Cardiac Biomarkers are Associated with Incident Fracture Risk in Advanced Chronic Kidney Disease.

Cardiovascular disease is associated with increased fracture risk in the general population. Few data exist on the association between cardiovascular health and incident fracture risk in patients with advanced CKD, a high-risk population for fractures. We aimed to assess the link between fracture risk and cardiovascular health in a prospective cohort of 210 patients with CKD stage G4-5. Incident fractures were recorded during a prospective follow-up of 5 years. Laboratory parameters, abdominal aortic calcification score, echocardiography, ultrasound assessment of brachial artery flow-mediated dilatation and carotid intima-media thickness, and maximal stress ergometry were obtained at baseline. A total of 51 fractures were observed in 40 (19%) patients during follow-up. In separate multivariable Cox proportional hazards models adjusted for age, gender, and baseline eGFR, TnT (HR 1.007, CI 95% 1.003-1.010, p < 0.001) and ProBNP (HR 1.000, CI 95% 1.000-1.000, p = 0.017) were associated with incident fractures and the association persisted after adjusting for coronary artery disease (CAD). The patients unable to perform the ergometry test had a higher risk of incident fractures compared to others (36.1% vs 15.5%, p = 0.009). A cardiovascular composite risk score summarizing TnT, ProBNP, and ergometry data was independently associated with incident fractures in a multivariable Cox model (HR 1.373, CI 95% 1.180-1.599, p < 0.001). Patients with the lowest score were observed with no fractures, while patients with the highest score were observed with a fracture risk of 40.5% during follow-up. Risk of incident fractures is associated with biomarkers of cardiovascular health and a composite cardiovascular risk score in patients with advanced CKD.

Furosemide versus placebo for fluid overload in intensive care patients-The randomised GODIF trial second version: Statistical analysis plan.

BACKGROUND: Fluid overload is associated with increased mortality in intensive care unit (ICU) patients. The GODIF trial aims to assess the benefits and harms of fluid removal with furosemide versus placebo in stable adult patients with moderate to severe fluid overload in the ICU. This article describes the detailed statistical analysis plan for the primary results of the second version of the GODIF trial. METHODS: The GODIF trial is an international, multi-centre, randomised, stratified, blinded, parallel-group, pragmatic clinical trial, allocating 1000 adult ICU patients with moderate to severe fluid overload 1:1 to furosemide versus placebo. The primary outcome is days alive and out of hospital within 90 days post-randomisation. With a power of 90% and an alpha level of 5%, we may reject or detect an improvement of 8%. The primary analyses of all outcomes will be performed in the intention-to-treat population. For the primary outcome, the Kryger Jensen and Lange method will be used to compare the two treatment groups adjusted for stratification variables supplemented with sensitivity analyses in the per-protocol population and with further adjustments for prognostic variables. Secondary outcomes will be analysed with multiple linear regressions, logistic regressions or the Kryger Jensen and Lange method as suitable with adjustment for stratification variables. CONCLUSION: The GODIF trial data will increase the certainty about the effects of fluid removal using furosemide in adult ICU patients with fluid overload. TRIAL REGISTRATIONS: EudraCT identifier: 2019-004292-40 and ClinicalTrials.org: NCT04180397.

New-onset atrial fibrillation in critically ill acute kidney injury patients on renal replacement therapy.

AIMS: The effect of new-onset atrial fibrillation (NOAF) on mortality in critically ill patients with acute kidney injury (AKI) treated in the intensive care unit (ICU) requiring continuous veno-venous haemodialysis (CVVHD) or intermittent haemodialysis (IHD) is unknown. Thus, we examined the incidence of NOAF in critically ill AKI patients undergoing CVVHD or IHD and the association between the timing of NOAF incidence in relation to renal replacement therapy (RRT) initiation and 1-year mortality. METHODS AND RESULTS: Out of the 733 consecutively recruited ICU patients requiring RRT within the study period of 2010-2019, 516 patients without prior atrial fibrillation history were included in this retrospective study. Clinical comorbidities, medications and biochemistry as well as outcome data for 1-year all-cause mortality were recorded. Episodes of NOAF were collected from the pooled rhythm data covering the entire ICU stay of every patient. The median age was 64 (inter-quartile range 19) years, 165 (32%) were female, and 356 and 160 patients received CVVHD and IHD, respectively. NOAF was observed in 190 (37%) patients during ICU care and 217 (42%) patients died within the 1-year follow-up. Incident NOAF was independently associated with 1-year mortality in the multivariable logistic regression analysis after adjusting for dialysis modality, need for mechanical ventilation or vasopressor support and Acute Physiology And Chronic Health Evaluation II score. However, NOAF diagnosed after RRT initiation was not associated with mortality. CONCLUSION: NOAF emerging before RRT initiation is associated with increased mortality in critically ill AKI patients requiring RRT. However, NOAF during RRT does not seem to be associated with mortality.

