U-NAG Levels Research Articles

High-expression of FABP4 in Tubules is a Risk Factor for Poor Prognosis in DKD Patients.

Lipid metabolism imbalance is involved in the mechanism of renal tubular injury in diabetic kidney disease (DKD). Fatty acid binding protein 4 (FABP4) has been reported to participate in cellular lipid toxicity. However, the expression of FABP4 in renal tissues of DKD and its correlation with clinical/ pathological parameters and prognosis have not been studied. A retrospective cohort study was conducted in 108 hospitalized Type 2 diabetes (T2D) patients with renal injury, including 70 with DKD and 38 with NDKD (non-DKD). Clinical features, pathological findings, and follow-up parameters were collected. Serum and urine FABP4 were detected by ELISA. An immunohistochemistry stain was used to determine FABP4 in renal tubulointerstitium. A double immunofluorescence stain was employed to assess FABP4- and CD68-positive macrophages. Correlation analysis, logistic regression models, receiver operating characteristic (ROC), and Kaplan-Meier survival curve were performed for statistical analysis. DKD patients had increased expression of FABP4 and ectopic fat deposition in tubules. As shown by correlation analyses, FABP4 expression in renal tubules was positively correlated with UNAG (r=0.589, p=0.044) and ESRD (r=0.740, p=0.004). Multivariate regression analysis revealed that UNAG level was correlated with FABP4 expression level above median value (odds ratio:1.154, 95% confidence interval:1.009-1.321, p=0.037). High-expression of FABP4 in renal tubules of DKD was at an increased risk of ESRD. Increased FABP4 expression in inflammatory cells was also associated with ESRD in DKD. High-expression of FABP4 is involved in the pathogenesis of renal tubular lipid injury and is a risk factor for poor prognosis in DKD patients.

Evaluation of N-acetyl-β-D-glucosaminidase as a prognostic marker for diabetic nephropathy in type 2 diabetics: systematic review and meta-analysis.

This review aimed to assess the utility of urinary N-acetyl-β-D-glucosaminidase (uNAG) as a prognostic biomarker for nephropathy in patients with type 2 diabetes mellitus. The search for relevant studies was conducted across multiple databases, including PubMed (Medline), EMBASE, LILACS, CENTRAL, IBECS, and gray literature. We employed a random effects model to calculate the standardized mean difference and 95% confidence interval. Furthermore, we assessed heterogeneity using Cochrane's Q test and Higgins' I2 statistics. This review included a total of 16 articles involving 1669 patients, with 13 being case-control studies and three being cohorts. The meta-analysis conducted across all studies revealed significant heterogeneity. However, subgroup analysis of four studies indicated that an increase in uNAG among normoalbuminuric patients was associated with the development of macroalbuminuria (DMP = -1.47; 95% CI = -1.98 to 0.95; p < 0.00001; I2 = 45%). Conversely, it did not demonstrate effectiveness in predicting the development of microalbuminuria (DMP = 0.26; 95% CI = -0.08 to 0.60; p = 0.13; I2 = 17%). Elevated uNAG levels in normoalbuminuric patients may indicate an increased risk for the development of macroalbuminuria, but not microalbuminuria. However, the high heterogeneity observed among the studies highlights the necessity for further research to validate these findings.

An analysis of the relationship between donor and recipient biomarkers and kidney graft function, dysfunction, and rejection

BackgroundThe study aimed to find predictive biomarkers to evaluate donor kidney function to predict graft dysfunction as well as to assess an early signs of acute graft rejection. MethodTwenty-seven deceased donors and 54 recipients who underwent a successful kidney transplantation were enrolled in the study. An assessment was made in serum and urine from donors and recipients to measure the following biomarkers: neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), tissue inhibitor of metalloproteinase 2 (TIMP-2) and urinary N-acetyl-b-D-glucosaminidase (uNAG). These biomarkers were used to establish a model for predicting a reduced graft function (RGF) classified as either a delayed or slow graft function. ResultOur analysis suggest that out of four tested biomarkers, the serum TIMP-2 and uNAG levels of the donors had a predictive value for RGF; the area under the receiver operating characteristic curves (AUROC) of serum TIMP-2 and uNAG were 0.714 and 0.779, respectively. The combined best fitting prediction model of serum TIMP-2, uNAG, and creatinine levels was better in predicting RGF than the serum creatinine level alone. In addition, the recipient serum TIMP-2 level on the third day post-transplantation (D3) was associated with the estimated glomerular filtration rate (eGFR) on the seventh day post-transplantation (D7; OR 1.119, 95% CI 1.016–1.233, p = 0.022). Furthermore, the ROC curve value revealed that the AUROC of TIMP-2 on D3 was 0.99 (95% CI 0.97–1, p < 0.001), and this was the best predictive value of the renal function on D7. ConclusionsDonor serum TIMP-2 and uNAG levels are useful predictive biomarkers because they can provide the donor-based prediction for RGF.

