Urine oxygenation predicts COVID-19 risk.

Since February, 2023, the omicron variant has accounted for essentially all new coronavirus infections in Japan. If future infections involve mutant strains with the same level of infectivity and virulence as omicron, the government's basic policy will be to prevent the spread of infection, without compromising socioeconomic activities. Objectives include protecting pregnant women and elderly persons, and focusing on citizens requiring hospitalization and those at risk of serious illness, without imposing new social restrictions. Although the government tries to raise public awareness through education, most people affected by COVID-19 stay at home, and by the time patients become aware of the seriousness of their disease, it has often reached moderate or higher severity. In this review, we discuss why this situation persists even though the disease seems to have become milder with the shift from the delta variant to omicron. We also propose a pathophysiological method to determine the risk of severe illness. This assessment can be made at home in the early stages of COVID-19 infection, using urine analysis. Applicability of this method to drug discovery and development is also discussed.

Urinary L-type fatty acid-binding protein is a predictor of cisplatin-induced acute kidney injury.

BACKGROUND: Although cisplatin-based chemotherapy is a standard treatment for urothelial carcinoma, it often causes acute kidney injury (AKI). AKI and dysfunction are observed in 25-35% of cisplatin-based chemotherapy patients, who may require treatment down-titration or withdrawal. In this study, we evaluated whether urinary L-FABP is a marker for early diagnosis of cisplatin-caused AKI. METHODS: We included 42 adult patients who underwent cisplatin-based chemotherapy for bladder cancer or upper tract urothelial carcinoma from January 2018 to March 2019. Urinary L-FABP and serum creatinine were measured at 2 and 6 h, and 1, 2, 3, 7 and 28 days after taking cisplatin. RESULTS: In the first week after receiving cisplatin, 10 patients (23.8%) were diagnosed with AKI (AKI+ group). Pre-treatment (baseline) measurements did not significantly differ between the AKI+ and AKI- groups. However, urinary L-FABP concentrations rapidly increased in the AKI+ group and were significantly greater than in the AKI- group at Hour 2, Hour 6, Day 1 and Day 2. Serum creatinine also significantly differed between the AKI+ group and the AKI- group on Days 3 and 7. ROC analysis was performed to evaluate the superiority of urinary L-FABP magnification which had the highest at the hour 6. The urinary L-FABP magnification and levels of aria under curve was 0.977. Based on ROC analysis, the best cut-off value of urinary L-FABP magnification was 10.28 times urinary L-FABP levels at the hour 0 (base line urinary L-FABP). CONCLUSIONS: Acute renal function deterioration was predicted by increased urinary L-FABP excretion within 6 h after receiving CIS-CT and, in those with AKI, the increase in urinary L-FABP excretion preceded the rise in sCr by over 2 days. In contrast, no appreciable changes in urinary L-FABP levels were observed in patients with stable renal function throughout the whole observation period. So early increase in urinary L-FABP may identify patients at risk of cisplatin-induced AKI, who might benefit from treatment to prevent nephrotoxicity. TRIAL REGISTRATION: This study was retrospectively registered.

Effects of dietary phosphorus concentration and phosphate salt form on renal tubule function in unilateral nephrectomized rats.

Background: Excessive consumption of phosphorus (P) impairs renal tubule function; however, the effects of different dietary phosphate salts on chronic kidney disease (CKD) are unclear. Aim: To examine the effects of potassium dihydrogen phosphate (KH2PO4) and potassium tripolyphosphate (K5P3O10) and P concentration on renal function in a rat model of early CKD. Methods: Male sham-operated Sprague-Dawley rats were fed a diet containing KH2PO4 with a normal P level. Kidney injury was induced by unilateral nephrectomy (UNx), and the rats were divided into four groups fed dietary KH2PO4 or K5P3O10 with a normal (UNx-NKH, UNx-NKP) or high (UNx-HKH, UNx-HKP) P concentration, respectively, for 21 days. Results: UNx-NKH rats showed significantly lower creatinine clearance (CCr) and higher albumin (ALB) compared with those of sham rats, confirming UNx-induced kidney injury. The urinary levels of liver-type fatty acid-binding protein (L-FABP) and ALB were significantly higher in UNx-HKP rats than in UNx-HKH rats. However, other markers of renal tubule function, such as CCr, serum creatinine (CRE), calcium (Ca), and hormones, only differed among groups according to the P concentration and not the dietary phosphate salt form. Histological examination showed higher incidence and severity of tubulointerstitial lesions, tubule regeneration, tubule dilation, and calcification in the high-phosphorus than in the normal-phosphorus UNx groups. These changes were more severe in the UNx-HKP group compared with the UNx-HKH group. Conclusion: This study highlights the importance of controlling dietary P intake in terms of both concentration and source to prevent the progression of CKD.