Progression of Aortic Calcification in Stage 4-5 Chronic Kidney Disease Patients Transitioning to Dialysis and Transplantation.

BACKGROUND AND AIMS: Abdominal aortic calcification (AAC) is common in chronic kidney disease (CKD) patients and associated with increased mortality. Comparative data on the AAC score progression in CKD patients transitioning from conservative treatment to different modalities of renal replacement therapy (RRT) are lacking and were examined. METHODS: 150 study patients underwent lateral lumbar radiograph to study AAC in the beginning of the study before commencing RRT (AAC1) and at 3 years of follow-up (AAC2). We examined the associations between repeated laboratory tests taken every 3 months, echocardiographic and clinical variables and AAC increment per year (ΔAAC), and the association between ΔAAC and outcomes during follow-up. RESULTS: At the time of AAC2 measurement, 39 patients were on hemodialysis, 39 on peritoneal dialysis, 39 had a transplant, and 33 were on conservative treatment. Median AAC1 was 4.8 (0.5-9.0) and median AAC2 8.0 (1.5-12.0) (p < 0.0001). ΔAAC was similar across the treatment groups (p = 0.19). ΔAAC was independently associated with mean left ventricular mass index (LVMI) (log LVMI: ß = 0.97, p = 0.02) and mean phosphorus through follow-up (log phosphorus: ß = 1.19, p = 0.02) in the multivariable model. Time to transplantation was associated with ΔAAC in transplant recipients (per month on the waiting list: ß = 0.04, p = 0.001). ΔAAC was associated with mortality (HR 1.427, 95% confidence interval 1.044-1.950, p = 0.03). CONCLUSION: AAC progresses rapidly in patients with CKD, and ΔAAC is similar across the CKD treatment groups including transplant recipients. The increment rate is associated with mortality and in transplant recipients with the time on the transplant waiting list.

Maximal Exercise Capacity in Chronic Kidney Disease Stage 4-5 Patients Transitioning to Renal Replacement Therapy or Continuing Conservative Care: A Longitudinal Follow-Up Study.

INTRODUCTION: Chronic kidney disease (CKD) is associated with impaired maximal exercise capacity (MEC). However, data are scarce on the development of MEC in CKD stage 4-5 patients transitioning to renal replacement therapy (RRT). METHODS: We explored the change in MEC measured in watts (Wlast4) with 2 consecutive maximal bicycle stress ergometry tests in 122 CKD stage 4-5 patients transitioning to dialysis and transplantation in an observational follow-up study. RESULTS: Mean age was 58.9 ± 13.9 years and 43 (35.2%) were female. Mean time between the baseline and follow-up ergometry tests was 1,012 ± 327 days and 29 (23.8%) patients had not initiated RRT, 50 (41.0%) were undergoing dialysis, and 43 (35.2%) had received a kidney transplant at the time of the follow-up ergometry test. The mean Wlast4 was 91 ± 37 W and 84 ± 37 W for the baseline and follow-up ergometry tests, respectively (p < 0.001). The mean Wlast4 declined between the baseline and follow-up ergometry tests in patients not requiring RRT (p = 0.001) and transplant recipients (p = 0.005), but not in dialysis patients (p = 0.478). There were no differences in the ratio of Wlast4 of the follow-up to the baseline ergometry tests (∆Wlast4) between patients on different treatment modalities at the time of the follow-up test (p = 0.097). Mean capillary blood bicarbonate was significantly associated with ∆Wlast4 after adjusting for age and treatment modality in the multivariate linear regression analysis (ß = 0.226, p = 0.012). CONCLUSION: MEC declined or remained poor in advanced CKD patients transitioning to RRT or continuing conservative care in this observational study. Mean capillary blood bicarbonate was independently associated with the development of MEC.