Prognostic Value of Urinary N-Acetyl-β-d-Glucosaminidase as a Marker of Tubular Damage in Patients with Heart Failure and Mitral Regurgitation.

Mitral regurgitation (MR) has a high prevalence and aggravates hypoperfusion and hypoxia in heart failure (HF). Renal tubular epithelial cells are sensitive to hypoxia, and therefore tubulointerstitial damage is quite common in HF. However, the correlation between tubular dysfunction and MR has not been studied. The aim of this work was to evaluate the prognostic significance of urinary N-acetyl- -d-glucosaminidase (uNAG), a biomarker of renal tubular damage, in patients with HF and MR. This was a prospective cohort study of 390 patients (mean age 64 years; 65.6% male) with uNAG measurement on admission (expressed as urinary NAG/urinary creatinine) and at least 1 year of follow-up data. The pre-defined primary endpoint was the composite of all-cause mortality or rehospitalization for HF after discharge. Cox regression analysis, restricted cubic splines, and subgroup analysis were used to investigate the prognostic value of uNAG modeled as a categorical (quartiles) or continuous (per SD increase) variable. A total of 153 (39.23%) patients reached the composite endpoint over a median follow-up time of 1.2 years. The uNAG level correlated with the severity of HF and with the incidence of adverse events. In a multivariable Cox regression model, each SD (13.80 U/g Cr) of increased uNAG was associated with a 17% higher risk of death or HF rehospitalization (95% confidence interval, 2-33%, p = 0.022), and a 19% higher risk of HF rehospitalization (p = 0.027). Subgroup analysis revealed the associations between uNAG and poor prognosis were only significant in younger patients ( 65 years) and in patients without obvious cardiovascular comorbidities. uNAG levels at admission were associated with the risk of adverse outcomes in patients with HF and MR. Additional studies are needed to further investigate the heart-kidney interaction.

Urinary N-Acetyl-Beta-D-Glucosaminidase levels predict immunoglobulin a nephropathy remission status

BackgroundTubulointerstitial lesions play a pivotal role in the progression of IgA nephropathy (IgAN). Elevated N-acetyl-beta-D-glucosaminidase (NAG) in urine is released from damaged proximal tubular epithelial cells (PTEC) and may serve as a biomarker of renal progression in diseases with tubulointerstitial involvement.MethodsWe evaluated the predictive value of urinary NAG (uNAG) for disease progression in 213 biopsy-proven primary IgAN patients from January 2018 to December 2019 at Zhongshan Hospital, Fudan University. We compared the results with those of serum cystatin C (sCysC).ResultsIncreased uNAG and sCysC levels were associated with worse clinical and histological manifestations. Only uNAG level was independently associated with remission status after adjustment. Patients with high uNAG levels (> 22.32 U/g Cr) had a 4.32-fold greater risk of disease progression. The combination of baseline uNAG and clinical data may achieve satisfactory risk prediction in IgAN patients with relatively preserved renal function (eGFR ≥ 60 ml/min/1.73 m2, area under the curve [AUC] 0.760).ConclusionOur results suggest that uNAG is a promising biomarker for predicting IgAN remission status.

Revisiting the Role of NAG across the Continuum of Kidney Disease.

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.

The role of urinary N-acetyl-β-D-glucosaminidase in early detection of acute kidney injury among pediatric patients with neoplastic disorders in a retrospective study

