The association between lead and cadmium co-exposure and renal dysfunction.

Both cadmium (Cd) and lead (Pb) exposure can induce kidney damage. However, the effects of combined exposure to Cd and Pb on renal function at environmental levels have not been fully clarified. In this study we investigated the renal function in a Chinese population co-exposed to Cd and Pb. A total of 331 subjects (215 women and 116 men), living in either a control or a polluted area, were included in this study. Cd and Pb in blood and urine (BCd, BPb, UCd, and UPb), and kidney effect markers including urinary N-acetyl-ß-D-glucosaminidase (UNAG) and estimated glomerular filtration rate (eGFR), were determined, and the association between exposure markers and renal effect biomarkers were analyzed. The exposure levels in the polluted area were significantly higher than in the control area (all p < 0.01). The eGFR of subjects in the polluted area was decreased compared with that in the control area (p < 0.01). The subjects with high BCd/BPb (BCd ≥ 2 µg/L, BPb ≥ 100 µg/L) or high UCd/UPb (UCd ≥ 3 µg/g creatinine, UPb ≥ 10 µg/g creatinine) showed higher UNAG and UALB levels compared with other subgroups (p < 0.01). The probability of having elevated UNAG in subjects with high BCd/BPb was greater than those with low BCd/BPb [odds ratio (OR) = 2.6, 95% confidence interval (CI): 1.4-4.7), low BCd/high BPb (OR =3.1, 95% CI: 1.4-6.6), and high BCd/low BPb (OR = 1.7, 95% CI: 0.9-3.2). The OR of subjects with low UCd and high UPb, high UCd and low UPb, and high UCd/UPb were 2.9 (95% CI: 1.4-5.7), 3.3 (95% CI: 1.5-7.2), and 7.7 (95% CI: 4.0-14.7), respectively, compared with those with low UCd/UPb. The risk of decrease in eGFR was also higher in subjects with high UCd/UPb than for those with low UCd/UPb (OR = 7.2, 95% CI: 0.8-62.2). Our data demonstrate that Cd and Pb exposure, alone or in combination, are associated with renal impairment. In addition, co-exposure to Pb and Cd propagates the renal tubular dysfunction compared with Cd or Pb exposure alone.

Uric acid lowering in relation to HbA1c reductions with the SGLT2 inhibitor tofogliflozin.

An integrated analysis was performed with data from 4 phase 2 and phase 3 studies of tofogliflozin in which patients with type 2 diabetes mellitus received the sodium-glucose cotransporter 2 inhibitor tofogliflozin for up to 24 weeks. Sex differences, baseline haemoglobin A1c (HbA1c) and serum uric acid (UA) levels, and log10 -transformed urinary N-acetyl-ß-D-glucosaminidase ratio were significantly correlated with the reduction in serum UA levels at both 4 and 24 weeks in multivariate analysis (respectively, P < .0001). The decrease in HbA1c levels was greatest in the group with the highest baseline HbA1c level (quartile 4; HbA1c > 8.6%) and lowest in the group with the lowest baseline HbA1c level (quartile 1; HbA1c ≤ 7.4%). The decrease in serum UA levels was greatest in the quartile 1 group and lowest in the quartile 4 group. In most groups, the maximum decrease in serum UA levels was seen in the first 4 weeks, while the maximum decrease in HbA1c was seen at week 24. Thus, serum UA levels were significantly decreased in patients with moderate HbA1c levels.

Effects of topiroxostat in hyperuricemic patients with chronic kidney disease.

BACKGROUND: Hyperuricemia is associated with chronic kidney disease (CKD). Although topiroxostat, a novel, non-purine, selective xanthine oxidase inhibitor, has a strong effect against hyperuricemia, limited data are available on its renoprotective effect against CKD. METHODS: This study was conducted between October 2014 and May 2016. Thirty patients (20 male, 10 female) were administered 40 mg/day of topiroxostat twice daily. All patients were followed for a year. To elucidate the effects of topiroxostat, we evaluated the clinically documented primary indication of progression, viz. laboratory evidence of kidney function decline (reference indicator), uric acid, and hypertension in different patient groups, separated according to their baseline uProt levels and baseline eGFR. RESULTS: Topiroxostat treatment resulted in significant reduction in SUA (-1.53 mg/dL), systolic blood pressure (-8.9 mmHg), diastolic blood pressure (-5.0 mmHg), and urinary protein excretion (-795.5 mg/gCr) compared with baseline values. However, serum creatinine and urinary NAG levels, and estimated glomerular filtration rate did not change significantly. CONCLUSIONS: Topiroxostat reduced SUA levels effectively and may exhibit renoprotective effect in hyperuricemic patients with CKD. Further studies are required to clarify whether topiroxostat prevents the progression of renal disease and improves the prognosis of CKD patients.

Effects of periodontal treatment on the medical status of patients with type 2 diabetes mellitus: a pilot study.

