.7 ml/min/1.73 m2. In the follow up period, 47 (81%) patients died. Cox regression analysis showed different hazard ratios (HRs) for death: for 51CrEDTA clearance HR 1.022 (95% CI 1.004-1.042; p = .015), serum creatinine HR 1.013 (95% CI 1.006-1.019; p = .001), serum cystatin C HR 2.028 (95% CI 1.267-3.241; p = .003), CKD-EPI creatinine equation HR 1.048 (95% CI 1.019-1.076; p = .001), BIS2 equation HR 1.055 (95% CI 1.021-1.088; p = .001), FAS creatinine equation HR 1.046 (95% CI 1.017-1.074; p = .001), FAS cystatin C equation HR 1.039 (95% CI 1.010-1.071; p = .009). CONCLUSIONS: Our results showed the highest HR for serum cystatin C among kidney function markers for prediction of outcome in elderly CKD patients.

Measurement of breath ammonia for detection of patients with chronic kidney disease.

BACKGROUND: In a healthy individual, ammonia is converted to urea in the liver. Urea is then transported through the bloodstream and then excreted into the urine by the kidneys. In patients with chronic kidney disease (CKD), the accumulated urea is degraded by salivary urease into ammonia, which is then excreted by breathing. Breath ammonia can therefore be used for detecting the increased nitrogen-bearing wastes. In our pilot study, an electrochemical sensor was used to measure and analyze breath ammonia in healthy volunteers and patients with CKD. PATIENTS AND METHODS: In our study, 8 patients with CKD (stages 4 and 5) and 6 healthy volunteers were enrolled. All participants were nonsmokers and without pulmonary or liver disease. One controlled breath sample was collected from each participant. Immediately after the sample was collected, a gas analyzer was used for measuring breath ammonia in our participants. RESULTS: Mean creatinine value of CKD patients was 455.2 ± 294.1 µmol/L and 62.1 ± 7.5 µmol/L for healthy volunteers. Breath ammonia levels (3.32 ± 2.19 ppm vs. 0.49 ± 0.08 ppm; p = 0.003) and measured electric current (4.33 ± 0.25 mA vs. 4.01 ± 0.01 mA; p = 0.003) were significantly higher in the CKD group. CONCLUSIONS: The results of our pilot study show that breath monitoring of ammonia can be a simple, useful, fast, and noninvasive tool for detection of advanced kidney impairment.
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Relationship between subendocardial viability ratio and hemoglobin in patients with chronic kidney disease.

AIMS: Pulse wave analysis (PWA) uses the technique of applanation tonometry to obtain a peripheral pulse pressure waveform from which central hemodynamic information is derived. Using PWA, subendocardial viability ratio (SEVR) can be measured. SEVR represents a noninvasive measure of myocardial perfusion. It is related to the work of the heart, the oxygen consumption, and the energy supply of the heart. Anemia is a common complication of chronic kidney disease (CKD). A complex relationship exists between CKD, cardiovascular disease (CVD), and anemia. The aim of our study was to assess the relationship between SEVR and hemoglobin in non-dialysis CKD patients. MATERIAL AND METHODS: We examined the associations between PWA hemodynamic parameters, 24-hour ambulatory blood pressure (BP) measurements, and laboratory variables including hemoglobin, cardiac biomarkers troponin I, NT-proBNP, and hs-CRP in a cohort of 91 nondialysis CKD patients. PWA was assessed by radial applanation tonometry (SphygmoCor, Atcor, Sydney, Australia). The patients were divided into two groups according to the median value of hemoglobin. RESULTS: Mean age of included patients was 60.2 years, 67% were men, 44% were smokers, 25.3% had diabetes. A significant correlation between hemoglobin and SEVR was found (r = 0.26; p = 0.012). With multivariate regression analysis, SEVR as dependent variable turned out to be statistically significantly associated with hemoglobin (ß = 0.344, p = 0.013) and with troponin I (ß = -0.217, p = 0.037). Patients in the group with lower hemoglobin had statistically-significantly higher serum creatinine, cystatin C, NT-proBNP, and 24-hour ambulatory systolic BP and lower e-GFR, SEVR, and office diastolic BP. CONCLUSIONS: Results of our study show that SEVR is independently associated with hemoglobin in nondialysis CKD patients. CKD patients with lower hemoglobin have lower SEVR.
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Ankle-Brachial Index and Long-Term (10 Years) Survival of Nondiabetic Hemodialysis Patients.

Low (<0.9) and high (>1.4) ankle brachial index (ABI) is associated with a higher cardiovascular (CV) mortality in the general and hemodialysis (HD) population. The aim of our study was to determine the impact of ABI on long-term survival of 52 non-diabetic HD patients. The ABI was determined using an automated, non-invasive waveform analysis device. Patients were divided into three groups: low (<0.9), normal (0.9-1.4) and high (>1.4) ABI. Patients were observed from the date of ABI measurement until their death or ten years. Survival analysis showed higher risk for CV death in HD patients with high ABI compared to normal ABI (log rank test P < 0.027). In Cox regression model adjusted for arterial hypertension, smoking, serum cholesterol and triglycerides, high ABI (P < 0.049) remained a predictor of mortality. The results indicate an association between ABI and long-term survival of non-diabetic HD patients and only high ABI was associated with higher CV mortality.

