BACKGROUND: Itai-itai disease is caused by environmental cadmium (Cd) pollution in the Jinzu River basin in Japan. To reduce the Cd contamination of rice, soil restoration of paddy fields was carried out. We evaluated the effect of soil restoration on the health status of residents of the former Cd-polluted area.
METHODS: Participants were 1,030 men and 944 women who lived in the area of restoration of Cd-polluted rice paddies. First morning urine was collected and urinary Cd, β2-microglobulin (β2MG), and N-acetyl-β-D-glucosaminidase (NAG) levels were measured. Associations among age, years of residence before and after soil restoration, and urinary Cd, β2MG, and NAG levels were evaluated by multiple regression analysis.
RESULTS: The geometric mean (interquartile range) of urinary Cd (µg/g Cr) was 1.00 (0.58-1.68) in men and 1.67 (1.02-2.91) in women. The geometric means of urinary β2MG (µg/g Cr) and NAG (U/g Cr) were 174.6 (92.6-234.2) and 1.47 (0.72-3.14) in men, and 217.6 (115.3-28.7) and 1.48 (0.73-2.96) in women, respectively. Urinary Cd, β2MG, and NAG were significantly positively correlated (p < 0.01 all). Age and duration of residence in the Cd-polluted area before soil restoration were independently associated with urinary Cd, β2MG, and NAG. Among the 916 participants who had resided in the area before the soil restoration, urinary Cd concentrations were significantly higher, thus by 1.03-fold (95% CI, 1.01-1.04) in men and 1.03-fold (95% CI, 1.01-1.05) in women, when the years of residence before soil restoration by each 5-years increment. By contrast, urinary Cd concentrations were significantly lower, thus 0.97-fold (95% CI, 0.96-0.99) lower in men and 0.97-fold (95% CI, 0.95-0.99) lower in women, by each 5-year increment of residence after soil restoration. A similar association was observed for urinary β2MG concentration, and no significant association was observed for urinary NAG levels in men or women.
CONCLUSIONS: Cd exposure and associated renal tubular dysfunction in residents of a former Cd-polluted area were influenced by Cd exposure from the environment prior to soil restoration. Soil restoration in Cd-polluted areas reduced the Cd exposure of local residents.

Kidney transplantation is the best option for end-stage chronic kidney disease. Transplant viability is conditioned by drugs\' nephrotoxicity, ischemia-reperfusion damage, or acute rejection. An approach to improve graft survival is the identification of post-transplant renal function prognostic biomarkers. Our objective was to study three early kidney damage biomarkers (N-acetyl-d-glucosaminidase, NAG; neutrophil gelatinase-associated lipocalin, NGAL; and kidney injury molecule-1, KIM-1) in the initial period after transplantation and to identify possible correlations with main complications. We analysed those biomarkers in urine samples from 70 kidney transplant patients. Samples were taken on days 1, 3, 5, and 7 after intervention, as well as on the day that renal function stabilised (based on serum creatinine). During the first week after transplant, renal function improved based on serum creatinine evolution. However, increasing levels of biomarkers at different times during that first week could indicate tubular damage or other renal pathology. A relationship was found between NGAL values in the first week after transplantation and delayed graft function. In addition, higher NAG and NGAL, and lower KIM-1 values predicted a longer renal function stabilisation time. Therefore, urinary NAG, NGAL, and KIM-1 could constitute a predictive tool for kidney transplant complications, contributing to improve graft survival rates.

