Serum Neutrophil Gelatinase Associated Lipocalin in Patients with Toxic Nephropathies. Prospective Study

Background. Drug induced kidney disorder (DIKD) is a frequent adverse event which contributes to morbidity and even incapacitation. Toxic nephropathy also is one of the pathological syndromes or complications in acute alcohol poisoning (AAP). Recent years experience shows the insensitivity of serum creatinine to the early stages of kidney damage. NGAL has been shown as a preferred marker of acute kidney damage in a variety of clinical settings. However, no similar studies of serum NGAL have been performed in patients with toxic nephropathy. The presence of markers discovers the possibility of earlier detection, timely treatment and prevention of disease progression to chronic kidney disease (CKD), which can improve the patients prognosis. Aims to study serum NGAL levels in patients with AAP and DIKD with clinically diagnosed nephropathy and without signs of kidney damage. The effect of glomerular filtration rate (GFR) on serum NGAL levels was studied. Materials. This prospective cross-sectional study was conducted on the basis of the biochemical laboratory of the Karaganda Medical University in conjunction with the toxicological department of the Regional Medical Center (from January 2018 to October 2019). The study included 89 patients with AAP and 50 patients with DIKD. 25 healthy donors (control group) and 25 patients with CKD served as comparison groups. Serum NGAL levels were measured using a commercially available ELISA kit. Results. We detected the increased serum NGAL level in both groups with drug-induced nephropathy and nephropathy, caused by AAP compared with the control group values (p 0.01). However, there were no significant differences in NGAL level, depending on the type of toxic nephropathy. After ranking the GFR, it was revealed that GFR did not affect the serum NGAL level (F = 2.21; p = 0.12) and its increase was observed both at reduced and increased GFR relative to the control group values (p 0.05). Conclusions. The results of our study showed a multiple increase in the concentration of NGAL in serum not only in patients with toxic nephropathy, but also in patients with increased GFR, even in the absence of clinical and laboratory signs of impaired renal function.

Mechanisms of toxic nephropathology

В обзоре предпринята попытка систематизировать новые сведения об особенностях поражения почек, обусловленных воздействием химических, природных веществ и лекарственных средств. Рассмотрены, главным образом, механизмы поражения почек прямыми нефротоксинами, действие которых на почки является первичным, а также механизмы развития тубулоинтерстициального нефрита и нефрофиброза. Обсуждаются современные концепции этиологии и патогенеза нефропатологии при экзогенных интоксикациях и осложнениях фармакотерапии. В статье показано, что дозозависимая токсичность прямых нефротоксинов реализуется посредством механизма гибели клеток по пути их некроза и апоптоза. Подробно рассматривается классификация нефротоксинов по месту их действия в почке. Обсуждаются некоторые аспекты патогенеза лекарственного тубулоинтерстициального нефрита. The review focused on systematizing new information about features of kidney damage induced by exposure to chemical or natural substances and medicines. This review mainly addressed mechanisms of kidney injury by direct nephrotoxins with a primary effect on kidneys and also mechanisms for development of tubulointerstitial nephritis and nephrofibrosis. The author discussed current concepts of the etiology and pathogenesis of toxic nephropathy, including nephropathies induced by exogenous intoxication and iatrogenic. The article showed that the dose-dependent toxicity of direct nephrotoxins is mediated by mechanisms of necrotic and apoptotic cell death. The classification of nephrotoxins based on their site of action in the kidney is analyzed in detail. Some aspects of the pathogenesis of drug-induced tubulointerstitial nephritis are discussed.

Functional changes in the activity of rats’ kidneys at cadmium intoxication in “mother-fetus” system

The article is devoted to the study of renal functions in 2- month old rats, born by females which had been injected some cadmium chloride during gestation (0,03 mg/kg per os during 30 days). Intoxication in the system “mother fetus” took place in the prenatal period and neonatal period of lactation. The animals have shown obvious signs of toxic nephropathy with the disorder of excretory, ion-regulative and acid-regulative functions of kidneys.

Emerging Biomarkers and Metabolomics for Assessing Toxic Nephropathy and Acute Kidney Injury (AKI) in Neonatology

Identification of novel drug-induced toxic nephropathy and acute kidney injury (AKI) biomarkers has been designated as a top priority by the American Society of Nephrology. Increasing knowledge in the science of biology and medicine is leading to the discovery of still more new biomarkers and of their roles in molecular pathways triggered by physiological and pathological conditions. Concomitantly, the development of the so-called “omics” allows the progressive clinical utilization of a multitude of information, from those related to the human genome (genomics) and proteome (proteomics), including the emerging epigenomics, to those related to metabolites (metabolomics). In preterm newborns, one of the most important factors causing the pathogenesis and the progression of AKI is the interaction between the individual genetic code, the environment, the gestational age, and the disease. By analyzing a small urine sample, metabolomics allows to identify instantly any change in phenotype, including changes due to genetic modifications. The role of liquid chromatography-mass spectrometry (LC-MS), proton nuclear magnetic resonance (1H NMR), and other emerging technologies is strategic, contributing basically to the sudden development of new biochemical and molecular tests. Urine neutrophil gelatinase-associated lipocalin (uNGAL) and kidney injury molecule-1 (KIM-1) are closely correlated with the severity of kidney injury, representing noninvasive sensitive surrogate biomarkers for diagnosing, monitoring, and quantifying kidney damage. To become routine tests, uNGAL and KIM-1 should be carefully tested in multicenter clinical trials and should be measured in biological fluids by robust, standardized analytical methods.