Urinary Kidney Injury Molecule-1 Levels Research Articles

Is the urinary kidney injury molecule an optimum biomarker for early detection of obstructive nephropathy? An experimental study

Abstract Objectives To evaluate the urinary kidney injury molecule-1 (KIM-1) as a predictor for early detection of acute kidney injury in cases with obstructive nephropathy in an animal model and to correlate urinary KIM-1 with the progress of obstructive nephropathy on a histopathological basis. Materials and methods Three models of obstruction were induced in 90 male rats: unilateral partial ureteral obstruction with a normal contra-lateral kidney, with nephrectomy of a contralateral kidney (solitary kidney), and bilateral partial ureteral obstruction. Each group was further divided into 2 subgroups; the sham-group (10 rats) and the disease group (20 rats). Serum creatinine, blood urea nitrogen, and urinary KIM-1 were collected on days 0, 7, and 14. Rats were sacrificed on the 7th and 14th day for histopathological examination of the obstructed kidney. Results By the end of first week, there was a significant rise of all biomarker levels in all groups when compared with basal levels. Similarly, biomarker levels at the 14th day were significantly higher than those obtained at the 7th day. The urinary KIM-1 level was not detected in the baseline condition. Expression of urinary KIM-1 showed a significant rise in all models ranging from 22 to 85 fold at the 7th day and even higher levels at the 14th day. Histopathological examination confirmed the presence of different forms of tubular injury. Conclusions Urinary KIM-1 is significantly elevated in obstructive uropathy. Such an elevation might be advantageous in the early diagnosis and subsequent early intervention of cases with partial ureteral obstruction.

Association between Enzyme-Linked Immunosorbent Assay-Measured Kidney Injury Markers and Urinary Cadmium Levels in Chronic Kidney Disease.

Cadmium exposure is associated with chronic kidney disease (CKD), but the optimal biomarker for early cadmium-associated nephrotoxicity in low-level exposure has not yet been established. We conducted a cross-sectional investigation involving 167 CKD patients stratified according to tertiles of urinary cadmium levels (UCd), in which enzyme-linked immunosorbent assay (ELISA)-measured novel renal biomarkers were utilized to assess the extent of renal injury associated with cadmium burden. In the analyses, urinary kidney injury molecule-1 (KIM-1) levels and age were the independent factors positively correlated with UCd after adjusting for covariates in non-dialysis-dependent CKD patients (high vs. low UCd, odds ratio (95% confidence interval), 1.0016 (1.0001–1.0032), p = 0.043, and 1.0534 (1.0091–1.0997), p = 0.018). Other conventional and novel renal biomarkers, such as serum creatinine, estimated glomerular filtration rate, CKD staging, urinary protein/creatinine ratio, urinary 8-hydroxy-2-deoxyguanosine (8-OHdG), and urinary epidermal growth factor (EGF) were not independently correlated with UCd in the analyses. In conclusion, our study found that the ELISA-measured urinary KIM-1 level could serve as an early renal injury marker in low-level cadmium exposure for non-dialysis-dependent CKD patients. In addition, age was an independent factor positively associated with UCd in this population.

Effect of a 3% gelatin solution on urinary KIM-1 levels in patients after thyroidectomy: a preliminary randomized controlled trial

