Echocardiographic parameters and hemodynamic instability at the initiation of continuous kidney replacement therapy.

OBJECTIVE: Investigate the association of echocardiographic parameters with hemodynamic instability after initiating continuous kidney replacement therapy (CKRT) in a cohort of intensive care unit (ICU) patients requiring CKRT. METHODS: Historical cohort study of consecutive adults admitted to the ICU at a tertiary care hospital from December 2006 through November 2015 who underwent CKRT and had an echocardiogram done within seven days before CKRT initiation. The primary outcome was hypotension within one hour of CKRT initiation. RESULTS: We included 980 patients, 804 (82%) with acute kidney injury (AKI) and 176 (18%) with end-stage kidney disease (ESKD). Median patient age was 63 (± 14) years, and median Sequential Organ Failure Assessment (SOFA) score on the day of CKRT initiation was 12 (IQR 10-14). Multivariable analysis showed that Left (OR 2.01, 95% CI 1.04-3.86), and Right (OR 1.5, 95% CI 1.04-2.25) moderate and severe ventricular enlargement, Vasoactive-Inotropic Score (VIS) one hour before CKRT initiation (OR 1.18 per 10 units increase, 95% CI 1.09-1.28) and high bicarbonate fluid replacement (OR 2.52, 95% CI 1.01-6.2) were associated with hypotension after CKRT initiation. CONCLUSION: Right and left ventricular enlargement are risk factors associated with hypotension after CKRT initiation.

Prolonged exposure to continuous renal replacement therapy in patients with acute kidney injury.

BACKGROUND: Little is known about the process of deciding to discontinue continuous renal replacement therapy (CRRT) in patients with acute kidney injury (AKI) and the impact of CRRT duration on outcomes. METHODS: We report the clinical parameters of prolonged CRRT exposure and predictors of doubling of serum creatinine or need for dialysis at 90 days after CRRT with propensity score matching, including covariates that were likely to influence patients in the prolonged CRRT group. RESULTS: Among 104 survey responders, most use urine output (87%) to guide CRRT discontinuation, 24% use improvement in clinical or hemodynamic status. In the cohort study, of 854 included patients, 465 participated in the assessment of kidney recovery. Patients with prolonged CRRT had higher SOFA scores (11.9 vs. 11.2) and were more likely to be mechanically ventilated (99% vs. 84%) at CRRT initiation compared to patients without prolonged CRRT, p-value < 0.05. In multivariable logistic regression, daily urine output and cumulative fluid balance leading to CRRT discontinuation or day seven were independently associated with lower [OR 0.87 per 200 ml/day increase] and higher odds [OR 1.03 per 1-L increase] of requiring prolonged CRRT, respectively. After propensity score matching, prolonged exposure to CRRT was independently associated with increased risk of doubling serum creatinine or dialysis at 90 days, OR 3.1 (95% CI 1.23-8.3 p = 0.017). CONCLUSIONS: Resolution of critical illness and signs of kidney recovery are important factors when considering CRRT discontinuation. Prolonged CRRT exposure may be associated with less chance of kidney recovery among survivors.

New-onset atrial fibrillation in patients with acute kidney injury on continuous renal replacement therapy.

PURPOSE: The mortality of critically ill patients with acute kidney injury (AKI) who require continuous renal replacement therapy (CRRT) remains high. We assessed the incidence and predictors of new-onset atrial fibrillation (NOAF) in this population and its impact on outcomes. MATERIALS AND METHODS: This is a retrospective cohort study of adult intensive care units (ICU) patients who had AKI and received CRRT from December 2006 through November 2015 in a tertiary academic medical center. Cox proportional hazard model was used to evaluate the impact of NOAF on overall mortality. RESULTS: Out of 1398 screened patients, NOAF occurred in 193 (14%) cases. NOAF occurring on CRRT was independently associated with an increased hazard of death at follow-up (HR: 1.26; 95% CI: 1.03-1.56), compared to the group who did not have NOAF. In the multivariable analysis using time-dependent covariates, higher potassium (HR 1.24, 95%CI: 1.01-1.54) and bicarbonate (HR 0.95, 95%CI: 0.92-0.98) levels were associated with increased and decreased risk of NOAF on CRRT, respectively. CONCLUSIONS: NOAF in critically ill patients with AKI receiving CRRT is common and carries an unfavorable prognosis. Prospective studies are required to elucidate modifiable risk factors for NOAF occurring on CRRT.

