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BackgroundThe coronavirus disease 2019 (COVID-19) is a recently emerged respiratory infectious disease with kidney injury as a part of the clinical complications. However, the dynamic change of kidney function and its association with COVID-19 prognosis are largely unknown.MethodsIn this multicenter retrospective cohort study, we analyzed clinical characteristics, medical history, laboratory tests, and treatment data of 12,413 COVID-19 patients. The patient cohort was stratified according to the severity of the outcome into three groups: non-severe, severe, and death.FindingsThe prevalence of elevated blood urea nitrogen (BUN), elevated serum creatinine (Scr), and decreased blood uric acid (BUA) at admission was 6.29%, 5.22%, and 11.66%, respectively. The trajectories showed the elevation in BUN and Scr levels, as well as a reduction in BUA level for 28 days after admission in death cases. Increased all-cause mortality risk was associated with elevated baseline levels of BUN and Scr and decreased levels of BUA.ConclusionsThe dynamic changes of the three kidney function markers were associated with different severity and poor prognosis of COVID-19 patients. BUN showed a close association with and high potential for predicting adverse outcomes in COVID-19 patients for severity stratification and triage.FundingThis study was supported by grants from the National Key R&D Program of China (2016YFF0101504), the National Science Foundation of China (81630011, 81970364, 81970070, 81970011, 81870171, and 81700356), the Major Research Plan of the National Natural Science Foundation of China (91639304), the Hubei Science and Technology Support Project (2019BFC582, 2018BEC473, and 2017BEC001), and the Medical Flight Plan of Wuhan University.

BackgroundThe coronavirus disease 2019 (COVID-19) is a recently emerged respiratory infectious disease with kidney injury as a part of the clinical complications. However, the dynamic change of kidney function and its association with COVID-19 prognosis are largely unknown.MethodsIn this multicenter retrospective cohort study, we analyzed clinical characteristics, medical history, laboratory tests, and treatment data of 12,413 COVID-19 patients. The patient cohort was stratified according to the severity of the outcome into three groups: non-severe, severe, and death.FindingsThe prevalence of elevated blood urea nitrogen (BUN), elevated serum creatinine (Scr), and decreased blood uric acid (BUA) at admission was 6.29%, 5.22%, and 11.66%, respectively. The trajectories showed the elevation in BUN and Scr levels, as well as a reduction in BUA level for 28 days after admission in death cases. Increased all-cause mortality risk was associated with elevated baseline levels of BUN and Scr and decreased levels of BUA.ConclusionsThe dynamic changes of the three kidney function markers were associated with different severity and poor prognosis of COVID-19 patients. BUN showed a close association with and high potential for predicting adverse outcomes in COVID-19 patients for severity stratification and triage.FundingThis study was supported by grants from the National Key R&D Program of China (2016YFF0101504), the National Science Foundation of China (81630011, 81970364, 81970070, 81970011, 81870171, and 81700356), the Major Research Plan of the National Natural Science Foundation of China (91639304), the Hubei Science and Technology Support Project (2019BFC582, 2018BEC473, and 2017BEC001), and the Medical Flight Plan of Wuhan University.

Increased intracranial pressure is a further effect of brain injury due to structural damage and osmotic and water imbalances (Edema). Mannitol works in the proximal tubules and mannitol in the absorption of tubular cells by the mechanism of pinocytosis. The fluid transfer will draw fluid into the intracellular, so that the cell will be switched and broke. This phenomenon is referred to as the phenomenon of "Nephrosis Osmotic", in which mannitol administration may occur as a result of accumulation of drugs in the kidneys due to prolonged exposure to mannitol in the kidney and given dosage. The effects of osmotic diuresis occurring plus the dose and duration of mannitol administration are reported to cause renal function disorders (Scr and BUN). The aim of this study was to analyze changes in serum creatinine and BUN in patients with brain injury from before receiving mannitol therapy and during mannitol treatment. From the results of the study the number of patients who met the inclusion criteria, 32 patients. Serum creatinine, the initial average of 0.85 ± 0.17 mg / dl and the last day of the mean SCr 0.74 ± 0.30 mg / dl. While the mean BUN (Blood Urea Nitrogen) was 11.27 ± 2.75 mg / dl and the mean last day was 17.08 mg / dl ± 8.59 mg / dl. From Serum Creatinine and BUN data it can be concluded that there is no significant change.

Acute kidney injury is associated with increased risk of heart failure and mortality. This study demonstrates that acute kidney injury induces remote cardiac dysfunction, damage, injury, and fibrosis via a galectin-3 (Gal-3) dependent pathway. Gal-3 originates from bone marrow-derived immune cells. Cardiac damage could be prevented by blocking this pathway.