Optimal fluid therapy significantly affects the maintenance of proper tissue perfusion and, consequently, kidney function. An adverse effect of colloids on kidney function is related to the incidence of postoperative kidney failure. The study aimed to assess the effect of a 3% gelatin solution on kidney function based on the urinary kidney injury molecule-1 (uKIM-1) level. This study used a parallel design and enrolled 64 adult patients with a mean age of 52.5 ± 13.1 years, all of whom underwent a thyroidectomy procedure under general anesthesia. Patients were randomly assigned to three comparison groups, each receiving a different dose of 3% gelatin solution during the thyroidectomy procedure. The patients from study groups A (n = 21) and B (n = 21) received a 3% gelatin solution at a dose of 30 ml/kg and 15 ml/kg body weight, respectively, during the first hour of the procedure. The patients from the control group C (n = 22) received an isotonic multi-electrolyte solution. Serum creatinine levels were determined, and urine samples were collected to determine levels of uKIM-1 before, 2 h, and 24 h after surgery. The patients’ demographic data, type and volume of fluid and hemodynamic status during the surgery were collected from relevant anesthesia protocols and were included in the study data. There were no statistically significant changes between groups in hemodynamic parameters such as systolic and diastolic blood pressure, heart rate, and oxygen saturation values. A statistically significant increase in uKIM-1 level was noted in patients receiving the 3% gelatin solution regardless of the dose. A statistically significant difference in uKIM-1 level was observed between groups A, B, and C measured 24 h after surgery, with the highest uKIM-1 level in group A. Measurement of uKIM-1 level could be an early and sensitive biomarker of kidney injury. Kidney toxicity of a 3% gelatin solution, evaluated based on the level of uKIM-1 in urine, correlates with transfused fluid volume. This study was retrospectively registered in the ISRCTN clinical trials registry (ISRCTN73266049, 08/04/2021: https://www.isrctn.com/ISRCTN73266049).

Tissue neutrophil elastase contributes to extracorporeal shock wave lithotripsy-induced kidney damage and the neutrophil elastase inhibitor, sivelestat, attenuates kidney damage with gratifying immunohistopathological and biochemical findings: an experimental study

Although the efficacy of extracorporeal shock wave lithotripsy (ESWL) has been well established within the literature, debate continues on the safety of the procedure while focusing on cellular injury and its long-term consequences. Here, we describe the role of neutrophil elastase (NE) in ESWL-related rat kidney damage and investigate the protective effects of sivelestat, an inhibitor of NE, during the early and late phases. Four groups including control, ESWL alone, ESWL with sivelestat 50mg/kg and ESWL with treatment of 100mg/kg, each consisting of ten rats were created. Biochemical parameters of kidney function and damage and immunohistopathological findings were compared in the early (72h after ESWL) and late (1week after ESWL) periods between the groups. During the early period, serum and urine creatinine levels and urine kidney injury molecule-1 (KIM-1) levels and the KIM-1/creatinine ratio increased in rats treated with ESWL compared to the control group. Furthermore, increased tissue inflammation, ductal dilatation and hemorrhage, and glomerular, tubular, and interstitial damage with increased NE staining were also detected in the ESWL treatment group. During the late phase, although urine KIM-1 levels remained stable at high levels, other parameters showed significant improvements. On the other hand, the administration of sivelestat 50mg/kg decreased serum creatinine and urine KIM-1 and KIM-1/creatinine levels significantly in rats treated with ESWL, during the early and late periods. Significant decreases in tissue inflammation, tubular, and interstitial tissue damage were also observed during the early period. In conclusion, ESWL-related kidney tissue damage occurs primarily during the early period, and NE is involved in this process. On the other hand, the NE inhibitor sivelestat attenuated this ESWL-induced kidney damage.

Kidney injury molecule-1 levels are associated with therapeutic outcomes and renal tubulointerstitial injury severity in idiopathic membranous nephropathy.

Kidney injury molecule-1 (KIM-1) has an important role in chronic kidney disease development. The present study aimed to retrospectively analyze patients with idiopathic membranous nephrology (IMN) with different therapeutic outcomes to investigate the association between KIM-1 levels and therapeutic outcomes. A total of 51 patients with IMN and 20 healthy controls were included. Patients were classified into three groups: Spontaneous remission, remission with immunosuppressive therapy (IST) and nonremission with IST. Clinical and biochemical variables were collected. Urinary KIM-1 levels were measured by ELISA and renal KIM-1 expression was evaluated by immunohistochemistry. Patients with IMN were characterized as having elevated urinary and renal KIM-1 levels compared with those in the controls. Significantly increased urinary and renal KIM-1 levels were observed in the nonremission with IST group compared with those in the spontaneous remission group, and the same trend was observed for the plasma anti-podocyte antigen phospholipase A2 receptor antibody levels. Patients with more severe tubular injury (T2 index) presented with significantly higher urinary and renal KIM-1 levels than those with the T0 index. Urinary and renal KIM-1 levels were positively correlated with blood urea nitrogen, serum creatinine, serum cystatin-C, urinary albumin/creatinine ratio, urinary β2-microglobulin and the renal interstitial fibrosis index, and they were negatively correlated with serum albumin. Furthermore, urinary KIM-1 levels were positively correlated with the renal KIM-1 levels. In conclusion, the measurement of urinary and renal KIM-1 levels may be helpful in guiding medication selection and predicting therapeutic outcomes for patients with IMN.