Toxigenic Vibrio cholerae serogroup O1 is the etiologic agent of the disease cholera, and strains of this serogroup are responsible for pandemics. A few other serogroups have been found to carry cholera toxin genes-most notably, O139, O75, and O141-and public health surveillance in the United States is focused on these four serogroups. A toxigenic isolate was recovered from a case of vibriosis from Texas in 2008. This isolate did not agglutinate with any of the four different serogroups\' antisera (O1, O139, O75, or O141) routinely used in phenotypic testing and did not display a rough phenotype. We investigated several hypotheses that might explain the recovery of this potential nonagglutinating (NAG) strain using whole-genome sequencing analysis and phylogenetic methods. The NAG strain formed a monophyletic cluster with O141 strains in a whole-genome phylogeny. Furthermore, a phylogeny of ctxAB and tcpA sequences revealed that the sequences from the NAG strain also formed a monophyletic cluster with toxigenic U.S. Gulf Coast (USGC) strains (O1, O75, and O141) that were recovered from vibriosis cases associated with exposures to Gulf Coast waters. A comparison of the NAG whole-genome sequence showed that the O-antigen-determining region of the NAG strain was closely related to those of O141 strains, and specific mutations were likely responsible for the inability to agglutinate. This work shows the utility of whole-genome sequence analysis tools for characterization of an atypical clinical isolate of V. cholerae originating from a USGC state. IMPORTANCE Clinical cases of vibriosis are on the rise due to climate events and ocean warming (1, 2), and increased surveillance of toxigenic Vibrio cholerae strains is now more crucial than ever. While traditional phenotyping using antisera against O1 and O139 is useful for monitoring currently circulating strains with pandemic or epidemic potential, reagents are limited for non-O1/non-O139 strains. With the increased use of next-generation sequencing technologies, analysis of less well-characterized strains and O-antigen regions is possible. The framework for advanced molecular analysis of O-antigen-determining regions presented herein will be useful in the absence of reagents for serotyping. Furthermore, molecular analyses based on whole-genome sequence data and using phylogenetic methods will help characterize both historical and novel strains of clinical importance. Closely monitoring emerging mutations and trends will improve our understanding of the epidemic potential of Vibrio cholerae to anticipate and rapidly respond to future public health emergencies.

The gradual spread of Aspergilli worldwide is adding to the global shortage of food and is affecting its safe consumption. Aspergillus-derived mycotoxins, including aflatoxins and ochratoxin A, and fumonisins (members of the fusariotoxin group) can cause pathological damage to vital organs, including the kidney or liver. Although the kidney functions as the major excretory system in mammals, monitoring and screening for mycotoxin induced nephrotoxicity is only now a developmental area in the field of livestock feed toxicology. Currently the assessment of individual exposure to mycotoxins in man and animals is usually based on the analysis of toxin and/or metabolite contamination in the blood or urine. However, this requires selective and sensitive analytical methods (e.g., HPLC-MS/MS), which are time consuming and expensive. The toxicokinetic of mycotoxin metabolites is becoming better understood. Several kidney biomarkers are used successfully in drug development, however cost-efficient, and reliable kidney biomarkers are urgently needed for monitoring farm animals for early signs of kidney disease. β2-microglobulin (β2-MG) and N-acetyl-β-D-glucosaminidase (NAG) are the dominant biomarkers employed routinely in environmental toxicology research, while kidney injury molecule 1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) are also emerging as effective markers to identify mycotoxin induced nephropathy. Pigs are exposed to mycotoxins due to their cereal-based diet and are particularly susceptible to Aspergillus mycotoxins. In addition to commonly used diagnostic markers for nephrotoxicity including plasma creatinine, NAG, KIM-1 and NGAL can be used in pigs. In this review, the currently available techniques are summarized, which are used for screening mycotoxin induced nephrotoxicity in farm animals. Possible approaches are considered, which could be used to detect mycotoxin induced nephropathy.