BackgroundThe 1-year cumulative incidence of AKI reportedly is high (52%) in pediatric neoplastic disorders. About half of these events occur within 2 weeks. However, subclinical AKI episodes may remain unrecognized by the conventional creatinine-based approaches. We investigated the diagnostic value of urinary N-acetyl-β-D-glucosaminidase (uNAG) as an early marker of acute kidney injury (AKI).MethodsIn our retrospective study, 33 children with neoplastic disorders were inculded who had serial uNAG tests (at least 5 samples/patient) with a total of 367 uNAG measurements. Renal function was determined by cystatin-C and creatinine based GFR, and relative increase of uNAG index (uNAGRI). We focused on detecting both clinical and subclinical AKI episodes (according to Biomarker-Guided Risk Assessment using pRIFLE criteria and /or elevated uNAG levels) and the incidence of chronic kidney damage.ResultsSixty episodes in 26 patients, with positivity at least in one parameter of kidney panel, were identified during the observation period. We detected 18/60 clinical and 12/60 subclinical renal episodes. In 27/60 episodes only uNAG values was elevated with no therapeutic consequence at presentation. Two patients were detected with decreased initial creatinine levels with 3 „silent” AKI.In 13 patients, modest elevation of uNAG persisted suggesting mild, reversible tubular damage, while chronic tubuloglomerular injury occurred in 5 patients.Based on ROC analysis for the occurence of AKI, uNAGRI significantly indicated the presence of AKI, the sensitivity and specificity are higher than the changes of GFRCreat. Serial uNAG measurements are recommended for the reduction of the great amount of false positive uNAG results, often due to overhydratation.ConclusionUse of Biomarker-guided Risk Assessment for AKI identified 1.5 × more clinical and subclinical AKI episodes than with creatinine alone in our pediatric cancer patients. Based on the ROC curve for the occurence of AKI, uNAGRI has relatively high sensitivity and specificity comparable to changes of GFRCysC. The advantage of serial uNAG measurements is to decrease the number of false positive results.Trial registrationThe consent to participate is not applicable because it was not reqired for ethical approval and it is a retrospectiv study.

Variations of urinary N-acetyl-β-D-glucosaminidase levels and its performance in detecting acute kidney injury under different thyroid hormones levels: a prospectively recruited, observational study

ObjectiveChanges in thyroid function will be accompanied by changes in urinary N-acetyl-β-D-glucosaminidase (uNAG) levels. Therefore, whether thyroid hormones interfere the ability of uNAG in detecting acute kidney injury (AKI) has...

Renal function in \u03b2-thalassemia major patients treated with two different iron-chelation regimes

BackgroundRenal injury in transfusion dependent β thalassemia patients (TDT) has been attributed to iron overload, chronic anemia and iron-chelation therapy (ICT) toxicity. We studied renal function in TDT patients treated with two different ICT regimes.Patients and methodsWe studied 36 TDT patients: 26 received deferasirox (DFX) and 10 were treated with deferoxamine (DFO) +/− deferiprone (DFP).ResultsIncreased uNAG was found in 30% of the DFX group vs. 10% of the DFO+/−DFP group, the mean uNAG level in the DFX group was significantly higher than in the DFO+/−DFP group, (P < 0.05). A moderate negative correlation was found between uNAG levels and mean serum ferritin for the prior 10 years (P = 0.03), more pronounced for the DFO+/−DFP group. Twenty nine patients had had their renal function evaluated 10 years earlier; eGFR significantly declined in patients switched to DFX (P = 0.0093) but not in patients who continued DFO+/−DFP.ConclusionsA high prevalence of renal tubular damage was observed in our TDT patients, particularly those treated with DFX; uNAG was negatively associated with mean 10-year serum ferritin, suggesting ICT’s involvement in tubular injury. A significant decline in eGFR compared to a decade earlier was observed only in patients currently treated with DFX. Strict follow-up of renal function in TDT patients is warranted.

Prognosis predictability of serum and urine renal markers in patients with decompensated cirrhosis: A multicentre prospective study.

This prospective observational study aimed to evaluate the best serum and urine markers to assess predictability for the prognosis of patients with decompensated cirrhosis. Serum creatinine and cystatin C (CysC), and urinary N-acetyl-beta-D glucosaminidase (uNAG) and neutrophil gelatinase-associated lipocalin (uNGAL) levels were measured from hospitalized patients with decompensated cirrhosis. In total, 328 patients (mean age, 57.2±12.0years; 237 men) with decompensated cirrhosis were included. Alcoholic liver disease was the most frequent underlying liver disease (68.0%). Acute kidney injury (AKI) was concomitantly present in 41 patients (12.5%) at baseline. INR, serum creatinine and CysC levels, and uNAG and uNGAL levels were significantly higher in patients with AKI. During hospitalization, AKI had progressed in 37 patients (11.3%). In 287 patients without AKI, the incidence of AKI at 3, 6, 9 and 12months was 15.4%, 22.2%, 28.6% and 32.5% respectively. On multivariate analysis, serum CysC and uNAG levels were independent predictors of AKI, and their optimal cut-off values were 1.055mg/L and 23.1U/g urinary Cr respectively. When patients were classified into three groups with these cut-off values of serum CysC and uNAG levels (group 1, both low; group 2, one of two high; and group 3, both high), progression of AKI during hospitalization (P=.001), incidence of AKI in patients without AKI at baseline (P=.001) and mortality rate (P<.001) differed significantly according to serum CysC and uNAG levels. Serum CysC and uNAG levels are useful prognostic markers for renal outcomes and mortality in patients with decompensated cirrhosis.