Goal directed fluid removal with furosemide versus placebo in intensive care patients with fluid overload: A trial protocol for a randomised, blinded trial (GODIF trial).

BACKGROUND: Fluid overload is a risk factor for mortality in intensive care unit (ICU) patients. Administration of loop diuretics is the predominant treatment of fluid overload, but evidence for its benefit is very uncertain when assessed in a systematic review of randomised clinical trials. The GODIF trial will assess the benefits and harms of goal directed fluid removal with furosemide versus placebo in ICU patients with fluid overload. METHODS: An investigator-initiated, international, randomised, stratified, blinded, parallel-group trial allocating 1000 adult ICU patients with fluid overload to infusion of furosemide versus placebo. The goal is to achieve a neutral fluid balance. The primary outcome is days alive and out of hospital 90 days after randomisation. Secondary outcomes are all-cause mortality at day 90 and 1-year after randomisation; days alive at day 90 without life support; number of participants with one or more serious adverse events or reactions; health-related quality of life and cognitive function at 1-year follow-up. A sample size of 1000 participants is required to detect an improvement of 8% in days alive and out of hospital 90 days after randomisation with a power of 90% and a risk of type 1 error of 5%. The conclusion of the trial will be based on the point estimate and 95% confidence interval; dichotomisation will not be used. CLINICALTRIALS: gov identifier: NCT04180397. PERSPECTIVE: The GODIF trial will provide important evidence of possible benefits and harms of fluid removal with furosemide in adult ICU patients with fluid overload.

Hemodynamic and respiratory effects of dexmedetomidine sedation in critically ill Covid-19 patients: A retrospective cohort study.

INTRODUCTION: Dexmedetomidine has been suggested to be a promising sedative for patients with Covid-19 infection (CV19). However, use of dexmedetomidine is limited by its heart rate (HR) and arterial blood pressure lowering effects. Moreover, CV19 is associated with cardiac manifestations including bradyarrythmias. The hemodynamic effects of dexmedetomidine have not been previously studied in CV19 patients. We evaluated the effects of dexmedetomidine on hemodynamic and respiratory parameters of CV19 patients. METHODS: In this single center study, all CV19 patients receiving dexmedetomidine for sedation during a one year period were included. Our primary outcomes included changes in HR, mean arterial pressure (MAP), respiratory rate (RR), partial oxygen pressure of arterial blood/fraction of inspired oxygen-ratio (PF-ratio), and Richmond Agitation and Sedation Score (RASS) during dexmedetomidine administration. RESULTS: We identified 39 patients with a mean (SD) age of 58.3 (12.7) years. After initiation of dexmedetomidine, HR decreased by 16.9 (3.3) beats/min (95% CI 9.5-22.4; p < 0.001). During the 12-hour follow-up period, HR decrease was significant at 2 to 12 h. Incident bradycardia (<45/min) was reported in 12 (30.8%) patients and it was associated with lower plasma C-reactive protein, Pro-calcitonin, and troponin T levels. There was no change in MAP compared to baseline. Dexmedetomidine administration was associated with improvement of PF-ratio (p < 0.001) and with decrease of RASS (p = 0.004). CONCLUSIONS: Dexmedetomidine is an effective sedative for CV19 patients and may improve their oxygenation. However, dexmedetomidine administration is associated with marked decline in HR and with a high incidence of bradycardia in patients with CV19.

Continuous hemodialysis with citrate anticoagulation and standard dialysate for managing acute kidney injury in patients with moderate to severe hyponatremia-A retrospective study.