Diagnosis of fatal hypothermia using biochemical markers from blood obtained post mortem has not been fully studied. The objective of this study was to investigate biochemical markers useful for diagnosis of fatal hypothermia. We investigated 573 cases that were autopsied within 72 hours of death in our laboratory between January 2015 and February 2018. Right cardiac blood, left cardiac blood and the femoral vein were used as blood sampling sites. Levels of troponin T, alanine aminotransferase, aspartate aminotransferase, blood urea nitrogen (BUN), creatinine (Cr), creatine kinase (CK), and CK-MB in the blood, and blood and urinary myoglobin (Mb) were measured. Mb staining of kidney specimens was also performed. Although BUN and Cr levels did not differ from their respective clinical reference values, very high levels of the other markers compared with their respective reference values were observed. BUN and Cr values did not differ among the right cardiac, left cardiac, and femoral vein blood. The BUN value of right cardiac blood in patients who died due to fatal hypothermia was significantly higher than that in patients who died due to burns, heart disease, suffocation, hemorrhagic shock, drowning, and trauma; however, the Cr value for fatal hypothermia was not different from that for other causes of death. Also, the BUN/Cr ratio was significantly higher for fatal hypothermia than for other causes of death. The positive rates of Mb staining in the kidney were as follows: fatal hypothermia, 75%; drowning, 56.7%; drug addiction, 53.3%; trauma, 51.4%; burning death, 47.4%; heart disease, 34.8%; and suffocation, 23.1%. In addition, the amount of urine in the urinary bladder was higher in cases of fatal hypothermia than that in cases of other causes of death. These results suggest that a high BUN value and high BUN/Cr ratio are useful for diagnosis of fatal hypothermia; the increase in BUN value may not be due to acute renal failure caused by rhabdomyolysis but may be, 博士（医学）・甲第708号・平成31年3月15日

Diagnosis of fatal hypothermia using biochemical markers from blood obtained post mortem has not been fully studied. The objective of this study was to investigate biochemical markers useful for diagnosis of fatal hypothermia. We investigated 573 cases that were autopsied within 72 hours of death in our laboratory between January 2015 and February 2018. Right cardiac blood, left cardiac blood and the femoral vein were used as blood sampling sites. Levels of troponin T, alanine aminotransferase, aspartate aminotransferase, blood urea nitrogen (BUN), creatinine (Cr), creatine kinase (CK), and CK-MB in the blood, and blood and urinary myoglobin (Mb) were measured. Mb staining of kidney specimens was also performed. Although BUN and Cr levels did not differ from their respective clinical reference values, very high levels of the other markers compared with their respective reference values were observed. BUN and Cr values did not differ among the right cardiac, left cardiac, and femoral vein blood. The BUN value of right cardiac blood in patients who died due to fatal hypothermia was significantly higher than that in patients who died due to burns, heart disease, suffocation, hemorrhagic shock, drowning, and trauma; however, the Cr value for fatal hypothermia was not different from that for other causes of death. Also, the BUN/Cr ratio was significantly higher for fatal hypothermia than for other causes of death. The positive rates of Mb staining in the kidney were as follows: fatal hypothermia, 75%; drowning, 56.7%; drug addiction, 53.3%; trauma, 51.4%; burning death, 47.4%; heart disease, 34.8%; and suffocation, 23.1%. In addition, the amount of urine in the urinary bladder was higher in cases of fatal hypothermia than that in cases of other causes of death. These results suggest that a high BUN value and high BUN/Cr ratio are useful for diagnosis of fatal hypothermia; the increase in BUN value may not be due to acute renal failure caused by rhabdomyolysis but may be, 博士（医学）・甲第708号・平成31年3月15日

Acute kidney injury is associated with increased risk of heart failure and mortality. This study demonstrates that acute kidney injury induces remote cardiac dysfunction, damage, injury, and fibrosis via a galectin-3 (Gal-3) dependent pathway. Gal-3 originates from bone marrow-derived immune cells. Cardiac damage could be prevented by blocking this pathway.