Apoptosis inhibitor of macrophage as a biomarker for disease activity in Japanese children with IgA nephropathy and Henoch-Schönlein purpura nephritis.

To evaluate the apoptosis inhibitor of macrophage (AIM) deposition patterns on the kidneys of children with IgA nephropathy (IgAN) and Henoch-Schönlein purpura nephritis (HSPN) and to investigate the clinical usefulness of serum and/or urinary AIM levels as biomarkers for the disease activity. Immunohistochemical study was performed in the kidneys of 37 patients with IgAN and 10 patients with HSPN. Serum and urinary AIM levels in the patients and 20 healthy controls (HCs) were quantified by enzyme-linked immunosorbent assay. The results were compared with clinical features. In patients with IgAN and HSPN, AIM expression was observed in various areas, including the glomerular mesangial and capillary areas, the proximal and distal tubular epithelial cells, and on infiltrating macrophages in the glomeruli and interstitial areas. Serum and urinary AIM levels were significantly elevated in these patients compared with the HCs. Urinary AIM levels were positively correlated with the histological severity and degree of proteinuria and hematuria as well as urinary β2 microglobulin and urinary N-acetyl-β-D-glucosaminidase levels. AIM plays an important role in the pathogenesis of IgAN and HSPN. Urinary AIM levels can potentially reflect active renal inflammation in these diseases and may represent a useful biomarker for disease activity. Urinary AIM levels may represent a useful biomarker for disease activity of IgAN and HSPN. AIM expression was observed in the glomeruli, tubular epithelial cells, and infiltrating macrophages in glomeruli and interstitial area. U-AIM/Cr were significantly correlated not only with proteinuria, hematuria, and u-β2MG and u-NAG levels but also with the activity index of histological findings in kidney biopsy specimens. Our results can emphasize the important role of AIM in the pathogenesis of IgAN and HSPN.

A cross-sectional study on school-age children living near a municipal waste incinerator: Urinary metal levels and renal impairment assessment.

To take an insight into the long-term accumulation of chromium (Cr) and cadmium (Cd) in school-age children living near an MWI and to assess their early renal impairment, we conducted a cross-sectional study in 2015. A total of 116 children from the exposure area and 122 from the control area were recruited. We measured the urinary levels of Cr (U-Cr) and Cd (U-Cd) by inductively coupled plasma mass spectrometry (ICP-MS), and detected three classic renal tubule indicators, including N-acetyl-β-d-glucosaminidase (NAG), β2-microglobulin (BMG), and retinol binding protein (RBP). The U-Cd and U-Cr levels in children living near the MWI were 0.11 and 1.57 μg/g creatinine, respectively. Both the U-Cd and U-Cr levels in the exposure group were lower than those in the control group, although only U-Cd showed a statistical difference (p < 0.01). The U-NAG and U-RBP levels in the exposure group were also statistically lower than those in the control group (0.80 vs. 1.74 IU/g creatinine, 0.26 vs. 0.48 mg/g creatinine, respectively). The U-Cd level in this study was positively correlated with the U-NAG level (r = 0.26, p < 0.01), as the U-Cr level was also positively correlated with the levels of U-NAG, U-RBP, and U-BMG (r = 0.21, 0.33, 0.18, p < 0.01, respectively). This study indicates that children living close to this particular MWI may not suffer considerable long-term accumulation of Cd or Cr, nor early renal impairment.

Epidemiological study of kidney health in an area with high levels of soil cadmium and selenium: Does selenium protect against cadmium-induced kidney injury?

Chronic exposure to cadmium (Cd) can cause renal dysfunction. Studies of animals, cell cultures, and plants have found that selenium (Se) can effectively alleviate the hazard generated by Cd, but there has been little study of this in general human populations. This study recruited 313 subjects from China's Hubei Province, including 160 living in areas with high soil Cd and Se (exposure group) and 153 living in clean areas (control group). The levels of the following were detected: Cd and Se in blood (B-Cd and B-Se), urine (U-Cd and U-Se), and hair (H-Cd and H-Se); N-acetyl-β-D-glucosaminidase (U-NAG), β2-microglobulin (U-β2-MG), and albumin (U-ALB) in urine; and malondialdehyde (S-MDA), superoxide dismutase (S-SOD), and glutathione peroxidase (S-GSH-Px) in serum. In addition, the interactions between Cd and Se were assessed. The median levels of B-Cd, B-Se, U-Cd, U-Se, H-Cd, H-Se, S-MDA, and S-GSH-Px of exposure group (2.60 ng/mL, 238.90 ng/mL, 3.13 μg/g Cr, 45.43 μg/g Cr, 0.06 μg/g, 0.70 μg/g, 5.22 nmol/mL, and 308.89 U, respectively) were significantly higher than of controls (0.95 ng/mL, 130.50 ng/mL, 1.08 μg/g Cr, 30.51 μg/g Cr, 0.04 μg/g, 0.49 μg/g, 4.71 nmol/mL, and 267.54 U, respectively), but there were no significant differences in U-NAG, U-β2-MG, U-ALB, or S-SOD between the two groups. U-NAG levels were significantly negatively associated with the interaction between Cd and Se (B: −0.511, 95% CI: −0.886, −0.136). Additionally, changes in the direction of the estimated regression coefficient in the low and high H-Se groups were observed for U-Cd and S-MDA (from 0.018 to −0.090), U-Cd and S-GSH-Px (from −0.039 to 0.101). This study found that populations living in areas with high levels of soil Cd and Se did not show greater Cd-induced renal tubular and glomerular injuries than the control population, which could attribute to the protective effects of Se. The protective effects may be related to the peculiar function of Se that Se can combine with free Cd to activate the antioxidant enzyme system.