BACKGROUND: The safety of continuous veno-venous hemodialysis (CVVHD) with citrate-calcium anticoagulation for acute kidney injury (AKI) with coincident hyponatremia remains unclear. We aimed to explore the feasibility of CVVHD with standard dialysate and citrate-calcium anticoagulation in hyponatremic critically ill AKI patients. METHODS: Thirty-seven of the 493 critically ill AKI patients requiring CVVHD and admitted to our intensive care unit during a 10-year period had hyponatremia (<130 mmol/L) and were included in this retrospective study. All patients received CVVHD with citrate-calcium anticoagulation and standard commercial dialysate and plasma sodium concentrations were frequently controlled until death or CVVHD discontinuation. Clinical data, mortalities and cases of central pontine myelinolysis within one-year follow-up were recorded. RESULTS: Median plasma sodium concentration was 127 (IQR 124-129) mmol/L at CVVHD initiation. CVVHD duration was median 3 (IQR 1.5-5.5) days and the mean daily sodium load of the trisodium citrate solution during the first 3 days of CVVHD was 1754 (SD 730) mmol. The plasma sodium concentration increased a median 8 (IQR 5-10) mmol/L during the first 24 hours of CVVHD and excessively high plasma sodium correction (>8 mmol/L/24 h) was observed in 18 (48.6%) patients. However, increased mortality in association to rapid plasma sodium correction was not observed in this study. CONCLUSIONS: CVVHD using standard citrate-calcium anticoagulation effectively increased plasma sodium concentration in this study. However, excessively high plasma sodium correction was observed in half of the patients and the sodium load provided by the standard citrate anticoagulation solutions was substantial.

Quality of Life Is Associated with Cardiac Biomarkers, Echocardiographic Indices, and Mortality in CKD Stage 4-5 Patients Not on Dialysis.

INTRODUCTION: Patients with CKD have an impaired health-related quality of life (QoL). Most studies have been conducted on dialysis patients, and less is known about QoL and its determinants in predialysis patients. We studied the association between QoL and comorbidities, cardiac biomarkers, echocardiography, and mortality in patients with CKD stage 4-5 not on dialysis. METHODS: A total of 140 patients enrolled in the Chronic Arterial Disease, Quality of Life and Mortality in Chronic Kidney Injury (CADKID) study filled the Kidney Disease Quality of Life Short Form (KDQOL-SF) at the beginning of the study. Echocardiography and biochemical parameters were obtained at baseline. Patients were followed up for at least 2 years or until death. RESULTS: The median age was 66 years, and 51 (36%) patients were female. The median estimated glomerular filtration rate was 13 mL/min per 1.73 m2. Obesity, diabetes, atrial fibrillation, and congestive heart failure were associated with lower QoL scores in multiple KDQOL-SF domains. Cardiac biomarkers, troponin T (p = 0.02), N-terminal pro-B-type natriuretic peptide (p = 0.006), and the echocardiographic parameter of cardiac systolic function left ventricular global longitudinal strain (p = 0.02) were significant predictors of lower physical component summary (PCS) score in multivariable regression models after controlling for age, BMI, and diabetes. A low PCS score predicted mortality in a multivariable Cox proportional hazards model [HR 0.96 (95% CI 0.92-0.99), p = 0.03]. QoL was not associated with kidney disease progression. CONCLUSION: Impaired QoL in CKD stage 4-5 patients not on dialysis is associated with cardiac biomarker levels, echocardiographic indices, and mortality.

Association of maximal stress ergometry performance with troponin T and abdominal aortic calcification score in advanced chronic kidney disease.

BACKGROUND: Cardiac biomarkers Troponin T (TnT) and N-terminal pro-B-type natriuretic peptide (proBNP) and abdominal aortic calcification score (AAC) are associated with cardiovascular events and mortality in patients with chronic kidney disease (CKD). The effects of cardiac biomarkers and AAC on maximal exercise capacity in CKD are unknown and were studied. METHODS: One hundred seventy-four CKD 4-5 patients not on maintenance dialysis underwent maximal bicycle ergometry stress testing, lateral lumbar radiograph to study AAC, echocardiography and biochemical assessments. RESULTS: The subjects with proportional maximal ergometry workload (WMAX%) less than 50% of the expected values had higher TnT, proBNP, AAC, left ventricular end-diastolic diameter, left ventricular mass index, E/e' and pulse pressure, and lower global longitudinal strain compared to the better performing patients. TnT (ß = - 0.09, p = 0.02), AAC (ß = - 1.67, p < 0.0001) and diabetes (ß = - 11.7, p < 0.0001) remained significantly associated with WMAX% in the multivariable model. Maximal ergometry workload (in Watts) was similarly associated with TnT and AAC in addition to age, male gender, hemoglobin and diastolic blood pressure in a respective multivariate model. AAC and TnT showed fair predictive power for WMAX% less than 50% of the expected value with AUCs of 0.70 and 0.75, respectively. CONCLUSIONS: TnT and AAC are independently associated with maximal ergometry stress test workload in patients with advanced CKD. TRIAL REGISTRATION: http://www.ClinicalTrials.gov NCT04223726.