Value of urine IL-8, NGAL and KIM-1 for the early diagnosis of acute kidney injury in patients with ureteroscopic lithotripsy related urosepsis

PurposeTo investigate the clinical value of urine interleukin-18 (IL-8), neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) for the early diagnosis of acute kidney injury (AKI) in patients with ureteroscopic lithotripsy (URL) related urosepsis. MethodsA retrospective study was carried out in 157 patients with urosepsis after URL. The patients were divided into AKI group and non-AKI group according to the Kidigo guideline and urine IL-8, NGAL and KIM-1 levels were detected by enzyme-linked immunosorbent assay at 0, 4, 12, 24 and 48 h after the surgery. Receiver operating characteristic curve (ROC) was used to evaluate the diagnostic value of these three biomarkers for postoperative AKI. ResultsThe level of urine IL-8, NGAL and KIM-1 in AKI group was significantly higher than that in non-AKI group at 4, 12, 24 and 48 h (p < 0.01). The ROC analysis showed the combined detection of urine IL-8, NGAL and KIM-1 at 12 h had a larger area under curve (AUC) than a single marker (0.997, 95% CI: 0.991–0.998), and the sensitivity and specificity were 98.2% and 96.7%, respectively. Pearson correlation analysis showed that the levels of urine NGAL at 4, 12, 24 and 48 h in AKI patients were positively correlated with the levels of urine KIM-1 and IL-18 (p < 0.01). ConclusionAKI could be quickly recognized by the elevated level of urine IL-8, NGAL and KIM-1 in patients with URL-related urosepsis. Combined detection of the three urine biomarkers at 12 h after surgery had a better diagnostic performance, which may be an important reference for the early diagnosis of AKI.

Serum Netrin-1 and Urinary KIM-1 levels as potential biomarkers for the diagnosis of early preeclampsia

The aim of this study was to evaluate whether the Serum Netrin-1 and Urinary KIM-1 (Kidney Injury Molecule-1) levels are associated with the detection of preeclampsia. A total of 90 patients, including 36 normal pregnant women, 29 patients with nonsevere preeclampsia and 25 patients with severe preeclampsia, were included in this study. Maternal serum Netrin-1 and Urinary KIM-1 levels were measured by using an enzyme-linked immunosorbent assay (ELISA). The results showed that the Levels of Netrin-1 and KIM-1 were statistically higher in women with preeclampsia as compared with normal pregnant women. Furthermore, the Netrin-1 level in women with severe preeclampsia was significantly higher than nonsevere preeclamptic women. inconclusion the current study showed that Maternal serum level of Netrin-1 and Urinary level of KIM-1 can be used as early biomarkers for the detection of preeclampsia. IMPACT STATEMENT What is already known on this subject? Preeclampsia is a disorder of widespread vascular endothelial malfunction and vasospasm that occurs after 20 weeks' gestation. Netrin-1 was found to promote angiogenesis. Alteration of placental angiogenesis in early pregnancy is a well-known reason for placental dysfunction such as preeclampsia. Kidney injury with proteinuria is a characteristic feature of preeclampsia. Urine KIM-1 is the most potential biomarker for renal injury in preeclampsia. Due to these facts, we aimed to investigate the role of maternal serum Netrin-1 and Urine KIM-1 levels in preeclampsia presence and severity. What the results of this study add? A significant relationship between Netrin-1 and KIM-1 levels with preeclampsia. What the implications are of these findings for clinical practice and/or further research? Based on these findings, we concluded that increased levels of Netrin-1 and KIM-1 are associated with severe preeclampsia.