Cisplatin is one of platinum cytostatic drug for the medication of solid cancers, one of which is head and neck cancer. Adverse event that resulted during drug treatment was acute or chronic nephrotoxicity. Cisplatin concentration in proximal tubular epithelial cells is about 5 times the serum concentration. Platinum exposure on renal tubular cells bonding covalent complex which stimulate production of inflammatory factors that lead to apoptosis and necrosis cell. Cisplatin nephrotoxicity can be prevented by aggressive hydration or alternate method of administration. The aim of this study was to analyze the effectiveness of NaCl-Mannitol hydration on renal function of head and neck cancer patients receiving cisplatin 100 mg/m2 chemotherapy combination with 5FU or paclitaxel. This was a cohort, prospective, and observational study to analyze renal function of head and neck cancer patients receiving cisplatin 100 mg/m2 chemotherapy combination with 5FU or paclitaxel. Inclusion criteria were BUN 7-18 mg/dl and serum creatinine < 2 mg/dl of any cycle. All patients received infuse NaCl-Mannitol hydration with term that provided in Surgeon Departement of Dr. Soetomo General Hospital. Data obtained were BUN, SCr, and eClCr Cockroft-Gault, each was measured pre- and post-hydration. In cisplatin and 5FU chemotherapy combination value BUN pre-hydration (11,99 + 4,62) mg/dl, value BUN post-hydration (12,14 + 4,74) mg/dl and value serum creatinine pre-hydration (0,97 + 0,34) mg/dl, value serum creatinine post-hydration (1,02 + 0,37) mg/dl. Meanwhile to the combination of cisplatin and paclitaxel chemotherapy, value BUN pre-hydration (10,19 + 2,58) mg/dl, value of BUN post-hydration (10,43 + 2,31) mg/dl and value of serum creatinine post- hydration (0,98 + 0,26) mg/dl. In conclusion, NaCl-Mannitol hydration administration is adequate which is shown by BUN and serum creatinine in pre- and post-hydration data within normal limits.

Cisplatin is one of platinum cytostatic drug for the medication of solid cancers, one of which is head and neck cancer. Adverse event that resulted during drug treatment was acute or chronic nephrotoxicity. Cisplatin concentration in proximal tubular epithelial cells is about 5 times the serum concentration. Platinum exposure on renal tubular cells bonding covalent complex which stimulate production of inflammatory factors that lead to apoptosis and necrosis cell. Cisplatin nephrotoxicity can be prevented by aggressive hydration or alternate method of administration. The aim of this study was to analyze the effectiveness of NaCl-Mannitol hydration on renal function of head and neck cancer patients receiving cisplatin 100 mg/m2 chemotherapy combination with 5FU or paclitaxel. This was a cohort, prospective, and observational study to analyze renal function of head and neck cancer patients receiving cisplatin 100 mg/m2 chemotherapy combination with 5FU or paclitaxel. Inclusion criteria were BUN 7-18 mg/dl and serum creatinine < 2 mg/dl of any cycle. All patients received infuse NaCl-Mannitol hydration with term that provided in Surgeon Departement of Dr. Soetomo General Hospital. Data obtained were BUN, SCr, and eClCr Cockroft-Gault, each was measured pre- and post-hydration. In cisplatin and 5FU chemotherapy combination value BUN pre-hydration (11,99 + 4,62) mg/dl, value BUN post-hydration (12,14 + 4,74) mg/dl and value serum creatinine pre-hydration (0,97 + 0,34) mg/dl, value serum creatinine post-hydration (1,02 + 0,37) mg/dl. Meanwhile to the combination of cisplatin and paclitaxel chemotherapy, value BUN pre-hydration (10,19 + 2,58) mg/dl, value of BUN post-hydration (10,43 + 2,31) mg/dl and value of serum creatinine post- hydration (0,98 + 0,26) mg/dl. In conclusion, NaCl-Mannitol hydration administration is adequate which is shown by BUN and serum creatinine in pre- and post-hydration data within normal limits.

Cisplatin is one of platinum cytostatic drug for the medication of solid cancers, one of which is head and neck cancer. Adverse event that resulted during drug treatment was acute or chronic nephrotoxicity. Cisplatin concentration in proximal tubular epithelial cells is about 5 times the serum concentration. Platinum exposure on renal tubular cells bonding covalent complex which stimulate production of inflammatory factors that lead to apoptosis and necrosis cell. Cisplatin nephrotoxicity can be prevented by aggressive hydration or alternate method of administration. The aim of this study was to analyze the effectiveness of NaCl-Mannitol hydration on renal function of head and neck cancer patients receiving cisplatin 100 mg/m2 chemotherapy combination with 5FU or paclitaxel. This was a cohort, prospective, and observational study to analyze renal function of head and neck cancer patients receiving cisplatin 100 mg/m2 chemotherapy combination with 5FU or paclitaxel. Inclusion criteria were BUN 7-18 mg/dl and serum creatinine < 2 mg/dl of any cycle. All patients received infuse NaCl-Mannitol hydration with term that provided in Surgeon Departement of Dr. Soetomo General Hospital. Data obtained were BUN, SCr, and eClCr Cockroft-Gault, each was measured pre- and post-hydration. In cisplatin and 5FU chemotherapy combination value BUN pre-hydration (11,99 + 4,62) mg/dl, value BUN post-hydration (12,14 + 4,74) mg/dl and value serum creatinine pre-hydration (0,97 + 0,34) mg/dl, value serum creatinine post-hydration (1,02 + 0,37) mg/dl. Meanwhile to the combination of cisplatin and paclitaxel chemotherapy, value BUN pre-hydration (10,19 + 2,58) mg/dl, value of BUN post-hydration (10,43 + 2,31) mg/dl and value of serum creatinine post- hydration (0,98 + 0,26) mg/dl. In conclusion, NaCl-Mannitol hydration administration is adequate which is shown by BUN and serum creatinine in pre- and post-hydration data within normal limits.