Renal Replacement Techniques in Septic Shock.

Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to an infection; it carries a risk for mortality, considerably exceeding that of a mere infection. Sepsis is the leading cause for acute kidney injury (AKI) and the requirement for renal replacement therapy (RRT) in intensive care unit (ICU) patients. Almost every second critically ill patient with sepsis will develop AKI. In septic shock, the dysregulated host response to infectious pathogens leads to a cytokine storm with uncontrolled production and release of humoral proinflammatory mediators that evoke cellular toxicity and promote the development of organ dysfunction and increased mortality. In addition to treating AKI, RRT techniques can be employed for extracorporeal adsorption of inflammatory mediators using specifically developed adsorption membranes, hemoperfusion sorbent cartridges or columns; these techniques are intended to decrease the level and early deleterious effects of circulating proinflammatory cytokines and endotoxins during the first hours and days of septic shock treatment, in order to improve patient outcomes. Several methods and devices, such as high cut-off membranes, the Oxiris®-AN69 membrane, CytoSorb® and HA380 cytokine hemoadsorption, polymyxin B endotoxin adsorption, and plasmapheresis have been examined in small study series or are under evaluation as ways of improving patient outcomes in septic shock. However, to date, the data on actual outcome benefits have remained controversial, as discussed in this review.

Cardiovascular Determinants of Mortality in Advanced Chronic Kidney Disease.

BACKGROUND: Patients with advanced chronic kidney disease (CKD stage 4-5) have an increased risk of death. To study the determinants of all-cause mortality, we recruited 210 consecutive CKD stage 4-5 patients not on dialysis to the prospective Chronic Arterial Disease, quality of life and mortality in chronic KIDney injury (CADKID) study. METHODS: One hundred seventy-four patients underwent maximal bicycle ergometry stress testing and lateral lumbar radiography to study abdominal aortic calcification score and echocardiography. Carotid and femoral artery intima-media thickness and elasticity and brachial artery flow-mediated dilatation were measured in 156 patients. RESULTS: The duration of follow-up was 42 ± 17 months (range 134-2,217 days). The mean age was 61 ± 14 years, and the estimated glomerular filtration rate was 12 (11-15) mL/min/1.73 m2. Thirty-six (21%) patients died during follow-up (time to death 835 ± 372 days). Seventy-five and 21 patients had diabetes and coronary artery disease, respectively, and all but one had hypertension. In the respective multivariate proportional hazards models adjusted for age, sex, and coronary artery disease, the significant determinants of mortality were troponin T, N-terminal pro-B-type natriuretic peptide, maximal ergometry performance, abdominal aortic calcification score, E/e' ratio, and albumin. CONCLUSION: Stress ergometry performance, abdominal aortic calcification score, E/e' of echocardiography, and plasma cardiac biomarkers and albumin predict mortality in advanced CKD.

Interatrial block, P terminal force or fragmented QRS do not predict new-onset atrial fibrillation in patients with severe chronic kidney disease.

BACKGROUND: The prevalence of left atrial enlargement (LAE) and fragmented QRS (fQRS) diagnosed using ECG criteria in patients with severe chronic kidney disease (CKD) is unknown. Furthermore, there is limited data on predicting new-onset atrial fibrillation (AF) with LAE or fQRS in this patient group. METHODS: We enrolled 165 consecutive non-dialysis patients with CKD stage 4-5 without prior AF diagnosis between 2013 and 2017 in a prospective follow-up cohort study. LAE was defined as total P-wave duration ≥120 ms in lead II ± > 1 biphasic P-waves in leads II, III or aVF; or duration of terminal negative portion of P-wave > 40 ms or depth of terminal negative portion of P-wave > 1 mm in lead V1 from a baseline ECG, respectively. fQRS was defined as the presence of a notched R or S wave or the presence of ≥1 additional R waves (R') or; in the presence of a wide QRS complex (> 120 ms), > 2 notches in R or S waves in two contiguous leads corresponding to a myocardial region, respectively. RESULTS: Mean age of the patients was 59 (SD 14) years, 56/165 (33.9%) were female and the mean estimated glomerular filtration rate was 12.8 ml/min/1.73m2. Altogether 29/165 (17.6%) patients were observed with new-onset AF within median follow-up of 3 [IQR 3, range 2-6] years. At baseline, 137/165 (83.0%) and 144/165 (87.3%) patients were observed with LAE and fQRS, respectively. Furthermore, LAE and fQRS co-existed in 121/165 (73.3%) patients. Neither findings were associated with the risk of new-onset AF within follow-up. CONCLUSION: The prevalence of LAE and fQRS at baseline in this study on CKD stage 4-5 patients not on dialysis was very high. However, LAE or fQRS failed to predict occurrence of new-onset AF in these patients.