The Association between Urinary N-Acetyl-ß-D-Glucosaminidase and Cardiovascular Autonomic Neuropathy in Patients with Diabetes

Background: Cardiovascular autonomic neuropathy (CAN) is a microvascular complication of diabetes, which involves autonomic nerve fibers innervating the heart and vessels, resulting in increased cardiovascular morbidity and mortality. Previous studies reported that diabetic CAN is related to microalbuminuria. However, it is unclear whether CAN is related with urinary N-acetyl-β-D-glucosaminidase (uNAG), which was suggested as an early marker of renal tubular injury in diabetic nephropathy recently. Methods: Cross-sectional data of 1052 patients with diabetes were analyzed who had tests for uNAG and autonomic function test at outpatient clinic. The presence and severity of CAN were assessed by the five autonomic function tests. Results: The association between uNAG and the presence of CAN in patients with type 1 diabetes (T1D) (n=161) was significant in multivariate analysis (OR 1.20, 95% CI 1.03-39; p = 0.018) after correction of variables including age, duration of diabetes, glycemic index and albuminuria, but it was insignificant in patients with type 2 diabetes (T2D) (n=891). Among quartile groups divided by uNAG levels, prevalence of CAN was significantly increased across with higher quartiles of uNAG level only in patients with T1D (p = 0.013). The association between uNAG and the total CAN score, assessed as the severity of CAN, was significant in both patients with T1D (p = 0.033) and T2D (p = 0.006) in multivariate analyses. Conclusion: Elevated uNAG is associated with the prevalence of CAN only in patients with T1D, and it is also related to the severity of CAN in both patients with T1D and T2D. It suggests that elevated uNAG might be a potential marker for the development and progression of CAN in patients with diabetes. Disclosure M. Choi: None. J. Jun: None. G. Kim: None. S. Jin: None. K. Hur: None. M. Lee: None. J. Kim: None.

Elevated urinary N-acetyl-\u03b2-D-glucosaminidase is associated with high glycoalbumin-to-hemoglobin A1c ratio in type 1 diabetes patients with early diabetic kidney disease

Urinary N-acetyl-β-D-glucosaminidase (uNAG) predicted the progression of diabetic kidney disease (DKD) prior to development of albuminuria in diabetes patients. We sought whether uNAG level is associated with glycoalbumin-to-hemoglobin A1c ratio (G/A ratio), a marker of postprandial hyperglycemia and glycemic excursion, independent of albuminuria and kidney function. The association between uNAG excretion and G/A ratio was assessed in 204 consecutive subjects with type 1 diabetes (T1D) (mean age 43.9 years; 49.0% men). uNAG excretion level increased along with older age, hyperglycemia, and degree of albuminuria, but was not correlated with body mass index or estimated glomerular filtration rate (eGFR). Elevated uNAG showed robust association with higher G/A ratio (adjusted β = 0.103, P = 0.020) after adjustment for age, sex, body mass index, duration of diabetes, uACR, angiotensin blockers use, fasting plasma glucose, and hemoglobin level. uNAG showed better discriminatory performance for individuals with high G/A ratio than albuminuria (AUC 0.613 vs. 0.518, P = 0.038). Measurement of uNAG improved AUC for high G/A ratio from 0.699 to 0.748 (P = 0.043) when added to conventional risk factors (cutoff 5.24 U/g creatinine; sensitivity 62.5% and specificity 58.0%). In conclusion, Elevated uNAG was found to be associated with high G/A ratio in patients with T1D with early stage DKD, independent of age and albuminuria.