Hemoglobinuria in the Early Poststem-Cell-Transplant Period: Risk Factors and Association with Outcomes.

Background: Information on risk factors of hemoglobinuria after hematopoietic stem-cell transplant (HSCT) and its association with AKI, mortality, and engraftment is limited. Methods: We conducted a retrospective cohort study on all consecutive adults that underwent HSCT from January 6, 1999, to November 6, 2017. The study included 6039 patients that underwent bone marrow transplantation (BMT), umbilical cord blood, and peripheral blood stem-cell transplantation (PBSCT). Results: Early post-HSCT, AKI occurred in 393 (7%) patients, and 52 (0.9%) patients had post-HSCT hemoglobinuria. Post-HSCT hemoglobinuria was associated with graft type (BMT+Cord), underlying disease (lymphoma, acute leukemia), and fludarabine-based conditioning regimen. Post-HSCT hemoglobinuria was associated with early (48-72 hours) post-HSCT AKI. Graft type (BMT+Cord) was associated with AKI among patients with hemoglobinuria. AKI in patients with hemoglobinuria was associated with delayed platelet engraftment and delayed WBC engraftment but not 100-day mortality. Conclusion: Close monitoring is recommended in this patient group to facilitate a good engraftment outcome.

Change in right ventricular systolic function after continuous renal replacement therapy initiation and renal recovery.

OBJECTIVE: To describe the associations between right ventricular (RV) function and outcomes of patients with acute kidney injury (AKI) requiring continuous renal replacement therapy (CRRT). METHODS: This is a retrospective study, conducted 2006-2015 at an academic hospital in USA. We included patients with AKI requiring CRRT who had paired echocardiograms within 2 weeks before and after CRRT initiation. We defined improvement in RV systolic function as 2-point improvement on the semiquantitative scale. RESULTS: The cohort included 201 patients. The mean(±SD) age was 59(±16) years with 83(41%) female. The median time of the pre and post echocardiograms relative to CRRT initiation were - 1 day (IQR-3;0) prior to and 3 days (IQR1;7) after CRRT initiation. Thirty-one (15%) patients showed an improvement in their RV function. Using a multivariable logistic regression model, improvement in RV systolic function was associated with lower odds of major adverse kidney events (composite of mortality, need for dialysis or persistently elevated serum creatinine) at 90 days with odds ratio (OR) of 0.37(95%CI:0.17-0.84, p.016). Positive cumulative fluid balance was associated with lower odds of improvement in RV function (OR 0.95 per 1-l increase, p 0.045). CONCLUSION: Serial assessment of RV function among patients with AKI requiring CRRT could provide prognostic value.

Short, and long-term mortality among cardiac intensive care unit patients started on continuous renal replacement therapy.