Mortality and renal prognosis in isolated metformin-associated lactic acidosis treated with continuous renal replacement therapy and citrate-calcium-anticoagulation.

INTRODUCTION: Use of metformin increases plasma lactate concentration and may lead to metformin-associated lactic acidosis (MALA). Previous studies have suggested severe MALA to have a mortality of 17%-21%, but have included patients with other coincident conditions such as sepsis. The treatment of choice is continuous renal replacement therapy (CRRT), which has been performed using heparin analogues or no anticoagulation in former studies. MATERIALS AND METHODS: Patients admitted to the Intensive Care Unit of Turku University Hospital Finland with lactic acidosis without any other recognizable etiology than concomitant metformin treatment who required CRRT between years 2010 and 2019 were included. CRRT was performed using regional citrate-calcium-anticoagulation. Data extracted included patient demographics, comorbidities, and clinical parameters at 6-hour intervals about 72 hours from admission. Creatinine and estimated glomerular filtration rate (eGFR) were measured at 1 year after MALA. RESULTS: A total of 23 patients with isolated MALA were included in the study. Median (IQR) pH was 6.88 (6.81-7.07) and lactate 16.1 (11.9-23.0) mmol/L on admission. Median (IQR) duration of CRRT was 62 (41-70) hours. Seven patients (30%) required mechanical ventilation with a mean duration of 6.0 ± 3.0 days. 90-day mortality was 4.3% and 1-year mortality 13.0%. Creatinine (P = .02) and eGFR (P = .03) remained significantly altered at 1 year of follow-up compared to baseline. CONCLUSIONS: MALA can be treated effectively and safely with CRRT and citrate-calcium-anticoagulation, usually required for 2-3 days. Mortality of patients with MALA treated with CRRT is low when other conditions inducing lactic acidosis are excluded. MALA episode may be associated with long-lasting kidney injury.

Markers of Poor Prognosis in Patients Requiring Continuous Renal Replacement Therapy After Cardiac Surgery.

OBJECTIVE: Acute kidney injury requiring renal replacement therapy after cardiac surgery has an incidence of 2% to 15%, and mortality in affected patients approximates 50%. The authors aimed to study the determinants of poor prognosis in patients receiving continuous renal replacement therapy (CRRT) after cardiac surgery. DESIGN: Retrospective, observational single-center study. SETTING: Tertiary care, university hospital. PARTICIPANTS: Cardiac surgery patients admitted to the intensive care unit (ICU) needing postoperative CRRT between January 1, 2010, and September 31, 2019. INTERVENTIONS: Predictors of mortality were examined using groupwide comparisons between ICU survivors versus nonsurvivors and univariate and multivariate Cox proportional hazards models. RESULTS: During the study period, 67 cardiac surgery patients without prior maintenance dialysis required CRRT postoperatively. ICU mortality was 47.7% and 90-day mortality was 58.2%. Only 37.3% of patients were alive at 1 year after surgery. Blood lactate at the start of dialysis was the most significant predictor of ICU and overall mortality. Eighty-seven percent of patients with lactate >3 mmol/L died in the ICU compared with 27.3% of patients with lactate ≤3 mmol/L (p < 0.0001). In patients with lactate exceeding 5.3 mmol/L, ICU mortality was 100%. In a stepwise multivariate Cox proportional hazards model, the association with mortality remained significant for lactate at the start of CRRT (per 1 mmol/L, hazard ratio [HR] 1.19 [95% confidence interval {CI} 1.11-1.28], p < 0.0001), troponin T on the first postoperative morning (per 0.1 µg/L, HR 1.004 [95% CI 1.001-1.008], p = 0.01), and 72-hour fluid balance (per 1000 mL, HR 1.12 [95% CI 1.04-1.21], p = 0.005). CONCLUSION: Blood lactate at the start of dialysis was the most significant predictor of ICU and overall mortality in patients with CRRT after cardiac surgery.