Urine Biomarkers for the Assessment of Acute Kidney Injury in Neonates with Hypoxic Ischemic Encephalopathy Receiving Therapeutic Hypothermia

To evaluate the predictive performance of urine biomarkers for acute kidney injury (AKI) in neonates with hypoxic ischemic encephalopathy (HIE) receiving therapeutic hypothermia. We performed a multicenter prospective observational study of 64 neonates. Urine specimens were obtained at 12, 24, 48, and 72hours of life and evaluated for neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), cystatin C, interleukin-18 (IL-18), tissue inhibitor of metalloproteinases 2 (TIMP2), and insulin-like growth factor-binding protein 7 (IGFBP7). Logistic regression models with receiver operating characteristics for area under the curve (AUC) were used to assess associations with neonatal modified KDIGO (Kidney Disease: Improving Global Outcomes) AKI criteria. AKI occurred in 16 of 64 infants (25%). Neonates with AKI had more days of vasopressor drug use compared with those without AKI (median [IQR], 2 [0-5] days vs 0 [0-2] days; P=.026). Mortality was greater in neonates with AKI (25% vs 2%; P=.012). Although NGAL, KIM-1, and IL-18 were significantly associated with AKI, the AUCs yielded only a fair prediction. KIM-1 had the best predictive performance across time points, with an AUC (SE) of 0.79 (0.11) at 48hours of life. NGAL and IL-18 had AUCs (SE) of 0.78 (0.09) and 0.73 (0.10), respectively, at 48hours of life. Urine NGAL, KIM-1, and IL-18 levels were elevated in neonates with HIE receiving therapeutic hypothermia who developed AKI. However, wide variability and unclear cutoff levels make their clinical utility unclear.

On normalizing of urinary KIM-1 level to urine creatinine in patients with renal cell cancer.

KIM-1 (kidney injury molecule 1), a marker of acute kidney injury, is produced by epithelial cells of renal proximal tubules. Elevated KIM-1 levels in urine and plasma are associated with renal cell carcinoma (RCC). The aim of this study was to compare the significance of non-normalized uKIM-1 values and those normalized to urine creatinine, as urinary biomarkers in RCC. The uKIM-1, urine creatinine and their ratio (uKIM-1/Cre) were studied in 118 RCC patients and 58 apparently healthy subjects. The median of uKIM-1 in the healthy group was 0.71 ng/ml (1st and 3rd quartiles were 0.35 and 1.23, respectively) and in RCC patients it was 2.36 (1.43; 5.93) ng/ml. The medians of uKIM-1/Cre were 0.77 (0.49; 1.18) and 2.42 (1.41; 4.61) ng/mgCre, respectively. Stage I RCC is statistically significantly different from stages II-III and stage IV using uKIM-1/Cre values (p = 0.0056 and p = 0.0012, respectively); using uKIM-1 values significant differences occur only when comparing stages I and IV (p = 0.015). In both healthy individuals and RCC patients, uKIM-1/Cre levels were slightly lower in subgroups younger than 50 years than in subgroups older than 50 years, whereas a similar trend was observed for uKIM-1 only in patients. In healthy men and male patients, uKIM-1 levels were higher than in the corresponding groups of women (the differences were not statistically significant), but the use of uKIM-1/Cre values eliminated the gender differences. A high correlation was found between the concentrations of uKIM-1 and urine creatinine in three healthy subjects followed up for 3 weeks (Spearman's correlation coefficients were 0.758, 0.825 and 0.933, respectively). The data obtained are clear evidence of the need for normalization uKIM-1 to urine creatinine in RCC patients.

Early kidney injury in immunoglobulin A vasculitis: Role of renal biomarkers.

We aimed to determine whether urine kidney injury molecule 1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) can be used as early noninvasive biomarkers of kidney injury in immunoglobulin A vasculitis. Patients who were diagnosed with immunoglobulin A vasculitis were included in the study. Urine samples were collected for determination of urine KIM-1 and NGAL levels. The control group consisted of age-matched healthy children. Sixty-one patients who were diagnosed with immunoglobulin A vasculitis were included in the study; 37.7% of these patients were determined to have renal involvement. Median KIM-1 was found to be significantly higher in the patient group (69.59pg/mL) than the control group (40.84pg/mL) (P = 0.001). Median NGAL was determined to be statistically significantly higher in the patient group (59.87ng/mL) compared with the control group (44.87ng/mL) (P = 0.013). In 23.6% of the patients without renal involvement at admission renal involvement developed within the following 6 months. When median KIM-1 and NGAL at admission of these patients were compared with the control group, they were determined to be statistically significantly higher (P = 0.001, P = 0.003). The fact that our patients with late-term nephropathy had no hematuria and / or proteinuria and that KIM-1 and NGAL levels were determined to be high indicates that these biomarkers might be potentially reliable, noninvasive and early determinants of kidney injury.