PURPOSE: Patients requiring continuous renal replacement therapy (CRRT) are at high risk of death. Predictors of hospital mortality and post-discharge survival in cardiac intensive care unit (CICU) patients requiring CRRT have not been reported. MATERIALS AND METHODS: Retrospective review of 198 CICU patients undergoing CRRT from 2006 to 2015. Multivariable regression identified predictors of hospital mortality and Cox proportional-hazards identified predictors of post-discharge mortality among hospital survivors. RESULTS: The indication for CRRT was volume overload in 129 (65%) and metabolic abnormalities in 76 (38%). 105 (53%) subjects died in hospital, with 22% dialysis-free hospital survival. Cardiogenic shock was present in 159 (80%) subjects; 150 (76%) subjects received vasopressors and 101 (51%) subjects required mechanical ventilation. Hospital mortality was similar in cardiogenic and non-cardiogenic causes of CICU admission. Predictors of hospital death included semi-quantitative RV function, Braden score, VIS, and PaO2/FIO2 ratio. Median post-discharge Kaplan-Meier survival was 1.9 years. Predictors of post-hospital death included age, VIS, diabetes, Braden score, semi-quantitative RV function, prior heart failure, and dialysis dependence. The indication for CRRT was not predictive of survival. CONCLUSION: Mortality is high among CICU patients requiring CRRT, and is predicted by the Braden score, RV dysfunction, respiratory failure and vasopressor load.

Hypotension within one-hour from starting CRRT is associated with in-hospital mortality.

PURPOSE: To investigate early hemodynamic instability and its implications on adverse outcomes in patients who require continuous renal replacement therapy (CRRT). MATERIALS AND METHODS: A retrospective study of patients admitted to the intensive care unit (ICU) and underwent CRRT at Mayo Clinic, Rochester, Minnesota between December 2006 through November 2015. RESULTS: Multivariate logistic regression was performed to identify predictors of in-hospital mortality and major adverse kidney events (MAKE) at 90 days. Hypotension was defined as any of the following criteria occurring during the first hour of CRRT initiation: mean arterial pressure < 60 mmHg, systolic blood pressure (SBP) <90 mmHg or a decline in SBP >40 mmHg from baseline, a positive fluid balance >500 mL or increased vasopressor requirement. The analysis included 1743 patients, 1398 with acute kidney injury (AKI). In-hospital mortality occurred in 884 patients (51%). Early hypotension occurred in 1124 patients (64.6%) and remained independently associated with in-hospital mortality (OR 1.56, 95% CI: 1.25-1.9). CONCLUSION: Hypotension occurs frequently in patients receiving CRRT despite having a reputation as the dialysis modality with better hemodynamic tolerance. It is an independent predictor for worse outcomes. Further studies are required to understand this phenomenon.

Echocardiographic parameters of patients in the intensive care unit undergoing continuous renal replacement therapy.

MAIN OBJECTIVES: Echocardiographic parameters have been used to predict outcomes for specific intensive care unit (ICU) populations. We sought to define echocardiographic parameters for ICU patients receiving continuous renal replacement therapy (CRRT). DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: This is a historical cohort study of consecutive ICU patients at Mayo Clinic (Rochester, Minnesota) who received CRRT from December 9, 2006, through November 13, 2015. Only patients with an echocardiographic examination within 7 days of CRRT initiation were considered. RESULTS: The study included 1,276 patients. Decreased left ventricular ejection fraction (LVEF; ≤45%) was noted in 361/1,120 (32%) and increased right ventricular systolic pressure (RVSP; ≥40 mm Hg) was noted in 529/798 (66%). Right ventricular systolic dysfunction was observed in 320/820 (39%). The most common valvular abnormality was tricuspid regurgitation (244/1,276 [19%]). Stratification of these parameters by ICU type (medical, surgical, cardiothoracic, cardiac) showed that most echocardiographic abnormalities were significantly more prevalent among cardiac ICU patients: LVEF ≤45% (67/105 [64%]), RVSP ≥40 mm Hg (63/79 [80%]) and tricuspid regurgitation (50/130 [38%]). We compared patients with acute kidney injury (AKI) vs end-stage renal disease and showed that decreased LVEF (284/921 [31%] vs 78/201 [39%]), was significantly less prevalent among patients with AKI, but increased RVSP was more prevalent (445/651 [68%] vs 84/147 [57%]) with AKI. CONCLUSIONS: ICU patients who required CRRT had increased prevalence of pulmonary hypertension and right and left ventricular systolic dysfunction. Prediction of adverse outcomes with echocardiographic parameters in this patient population can lead to identification of modifiable risk factors.