Survival, cumulative hospital days and infectious complications in urgent-start PD compared with urgent-start HD.

BACKGROUND: Urgent-start peritoneal dialysis (PD) carries a similar efficacy and safety profile compared to urgent-start haemodialysis (HD) but is only sparsely applied due to resource issues and concerns of complication risks. Furthermore, few data exist on adverse outcomes associated with central venous catheter (CVC) insertions in urgent-start HD patients. Thus, we sought to compare patient and dialysis-related outcomes in patients undergoing urgent-start PD or HD. METHODS: All patients initiating urgent-start PD in a tertiary research hospital in 2005-2018 were included in this retrospective, single-centre, comparative study and matched with urgent-start HD patients of similar age and chronic kidney disease aetiology. All urgent-start PDs were initiated within 72 h after catheter insertion, and urgent-start HDs were performed via a CVC. All analyses were performed at 3 months and at 1 year of follow-up, respectively. RESULTS: Thirty-three patients who commenced urgent-start PD and 58 matched urgent-start HD control patients were included. Altogether, 26 patients (29%; PD: 36%, HD 24%) died within the 1-year follow-up, and patient survival was similar at 3 months (hazard ratio (HR): 1.15, 95% confidence interval (CI): 0.35-3.81, p = 0.82) and at 1 year of follow-up (HR: 0.64, 95% CI: 0.30-1.39, p = 0.26) between the study groups. There were no differences in the total kidney replacement therapy (KRT)-related infection rate (p = 0.66) or cumulative first-year hospital care days (p = 0.43) between the treatment groups. Altogether, 139 CVCs were inserted during the 1-year follow-up. The number of CVCs per patient was associated with the emergence of blood culture-positive bacteraemia and increased cumulative first-year hospital care days. CONCLUSIONS: Patient survival, cumulative first-year hospital care days and total KRT-related infection rate at 3 months and 1-year follow-up are similar between urgent-start PD and urgent-start HD patients. Furthermore, CVC insertion rate is associated with incident blood culture-positive bacteraemia and increased cumulative first-year hospital care days.

Chloride, Sodium and Calcium Intake Are Associated with Mortality and Follow-Up Kidney Function in Critically Ill Patients Receiving Continuous Veno-Venous Hemodialysis-A Retrospective Study.

BACKGROUND: Studies on the association between solute, nutrition and fluid intakes and mortality and later kidney function in critically ill acute kidney injury (AKI) patients receiving continuous veno-venous hemodialysis (CVVHD) are scarce. METHODS: Altogether, 471 consecutive critically ill AKI patients receiving CVVHD in the research intensive care unit (ICU) were recruited in this single-center, retrospective study. RESULTS: The median age was 66 (58-74) years, and 138 (29.3%) were female. The 90-day and one-year mortalities were 221 (46.9%) and 251 (53.3%), respectively. After adjusting for age, sex, Acute Physiology and Chronic Health Evaluation II (APACHE) score, coronary artery disease, immunosuppression, ICU care duration, mechanical ventilation requirement, vasopressor requirement and study time period, the cumulative daily intake of potassium, chloride, sodium, phosphate, calcium, glucose, lipids and water was associated with one-year mortality in separate multivariable cox proportional hazards models. In a sensitivity analysis excluding patients who died within the first three days of ICU care, the daily intake of chloride (hazard ratio (HR) 1.001, confidence interval (CI) 95% 1.000-1.003, p = 0.032), sodium (HR 1.001, CI 95% 1.000-1.002, p = 0.031) and calcium (HR 1.129, CI 95% 1.025-1.243, p = 0.014) remained independently associated with mortality within one-year in the respective, similarly adjusted multivariable cox analyses. The cumulative daily intake of chloride, sodium, calcium and water was independently associated with the estimated glomerular filtration rate (eGFR) at 90 days follow-up in separate substantially adjusted multivariable cox proportional hazards models. CONCLUSION: The cumulative daily intake of chloride, sodium and calcium is associated with mortality and daily chloride, sodium, calcium and water intake is associated with follow-up eGFR in critically ill patients with CVVHD-treated AKI.

