The role of biomarkers in early identification of acute kidney injury among non-critically ill patients.

BACKGROUND: Prediction and/or early identification of acute kidney injury (AKI) and individuals at greater risk remains of great interest in clinical medicine. Acute kidney injury continues to be a common complication among hospitalized patients, with an incidence ranging from 6 to 58%, depending on the setting. Aim of this study was to determine the performance of Insulin-like growth factor binding protein-7 (IGFBP7), tissue metallopeptidase inhibitor 2 (TIMP2), and urinary neutrophil gelatinase-associated lipocalin (uNGAL) in early detection of AKI among non-critically ill patients. METHODS: In this prospective observational study at Mayo Clinic Hospitals in Rochester, Minnesota, USA, non-critically ill patients admitted from the emergency department between October 31st, 2016 and May 1st, 2018, who had an acute kidney injury (AKI) probability of 5% or higher were included. Biomarkers were measured in residual urine samples collected in the emergency department. The primary outcome was biomarker performance in predicting AKI development within the first 72 h. RESULTS: Among 368 included patients, the mean age was 79 ± 12 years, and 160 (43%) were male. Acute kidney injury occurred in 62 (17%) patients; 11.5% stage 1, 2.5% stage 2, and 3% stage 3. Twelve patients (3%) died during hospitalization and 102 (28%) within nine months after admission. The median uNGAL and IGFBP7-TIMP2 were 57 [20-236 ng/ml], and 0.3 [0.1-0.8], respectively. The C-statistic of uNGAL and IGFBP7-TIMP2 of > 0.3 and > 2.0 for AKI prediction were 0.56, 0.54, and 0.53, respectively. In a model where one point is assigned to each marker of AKI (elevated serum creatinine, IGFBP7-TIMP2 > 0.3, and uNGAL), a higher score correlated with higher nine-month mortality [OR of 1.32 per point (95% CI 1.02-1.71)]. CONCLUSION: Among non-critically ill hospitalized patients, the performance of uNGAL and IGFBP7-TIMP2 for AKI prediction within 72 h of admission was modest. This suggests a limited role for these biomarkers in AKI risk stratification among non-critically ill patients. Key learning points What was known Acute kidney injury (AKI) is a common complication among hospitalized patients. It is associated with increased morbidity and mortality. Various clinical prediction models and biomarkers have been developed to identify patients in special populations (such as ICU and cardiac surgery) who are at risk of AKI and diagnose AKI early. This study adds The performance of the biomarkers uNGAL, TIMP-2, and IGFBP-7 in predicting AKI within 72 h of admission in non-critically ill patients was modest. However, these biomarkers were found to have a prognostic value for predicting 9-month mortality. One potential application of these biomarkers is identifying patients at higher AKI risk before exposing them to nephrotoxic agents. Potential impact This study provides evidence regarding the real-world performance of current FDA-approved biomarkers (uNGAL, TIMP-2, and IGFBP-7) for predicting acute kidney injury (AKI) within 72 h of hospital admission among noncritically ill patients. While the performance of these biomarkers for predicting short-term AKI was modest, they may have a prognostic value for predicting 9-month mortality.

Use of Ultrasound to Assess Hemodynamics in Acutely Ill Patients.

Early diagnosis of AKI and preventive measures can likely decrease the severity of the injury and improve patient outcomes. Current hemodynamic monitoring variables, including BP, heart and respiratory rates, temperature, and oxygenation status, have been used to identify patients at high risk for AKI. Despite the widespread use of such variables, their ability to accurately and timely detect patients who are high risk has been questioned. Therefore, there is a critical need to develop and validate tools that can measure new and more kidney-specific hemodynamic and laboratory variables, potentially assisting with AKI risk stratification, implementing appropriate and timely preventive measures, and hopefully improved outcomes. The new ultrasonography techniques provide novel insights into kidney hemodynamics and potential management and/or therapeutic targets. Contrast-enhanced ultrasonography; Doppler flow patterns of hepatic veins, portal vein, and intrakidney veins; and ultrasound elastography are among approaches that may provide such information, particularly related to vascular changes in AKI, venous volume excess or congestion, and fluid tolerance. This review summarizes the current state of these techniques and their relevance to kidney hemodynamic management.