Acute and chronic kidney diseases are an evolving continuum for which reliable biomarkers of early disease are lacking. The potential use of glycosidases, enzymes involved in carbohydrate metabolism, in kidney disease detection has been under investigation since the 1960s. N-acetyl-beta-D-glucosaminidase (NAG) is a glycosidase commonly found in proximal tubule epithelial cells (PTECs). Due to its large molecular weight, plasma-soluble NAG cannot pass the glomerular filtration barrier; thus, increased urinary concentration of NAG (uNAG) may suggest injury to the proximal tubule. As the PTECs are the workhorses of the kidney that perform much of the filtration and reabsorption, they are a common starting point in acute and chronic kidney disease. NAG has previously been researched, and it is widely used as a valuable biomarker in both acute and chronic kidney disease, as well as in patients suffering from diabetes mellitus, heart failure, and other chronic diseases leading to kidney failure. Here, we present an overview of the research pertaining to uNAG\'s biomarker potential across the spectrum of kidney disease, with an additional emphasis on environmental nephrotoxic substance exposure. In spite of a large body of evidence strongly suggesting connections between uNAG levels and multiple kidney pathologies, focused clinical validation tests and knowledge on underlining molecular mechanisms are largely lacking.

Creatinine only allows detection of kidney disease when 60 to 75% of the glomerular function is lost and is therefore not an ideal marker of disease. Additional biomarkers could be beneficial to assess kidney function and disease. The objectives are to describe new equine kidney biomarkers. This systematic review assesses the available literature, including the validation process and reference values, following which the authors suggest recommendations for clinical use. SDMA may have some potential as equine kidney biomarker, but there is currently a lack of evidence that SDMA offers any advantage compared to creatinine in detecting Acute Kidney Injury (AKI). Cystatin C and podocin show potential as biomarkers for kidney disease (including detecting AKI earlier than creatinine) and should be studied further. NGAL has potential as a biomarker of kidney disease (including detecting AKI earlier than creatinine), and potential as an inflammatory marker. Literature on MMP-9 does not allow for conclusive statements about its potential as a biomarker for kidney disease. The future may show that NAG has potential. For all biomarkers, at this stage, available scientific information is limited or too scarce to support clinical use, and only SDMA can be measured for clinical purposes. In conclusion, there are multiple new biomarkers with the potential to diagnose kidney problems. However, there are only a few studies available and more data is needed before these biomarkers can be applied and recommended in our daily practice.

UNASSIGNED: Cardiac surgery associated AKI (CSA-AKI) complicates recovery and may be associated with a greater risk of developing chronic kidney disease and mortality. The aim of this study was to assess long-term clinical consequences of transient increased activity of urinary enzymes after cardiac surgery (CS).
UNASSIGNED: An observational study was conducted in a group of 88 adult patients undergoing planned coronary artery bypass grafting (CABG), but all samples were obtained from 79 patients. The activity of urinary enzymes: N-acetyl-beta-glucosaminidase (NAG), arylsulfatase A (ASA) and beta-glucuronidase was evaluated in sequential urine samples. A comparative analysis of biochemical parameters was performed regarding the occurrence of acute kidney injury (AKI) defined by KIDGO at 24 hours, at day 30 and 5-years after the operation.
UNASSIGNED: During the first 24 hours after CS AKI was diagnosed in 13 patients. A comparison of the activity of urinary enzymes in pre-defined time-points showed significant differences for ASA and NAG (post OP-sample p < 0.028 and p < 0.022; POD 1 sample p < 0.004 and p < 0.001 respectively). No patient had any biochemical or clinical features of kidney failure at day 30. In the AKI group kidney failure was diagnosed in 36% of patients within 5 years of follow-up as opposed to 5% in the no AKI group. The activities of tubular enzymes in urine reflect a general injury of kidney tubules during and after the operation. However, they are not ideal biomarkers for prediction of the degree of kidney injury and further poor prognosis of CS-AKI.