Amniotic Fluid L-Type Fatty Acid-Binding Protein in Predicting Fetal Condition.

Ultrasonography and fetal heart rate monitoring are subjective assessments of fetal condition, which warrants the need for objective markers to predict fetal condition. Urinary L-type fatty acid-binding protein (L-FABP) levels correlate with hypoperfusion. Elevated amniotic fluid L-FABP levels may represent fetal tissue hypoperfusion since the amniotic fluid contains fetal urine. In this study, we aimed to analyze the effectiveness of amniotic fluid L-FABP as a predictor of fetal condition. We classified singleton pregnancies into groups based on fetal growth restriction (FGR) with and without fetal blood flow abnormalities (FGR and healthy-FGR groups, respectively) and the non-FGR group (control group). We collected amniotic fluid at the time of vaginal delivery, cesarean section and amniocentesis, and compared the patient characteristics, clinical outcomes and amniotic fluid levels of L-FABP between the groups. We analyzed 153 singleton pregnancies and 186 amniotic fluid samples (FGR group, 6 (3.9%) pregnancies and 23 (12.4%) samples; healthy-FGR group, 15 (9.8%) pregnancies and 20 (10.7%) samples; control group, 132 (86.3%) pregnancies and 143 (76.9%) samples). The amniotic fluid L-FABP level was significantly higher in the FGR group compared to that in the healthy-FGR and control groups. Multivariate analysis revealed that the amniotic fluid L-FABP level was not affected by fetal body weight. Additionally, the amniotic fluid L-FABP levels increased significantly in cases with fetal blood flow abnormalities or early gestational age. Therefore, amniotic fluid L-FABP level may be an objective and accurate predictive marker of fetal condition.

Amniotic fluid neutrophil gelatinase-associated lipocalin and L-type fatty acid-binding protein in predicting fetal inflammatory response syndrome.

AIM: To analyze the effectiveness of amniotic fluid neutrophil gelatinase-associated lipocalin and L-type fatty acid-binding protein as predictive factors for fetal inflammatory response syndrome. METHODS: We classified single pregnancy cases into the fetal inflammatory response syndrome and nonfetal inflammatory response syndrome groups. We collected amniotic fluid at vaginal delivery and cesarean section and compared the patient characteristics, maternal white blood cell count, C-reactive protein level, and amniotic fluid interleukin-6; neutrophil gelatinase-associated lipocalin; and L-type fatty acid-binding protein levels between the groups. We further analyzed the relationship between L-type fatty acid-binding protein levels and neonatal clinical outcomes. RESULTS: We analyzed 129 pregnancies, of which 36 and 93 (27.9% and 72.1%, respectively) were classified into the fetal inflammatory response syndrome and nonfetal inflammatory response syndrome groups, respectively. We observed significant differences in the maternal white blood cell counts and amniotic fluid interleukin-6 and neutrophil gelatinase-associated lipocalin levels. On the multivariate analysis, the useful predictive factors were maternal white blood cell count and amniotic fluid interleukin-6 and neutrophil gelatinase-associated lipocalin levels. Furthermore, the level of L-type fatty acid-binding protein was significantly higher in the transient tachypnea of the newborn and postnatal respiratory support group than in the control group. CONCLUSIONS: The maternal white blood cell count and amniotic interleukin-6 and neutrophil gelatinase-associated lipocalin levels were effective predictors of fetal inflammatory response syndrome. Amniotic fluid L-type fatty acid-binding protein level was an effective predictor of neonatal respiratory support.

Utility of urinary tubular markers for monitoring chronic tubulointerstitial injury after ischemia-reperfusion.