A novel method of calculating stroke volume using point-of-care echocardiography.

BACKGROUND: Point-of-care transthoracic echocardiography (POC-TTE) is essential in shock management, allowing for stroke volume (SV) and cardiac output (CO) estimation using left ventricular outflow tract diameter (LVOTD) and left ventricular velocity time integral (VTI). Since LVOTD is difficult to obtain and error-prone, the body surface area (BSA) or a modified BSA (mBSA) is sometimes used as a surrogate (LVOTDBSA, LVOTDmBSA). Currently, no models of LVOTD based on patient characteristics exist nor have BSA-based alternatives been validated. METHODS: Focused rapid echocardiographic evaluations (FREEs) performed in intensive care unit patients over a 3-year period were reviewed. The age, sex, height, and weight were recorded. Human expert measurement of LVOTD (LVOTDHEM) was performed. An epsilon-support vector regression was used to derive a computer model of the predicted LVOTD (LVOTDCM). Training, testing, and validation were completed. Pearson coefficient and Bland-Altman were used to assess correlation and agreement. RESULTS: Two hundred eighty-seven TTEs with ideal images of the LVOT were identified. LVOTDCM was the best method of SV measurement, with a correlation of 0.87. LVOTDmBSA and LVOTDBSA had correlations of 0.71 and 0.49 respectively. Root mean square error for LVOTDCM, LVOTDmBSA, and LVOTDBSA respectively were 13.3, 37.0, and 26.4. Bland-Altman for LVOTDCM demonstrated a bias of 5.2. LVOTDCM model was used in a separate validation set of 116 ideal images yielding a linear correlation of 0.83 between SVHEM and SVCM. Bland Altman analysis for SVCM had a bias of 2.3 with limits of agreement (LOAs) of - 24 and 29, a percent error (PE) of 34% and a root mean square error (RMSE) of 13.9. CONCLUSIONS: A computer model may allow for SV and CO measurement when the LVOTD cannot be assessed. Further study is needed to assess the accuracy of the model in various patient populations and in comparison to the gold standard pulmonary artery catheter. The LVOTDCM is more accurate with less error compared to BSA-based methods, however there is still a percentage error of 33%. BSA should not be used as a surrogate measure of LVOTD. Once validated and improved this model may improve feasibility and allow hemodynamic monitoring via POC-TTE once it is validated.

Successful Moderation in Online Patient Communities: Inductive Case Study.

BACKGROUND: Online patient communities are becoming more prevalent as a resource to help patients take control of their health. However, online patient communities experience challenges that require active moderation. OBJECTIVE: This study aimed to identify the challenges of sustaining a thriving online patient community and the moderation practices employed to address the challenges and manage the online patient community successfully. METHODS: An inductive case study of Mayo Clinic Connect was analyzed using the grounded theory methodology. Insights for the analysis were obtained from semistructured interviews with community managers and community members. Secondary data sources, such as community management documents, observational meeting notes, and community postings, were used to validate and triangulate the findings. RESULTS: We identified four challenges unique to online patient communities. These challenges include passion, nonmedical advice, personal information, and community participation. We identified five categories of practices that community members used to address these challenges and moderate the community successfully. These practices include instructive, semantic, connective, administrative, and policing practices. CONCLUSIONS: Successful moderation in online patient communities requires a multitude of practices to manage the challenges that arise in these communities. Some practices are implemented as preventive measures while other practices are more interventive. Additionally, practices can come from both authority figures and exemplary members.

Risk Factors for Acute Kidney Injury in Hospitalized Non-Critically Ill Patients: A Population-Based Study.