The aim of the current study was to evaluate whether tubular markers kidney injury molecule-1 (KIM-1) and N-acetyl-ß-glucosaminidase (NAG) are related to acute kidney injury (AKI) and severe disease in patients with COVID-19.
In this prospective observational clinical trial we examined a cohort of 80 patients with proof of acute respiratory infection and divided them into a COVID-19 cohort (n = 54) and a control cohort (n = 26). KIM-1 and NAG were measured from urine samples collected in the emergency department. We assessed the development of AKI, admission to the intensive care unit (ICU) and intrahospital death as clinical endpoints. Urinary KIM-1 and NAG were not significantly different between patients with SARS-CoV-2 and those with other respiratory infections (each p = n.s.). Eight patients from the COVID-19 cohort and five of the non-COVID-19-patients suffered from acute kidney injury during their stay. Nine COVID-19 patients and two non-COVID-19 patients were admitted to the ICU. KIM-1 was significantly elevated in COVID-19 patients with, compared to those without AKI (p = 0.005), as opposed to NAG and creatinine (each p = n.s.). Furthermore, KIM-1 was significantly elevated in the patients with COVID-19 that had to be transferred to the ICU (p = 0.015), in contrast to NAG and creatinine (each p = n.s.).
Assessing KIM-1 in patients with COVID-19 might provide additional value in recognizing AKI at an early stage of disease. Further, KIM-1 might indicate higher risk for clinical deterioration as displayed by admission to the ICU.

BACKGROUND: The kidney deterioration, which starts in childhood often leads to end-stage renal failure in the future. Therefore, searching for an early, sensitive, and specific biomarkers became a paramount for chronic kidney disease diagnosis. The aim of this study was the assessment of markers: KIM-1, FGF-23, NAG, NGAL, and uromodulin for diagnosis of preclinical phase of the disease in children.
METHODS: 59 children (15 boys, 44 girls from 6 months to 17 years old) with kidney disorders, which had clinical indications for renoscintigraphy, were included in the study. All patients were divided depending on the result of renoscintigraphy (renal scarring vs normal kidney picture) and depending on the level of estimated glomerular filtration rate (glomerular hyperfiltration vs normal filtration rate). The concentration of uromoduline, KIM-1, FGF-23, NAG, and NGAL in serum and of NGAL and uromoduline in urine were measured in all studied groups.
RESULTS: The children with glomerular hyperfiltration had a statistically significantly higher serum values of FGF-23 and NGAL than the children with normal filtration rate (P < .05). There were no statistically significant differences in serum concentrations of tested markers in children with renal scars in comparison to children with normal renal image. There was no statistically significant difference in the concentration of tested markers in urine.
CONCLUSIONS: The study confirmed the possible usefulness of FGF-23 and NGAL in detecting the preclinical-stage of renal disease associated with glomerular hyperfiltration in children. The study do not allow to indicate markers, which could be useful in the early diagnosis of kidney damage visible in the scintigraphic examination.

This study aims to evaluate the body burdens of cadmium (Cd) associated with potential health impairment in residents living near electroplating industries. A total of 269 residents from exposure area and 106 from control area were recruited. We measured the blood and urinary Cd levels using an inductively coupled plasma mass spectrometer (ICP-MS); performed physical examinations; determined the urinary levels of β2-microglobulin (β2-MG), Nacetyl-β-D-glucosaminidase (NAG), and 8-hydroxy-2\'-deoxyguanosine (8-OHdG); and evaluated the associations between Cd and these biomarkers. Blood and urinary Cd levels in exposure group were statistically higher than in control group (1.712 vs. 1.159 μg/L; 1.980 vs. 1.740 μg/L, respectively, p < 0.05). Urinary β2-MG and 8-OHdG levels in exposure group were also statistically higher (0.448 vs. 0.090 mg/L; 12.759 vs. 12.115 μg/L, respectively, p < 0.05), but urinary NAG levels showed no significant difference between the two groups (13.614 vs. 8.246 IU/L, p > 0.05). The proportion of abnormal nasal symptoms occurring in exposed subjects (88.8%) was much higher than in control subjects (78.2%, p < 0.05). Urinary Cd levels were positively correlated with blood Cd levels, urinary 8-OHdG, and NAG levels (r = 0.307, r = 0.185, r = 0.150, p < 0.05), but not correlated with urinary β2-MG levels (p > 0.05). In conclusion, our study revealed that residents living in close proximity to electroplating industries had elevated body burdens of Cd levels, as well as slight renal dysfunction and DNA oxidation damage.