AIM: The aim of this study was to elucidate whether urinary tubular markers during the chronic phase of acute kidney injury (AKI) are associated with chronic tubulointerstitial damage. METHODS: Male human L-type fatty acid binding protein (L-FABP) chromosomal transgenic (Tg) mice underwent ischaemic reperfusion (I/R) injury via renal pedicle clamping for either 10 min or 20 min. Contralateral nephrectomy was performed at the time of tissue reperfusion. The kidneys were analyzed 20 days after the last I/R. RESULTS: Serum creatinine levels 20 days post-I/R were significantly higher in the 20 min I/R than in the 10 min I/R and control groups and were similar between the 10 min I/R and control groups. The degree of tubulointerstitial damage 20 days post-I/R was significantly more severe in the 20 min I/R than in the 10 min I/R and control groups, as well as in the 10 min I/R than in the control group. Urinary levels of human L-FABP, albumin, and kidney injury molecule-1 (KIM-1) 20 days post-I/R were significantly higher in the 20 min I/R than in the control group, whereas urinary L-FABP was significantly higher in the 10 min I/R than in the control group. Conversely, urinary neutrophil gelatinase-associated lipocalin levels did not significantly differ between the three groups. Finally, the urinary levels of human L-FABP, albumin, and KIM-1 levels 20 days post-I/R were significantly correlated with the degree of renal damage. CONCLUSIONS: Urinary levels of human L-FABP, albumin and, KIM-1 may be useful for monitoring AKI-to-CKD transition in clinical practice.

Urinary l-type fatty acid-binding protein is a predictor of early renal function after partial nephrectomy.

PURPOSE: Urinary biomarkers of renal injury urinary may identify loss of renal function following nephron-sparing surgery (NSS). This study was designed to evaluate whether urinary l-type fatty acid-binding protein (l-FABP) is an early biomarker of loss of renal function after NSS. Specifically, the kinetics of urinary l-FABP level after NSS and its correlation with factors related to ischemic renal injury were analyzed. METHODS: This study prospectively evaluated 18 patients who underwent NSS between July and December 2014, including 12 who underwent laparoscopic and six who underwent robot-assisted partial nephrectomy. Urinary l-FABP concentrations were measured preoperatively and 1, 2, 3, 6, 12, 24, 48, and 72 h after renal artery declamping. Loss of renal function loss was calculated by comparing the effective renal plasma flow, as determined by 99mTc-mercaptoacetyltriglycine (MAG3) clearance, on the operated and normal sides. The decrease in estimated glomerular filtration rate from before surgery to six months after surgery was also measured. RESULTS: Urinary l-FABP concentration peaked within 2 h of declamping, which may quantify nephron damage caused by ischemia. The decrease in MAG3 reduction ratio correlated with both the ischemia time and peak urinary l-FABP concentration. Peak urinary l-FABP concentration showed a significant correlation with MAG3 reduction ratio. CONCLUSIONS: l-FABP is a suitable urinary biomarker for predicting the extent of ischemic renal injury.

Mortality prediction by acute kidney injury biomarkers in comparison with serum creatinine.

OBJECTIVES: To investigate the performance of acute kidney injury (AKI) biomarkers for mortality prediction. MATERIALS AND METHODS: Cutoff values of urinary L-type fatty acid-binding protein (L-FABP) and N-acetyl-ß-d-glucosaminidase (NAG) for AKI diagnosis in ICU were determined in the derivation cohort. The performance of these AKI biomarkers for mortality prediction was evaluated in the validation cohort with stratification of serum-creatinine based AKI diagnosis. RESULTS: Mortality in the AKI patients diagnosed by serum creatinine was increased remarkably when urinary L-FABP and NAG were positive. CONCLUSIONS: These AKI biomarkers can specifically detect high-risk patients among creatinine-base diagnosed AKI.

Fat emulsion given to very low-birthweight infants increases urinary L-FABP.

BACKGROUND: In premature infants, many factors influence the function of renal tubules, such as asphyxia, respiratory disorders, use of high-concentration oxygen, hypotension, and drug treatment. When tubular ischemia and oxidative stress develop due to renal microcirculatory pathology, urinary L-type fatty acid-binding protein (L-FABP) level increases. METHODS: Urinary L-FABP level was measured over time in very low-birthweight infants (VLBWI), and the effect of fat emulsion on L-FABP level was investigated. Thirty-one VLBWI were divided into two groups with regard to treatment with fat emulsion: the lipid group (n = 20) and the control group (n = 11). Urinary L-FABP was measured before (0-3 days of age), during (7-14 days of age), and after fat emulsion treatment (21-28 days of age) in the two groups. RESULTS: Median urinary L-FABP level before treatment was 459 ng/mgCr (range, 22.7-5100 ng/mgCr; mean, 1067 ± 1570 ng/mgCr) and 797 ng/mgCr (range, 69-3900 ng/mgCr; mean, 1066 ± 1188 ng/mgCr) in the lipid and control groups, respectively, showing no significant difference. Median urinary L-FABP level was 624 ng/mgCr (range, 50-2050 ng/mgCr; mean ± SD, 799 ± 655 ng/mgCr) and 273 ng/mgCr (range, 31-987 ng/mgCr; mean ± SD, 359 ± 323 ng/mgCr) at 7-14 days of age, respectively, showing that the level was significantly higher in the lipid group. At 21-28 days of age, the median level was 462 ng/mgCr (range, 49-1867 ng/mgCr; mean ± SD, 557 ± 534 ng/mgCr) and 130 ng/mgCr (range, 20-993 ng/mgCr; mean ± SD, 290 ± 329 ng/mgCr), respectively, showing that L-FABP level tended to be higher in the lipid group. CONCLUSIONS: Fat emulsion treatment induced a significant increase in urinary L-FABP level, suggesting that fat emulsion affected the proximal tubule in VLBWI.