Diagnostic performance of kidney injury molecule‐1 for detection of abnormal urinary albumin‐to‐creatinine ratio in type 2 diabetes mellitus

ABSTRACT In this study, we aimed to investigate whether serum and urinary levels of kidney injury molecule 1 (KIM-1) are increased in type 2 diabetes mellitus (DM) patients with albuminuria. While the correlation of urinary KIM-1 with renal impairment has been well established, the association with serum KIM-1 has not yet been so well documented. The present pilot study included Egyptian patients with type 2 diabetes (T2D): A total of 84 patients with T2D (age 49–64 years; 20 men) were included in the analysis of the present study. They were divided into two groups according to Alb/Cr ratio: the first group included 32 patients (38.1%) with abnormal Alb/Cr ratio (38.6 mg/g·Cr), and the second group included 52 patients with normal Alb/Cr ratio (17.9 mg/g·Cr). Serum and urinary KIM-1 were measured using enzyme-linked immunoassays. There was a significant difference between both serum and urine KIM-1 and Alb/Cr ratio. Patients with abnormal Alb/Cr ratio had significantly higher serum and urinary KIM-1. These results yielded sensitivity (75.0%) and specificity (96.2%) regarding serum KIM-1 with a cut-off point of 37.5 pg/mL, and sensitivity (93.8%) and specificity (88.5%) regarding urinary KIM1 with a cut-off point of 32.00 ng/g.Cr. Serum KIM-1 and urinary KIM-1 were significantly correlated with eGFR and Alb/Cr ratio. In this pilot study, we found that urinary, serum, and urinary levels of KIM-1 are associated with significant impairments in renal function among diabetic patients. Our results also showed that serum and urine KIM-1 can be used as potential biomarkers for diabetic kidney disease.

Correlation between urinary KIM-1 and kidney protein expression of p-ERK following damage in rats exposed to gentamicin or lead acetate.

Kidney injury molecule-1 (KIM-1) is a membrane receptor upregulated in the proximal tubule cells following various types of kidney injuries. Notably, studies have suggested a correlation between KIM-1 expression and extracellular signal-regulated kinase (ERK) activation. In this study, we aimed to investigate the association between the kidney overexpression pattern of cytoplasmic phosphorylated-ERK (p-ERK) protein and increased urinary KIM-1 levels in rats exposed to gentamicin or lead acetate, both at the end of toxic exposure and after a 4-week recovery period. Although other proteins were evaluated, only kidney overexpression of cytoplasmic p-ERK protein correlated with increased urinary KIM-1 levels. For both toxic substances, the increased urinary KIM-1 levels corresponded with kidney inflammation. Our results suggest that KIM-1 and p-ERK share a common mechanism in kidney injury mediated by both toxic substances that induce proximal tubule damage.

The role of urinary kidney injury molecule-1 in monitoring the child with idiopathic microscopic hematuria

Background/Aim: Idiopathic microscopic hematuria is common during childhood, and numerous factors play a role with varying degrees in its etiopathogenesis. We aimed to investigate whether urinary kidney injury molecule-1 level could be a new indicator to detect a possible renal injury that may cause idiopathic microscopic hematuria. Methods: This prospective case-control study included 38 children between 1-15 years of age who were followed up due to idiopathic microscopic hematuria without hypertension and/or edema and 39 healthy individuals with similar gender distribution. Kidney injury molecule-1, urine culture, microalbumin, calcium, magnesium, uric acid, and creatinine levels in spot urine were measured in both groups. A throat culture and abdominal ultrasound were performed on all those included. Results: No significant differences were found between the patient and control groups in terms of age, gender, weight, and height (P>0.05). Microalbumin, microalbumin to creatinine ratio in spot urine, urinary kidney injury molecule-1 levels, and kidney injury molecule-1 to creatinine ratio were higher among the patients than the controls (P=0.016, P=0.013, P=0.001, and P=0.001, respectively). Conclusion: Urinary microalbumin and kidney injury molecule-1 levels, as well as rates of these two markers to creatinine, may be higher in the children with idiopathic microscopic hematuria. Our findings show that children with microscopic hematuria should be monitored for renal tubular injury and the development of chronic renal disease.