This research was performed in four milking farms located at la Sabana de Bogotá. 78 animals were studied and divided in three age groups: cows, heifers and calves. The leptospira spp was diagnosed by the microagglutination – Lisis (MAT) method. A serological follow up was done for a year with nine samplings and L. hardjo, L. icterohaemorrhagiae, L. pomona, L. canicola y L. grippotyphosa, were evaluated with hepatic tests such as: Alanino amino transferasa (ALAT), Aspartato amino transferasa (ASAT); and renal tests such as: Ureic Nitrogen in Blood (BUN) and CREATININE. There were compared to records of productive variables like milk production and reproductive variables like the period of time between deliveries, open days and conception services. Prevalence of Leptospira spp found in bovines of four farms at Sabana de Bogotá was 31.74%. The highest prevalence during the study was 12.7% for serovar L. hardjo (90/711), regarding the farms the serovar with the highest prevalence was L. icterohaemorrhagiae in the farm with 29% (24/85). The age group number two (heifers) reported the highest prevalence to serovar L. icterohaemorrhagiae with 16.5% (20/127). There were no physilogical changes in age groups and farms in the following variables: ALAT with 20.452 U/L in average and CREATININE 1.2769 mg/dl in average, but there was a slightly decrease in BUN 12.934 mg/dl. There were some alterations in variable values: ASAT 108.96 U/L, 238.64 open days, Interval between deliveries 522.78 days, conception Services 2.56 and with the milk production, there is no a statistical relation during the samplings between serovares and milk production variable., La presente investigación se llevó a cabo en cuatro fincas con ganaderías lecheras especializadas localizadas en la sabana de Bogotá, de las cuales se tomaron un total de 78 animales divididos en tres grupos etáreos: vacas, novillas y terneras. La leptospira spp se diagnosticó por el método de Microaglutinación-Lisis (MAT); se realizó un seguimiento serológico durante un año en nueve muestreos y se evaluaron títulos a L. hardjo, L. icterohaemorrhagiae, L. pomona, L. canicola y L. grippotyphosa, pruebas hepáticas como: alanino amino transferasa (ALAT), aspartato amino transferasa (ASAT) y pruebas renales como: nitrógeno ureico en sangre (BUN) y creatinina, estas se compararon con los registros de variables productivas como: producción de leche y variables reproductivas como: intervalo entre partos, días abiertos y servicios por concepción. La prevalencia a Leptospira spp encontrada en bovinos en cuatro fincas de la sabana de Bogotá, fue de 31,74%. La mayor prevalencia durante el estudio fue para el serovar L. hardjo 12,7% (90/711); con respecto a las fincas el serovar que presentó la mayor prevalencia fue L. icterohaemorrhagiae en la finca cuatro con 29% (24/85). El grupo etáreo número dos (novillas) reportó la mayor prevalencia al serovar L. icterohaemorrhagiae con 16,5% (20/127). No se reportan cambios en los rangos fisiológicos para los grupos etáreos y fincas en las variables hepáticas y renales: ALAT con 20.452 U/L en promedio y creatinina 1,2769 mg/dl en promedio. Existió una leve disminución del BUN 12,934 mg/dl. El valor de ASAT estuvo por encima del rango normal 108,96 U/L. Los valores para las variables productivas fueron los siguientes: días abiertos 238,64 días, intervalo entre partos 522,78 días, servicios por concepción 2,56 servicios; no hubo una asociación directa entre los serovares en los diferentes muestreos con la variable producción de leche.