OBJECTIVE: To develop and validate an acute kidney injury (AKI) risk prediction model for hospitalized non-critically ill patients. PATIENTS AND METHODS: We retrospectively identified all Olmsted County, Minnesota, residents admitted to non-intensive care unit (ICU) wards at Mayo Clinic Hospital, Rochester, Minnesota, in 2013 and 2014. The cohort was divided into development and validation sets by year. The primary outcome was hospital-acquired AKI defined by Kidney Disease: Improving Global Outcomes criteria. Cox regression was used to analyze mortality data. Comorbid risk factors for AKI were identified, and a multivariable model was developed and validated. RESULTS: The development and validation cohorts included 3816 and 3232 adults, respectively. Approximately 10% of patients in both cohorts had AKI, and patients with AKI had an increased risk of death (hazard ratio, 3.62; 95% CI, 2.97-4.43; P<.001). Significant univariate determinants of AKI were preexisting kidney disease, diabetes mellitus, hypertension, heart failure, vascular disease, coagulopathy, pulmonary disease, coronary artery disease, cancer, obesity, liver disease, and weight loss (all P<.05). The final multivariable model included increased baseline serum creatinine value, admission to a medical service, pulmonary disease, diabetes mellitus, kidney disease, cancer, hypertension, and vascular disease. The area under the receiver operating characteristic curves for the development and validation cohorts were 0.71 (95% CI, 0.69-0.75) and 0.75 (95% CI, 0.72-0.78), respectively. CONCLUSION: Hospital-acquired AKI is common in non-ICU inpatients and is associated with worse outcomes. Patient data at admission can be used to identify increased risk; such patients may benefit from more intensive monitoring and earlier intervention and testing with emerging biomarkers.

Tele-Ultrasound in Resource-Limited Settings: A Systematic Review.

Background: Telemedicine, or healthcare delivery from a distance, has evolved over the past 50 years and helped alter health care delivery to patients around the globe. Its integration into numerous domains has permitted high quality care that transcends obstacles of geographic distance, lack of access to health care providers, and cost. Ultrasound is an effective diagnostic tool and its application within telemedicine ("tele-ultrasound") has advanced substantially in recent years, particularly in high-income settings. However, the utility of tele-ultrasound in resource-limited settings is less firmly established. Objective: To determine whether remote tele-ultrasound is a feasible, accurate, and care-altering imaging tool in resource-limited settings. Data Sources: PubMed, MEDLINE, and Embase. Study Eligibility Criteria: Twelve original articles met the following eligibility criteria: full manuscript available, written in English, including a direct patient-care intervention, performed in a resource-limited setting, images sent to a remote expert reader for interpretation and feedback, contained objective data on the impact of tele-ultrasound. Study Appraisal and Synthesis Methods: Abstracts were independently screened by two authors against inclusion criteria for full-text review. Any discrepancies were settled by a senior author. Data was extracted from each study using a modified Cochrane Consumers and Communication Review Group's data extraction template. Study bias was evaluated using the ROBINS-I tool. Results: The study results reflect the diverse applications of tele-ultrasound in low-resource settings. Africa was the most common study location. The specialties of cardiology and obstetrics comprised most studies. Two studies primarily relied on smartphones for image recording and transmission. Real-time, rather than asynchronous, tele-ultrasound image interpretation occurred in five of the 12 studies. The most common outcome measures were image quality, telemedicine system requirements, diagnostic accuracy, and changes in clinical management. Limitations: The studies included were of poor quality with a dearth of randomized control trials and with significant between study heterogeneity which resulted in incomplete data and made cross study comparison difficult. Conclusions and Implications of Key Findings: Low-quality evidence suggests that ultrasound images acquired in resource-limited settings and transmitted using a telemedical platform to an expert interpreter are of satisfactory quality and value for clinical diagnosis and management.

Prospective Study of Routine Heparin Avoidance Hemodialysis in a Tertiary Acute Care Inpatient Practice.