Changes in urinary kidney injury molecule-1 levels after blood transfusions in preterm infants

Literature supports an association between transfusions and gut injury in preterm infants. We hypothesized that packed red blood (PRBC) transfusions are associated with kidney inflammation marked by a rise in urinary levels of Kidney Injury Molecule 1 (KIM-1). Prospectively, KIM-1 levels were measured before and then at 6, 12 and 24 h after a PRBC transfusion. Results are presented as mean (± SD) and median (IQR). Thirty-four infants, birth weight 865 (± 375) g, had higher pretransfusion KIM-1 levels of 2270 (830, 3250) pg/mg than what is normal for age. These were not associated with hematocrit levels. KIM-1 levels peaked between 6 and 12 h after the transfusion. Levels peaked to 3300 (1990, 6830) pg/mg; levels returned to pretransfusion levels of 2240 (1240, 3870) pg/mg by 24 h, p < 0.01. The 24-h post-transfusion KIM-1 levels were similar to pretransfusion levels, p = 0.63. PRBC transfusions in preterm infants are associated with an elevation in urinary KIM-1 levels. The mechanism of this association may be important in studying transfusion associated organ injury. KIM-1, as an inflammatory marker, may be helpful in assessing the effect of different transfusion volumes or in evaluating operational thresholds of anemia in premature infants.

Importance of KIM-1 and MCP-1 in Determining the Leptospirosis-Associated AKI: A Sri Lankan Study.

Background Acute kidney injury (AKI) is one of most prevalent and serious complications of leptospirosis, a prevalent zoonotic disease in tropical countries. Prompt diagnosis of the leptospirosis-associated AKI is a challenge as there are no proper diagnostic tools that can identify patients in the early stage. Kidney injury molecule-1 (KIM-1) and monocyte chemoattractant protein-1 (MCP-1) are widely used novel AKI biomarkers that are studied in various disease conditions with AKI, but not in leptospirosis. Thus, this study is aimed at seeking the importance of KIM-1 and MCP-1 in determining the leptospirosis-associated AKI. Methods Leptospirosis-suspected patients who were admitted to medical wards of two selected hospitals in the Western province of Sri Lanka were recruited. Leptospirosis was confirmed by three diagnostic tests: PCR, MAT, and culture, and the status of AKI was determined by Kidney Disease Improving Global Outcomes (KDIGO) criteria. Results Of 170 leptospirosis-suspected patients, 79 were leptospirosis confirmed, and among them, 24.05% of patients were diagnosed to have AKI according to KDIGO criteria. Median serum KIM-1 (p < 0.0001), urine KIM-1 (0.0053), serum MCP-1 (0.0080), and urine MCP-1 (0.0019) levels in those developing AKI were significantly higher than in patients not developing AKI. The biomarker levels associated with leptospirosis AKI had AUC-ROC of 0.8565, 0.7292, 0.7024, and 0.7282 for serum KIM-1, urine KIM-1, serum MCP-1, and urine MCP-1, respectively. Conclusion This study revealed serum KIM-1 as a promising marker for leptospirosis-associated AKI among the tested biomarkers. Thus, further validation is recommended with a larger study group.

Are Tubular Injury Markers NGAL and KIM-1 Useful in Pediatric Neurogenic Bladder?