Glycated Albumin Is a More Useful Glycation Index than HbA1c for Reflecting Renal Tubulopathy in Subjects with Early Diabetic Kidney Disease.

BackgroundThe aim of this study was to investigate which glycemic parameters better reflect urinary N-acetyl-β-D-glucosaminidase (uNAG) abnormality, a marker for renal tubulopathy, in subjects with type 2 diabetes mellitus (T2DM) subjects with normoalbuminuria and a normal estimated glomerular filtration rate (eGFR).MethodsWe classified 1,061 participants with T2DM into two groups according to uNAG level—normal vs. high (>5.8 U/g creatinine)—and measured their biochemical parameters.ResultsSubjects with high uNAG level had significantly higher levels of fasting and stimulated glucose, glycated albumin (GA), and glycosylated hemoglobin (HbA1c) and lower levels of homeostasis model assessment of β-cell compared with subjects with normal uNAG level. Multiple linear regression analyses showed that uNAG was significantly associated with GA (standardized β coefficient [β]=0.213, P=0.016), but not with HbA1c (β=−0.137, P=0.096) or stimulated glucose (β=0.095, P=0.140) after adjusting confounding factors. In receiver operating characteristic analysis, the value of the area under the curve (AUC) for renal tubular injury of GA was significantly higher (AUC=0.634; 95% confidence interval [CI], 0.646 to 0.899) than those for HbA1c (AUC=0.598; 95% CI, 0.553 to 0.640), stimulated glucose (AUC=0.594; 95% CI, 0.552 to 0.636), or fasting glucose (AUC=0.558; 95% CI, 0.515 to 0.600). The optimal GA cutoff point for renal tubular damage was 17.55% (sensitivity 59%, specificity 62%).ConclusionGA is a more useful glycation index than HbA1c for reflecting renal tubulopathy in subjects with T2DM with normoalbuminuria and normal eGFR.

Renal Function in Transfusion-Dependent β-Thalassemia Patients: A Decade of Follow-up and Comparison between Chelation Regimes

Introduction: Glomerular and tubular dysfunctions in β-thalassemia major (β-TM) patients (pts) have been attributed to iron overload, chronic anemia and iron-chelation therapy (ICT) toxicity. We studied glomerular and tubular function in β-TM pts treated with 2 different ICT regimes.Patients and methods: We studied 36 β-TM pts (18 females and 18 males). Mean age was 20.92 ± 9.7 (range 5-45) years. Pts were treated at Emek Medical Center under standard protocols for regular blood transfusions and ICT: 26 pts received deferasirox (DFX) for a mean period of 59 months; this was the first ICT for 6 of them; 10 pts were treated with deferoxamine (DFO) or DFO + deferiprone (DFP) (4 and 6 pts, respectively; hereafter DFO+/-DFP group). Clinical data were collected from pts' files.We evaluated serum urea, creatinine (sCr) and electrolytes, and estimated glomerular filtration rate (eGFR) according to the Schwartz formula for pediatric pts and the Chronic Kidney Disease Epidemiology Collaboration formula for adults; fractional excretion of sodium (feNa), fractional excretion of potassium (feK), calcium-to-creatinine ratio (Ca/Cr), uric acid excretion (UAE), and tubular phosphorus reabsorption were calculated. Urinary N-acetyl-β-D-glucosaminidase (uNAG) was also measured as a marker of tubular injury.Results: No significant differences were found in age, gender or mean hemoglobin (Hb) level between the groups. Levels of sCr, K, Na and feNa were in the normal range for all pts, as was eGFR (mean 104.6 ± 19 mL/min per 1.73 m2); in the DFX group, eGFR was slightly lower than in the DFO+/-DFP group (100.9 ± 17.09 vs. 114.0 ± 22.31 mL/min per 1.73 m2; p= 0.0676). Hypercalciuria (Ca/Cr > 0.25) was found in 28% of pts, increased feK (>15%) in 33%, high UAE (>0.56 mg/dL) in 64%, and high levels of TmP /GFR (>5mg/dL) in 25%. There were no differences in these parameters between the DFX and DFO+/-DFP groups.Increased uNAG was found in 9 pts (25%)-30% in the DFX group vs. 10% in the DFO+/-DFP group, and was significantly higher in the DFX group (mean 10.4 ± 6.1 vs. 5.3 ± 2.7 IU/L, p= 0.012). A moderate negative correlation was found between uNAG levels and mean serum ferritin for the prior 10 years (r= -0.35, p= 0.03). In the DFO+/-DFP group, a strong positive correlation was found between uNAG levels and the amount of iron transfused over the prior 10 years (r= 0.7647, p= 0.021); this correlation was not found in DFX pts. A moderate negative correlation was found for urinary Ca/Cr ratio with 10-year mean serum ferritin level and with 10-year amount of transfused iron (r= -0.35, p= 0.34; r= -0.4, p= 0.014, respectively). These correlations were stronger in the DFO+/-DFP group. A positive correlation was found between urinary Ca/Cr ratio and Hb levels, strongest in the DFO+/-DFP group than the DFX group (r= 0.41, p= 0.001, r= 0.7, p= 0.018), respectively.Renal function had been previously evaluated in 20 pts treated with DFO (Smolkin et al, 2008) and those results were compared with the current values. The eGFR significantly declined in pts switched to DFX (mean eGFR in first study 113.5 ± 26 vs. 100.1 ± 17 mL/min per 1.73 m2, p= 0.0093) but not in pts who continued DFO+/-DFP. A significant increase in sCr compared to the previous study was found in pts who switched to DFX (mean 0.51 ± 0.9 vs. 0.67 ± 0.1 mg/dl, p= 0.0008), but not in pts who continued treatment with DFO+/-DFP. The same observation was made regarding urine Ca/Cr (mean 0.08 ± 0.11 vs. 0.176 ± 0.12, p= 0.001).Conclusion: Ahigh prevalence of renal tubular abnormalities was observed in our pediatric and adult β-TM pts, particularly in the DFX group. The marker of tubular injury-uNAG-was negatively associated with mean 10-year serum ferritin, suggesting ICT's involvement in tubular injury. Moreover, uNAG was associated with transfusional iron burden in the DFO+/-DFP group, but not in the DFX group, proposing a mechanism other than iron overload for the pathogenesis of tubular injury in DFX-treated pts. Finally, glomerular function remained within the normal range in all pts; however a significant decline in glomerular function compared to a decade earlier was observed only in the pts currently treated with DFX. Strict follow-up of renal function in β-TM pts, especially children, is warranted. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