INTRODUCTION: Extracorporeal circuit (EC) anticoagulation with heparin is a key advance in hemodialysis (HD), but anticoagulation is problematic in inpatients at risk of bleeding. We prospectively evaluated a heparin-avoidance HD protocol, clotting of the EC circuit (CEC), impact on dialysis efficiency, and associated risk factors in our acute care inpatients who required HD (January 17, 2014 to May 31, 2015). METHODS: HD sessions without routine EC heparin were performed using airless dialysis tubing. Patients received systemic anticoagulation therapy and/or antiplatelets for non-HD indications. We observed patients for indications of CEC (interrupted HD session, circuit loss, or inability to return blood). The primary outcome was CEC. Logistic regression with generalized estimating equations assessed associations between CEC and other variables. RESULTS: HD sessions (n = 1200) were performed in 338 patients (204 with end-stage renal disease; 134 with acute kidney injury); a median session was 211 minutes (interquartile range [IQR]: 183-240 minutes); delivered dialysis dose measured by Kt/V was 1.4 (IQR: 1.2 Kt/V 1.7). Heparin in the EC was prescribed in only 4.5% of sessions; EC clotting rate was 5.2%. Determinants for CEC were temporary catheters (odds ratio [OR]: 2.8; P < 0.01), transfusions (OR: 2.4; P = 0.04), therapeutic systemic anticoagulation (OR: 0.2; P < 0.01), and antiplatelets (OR: 0.4; P < 0.01). CEC was associated with a lower delivered Kt/V (difference: 0.39; P < 0.01). Most CEC events during transfusions (71%) occurred with administration of blood products through the HD circuit. DISCUSSION: We successfully adopted heparin avoidance using airless HD tubing as our standard inpatient protocol. This protocol is feasible and safe in acute care inpatient HD. CEC rates were low and were associated with temporary HD catheters and transfusions. Antiplatelet agents and systemic anticoagulation were protective.ClinicalTrials.gov Identifier:NCT02086682.

Association between kidney intracapsular pressure and ultrasound elastography.

BACKGROUND: Kidney congestion is a common pathophysiologic pathway of acute kidney injury (AKI) in sepsis and heart failure. There is no noninvasive tool to measure kidney intracapsular pressure (KIP) directly. METHODS: We evaluated the correlation of KIP with kidney elasticity measured by ultrasound surface wave elastography (USWE). We directly measured transcatheter KIP in three pigs at baseline and after bolus infusion of normal saline, norepinephrine, vasopressin, dopamine, and fenoldopam; infiltration of 2-L peritoneal dialysis solution in the intra-abdominal space; and venous, arterial, and ureteral clamping. KIP was compared with USWE wave speed. RESULTS: Only intra-abdominal installation of peritoneal dialysis fluid was associated with significant change in KIP (mean (95% CI) increase, 3.7 (3.2-4.2)] mmHg; P < .001). Although intraperitoneal pressure and KIP did not differ under any experimental condition, bladder pressure was consistently and significantly greater than KIP under all circumstances (mean (95% CI) bladder pressure vs. KIP, 3.8 (2.9-4.) mmHg; P < .001). USWE wave speed significantly correlated with KIP (adjusted coefficient of determination, 0.71; P < .001). Estimate (95% CI) USWE speed for KIP prediction stayed significant after adjustment for KIP hypertension (-0.8 (- 1.4 to - 0.2) m/s; P = .008) whereas systolic and diastolic blood pressures were not significant predictors of KIP. CONCLUSIONS: In a pilot study of the swine model, we found ultrasound surface wave elastography speed is significantly correlated with transcatheter measurement of kidney intracapsular and intra-abdominal pressures, while bladder pressure overestimated kidney intracapsular pressure.

Disappearance of immunoglobulins from persistent renal amyloid deposits following stem cell transplantation for heavy-and light-chain amyloidosis.