Albuminuria is Associated With Subendocardial Viability Ratio in Chronic Kidney Disease Patients.

BACKGROUND/AIMS: Albuminuria is a well-established marker of subclinical organ damage. Pulse-wave analysis (PWA) employs the technique of applanation tonometry to obtain a peripheral pulse pressure waveform, from which central hemodynamic data are derived by application of the transfer function. Using PWA we can measure the subendocardial viability ratio (SEVR) and ejection duration (ED). SEVR or the Buckberg index is a non-invasive estimate of myocardial workload, oxygen supply and perfusion and a measure of the ability of the arterial system to meet the heart`s energy requirements. ED is the duration of ventricular ejection. The objective of this study was to evaluate the relationship between albuminuria and PWA parameters in chronic kidney disease (CKD) patients. METHODS: We studied 86 CKD patients aged 59.8±13.5 years, 56 (65.1%) were male. PWA analysis and 24-hour ambulatory blood pressure (24hABP) monitoring were performed. The following parameters were calculated: (1) aortic augmentation index with and without correction for a heart rate of 75 (Aix and AIx@ HR75), (2) SEVR, calculated as the ratio of the diastolic pressure time index and the systolic pressure time index, (3) ED, (4) estimated central aortic systolic and diastolic pressure and (5) central aortic pulse pressure calculated as the difference between estimated aortic systolic and diastolic BP. Blood samples and urine albumin-to-creatinine ratio (UACR) were analyzed; UACR values were natural log transformed (lnUACR). RESULTS: Using CKD-EPI creatinine-cystatin C formula the eGFR in patients was 7-130 ml/min/1.73 m² (mean 32.6; SD±24.6). We found statistically significant correlation between lnUACR and cystatin C (r=0.308; P=0.004), eGFR (r=-0.219; P=0.04), hemoglobin (r=-0.255; P=0.02), phosphorus (r=0.222; P=0.04), iPTH (r=0.268; P=0.01), SEVR (r=-0.254; P=0.02) and ED (r=0.315; P=0.003). No statistically significant correlations between lnUACR and cardiac biomarkers TnI, NT-proBNP, central aortic BP and 24h ABP values were found. Using multiple regression analysis statistically significant association was found between SEVR as dependent variable and lnUACR (ß=-0.223, P=0.039), sex (ß=-0.216, P=0.035), and diabetes (ß=0.332, P=0.001). Multiple regression analysis with ED as dependent variable has shown statistically significant association with lnUACR (ß=0.242, P=0.031) and diabetes (ß=-0.275, P=0.01). Patients were stratified into tertiles according to the lnUACR. Statistically significant differences in serum creatinine (P=0.001), cystatin C (P=0.012), hemoglobin (P=0.03), calcium (P=0.036), iPTH (P=0.008), SEVR (P=0.007) and ED (P=0.004) were found between tertiles. In post hoc analysis we found statistically significant differences between first and third tertile in SEVR (P=0.002; 95% CI:10.5-45) and in ED (P=0.001; 95% CI:-6.89-(-1.87)). CONCLUSIONS: Nondialysis CKD patients with higher levels of albuminuria have lower SEVR and higher ED and our results have shown the importance of central hemodynamic parameters like are SEVR and ED as a better or earlier noninvasive hemodynamic indexes in these patients.

Platelet-related hemostasis before and after hemodialysis with five different anticoagulation methods.

PURPOSE: To evaluate platelet-related hemostasis during hemodialysis performed with five different anticoagulation methods. METHODS: 31 chronic hemodialysis patients, 71% men, aged 57.5 ± 17.4 years, participated in our prospective study. Platelet function analyzer PFA -100 closure time (collagen/epinephrine -CEPI, collagen/adenosine diphosphate -CADP) was measured before and after hemodialysis, which was performed consecutively with five different anticoagulation methods: full-dose unfractionated heparin (UFH) and low-molecular weight heparin (LMWH): 31 patients, regional citrate anticoagulation (RCA): 28 patients, low-dose heparin: 25 patients and "heparin-free'' dialysis: 9 patients. The degree of clotting in the dialysis system was graded on a 5 point scale. RESULTS: CEPI (mean ± SD, reference range 80-160 sec) before vs. after hemodialysis: UFH: 171.7 ± 62.1 vs. 170.8 ± 67.3; LMWH: 167.4 ± 56.9 vs. 159.4 ± 56.4; low-dose heparin: 175.3 ± 69.0 vs. 183.1 ± 60.5; RCA: 172.6 ± 57.4 vs. 161.6 ± 57.0; "heparin-free'': 181.7 ± 56.8 vs. 209.0 ± 66.5; all differences nonsignificant. CADP (mean ± SD, reference range: 68-121 sec) before vs. after hemodialysis: UFH: 132.0 ± 56.6 vs.146.3 ± 68.4; LMWH: 132.4 ± 57,0 vs. 123.1 ± 50.8; low-dose heparin: 137.2 ± 64.2 vs. 143.8 ± 55.5; RCA: 140.7 ± 48.2 vs. 132.9 ± 48.1; "heparin-free'': 137.1 ± 68.0 vs.139.2 ± 29.7; all differences nonsignificant. Before hemodialysis procedure CEPI was increased in 51.2% and CADP in 48.4% of the patients. The best dialysis system clotting score was found with UFH, LMWH and RCA. CONCLUSIONS: Platelet dysfunction was demonstrated in approximately half of the chronic hemodialysis patients and was not improved after hemodialysis, regardless of the anticoagulation regimen used.