Evaluation of amniotic fluid neutrophil gelatinase-associated lipocalin and L-type fatty acid-binding protein levels during pregnancy.

Objective: We aimed to examine amniotic fluid neutrophil gelatinase-associated lipocalin (NGAL) and L-type fatty acid-binding protein (L-FABP) levels during pregnancy. Study design: This study included singleton pregnancies. Amniotic fluid samples were collected at the time of vaginal delivery, cesarean section, amniocentesis, amnioreduction, and amnioinfusion. We analyzed changes of the NGAL and L-FABP levels during pregnancy and the factors affecting these values and their association with clinical outcomes. Results: Three hundred and one pregnancies were analyzed. Respective Pearson correlation coefficients for the NGAL and L-FABP levels and gestational age at inspection were - 0.351 and - 0.819 (p <0.001 and p < 0.001, respectively); weak and strong negative correlation were observed. The NGAL level was significantly higher in the intra-amniotic infection group than in the control group (p < 0.001). The L-FABP level was significantly higher in the fetal blood flow abnormalities group than in the control group (p < 0.001). The NGAL and L-FABP levels were significantly higher in the adverse outcomes group than in the control group (p = 0.019 and p < 0.001, respectively), and the respective areas under the concentration-time curve, with optimal cutoff values, for the NGAL and L-FABP levels were 0.693 (14,800 µg/gCr) and 0.864 (378 µg/gCr). Conclusions: Amniotic fluid NGAL and L-FABP levels reflect fetal and neonatal immaturity. Additionally, the NGAL level is a useful predictive factor of intra-amniotic infection, and the L-FABP level is a useful predictive factor of fetal condition and short- and long-term prognoses.

MicroRNA expression profiling in acute kidney injury.

The aim of this study was to identify miRNAs that regulate AKI and develop their applications as diagnostic biomarkers and therapeutic agents. First, kidney tissues from two different AKI mouse models, namely, AKI induced by the administration of lipopolysaccharide (LPS) causing sepsis (LPS-AKI mice) and AKI induced by renal ischemia-reperfusion injury (IRI-AKI mice), were exhaustively screened for their changes of miRNA expression compared with that of control mice by microarray analysis followed by quantitative RT-PCR. The initial profiling newly identified miRNA-5100, whose expression levels significantly decreased in kidneys in both LPS-AKI mice and IRI-AKI mice. Next, the administration of miRNA-5100-mimic conjugated with a nonviral vector, polyethylenimine nanoparticles (PEI-NPs), via the tail vein significantly induced miRNA-5100 overexpression in the kidney and prevented the development of IRI-AKI mice by inhibiting several apoptosis pathways in vivo. Furthermore, serum levels of miRNA-5100 in patients with AKI were identified as significantly lower than those of healthy subjects. ROC analysis showed that the serum expression level of miRNA-5100 can identify AKI (cut-off value 0.14, AUC 0.96, sensitivity 1.00, specificity 0.833, p<0.05). These results suggest that miRNA-5100 regulates AKI and may be useful as a novel diagnostic biomarker and therapeutic target for AKI.

Renoprotective effects of voluntary running exercise training on aldosterone-induced renal injury in human L-FABP chromosomal transgenic mice.