MP06-10 THE ACTIVATION OF INFLAMMATION AMPLIFIER IN KIDNEY TRANSPLANT GRAFT AND URINARY BIOMARKER FOR CHRONIC REJECTION

You have accessJournal of UrologyTransplantation & Vascular Surgery: Renal Transplantation & Vascular Surgery I1 Apr 2017MP06-10 THE ACTIVATION OF INFLAMMATION AMPLIFIER IN KIDNEY TRANSPLANT GRAFT AND URINARY BIOMARKER FOR CHRONIC REJECTION Haruka Higuchi, Daiki Iwami, Kiyohiko Hotta, Nobuo Shinohara, and Masaaki Murakami Haruka HiguchiHaruka Higuchi More articles by this author , Daiki IwamiDaiki Iwami More articles by this author , Kiyohiko HottaKiyohiko Hotta More articles by this author , Nobuo ShinoharaNobuo Shinohara More articles by this author , and Masaaki MurakamiMasaaki Murakami More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.255AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Inflammation amplifier (IA), a local chemokine inducer in non-immune cells is induced by the simultaneous activation of NF?B and STATs (IL-17, TNFa, and IL-6) and leads to a synergistic production of chemokines, growth factors, and cytokines. IA was essential for the development of inflammation in various autoimmune disease models. More recently, IA was critical for the development of chronic rejections both in murine models and human allogeneic lung transplantations (J Immunol. 189, 1928 and Int. Immunol. 25, 319). The status of IA can be a new biomarker and its regulator can be a new therapeutic target in rejected kidney allografts (KA). The objective of this study was to investigate the contribution of IA during the rejection process in KA and to identify genes regulating IA. METHODS Primary human kidney cells (PHKC) were stimulated with IL-17, IL-6, TNFa, and expressions of chemokines and IL-6 were measured by RT-PCR. Among the genes highly expressed in PHKC with IA activation, we focused on a gene named Renal NFkB Enhancer-1 (RNE1). A deficiency of RNE1 suppressed chemokines and IL-6 after IA activation in PHKC, indicating that RNE1 might be a positive regulator in IA. In another experiment, urinary RNE1 in kidney transplant recipients (KTR) were measured by ELISA and clinical data (serum creatinine, CRP, urinary protein, urinary albumin, urinary NAG, and eGFR) were also compared among the KTR patient groups with normal histology, interstitial fibrosis and tubular atrophy (IF/TA), or chronic active antibody-mediated rejection (CAAMR). RESULTS PHKC expressed excess amounts of chemokines and IL-6 after IA activation by IL-17, IL-6, and TNFa. Urinary RNE1 in KTR showed significantly higher amount in CAAMR patients (48606 ng/mgCre, n=9) compared to IF/TA (10744 ng/mgCre, n=21) and normal (6081 ng/mgCre, n=13). In contrast, serum creatinine, CRP, eGFR, U-NAG levels showed no significant difference among patient groups. CONCLUSIONS IA was activated in PHKC, and urinary RNE1 was elevated in rejected KA. These results suggested that activation of IA is involved in KA rejection, and RNE1 could be a new biomarker. Now, we are planning to examine detailed molecular mechanisms how RNE1 regulates NF-kB pathway in kidney cells and to examine if it will be a new therapeutic target for allogeneic kidney transplantations. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e76 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Haruka Higuchi More articles by this author Daiki Iwami More articles by this author Kiyohiko Hotta More articles by this author Nobuo Shinohara More articles by this author Masaaki Murakami More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Urinary albumin and TGF β1 levels as renal damage indices in patients with congestive heart failure

