Urinary Trace Elements Are Biomarkers for Early Detection of Acute Kidney Injury.

Introduction: Acute kidney injury (AKI) is common in hospitalized patients and associated with poor outcomes. Current methods for identifying AKI (rise in serum creatinine [sCr] or fall in urine output [UO]) are inadequate and delay detection. Early detection of AKI with easily measurable biomarkers might improve outcomes by facilitating early implementation of AKI care pathways. Methods: From a porcine model of AKI, we identified trace elements (TEs) in urine that were associated with subsequent development of AKI. We tested these putative biomarkers in 2 observational cohort studies of patients at high risk of AKI: 151 patients undergoing cardiac surgery and 150 patients admitted to a general adult intensive care unit (ICU). Results: In adults admitted to the ICU, urinary cadmium (Cd) (adjusted for urinary creatinine) had area under the receiver operating characteristic curve (AUROC) 0.70 and negative predictive value (NPV) 89%; copper (Cu) had AUROC 0.76 and NPV 91%. In humans (but not pigs), urinary zinc (Zn) was also associated with AKI and, in the ICU study, had AUROC 0.67 and NPV 80%. In patients undergoing cardiac surgery, Zn had AUROC 0.77 and NPV 91%; urinary Cd and Cu had poor AUROC but NPV of 93% and 95%, respectively. In control studies, we found that the urinary biomarkers are stable at room temperature for at least 14 days and are not affected by other confounding factors, such as chronic kidney disease (CKD). Conclusion: Urinary Cd, Cu, and Zn are novel biomarkers for early detection of AKI. Urinary trace metals have advantages over proteins as AKI biomarkers because they are stable at room temperature and have potential for cheap point-of-care testing using electrochemistry.

Definition of hourly urine output influences reported incidence and staging of acute kidney injury.

BACKGROUND: Acute kidney injury (AKI) is commonly defined using the KDIGO system, which includes criteria based on reduced urine output (UO). There is no consensus on whether UO should be measured using consecutive hourly readings or mean output. This makes KDIGO UO definition and staging of AKI vulnerable to inconsistency which has implications both for research and clinical practice. The objective of this study was to investigate whether the way in which UO is defined affects incidence and staging of AKI. METHODS: We conducted a retrospective analysis of two single centre observational studies investigating (i) patients undergoing cardiac surgery and (ii) patients admitted to general intensive care units (ICU). AKI was identified using KDIGO serum creatinine (SCr) criteria and two methods of UO (UOcons: UO meeting KDIGO criteria in each consecutive hour; UOmean: mean hourly UO meeting KDIGO criteria). RESULTS: Data from 151 CICU and 150 ICU admissions were analysed. Incidence of AKI using SCr alone was 23.8% in CICU and 32% in ICU. Incidence increased in both groups when UO was considered, with inclusion of UOmean more than doubling reported incidence of AKI (CICU: UOcons 39.7%, UOmean 72.8%; ICU: UOcons 51.3%, UOmean 69.3%). In both groups UOcons led to a larger increase in KDIGO stage 1 but UOmean increased the incidence of KDIGO stage 2. CONCLUSIONS: We demonstrate a serious lack of clarity in the internationally accepted AKI definition leading to significant variability in reporting of AKI incidence.

Micronutrient and Amino Acid Losses During Renal Replacement Therapy for Acute Kidney Injury.

INTRODUCTION: Malnutrition is common in patients with acute kidney injury (AKI), particularly in those requiring renal replacement therapy (RRT). Use of RRT removes metabolic waste products and toxins, but it will inevitably also remove useful molecules such as micronutrients, which might aggravate malnutrition. The RRT modalities vary in mechanism of solute removal; for example, intermittent hemodialysis (IHD) uses diffusion, continuous veno-venous hemofiltration (CVVH) uses convection, and sustained low-efficiency diafiltration (SLEDf) uses a combination of these. METHODS: We assessed micronutrient and amino acid losses in 3 different RRT modalities in patients with AKI (IHD, n = 27; SLEDf, n = 12; CVVH, n = 21) after correction for dialysis dose and plasma concentrations. RESULTS: Total losses were affected by modality; generally CVVH >> SLEDf > IHD (e.g., amino acid loss was 18.69 ± 3.04, 8.21 ± 4.07, and 5.13 ± 3.1 g, respectively; P < 0.001). Loss of specific trace elements (e.g., copper and zinc) during RRT was marked, with considerable heterogeneity between RRT types (e.g., +849 and +2325 µg/l lost during SLEDf vs. IHD, respectively), whereas effluent losses of copper and zinc decreased during CVVH (effect size relative to IHD, -3167 and -1442 µg/l, respectively). B vitamins were undetectable in effluent, but experimental modeling estimated 40% to 60% loss within the first 15 minutes of RRT. CONCLUSION: Micronutrient and amino acid losses are marked during RRT in patients with AKI, with variation between RRT modalities and micronutrients.

A narrative review of secondary hazards in hospitals from cases of chemical self-poisoning and chemical exposure.

Secondary hazards are an important consideration when dealing with both self-poisoned and chemically contaminated patients. Secondary exposure of hospital staff following the admission of a poisoned patient is relatively rare but potentially serious. Risks usually arise from chemical conversion of a deliberately ingested toxic substance and subsequent offgassing, but there may be toxic substances on the victim or their clothing. Surface contamination is a more common concern in cases where patients have been exposed to chemical releases. This paper presents a narrative review that considers some of the more commonly encountered toxic chemicals and situations that may present secondary hazards in hospitals. Risks to staff can be lowered by reducing the potential for, and duration of, exposure wherever possible. Good communication with the first responders at the scene, consultation with experts, decontamination and use of personal protective equipment, together with regular training, can minimize risks in the hospital environment.

Distinguishing C1q nephropathy from lupus nephritis.

BACKGROUND: 'Seronegative lupus nephritis' describes patients with renal histology typical of lupus nephritis who have no clinical or serological evidence of systemic lupus erythematosus (SLE). We report our experience in nine patients identified as having 'seronegative lupus nephritis' who met the diagnostic criteria for C1q nephropathy. METHODS: A retrospective review of clinical case notes and renal histology was carried out. RESULTS: We describe nine patients with C1q nephropathy in whom the diagnosis of 'seronegative lupus nephritis' was initially considered. All had renal histological features typical of lupus nephritis with 'wire loop' appearances on light microscopy, 'full house' immunoglobulin and complement deposition by immunoperoxidase, and electron-dense deposits in at least two glomerular locations. None of these nine patients developed clinical or serological evidence of SLE over a median follow-up of 6 years (range 0.1-9). There was no consistent evidence of a response to immunosuppressive therapy. In all cases, C1q staining was dominant on immunoperoxidase, and no tubuloreticular inclusions were seen. These appearances accord with previous descriptions of C1q nephropathy. CONCLUSIONS: The implications of a diagnosis of lupus are considerable, and we propose that the term 'seronegative lupus nephritis' is unhelpful, and should be avoided when there is diagnostic uncertainty. The term C1q nephropathy should be preferred when these histological features are seen in the absence of overt lupus, when C1q deposition is dominant and when tubuloreticular bodies are absent. The clinical course in the cases reported here does not support the use of immunosuppressive therapy in C1q nephropathy.