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1.
Acute Kidney Injury, Fluid Overload, and Outcomes in Children Supported With Extracorporeal Membrane Oxygenation for a Respiratory Indication.
Mallory, PP, Selewski, DT, Askenazi, DJ, Cooper, DS, Fleming, GM, Paden, ML, Murphy, L, Sahay, R, King, E, Zappitelli, M, et al
ASAIO journal (American Society for Artificial Internal Organs : 1992). 2020;(3):319-326
Abstract
This study seeks to evaluate the association between acute kidney injury (AKI), fluid overload (FO), and mortality in children supported with extracorporeal membrane oxygenation (ECMO) for refractory respiratory failure. This retrospective observational cohort study was performed at six tertiary care children's hospital intensive care units, studying 424 patients < 18 years of age supported with ECMO for ≥ 24 hours for a respiratory indication from January 1, 2007, to December 31, 2011. In a multivariate analysis, FO level at ECMO initiation was not associated with hospital mortality, whereas peak FO level during ECMO was associated with hospital mortality. For every 10% increase in peak FO during ECMO, the odds of hospital mortality were approximately 1.2 times higher. Every 10% increase in peak FO during ECMO resulted in a significant relative change in the duration of ECMO hours by a factor of 1.08. For hospital survivors, every 10% increase in peak FO level during ECMO resulted in a significant relative change in the duration of mechanical ventilation hours by a factor of 1.13. In this patient population, AKI and FO are associated with increased mortality and should be considered targets for medical interventions including judicious fluid management, diuretic use, and renal replacement therapy.
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2.
Osmolar-gap in the setting of metformin-associated lactic acidosis: Case report and a literature review highlighting an apparently unusual association.
Elshafei, MN, Alamin, M, Mohamed, MFH
Medicine. 2020;(41):e22492
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Abstract
RATIONALE Metformin-associated lactic acidosis (MALA) is a rare adverse effect that has significant morbidity and mortality. MALA is a high anion gap (AG), nonosmolar acidosis. Associated osmolar-gap (OG) is rarely reported, so finding an OG may make the diagnosis of MALA challenging. PATIENT CONCERNS Forty-five years' old type II diabetic patient on metformin presented to emergency with a two-day history of vomiting, watery diarrhea, and mild abdominal discomfort. On examinations, he looked dehydrated. Investigation revealed acute kidney injury (AKI) with a high lactic acid (LA) level of 24 mmol/L, pH of 6.8, AG of 40, and an OG of 20 mOsm/kg DIAGNOSES The presence of an OG made the diagnosis challenging; the history was negative for alcohol, osmolar substance, or illicit drug ingestion or use. The toxicology screen was negative. After ruling out plausible causes of AG and OG, MALA was deemed the likely reason for his presentation likely precipitated by dehydration and AKI. INTERVENTIONS He underwent two sessions of hemodialysis, afterward managed with fluid hydration. OUTCOMES On day 3, he was in the polyuric phase suggestive of acute tubular necrosis. His serum creatinine improved afterward with improved acidosis; after 8 days, he was discharged in stable condition. LESSONS MALA is a rare side effect of metformin therapy. Acute kidney injury is a known precipitant of MALA. In our review, we highlight the association of MALA and the presence of an OG. We believe that treating physicians should be aware of this relationship to avoid delaying or overlooking such an important diagnosis.
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Intensity of renal replacement therapy and outcomes in critically ill patients with acute kidney injury: Critical appraisal of the dosing recommendations.
Schiffl, H
Therapeutic apheresis and dialysis : official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy. 2020;(6):620-627
Abstract
The current care of critically ill patients with severe acute kidney injury requiring dialysis (AKI-D) is limited to supportive management in which renal replacement therapy (RRT) plays a central role. Renal replacement techniques are invasive bioincompatible procedures and are therefore associated with complications that may prove harmful to fragile patients. Inexperience with the standards and lacking or misinterpreted recommendations for the delivery of the RRT dose increases the risk of serious complications. Neither the optimal doses of intermittent or continuous RRTs nor the minimal or maximal effective doses are known. The Kidney Disease Improving Global outcomes (KDIGO) AKI guidelines for RRT dosing recommendations are inflexible, based on limited research, and may be at least partially outdated. High-intensity therapy may be associated with clinically relevant alterations in systemic and renal hemodynamics, profound electrolyte imbalances, the loss of nutrients or thermal energy, and underdosing of antimicrobial agents. However, higher doses of continuous renal replacement therapy (CRRT) may confer a survival benefit for certain subgroups of intensive care patients with severe AKI. Lower CRRT doses than the recommended adequate dosage may not lead to negative health outcomes, at least in Asian patients. Future research should evaluate the demand-capacity concept, recognizing that the delivery of the RRT dose is dynamic and should be modified in response to patient-related factors. There is a need for large-scale studies evaluating whether precision RRT dose modifications may improve patient-centered outcomes in subgroups of critically ill patients.
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Biologic excipients: Importance of clinical awareness of inactive ingredients.