The lack of early biomarkers of renal damage in children with neurogenic bladder (NB) prompts us to investigate the role of promising proteins: neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1). This prospective analysis was conducted on 58 children with NB and 25 healthy children. We assessed urinary levels of NGAL and KIM-1 in both groups. Age, sex, anthropometric measurements, activity assessment, renal function, and urodynamics parameters were analyzed. The differences between the median uNGAL and uKIM-1 in the NB group compared to control were recorded. However, only uNGAL levels were statistically significantly higher. Statistically significant correlation was found between gender, recurrent urinary tract infections, bladder trabeculation, its compliance, activity assessment, and uNGAL. To conclude, elevated levels of uNGAL may be considered a biomarker of tubular injury in children with NB due to MMC in contrast to uKIM-1.

Poor Glycemic Control Can Increase the Plasma Kidney Injury Molecule-1 Concentration in Normoalbuminuric Children and Adolescents with Diabetes Mellitus.

Diabetic nephropathy (DN) is a serious microvascular complication in childhood diabetes and microalbuminuria has been a solid indicator in the assessment of DN. Nevertheless, renal injury may still occur in the presence of normoalbuminuria (NA) and various tubular injury biomarkers have been proposed to assess such damage. This case-controlled study aimed to evaluate plasma and urinary neutrophil gelatinase-associated lipocalin and kidney injury molecule-1 (KIM-1) levels in diabetic children particularly in those with normo- and high-NA stages and determine their role in predicting DN. Fifty-four children/adolescents with type 1 and 2 diabetes and forty-four controls aged 7–18 years were included. The baseline clinical and laboratory characteristics including plasma and urinary biomarkers were compared. The plasma KIM-1 levels were significantly higher in diabetic children than in the controls and in high-NA children than normo-NA children. Glycosylated hemoglobin (HbA1c) was identified as a significant risk factor for increased plasma KIM-1. The optimal cutoff for HbA1c when the plasma KIM-1 was > 23.10 pg/mL was 6.75% with an area under the curve of 0.77. For diabetic children with mildly increased albuminuria, the plasma KIM-1 complementary to MA may help increase the yield of detecting DN. Our findings also suggested an HbA1c cutoff of 6.75% correlated with increased plasma KIM-1.

Ablation of TRPV1 Abolishes Salicylate-Induced Sympathetic Activity Suppression and Exacerbates Salicylate-Induced Renal Dysfunction in Diet-Induced Obesity.

Sodium salicylate (SA), a cyclooxygenase inhibitor, has been shown to increase insulin sensitivity and to suppress inflammation in obese patients and animal models. Transient receptor potential vanilloid 1 (TRPV1) is a nonselective cation channel expressed in afferent nerve fibers. Cyclooxygenase-derived prostaglandins are involved in the activation and sensitization of TRPV1. This study tested whether the metabolic and renal effects of SA were mediated by the TRPV1 channel. Wild-type (WT) and TRPV1−/− mice were fed a Western diet (WD) for 4 months and received SA infusion (120mg/kg/day) or vehicle for the last 4 weeks of WD feeding. SA treatment significantly increased blood pressure in WD-fed TRPV1−/− mice (p < 0.05) but not in WD-fed WT mice. Similarly, SA impaired renal blood flow in TRPV1−/− mice (p < 0.05) but not in WT mice. SA improved insulin and glucose tolerance in both WT and TRPV1−/− mice on WD (all p < 0.05). In addition, SA reduced renal p65 and urinary prostaglandin E2, prostaglandin F1α, and interleukin-6 in both WT and TRPV1−/− mice (all p < 0.05). SA decreased urine noradrenaline levels, increased afferent renal nerve activity, and improved baroreflex sensitivity in WT mice (all p < 0.05) but not in TRPV1−/− mice. Importantly, SA increased serum creatinine and urine kidney injury molecule-1 levels and decreased the glomerular filtration rate in obese WT mice (all p < 0.05), and these detrimental effects were significantly exacerbated in obese TRPV1−/− mice (all p < 0.05). Lastly, SA treatment increased urine albumin levels in TRPV1−/− mice (p < 0.05) but not in WT mice. Taken together, SA-elicited metabolic benefits and anti-inflammatory effects are independent of TRPV1, while SA-induced sympathetic suppression is dependent on TRPV1 channels. SA-induced renal dysfunction is dependent on intact TRPV1 channels. These findings suggest that SA needs to be cautiously used in patients with obesity or diabetes, as SA-induced renal dysfunction may be exacerbated due to impaired TRPV1 in obese and diabetic patients.