BACKGROUND: Immunoglobulin (Ig)-related amyloidosis is the most common type of systemic amyloidosis in the developed countries and involves the kidney in most cases. Clinical remission can be achieved with chemotherapy and/or autologous stem cell transplantation (ASCT). Previous case reports have showed persistence of renal amyloid mass in light-chain amyloidosis (AL) even in the setting of hematologic and renal response. METHODS: We report a novel finding in two cases of heavy- and light-chain amyloidosis (AHL) in which monoclonal Ig but not serum amyloid P (SAP), apolipoprotein E (ApoE) or amyloid bulk in the kidney regressed after successful therapy. RESULTS: In the pre-treatment renal biopsies, the amyloid deposits stained for one heavy and one light chains (IgG + λ in one case and IgA + κ in one case). Laser microdissection followed by mass spectrometry (LMD/MS) in both cases showed abundant spectra for Ig heavy and light chains, SAP and ApoE. Both patients achieved a hematologic response with disappearance of the monoclonal protein from serum and urine and normalization of serum-free light chain ratio, but renal response occurred in only one patient. Repeat kidney biopsies showed persistence of fibrillar amyloid deposits, but regression of Ig from the amyloid deposits based on immunofluorescence. LMD/MS on the repeat biopsy performed in one case also showed disappearance of Ig but not SAP or ApoE. CONCLUSIONS: Our finding suggests that effective chemotherapy and/or ASCT in some patients with AHL not only eliminates the circulating pathogenic monoclonal Ig but also the Ig component of amyloid deposits, which may translate into renal response. This, however, may not lead to regression of amyloid deposits themselves. The latter may require more time or addition of therapeutic agents that target amyloid-associated proteins such as SAP, which are not commercially available.

Is routine multivitamin supplementation necessary in US chronic adult hemodialysis patients? A systematic review.

Because of concern that United States (US) chronic hemodialysis patients are at high risk for the development of vitamin deficiencies, the great majority of such patients are routinely supplemented with a multivitamin. This policy is supported by major US dialysis providers and nonprofit organizations. Yet routine multivitamin supplementation expands hemodialysis patients' already large pill burden, probably accounts for many millions of dollars in annual costs, and in light of previous reports may even carry with it the possibility of increased risk of adverse outcomes. An analysis of the benefits of routine multivitamin supplementation in US patients is therefore in order. We performed a systematic review of the medical literature between 1970 and 2014 using the Ovid MEDLINE database to address this question. We conclude that there is insufficient evidence to support routine multivitamin use and recommend that the decision to supplement be made on an individual basis.

Multiple myeloma after kidney transplantation.

BACKGROUND: Data regarding multiple myeloma (MM) that develops after kidney transplantation (KTx) are scarce. The outcomes of these patients were evaluated in a retrospective study. METHODS: Patients with newly diagnosed MM after KTx were selected. Patients with a diagnosis of MM or those who received treatment for monoclonal gammopathy of renal significance (MGRS) prior to KTx were excluded. RESULTS: Between 2001 and 2012, seven patients developed MM after KTx. Reasons for ESRD included ADPKD (1), C1q nephropathy (1), MPGN (2), hypertensive nephrosclerosis (2), and chronic interstitial nephritis (1). Before KTx, only four patients had monoclonal protein studies, four had monoclonal gammopathy of undermined significance (MGUS), and two of them had clonal plasma cells in bone marrow. Median follow-up after MM was 70 months (range 19-100). Median survival was 80 months. Median time from KTx to MM was 72 months (range 3-204 months). The Kidney allograft failed in four patients due to monoclonal protein-related renal disease. Five patients received chemotherapy: bortezomib (n = 3), lenalidomide (n = 2), melphalan (n = 1), thalidomide (n = 1), pomalidomide (n = 1), and high-dose dexamethasone (n = 1). Three patients received ASCT. CONCLUSION: Multiple myeloma after KTx is rare. Most patients who develop MM had MGUS prior to KTx. There is significant renal involvement in these patients. Survival is not worse when compared to MM without KTx. Further work is needed to identify the best treatment options for these patients.

Ceftriaxone-induced acute encephalopathy in a peritoneal dialysis patient.

Encephalopathy is a rare side effect of third and fourth generation cephalosporins. Renal failure and preexisting neurological disease are notable risk factors. Recognition is important as discontinuing the offending agent usually resolves symptoms. We present a case of acute encephalopathy in a patient with end stage renal disease (ESRD) treated with peritoneal dialysis (PD) who received intravenous ceftriaxone for peritonitis. This case illustrates the potential severe neurologic effects of cephalosporins, which are recommended by international guidelines as first-line antimicrobial therapy for spontaneous bacterial peritonitis.