Pre-emptive vs. classic criteria for initiation of dialysis in critically ill patients with acute kidney injury (AKI) - A retrospective real-world study.

INTRODUCTION: Guidelines recommend starting renal replacement therapy (RRT) in critically ill acute kidney injury (AKI) patients according to classic criteria for the initiation of dialysis (CCID). However, comparative data on the presence or absence of CCID in patients receiving continuous veno-venous hemodialysis (CVVHD) or intermittent hemodialysis (IHD) as the initial modality are scarce. METHODS: Altogether 733 critically ill AKI patients receiving CVVHD or IHD at the research hospital between 2010 and 2019 were screened for this real-world study. All patients on maintenance dialysis were excluded. Patient survival was studied in 662 patients and adverse renal outcomes in 375 surviving patients at 90 days follow-up. The adverse renal outcome was defined as RRT requirement and the secondary outcome was estimated glomerular filtration rate (eGFR) at 90 days follow-up. FINDINGS: Altogether 472 (71.3%) patients received CVVHD and 190 (28.7%) IHD, and CCID was present at the time of RRT initiation in 250 (37.8%). The CCID was independently associated with mortality in a multivariable logistic regression analysis (odds ratio [OR] 2.226, 95% confidence interval [CI] 1.455-3.407, p < 0.001) adjusted for age, sex, baseline eGFR, disease severity, RRT modality, hypertension, and diabetes. The presence of CCID at the start of RRT was not associated with adverse renal outcome (OR 0.548, 95% CI 0.230-1.305, p = 1.74) nor eGFR (ß = 0.155, p = 0.066) at 90 days follow-up. However, starting RRT in the presence of CCID was independently associated with eGFR at 90 days follow-up in a multivariable ordinal regression analysis (ß = 0.930, p = 0.018) after adjusting for age, sex, baseline eGFR, disease severity markers, hypertension, and diabetes in patients receiving CVVHD but not IHD as the initial modality. DISCUSSION: The presence of CCID at the initiation of RRT was associated with mortality but not adverse renal outcomes in this large real-world study on critically ill AKI patients requiring RRT. Initiating RRT in the presence of CCID was associated with improved eGFR at 90 days follow-up in patients receiving CVVHD as the initial modality.

Predicting mortality in critically ill patients requiring renal replacement therapy for acute kidney injury in a retrospective single-center study of two cohorts.

Half of the critically ill patients with renal replacement therapy (RRT) dependent acute kidney injury (AKI) die within one year despite RRT. General intensive care prediction models perform inadequately in AKI. Predictive models for mortality would be an invaluable complementary tool to aid clinical decision making. We aimed to develop and validate new prediction models for intensive care unit (ICU) and hospital mortality customized for patients with RRT dependent AKI in a retrospective single-center study. The models were first developed in a cohort of 471 critically ill patients with continuous RRT (CRRT) and then validated in a cohort of 193 critically ill patients with intermittent hemodialysis (IHD) as the primary modality for RRT. Forty-two risk factors for mortality were examined at ICU admission and CRRT initiation, respectively, in the first univariate models followed by multivariable model development. Receiver operating characteristics curve analyses were conducted to estimate the area under the curve (AUC), to measure discriminative capacity of the models for mortality. AUCs of the respective models ranged between 0.76 and 0.83 in the CRRT model development cohort, thereby showing acceptable to excellent predictive power for the mortality events (ICU mortality and hospital mortality). The models showed acceptable external validity in a validation cohort of IHD patients. In the IHD validation cohort the AUCs of the MALEDICT RRT initiation model were 0.74 and 0.77 for ICU and hospital mortality, respectively. The MALEDICT model shows promise for mortality prediction in critically ill patients with RRT dependent AKI. After further validation, the model might serve as an additional clinical tool for estimating individual mortality risk at the time of RRT initiation.