Association between urologic malignancies and end-stage renal disease: A meta-analysis.

AIM: Previous studies have suggested a higher incidence of urologic malignancies in end-stage renal disease (ESRD) patients. However, incidence trends of urologic malignancies in ESRD patients remain unclear. The aims of the present study were: (i) to investigate the pooled incidence/incidence trends; and (ii) to assess the risk of urologic malignancies in ESRD patients. METHODS: A literature search was conducted using MEDLINE, EMBASE and Cochrane Database from inception through April 2017. Studies that reported incidence or odds ratios of urologic malignancies among ESRD patients were included. Pooled odds ratios (OR) and 95%CI were calculated using a random-effect model. The protocol for this meta-analysis is registered with PROSPERO (International Prospective Register of Systematic Reviews; no. CRD42017067687). RESULTS: Nineteen observational studies with 1 931 073 ESRD patients were enrolled. The pooled estimated incidence of kidney cancer and urothelial cancers (carcinomas of the bladder, ureters, and renal pelvis) in ESRD patients were 0.3% (95%CI: 0.2-0.5%) and 0.5% (95%CI: 0.3-0.8%), respectively. Meta-regression showed significant positive correlation between incidence of urologic malignancies in ESRD patients and year of study (slopes = +0.05 and +0.07, P < 0.001 for kidney cancer and urothelial cancers, respectively). Compared to non-ESRD status, ESRD was significantly associated with both kidney cancer (pooled OR 6.04; 95% CI 4.70-7.77) and urothelial cancers (pooled OR 4.37; 95% CI 2.40-7.96). CONCLUSION: Our study demonstrates a significant association between ESRD and urologic malignancies. The overall estimated incidence rates of kidney cancer and urothelial cancers are 0.4% and 0.5%, respectively. There is a significant positive correlation between the incidence of urologic malignancies and year of study.

Programmed cell death protein 1 inhibitor treatment is associated with acute kidney injury and hypocalcemia: meta-analysis.

Background: The aim of this meta-analysis was to assess the risks and incidence of nephrotoxicity and electrolyte abnormalities in patients receiving programmed cell death protein 1 (PD-1) inhibitors. Methods: We conducted a meta-analysis of clinical trials that monitored electrolyte levels and kidney functions during treatment with nivolumab or pembrolizumab by searching MEDLINE, EMBASE and the Cochrane Database from inception through April 2017. Our protocol is registered with International Prospective Register of Systematic Reviews; no.CRD42017060579. Results: A total of 48 clinical trials with a total of 11 482 patients were included. The overall pooled risk ratios (RR) of all acute kidney injury (AKI) and all electrolyte abnormalities in patients treated with PD-1 inhibitors were 1.86 [95% confidence interval (CI) 0.95-3.64] and 1.67 (95% CI 0.89-3.12), respectively. Compared with non-nephrotoxic controls, the pooled RR of AKI in patients treated with PD-1 inhibitors was 4.19 (95% CI 1.57-11.18). Prespecified subgroup analyses demonstrated a significant association between PD-1 inhibitors and hypocalcemia with a pooled RR of 10.87 (95% CI 1.40-84.16). The pooled estimated incidence rates of AKI and hypocalcemia in patients treated with PD-1 inhibitors were 2.2% (95% CI 1.5-3.0%) and 1.0% (95% CI 0.6-1.8%), respectively. Among patients who developed AKI with PD-1 inhibitors, the pooled estimated rate of interstitial nephritis was 16.6% (95% CI 10.2-26.0%). Conclusions: Treatment with PD-1 inhibitors is associated with a higher risk of AKI compared with non-nephrotoxic agents. It will be important to characterize the AKI patients to better understand the etiology behind the event. In addition, treatment with PD-1 inhibitors is associated with an increased risk of hypocalcemia. This study highlights a rare but serious adverse event of anti-PD-1 antibodies and we recommend, in addition to electrolytes panel, routine calcium monitoring.