A case of phospholipase A2 receptor-positive membranous nephropathy preceding sarcoid-associated granulomatous tubulointerstitial nephritis.

We report the case of a 29-year-old man with membranous nephropathy that was associated with a sarcoidosic granulomatous tubulointerstitial nephritis, but was without an apparent calcium metabolism disorder. Corticosteroid treatment was associated with remission of nephrotic syndrome. We discuss the relationship between membranous nephropathy and sarcoidosis based on the close appearance of the 2 diseases and the detection of phospholipase A2 receptor in glomerular immune deposits.

Fetuin-A as a risk factor for mortality in hemodialysis patients.

OBJECTIVES: Fetuin A, a circulating inhibitor of calcification, is regulated as a negative acute-phase protein. However, its relationship with outcomes of patients undergoing hemodialysis has not been well evaluated. The aim of our study was to determine the association between fetuin-A and some factors of metabolism and their impact on all-cause mortality in hemodialysis patients. PATIENTS AND METHODS: The study comprised 106 hemodialysis patients, 45 of whom were women. Levels of serum fetuin-A were measured by ELISA and serum intact parathyroid hormone (iPTH) by immunoassay in each patient. Serum Ca, serum P, Ca x P product, alkaline phosphatase, cholesterol, triglycerides, bicarbonate, albumin, homocysteine and C-reactive protein (CRP) were measured using routine laboratory methods. Survival rates were analyzed using Kaplan-Meier survival curves. A Cox regression model was used to access the possible influence of variables on all-cause mortality. RESULTS: The mean value of fetuin-A was 15.3 +/- 3.8 g/l, range 5.5-23.7 g/l. Significant correlations were found between serum fetuin-A and serum iPTH (r = -0.239; P = 0.014), alkaline phosphatase (r = -0.240; P = 0.013), triglycerides (r = +0.236; P = 0.015) and serum albumin level (r = +0.286; P = 0.003). Patients were followed-up prospectively from the first day of the laboratory measurement for a maximum of 752 days or until death. A total of 24 patients died. Surviving patients had higher levels of fetuin-A (P = 0.005), serum cholesterol (P = 0.0001), triglycerides (P = 0.004), albumin (P = 0.0001) and homocysteine (P = 0.028). Kaplan-Meier survival analysis showed higher mortality in the first tertile of fetuin-A than in the third tertile (P = 0.0297). In our patients, serum Ca (P = 0.025), serum P (P = 0.040) and the Ca x P product (P = 0.039) were found to be predictors of mortality in the Cox multivariable regression model. CONCLUSIONS: In patients undergoing hemodialysis, lower fetuin-A levels are associated with higher mortality. Metabolism of Ca and P were directly associated with higher mortality.

Vitamin D as a novel nontraditional risk factor for mortality in hemodialysis patients.

We examined the prevalence of vitamin D deficiency in hemodialysis patients and tested the hypothesis that decreased levels of 25-hydroxyvitamin D (25D) are associated with an increased risk for early all-cause mortality. One hundred and two patients, 57 (56%) men and 45 (44%) women, mean age 60.5 +/- 13.1 years, were included in our study. Serum calcium and phosphorus levels were measured by routine laboratory methods. Parathyroid hormone (PTH) was measured by immunoassay and 25D by enzyme immunoassay. Patients were divided into two groups depending on the serum concentration of 25D: below or above 50 nmol/L. Survival rates were analyzed using the Kaplan-Meier survival curves. The Cox regression model was used to define potential variables effecting all-cause mortality. The mean level of 25D in all patients was 58 +/- 35.6 nmol/L, 52% of patients had 25D levels >50 nmol/L and 48% had levels of 10.5-50 nmol/L. Compared with men, women were more likely to be 25D deficient (67% vs. 37%; P = 0.005). Patients were observed from the date of laboratory measurement until their death or to a maximum of 730 days. Kaplan-Meier survival analysis showed that mortality in patients was significantly higher in the group with 25D levels < or =50 nmol/L (P < 0.033). With Cox multivariable regression modeling, the PTH level (P < 0.029) turned out to be the only predictor of mortality in our patients. Using the definitions recommended in the National Kidney Foundation Kidney Disease Outcomes Quality Initiative guidelines, we found that our hemodialysis patients on average have vitamin D insufficiency. Our results indicate that patients with 25D levels < or =50 nmol/L are associated with higher all-cause early mortality.