This research was performed in four milking farms located at la Sabana de Bogotá. 78 animals were studied and divided in three age groups: cows, heifers and calves. The leptospira spp was diagnosed by the microagglutination – Lisis (MAT) method. A serological follow up was done for a year with nine samplings and L. hardjo, L. icterohaemorrhagiae, L. pomona, L. canicola y L. grippotyphosa, were evaluated with hepatic tests such as: Alanino amino transferasa (ALAT), Aspartato amino transferasa (ASAT); and renal tests such as: Ureic Nitrogen in Blood (BUN) and CREATININE. There were compared to records of productive variables like milk production and reproductive variables like the period of time between deliveries, open days and conception services. Prevalence of Leptospira spp found in bovines of four farms at Sabana de Bogotá was 31.74%. The highest prevalence during the study was 12.7% for serovar L. hardjo (90/711), regarding the farms the serovar with the highest prevalence was L. icterohaemorrhagiae in the farm with 29% (24/85). The age group number two (heifers) reported the highest prevalence to serovar L. icterohaemorrhagiae with 16.5% (20/127). There were no physilogical changes in age groups and farms in the following variables: ALAT with 20.452 U/L in average and CREATININE 1.2769 mg/dl in average, but there was a slightly decrease in BUN 12.934 mg/dl. There were some alterations in variable values: ASAT 108.96 U/L, 238.64 open days, Interval between deliveries 522.78 days, conception Services 2.56 and with the milk production, there is no a statistical relation during the samplings between serovares and milk production variable., La presente investigación se llevó a cabo en cuatro fincas con ganaderías lecheras especializadas localizadas en la sabana de Bogotá, de las cuales se tomaron un total de 78 animales divididos en tres grupos etáreos: vacas, novillas y terneras. La leptospira spp se diagnosticó por el método de Microaglutinación-Lisis (MAT); se realizó un seguimiento serológico durante un año en nueve muestreos y se evaluaron títulos a L. hardjo, L. icterohaemorrhagiae, L. pomona, L. canicola y L. grippotyphosa, pruebas hepáticas como: alanino amino transferasa (ALAT), aspartato amino transferasa (ASAT) y pruebas renales como: nitrógeno ureico en sangre (BUN) y creatinina, estas se compararon con los registros de variables productivas como: producción de leche y variables reproductivas como: intervalo entre partos, días abiertos y servicios por concepción. La prevalencia a Leptospira spp encontrada en bovinos en cuatro fincas de la sabana de Bogotá, fue de 31,74%. La mayor prevalencia durante el estudio fue para el serovar L. hardjo 12,7% (90/711); con respecto a las fincas el serovar que presentó la mayor prevalencia fue L. icterohaemorrhagiae en la finca cuatro con 29% (24/85). El grupo etáreo número dos (novillas) reportó la mayor prevalencia al serovar L. icterohaemorrhagiae con 16,5% (20/127). No se reportan cambios en los rangos fisiológicos para los grupos etáreos y fincas en las variables hepáticas y renales: ALAT con 20.452 U/L en promedio y creatinina 1,2769 mg/dl en promedio. Existió una leve disminución del BUN 12,934 mg/dl. El valor de ASAT estuvo por encima del rango normal 108,96 U/L. Los valores para las variables productivas fueron los siguientes: días abiertos 238,64 días, intervalo entre partos 522,78 días, servicios por concepción 2,56 servicios; no hubo una asociación directa entre los serovares en los diferentes muestreos con la variable producción de leche.

Halocarbon 27-S (HC 27-S), a polymer of chlorotrifluoroethylene (CTFE), is used as a lubricating oil for pumps in hyperbaric chambers. Although monomeric CTFE has been shown to produce renal lesions in rats, the toxicity of CTFE polymers have been investigated. To assess the toxicity of repeated exposure to HC 27-S, three groups of male and female Fischer-344 rats were dosed. Decreased water consumption and urine output were apparent in all test groups. Statistically significant increases in fluoride excretion were noted in 24-hr urine samples assessed periodically during the study. Neurotoxic signs were observed in female rats but not in male rats. Significant increases in liver and kidney weights were seen in all rats, regardless of number of dosing days. The increased fluoride burden in treated animals appeared sufficient to alter bone calcium/phosphate ratios in male rats but not female rats. Gross liver enlargement and hepatocellular cytomegaly indicated that the liver was probably the primary target organ following repeated administration of HC 27-S. Keywords: Oral toxicity, Halocarbon oil, Industrial health, Hyperbaric chambers, Fluoride, BUN, CAP, CTFE, F-344, HC 27-S, LDH, SEM, Reprints, Bone, Calcium, Phosphates, Rats., Pub. Toxicology and Industrial Health, v6 n1 p17-32 1990.