Background. In patients with congestive heart failure (CHF), the pathogenic role of angiotensin II in the development of cardiovascular death has widely been accepted. To study the pathophysiological mechanisms of CHF-associated renal damage, we examined urinary albumin levels as a clinical marker of glomerular hyperfiltration and sclerosis, which may be attributed to the upregulated function of angiotensin II. Methods. Twenty outpatients with mild to moderate CHF without renal failure were examined. They were treated with various combinations of angiotensin-converting enzyme inhibitors (ACEI), (n = 9), calcium antagonists (n = 9), β-blockers (n = 6), and diuretics (n = 12). Urinary (u-) levels of albumin, N-acetyl-β-d-glucosaminidase (NAG), and transforming growth factor β-1 (TGF β1), and circulating levels of endothelin-1 (ET-1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) were measured and examined in relation to various clinical parameters and the mode of treatment. Results. (1) CHF patients showed significantly higher mean levels of u-albumin, u-NAG, u-TGF β1, plasma ET-1, and serum TIMP-1 than normal controls. In an age-matched comparison, the u-albumin levels in CHF patients were as high as those in diabetic patients without overt nephropathy and hypertension. (2) The u-albumin level tended to correlate with the u-NAG level (P = 0.051), however, there was no patient with high u-NAG in the subgroup with negative u-albumin levels. (3) The u-albumin level, like the u-TGF β1 and serum TIMP-1 levels, showed a significant positive correlation with the mean arterial pressure (MAP) level (each, P < 0.05), and showed slight, but nonsignificant correlations with the u-TGF β1 (P = 0.08) and serum TIMP-1 levels (P = 0.06). (4) The patients treated with an ACEI showed significantly lower levels of u-albumin (P < 0.01) and serum TIMP-1 (P < 0.05) than those not treated with an ACEI. Treatment with an ACEI tended to decrease positivity for u-TGF β1 (P = 0.09). Conclusions. The correlation between MAP and u-albumin levels and the ameliorative effect of ACEI on u-albumin excretion suggest that urinary albumin excretion may be caused by a glomerular hyperfiltration mechanism produced by both preloading of the systemic blood pressure and afterloading by angiotensin II-mediated constriction of efferent arterioles. In addition, the suppressive effects of ACEI on u-TGF β1 and serum TIMP-1 levels suggest that angiotensin II may accelerate TGF β1-mediated tissue remodeling, including nephrosclerosis, in CHF.

Iron deposition in renal biopsy specimens from patients with kidney diseases

This study was performed to investigate the correlation between clinical parameters and grading of iron deposition in renal biopsy specimens from 102 patients with various kidney diseases. Iron deposition in renal tissues was detected by Berlin blue staining. The extent of iron staining was semiquantitatively graded as negative (Fe−), grade 0, or positive (Fe+), including faint, grade 1; moderate, grade 2; or severe, grade 3, by light microscopy. Thirty-four of 102 patients (33%) showed positive iron staining. Fe+ patients had various renal diseases, mainly consisting of 12 patients with immunoglobulin A nephropathy and 5 patients with benign nephrosclerosis. Mean arterial pressure (MAP), serum creatinine (sCr) levels, incidence of hematuria, and urinary N-acetylβ-d-glucosaminidase (u-NAG) levels in Fe+ patients were significantly greater than those in Fe− patients, and u-NAG levels correlated positively with the extent of iron deposition. Study patients were tentatively divided into two groups according to the extent of iron deposition: group A, patients with grades 2 and 3 staining, and group B, patients with grades 0 and 1 staining. In group A, MAP, sCr level, urinary protein excretion, and the incidence of hematuria were significantly greater than in group B. Our results suggest that the amount of iron deposition in renal tissue may contribute to the progression of chronic renal disease and may be an early and sensitive indicator of renal damage in certain renal diseases. © 2001 by the National Kidney Foundation, Inc.