Tubulointerstitial damage is a crucial therapeutic target in preventing chronic kidney disease (CKD) progression. Inappropriately activated renin-angiotensin-aldosterone system (RAAS) in the tubulointerstitial area is strongly associated with tubulointerstitial damage progression. Therefore, this study aimed to determine whether there is a beneficial effect of voluntary running exercise training on aldosterone-induced renal injury. Human L-type fatty acid-binding protein (L-FABP) chromosomal transgenic (L-FABP+/-) male mice were used to evaluate the effect of exercise by using urinary L-FABP, a tubular marker. The mice were assigned to either the exercise group that performed voluntary running exercise training using a running wheel or the control group. Subsequently, two groups were injected with aldosterone (0.125 µg kg-1 min-1) and administered 1% NaCl water, and two groups were administered aldosterone only in solvent 4 weeks after initiating the exercise. Aldosterone was injected for another 4 weeks, and NaCl water was administered from 5 weeks after starting the exercise until 8 weeks. Although both aldosterone and NaCl water significantly decreased the running distance, tubulointerstitial damage involving interstitial infiltration of macrophages and fibrosis and the elevation of urinary human L-FABP induced by aldosterone injection was prevented by voluntary running exercise training. Urinary human L-FABP levels were significantly correlated with the degree of tubulointerstitial damage. In conclusion, voluntary running exercise training delayed tubulointerstitial damage progression in the aldosterone-induced renal injury model and therefore may be a promising nonpharmacological strategy in CKD.

Magnesium supplementation therapy to prevent cisplatin-induced acute nephrotoxicity in pediatric cancer: A protocol for a randomized phase 2 trial.

Although cisplatin is one of the most effective agents against various pediatric cancers, it is sometimes difficult to manage due to its dose-limiting nephrotoxicity. Magnesium sulfate (Mg) showed a kidney-protective effect against cisplatin-induced nephrotoxicity (CIN) by regulating renal platinum accumulation both in vitro and in vivo, and the body of clinical data demonstrating the efficacy of this drug in adult cancer patients is increasing.In this open, multicenter, phase-2, randomized trial, patients under age 18 years who are scheduled to receive cisplatin-containing chemotherapy will be enrolled and randomly allocated either to an Mg supplementation arm in even-numbered chemotherapy courses (arm AB) or to another arm in odd-numbered courses (arm BA), with a 1:1 allocation. Analysis objects will be reconstructed into two groups depending on whether the chemotherapy course has Mg supplementation (group B) or not (group A). The primary endpoint is the proportion of chemotherapy courses resulting in elevated serum creatinine equal to or greater than 50% of the prechemotherapy value. For the secondary endpoints, various parameters for measuring kidney function, such as serum cystatin-C, B2M, L-FABP, NGAL, and urinary NAG in the two groups will be compared. A sample size based on alpha = 5% and 80% power requires at least 40 samples per group (ideally, 60 samples per group).If Mg demonstrates efficacy, a phase-3 study to confirm the prophylactic effect of Mg supplementation in both acute and chronic CIN will be developed using novel and better biomarkers. TRIAL REGISTRATION: UMIN-CTR (http://www.umin.ac.jp/icdr/index.html) Identifier UMIN000029215.

Comparison of three early biomarkers for acute kidney injury after cardiac surgery under cardiopulmonary bypass.

BACKGROUND: Acute kidney injury (AKI) is a serious complication after cardiac surgery, being associated with a high mortality. We assessed three urinary biomarkers, L-type fatty acid-binding protein (L-FABP), neutrophil gelatinase-associated lipocalin (NGAL), and angiotensinogen, which are elevated through different mechanisms, and investigated which of these biomarkers was the earliest and most useful indicator of AKI after cardiac surgery. METHODS: This study was a prospective observational study conducted at a single-institution university hospital. All patients were adults aged under 80 years who underwent cardiac surgery with cardiopulmonary bypass between November 2013 and January 2015. Perioperatively, urine samples were obtained from all patients at five points. Based on AKI criteria, patients were divided into two groups: AKI group (n = 11) and non-AKI group (n = 39), according to postoperative serum creatinine (Cr) levels. RESULTS: Urinary L-FABP, NGAL, angiotensinogen, and Cr were measured perioperatively. L-FABP was significantly higher in the AKI group than in the non-AKI group at the end of surgery and 3 h after surgery. L-FABP levels were 601.5 ± 341.7 and 233.8 ± 127.2 µg/g Cr in the AKI and non-AKI groups, respectively. Three hours after surgery, NGAL levels were 950.5 ± 827.9 and 430.0 ± 250.6 µg/g Cr in the AKI and non-AKI groups, respectively, the level being significantly higher in the AKI group than in the non-AKI group. There were no significant differences in urinary angiotensinogen levels between the two groups at any time point. CONCLUSIONS: We demonstrated the utility of L-FABP and NGAL, but not angiotensinogen in the early recognition of AKI. The problem of the different peak points among biomarkers needs to be resolved for discovery of a panel of biomarkers.