Ionova, Y, Wilson, L
PloS one. 2020;(6):e0235076
Abstract
Due to the complexity and fragility of biological drug products, several challenges exist in their formulation development. Excipients are added to increase product stability, maintain tonicity, and facilitate drug delivery. The potential implications of these additive substances merit clinical consideration. We assessed the safety risk of excipients on the basis of their type and variability through an assessment framework, which quantifies excipient complexity in 230 biological formulations, and identifies excipient-related adverse events through published case reports. A biologic on average contained 4.45 excipients, half of that found in oral medications. The frequency distribution was heavily skewed towards the most commonly occurring excipients: water (40.4%), sodium chloride (38.3%), polysorbate 80 (28.7%), sucrose (24.4%), and mannitol (20.9%), with 44.4% of formulations not listing the concentration of the most commonly occurring inactive ingredients. A literature search revealed only 17 case reports of excipient-related adverse events, suggesting the need for more clarity for clinicians on the safety of chemical additives. These cases included injection site reactions, anaphylaxis, hyperglycemia, and acute renal failure. With the expansion of the biopharmaceutical market, it is important to consider the safety data of biologic excipients, so that therapy can be tailored appropriately for a specific patient.
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Network Meta-Analysis of Novel Glucose-Lowering Drugs on Risk of Acute Kidney Injury.
Zhao, M, Sun, S, Huang, Z, Wang, T, Tang, H
Clinical journal of the American Society of Nephrology : CJASN. 2020;(1):70-78
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Abstract
BACKGROUND AND OBJECTIVES Little is known about the comparative effects of dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1RAs), or sodium glucose cotransporter-2 (SGLT2) inhibitors on risk of AKI. This study aimed to compare the effects of these three novel classes of glucose-lowering drugs on AKI risk in patients with or without type 2 diabetes, by network meta-analysis of event-driven cardiovascular or kidney outcome trials. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We systematically searched electronic databases up to September 2020, and included 20 event-driven cardiovascular or kidney outcome trials (18 trials included patients with type 2 diabetes only, and two trials included patients with or without type 2 diabetes). A network meta-analysis using a frequentist approach was performed to compare the effects of DPP-4 inhibitors, GLP-1RAs, or SGLT2 inhibitors on risk of AKI, and estimate the probability for each intervention as the safest one. The primary analysis included 18 trials with type 2 diabetes only, and a secondary analysis included 20 trials. RESULTS In the 18 trials with a total of 2051 AKI events (range: 1-300) among 156,690 patients with type 2 diabetes only, our network meta-analysis showed that SGLT2 inhibitors were associated with a lower risk of AKI compared with placebo (odds ratio, 0.76; 95% confidence interval, 0.66 to 0.88), whereas both DPP-4 inhibitors and GLP-1RAs had neutral effects on risk of AKI. Moreover, SGLT2 inhibitors were significantly associated with a lower risk in AKI than both GLP-1RAs (odds ratio, 0.79; 95% confidence interval, 0.65 to 0.97) and DPP-4 inhibitors (odds ratio, 0.68; 95% confidence interval, 0.54 to 0.86). SGLT2 inhibitors have the highest probability of being the safest intervention (84%). The results were similar in the secondary analysis. CONCLUSIONS Current evidence indicates that SGLT2 inhibitors have a lower risk of AKI than both DPP-4 inhibitors and GLP-1RAs.
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Rhabdomyolysis associated acute renal failure - Report of two fatal cases and a brief review of literature.
Das, S, Hanuman, SB, Mylapalli, JL
Journal of forensic and legal medicine. 2020;:101941
Abstract
BACKGROUND Rhabdomyolysis is a potentially fatal condition which occurs due to skeletal muscle injury and classically presents with myalgia and red-brown coloured urine. Presence of excess myoglobin in the glomerular filtrate forms myoglobin casts which causes severe obstruction and necrosis of the tubules leading to acute renal failure. METHODS We report two fatal cases of rhabdomyolysis associated acute renal failure. The first victim died in police custody and the second victim died due to severe physical exertion. RESULTS In both the cases, creatine kinase levels were elevated and myoglobin was detected in urine in the second case. Myoglobin immunohistochemistry detected the presence of myoglobin cast in the glomerular tubules of kidney in both the cases. CONCLUSIONS Myoglobin immunohistochemistry of renal tissues, serum creatine kinase, urine myoglobin analysis and muscle histopathology are the laboratory tests that should be considered at autopsy where rhabdomyolysis is suspected.
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Estimating glomerular filtration rate in patients with acute kidney injury: a prospective multicenter study of diagnostic accuracy.