Evaluation Of Novel Biomarkers For Early Detection Of Acute Kidney Injury In Children With B-Thalassemia Major

Background: Improved survival in patients with β-thalassemia has enabled the appearance of several clinical morbidities, involving renal problems. Incredibly important is the early detection of persons at higher risk of getting renal failure. Aim of work: To compare the sensitivity of KIM-1, NGAL and microalbuminuria in early detection of kidney injury in thalassemic children. Subjects and methods: A cross sectional study was conducted in the Outpatient Clinic of Hematology Unit of Pediatric Department and Clinical Pathology Department at Zagazig University Hospitals on thirty thalassemic patients during their regular follow-up visits and thirty age- and sex-matched healthy children as a control group from June to December 2017. All thalassemic patients were subjected to full medical history. Periodic thorough clinical examination was done with special emphasis on disease-related complications. Routine laboratory investigations were performed in addition to serum concentrations of Neutrophil Gelatinase-Associated Lipocalin (NGAL) protein (ng/ml), urine concentration of kidney injury molecule-1 (KIM-1) and microalbuminuria. Results: A highly statistically significant increase in the levels of urinary KIM-1, serum NGAL and albumin in urine among cases compared to controls was found. We found that the sensitivity of KIM-1 biomarker in prediction of kidney injury among thalassemia patients was 93.3%, higher than sensitivity of NGAL and microalbuminuria biomarkers. Conclusion: In early identification of acute renal failure in thalassemia patients, urinary KIM-1 is more sensitive than serum NGAL and microalbuminuria.

Occupational Paraquat and Glyphosate Exposure May Decline Renal Functions among Rural Farming Communities in Sri Lanka

Extensive use of herbicides is common among rural agricultural workers in Sri Lanka. Recent studies have postulated their role in the development of chronic kidney disease of unknown etiology (CKDu). Paraquat and glyphosate are leading herbicides used by sugarcane farmers (SF), hence occupational exposure is inevitable. This study examined the expression of urinary paraquat, glyphosate and biomarkers among residential SF in CKDu emerging regions, Warunagama (WA) and Rahathangama (RH), in the Uva Province with non-endemic Matara (MA) in the Southern Province of Sri Lanka. Urinary glyphosate, Paraquat, kidney injury molecule -1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL) and β2-microglobulin (B2M) were determined using enzyme-linked immunosorbent assays (ELISA). Urinary creatinine, microalbumin, serum creatinine (SCr), serum cystatin C, estimated glomerular filtration rate (eGFR), and albumin creatinine ratio (ACR) were also assessed. Generally, herbicide residues and kidney injury biomarkers were higher in SF compared to the non-endemic MA. Creatinine-adjusted urinary glyphosate and paraquat levels were significantly higher in WA compared to MA. ACR in RH (median 14.9; IQR 5.4–393.1 mg/g) and WA (23.7; 11.5–64.6) was significantly higher than MA (4.3; 2.2–6.7). This study reports 39 individuals with impaired kidney function among SF in Sri Lanka for the first time. Urinary NGAL levels were significantly higher in both WA (median 2.14; IQR 1.28–6.15 ng/mg Cr) and RH (3.09; 1.15–9.09) compared to MA (1.28; 0.56–2.81). However, urinary KIM-1 levels in RH (3.2; 1.29–106.1 ng/g Cr) and WA (3.6; 1.94–115.1) were not significantly higher in MA (1.74; 0.76–116.9). Urinary NGAL (r = 0.493), eGFR (r = −0.147) and ACR (r = 0.171) significantly correlated with urinary glyphosate, but not with urinary paraquat levels. Urinary KIM-1 levels did not correlate with either urinary glyphosate or paraquat, while urinary B2M and serum cystatin C levels showed significant correlation with urinary glyphosate levels. The current study reports higher urinary herbicide levels among sugarcane farmers in WA and RH, and that is potentially linked to the subsequent decline in kidney function, as indicated by ACR, eGFR, and NGAL. We posit that these indicators may serve as markers to detect renal injury among herbicide-exposed SF in Rural Sri Lanka.