Pelletier, K, Lafrance, JP, Roy, L, Charest, M, Bélanger, MC, Cailhier, JF, Albert, M, Duca, A, Elftouh, N, Bouchard, J
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 2020;(11):1886-1893
Abstract
BACKGROUND Estimating glomerular filtration rate (GFR) in acute kidney injury (AKI) is challenging, with limited data comparing estimated and gold standard methods to assess GFR. The objective of our study was to assess the performance of the kinetic estimated GFR (KeGFR) and Jelliffe equations to estimate GFR in AKI, using a radioisotopic method (technetium-diethylenetriaminepentaacetic acid) as a reference measure. METHODS We conducted a prospective multicenter observational study in hospitalized patients with AKI. We computed the Jelliffe and KeGFR equations to estimate GFR and compared these estimations to measured GFR (mGFR) by a radioisotopic method. The performances were assessed by correlation, Bland-Altman plots and smoothed and linear regressions. We conducted stratified analyses by age and chronic kidney disease (CKD). RESULTS The study included 119 patients with AKI, mostly from the intensive care unit (63%) and with Stage 1 AKI (71%). The eGFR obtained from the Jelliffe and KeGFR equations showed a good correlation with mGFR (r = 0.73 and 0.68, respectively). The median eGFR by the Jelliffe and KeGFR equations was less than the median mGFR, indicating that these equations underestimated the mGFR. On Bland-Altman plots, the Jelliffe and KeGFR equations displayed a considerable lack of agreement with mGFR, with limits of agreement >40 mL/min/1.73 m2. Both equations performed better in CKD and the KeGFR performed better in older patients. Results were similar across AKI stages. CONCLUSIONS In our study, the Jelliffe and KeGFR equations had good correlations with mGFR; however, they had wide limits of agreement. Further studies are needed to optimize the prediction of mGFR with estimatation equations.
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The multifaceted role of iron in renal health and disease.
van Swelm, RPL, Wetzels, JFM, Swinkels, DW
Nature reviews. Nephrology. 2020;(2):77-98
Abstract
Iron is an essential element that is indispensable for life. The delicate physiological body iron balance is maintained by both systemic and cellular regulatory mechanisms. The iron-regulatory hormone hepcidin assures maintenance of adequate systemic iron levels and is regulated by circulating and stored iron levels, inflammation and erythropoiesis. The kidney has an important role in preventing iron loss from the body by means of reabsorption. Cellular iron levels are dependent on iron import, storage, utilization and export, which are mainly regulated by the iron response element-iron regulatory protein (IRE-IRP) system. In the kidney, iron transport mechanisms independent of the IRE-IRP system have been identified, suggesting additional mechanisms for iron handling in this organ. Yet, knowledge gaps on renal iron handling remain in terms of redundancy in transport mechanisms, the roles of the different tubular segments and related regulatory processes. Disturbances in cellular and systemic iron balance are recognized as causes and consequences of kidney injury. Consequently, iron metabolism has become a focus for novel therapeutic interventions for acute kidney injury and chronic kidney disease, which has fuelled interest in the molecular mechanisms of renal iron handling and renal injury, as well as the complex dynamics between systemic and local cellular iron regulation.
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Imaging of Acute Renal Failure in the Hospital Setting.
Alabousi, M, Alabousi, A, Patlas, MN
Radiologic clinics of North America. 2020;(1):59-71
Abstract
Acute kidney injury (AKI) is characterized by a decline in the glomerular filtration rate. AKI affects up to 20% of hospitalized patients, and is even more common among intensive care unit admissions. Complications of AKI are related to uremia (encephalopathy, neuropathy, pericarditis), volume overload (pulmonary edema), and electrolyte disturbances (hyperkalemia). In addition to having increased associated morbidity and mortality, patients who develop AKI may never fully recover their baseline kidney function. Imaging can play a valuable role in the work-up of AKI. This article discusses the utility of imaging in characterizing AKI in adult patients in a hospital setting.
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Acute kidney injury from contrast-enhanced CT procedures in patients with cancer: white paper to highlight its clinical relevance and discuss applicable preventive strategies.
Cosmai, L, Porta, C, Privitera, C, Gesualdo, L, Procopio, G, Gori, S, Laghi, A
ESMO open. 2020;(2)
Abstract
Patients with cancer are subjected to several imaging examinations which frequently require the administration of contrast medium (CM). However, it has been estimated that acute kidney injury (AKI) due to the injection of iodinated CM accounts for 11% of all cases of AKI, and it is reported in up to 2% of all CT examinations. Remarkably, the risks of developing AKI are increased in the elderly, in patients with chronic kidney disease or diabetes, and with dehydration or administration of nephrotoxic chemotherapeutics. Given the common occurrence of postcontrast acute kidney injury (PC-AKI) in clinical practice, primary care physicians and all specialists involved in managing patients with cancer should be aware of the strategies to reduce the risk of this event. In 2018, a panel of four experts from the specialties of radiology, oncology and nephrology were speakers at the annual meeting of the Italian Society of Medical Radiology (Società Italiana di Radiologia Medica e Interventistica), with the aim of commenting on existing evidence and providing their experience on the incidence and management of PC-AKI in patients with cancer. The discussion represented the basis for this white paper, which is intended to be a practical guide organised by statements describing methods to reduce renal injury risks related to CM-enhanced CT examinations in patients with cancer.