BACKGROUND: Studies have demonstrated that periodontal disease is associated with the development of systemic complications in patients with type 2 diabetes mellitus (T2DM). The purpose of this pilot study was to investigate which markers among various systemic disease parameters are affected by periodontal treatment in patients with T2DM. METHODS: Twelve patients with T2DM were given oral hygiene instructions and subsequent subgingival scaling and root planing. The periodontal status was recorded, and blood and urine samples were taken to measure various parameters of glucose control and systemic status at baseline and 1 month following the periodontal treatment. Serum concentrations of tumor necrosis factor-α and high-sensitivity C-reactive protein were measured by enzyme-linked immunosorbent assay. RESULTS: After the periodontal treatment, the glycated hemoglobin value was significantly improved. The levels of urinary N-acetyl-ß-D-glucosaminidase and albumin, which are markers of renal dysfunction, also decreased significantly after treatment. Among the parameters measured in serum, the γ-glutamyl transpeptidase level, which is usually interpreted as a marker of liver dysfunction, was significantly reduced. The serum concentrations of tumor necrosis factor-α and high-sensitivity C-reactive protein were also significantly reduced by periodontal treatment. CONCLUSION: Within the limitations of this pilot study, periodontal treatment may be effective not only in improving metabolic control, but also in reducing the risk of diabetic kidney and liver disease in patients with T2DM.

The ratios of urinary ß2-microglobulin and NAG to creatinine vary with age in children.

BACKGROUND: Although urinary biochemical markers can be assessed by their ratio to urinary creatinine (U-Cr) concentration, reference values in adults may not be applicable to children because the amount of Cr excreted varies by body size. We therefore measured the relationship between age and the ratios of urinary ß-2-microglobulin (U-ß2MG), N-acetyl-ß-d-glucosaminidase (U-NAG), calcium (U-Ca) and protein (U-Pr) concentration to those of U-Cr in children. METHODS: Fifty-seven patients aged >1 year with benign familial hematuria (median age, 6.3 years) were divided into three age groups: 1-4, 5-9, and ≥10 years. Urinary biomarkers were assayed using actual values; ratios to actual U-Cr values; and our standardized metric, namely 100-fold the ratio of serum Cr to U-Cr concentration; and the relationship of each of these to age was determined. RESULTS: The ratios of U-ß2MG, U-NAG and U-Ca to Cr varied significantly by age, being higher in younger than in older children, but the actual and standardized values of each did not vary by age, nor did any measurement of U-Pr. CONCLUSIONS: The ratios of urinary markers of tubular function, including U-ß2MG, U-NAG and U-Ca, to Cr vary by age, being higher in younger children. In contrast, the ratios of urinary markers of glomerular filtration (such as U-Pr)to Cr do not vary by age, making them suitable for corrections relative to Cr.

Association between continuous glucose monitoring-derived glycemic control indices and urinary biomarkers of diabetic kidney disease: Hyogo Diabetes Hypoglycemia Cognition Complications study.

AIMS: Glomerular damage and proximal tubular damage play an important role in the pathogenesis of diabetic kidney disease. This study aimed to investigate the relationship between the urinary markers of proximal tubular injury, including urinary liver-type fatty acid-binding protein-to-creatinine ratio (uL-FABP/Cr) and urinary N-acetyl-ß-D-glucosaminidase-to-creatinine ratio (uNAG/Cr), and glycemic control status. METHODS: This cross-sectional study included 245 and 39 patients with type 2 diabetes mellitus (T2DM) and non-T2DM (NDM), respectively. The participants of this study were fitted with retrospective CGM, and glycemic control indices, such as time in range (TIR) and glycemia risk index (GRI), were calculated. RESULTS: The results were presented as medians (interquartile ranges). The uL-FABP/Cr was significantly higher in the microalbuminuria than in the normo-albuminuria group [4.2 (2.7-7.1) and 2.2 (1.4-3.4) µg/gCr, respectively, P < 0.001], while the uNAG/Cr in the normo-albuminuria group [6.3 (4.5-10.1) U/gCr] was significantly higher than that in the NDM group [5.3 (3.8-6.3) U/gCr, P = 0.048] but significantly lower than that in the microalbuminuria group [9.2 (6.4-11.1) U/gCr, P = 0.004]. The multivariate logistic regression analysis indicated that CGM-derived TIR was significantly associated with the urinary albumin-to-creatinine ratio [uAlb/Cr, odds ratio (OR) 0.985, 95% confidence interval (CI) 0.971-0.998, P = 0.029] and uNAG/Cr (OR 0.973, 95% CI 0.957-0.989, P = 0.001) independent of renal function. GRI was similarly associated with uAlb/Cr and uNAG/Cr. CONCLUSION: The findings of this study indicated that uNAG/Cr was elevated before albuminuria development and was associated with CGM-derived TIR and GRI.

Application of urinary N-acetyl-ß-D-glucosaminidase combined with serum retinol-binding protein in early detection of diabetic nephropathy.

BACKGROUND: Diabetic nephropathy (DN) is a microangiopathy of type 2 diabetes mellitus (T2DM), which can damage the kidney through various ways and mechanisms due to the nature of the disease, involving the renal interstitium and glomeruli. However, in the early stage of the disease, patients only showed kidney volume increase and glomerular hyperthyroidism, and typical symptoms that are difficult to arouse individual attention were noticed. AIM: To observe the expression of serum retinol-binding protein (RBP) and urinary N-acetyl-ß-D-glucosaminidase (NAG) in patients with DN, and to analyze their value in disease prediction, so as to provide new targets for early diagnosis and treatment of DN. METHODS: The baseline data of 50 T2DM patients treated in our hospital between January 2021 and December 2022 were retrospectively reviewed and included in group A. The baseline data of 50 patients with type 2 DN admitted to our hospital during the same period were collected and included in group B. The baseline data and serum RBP and urine NAG expression were compared between the two groups to analyze their value in the early prediction of DN. RESULTS: There was no significant difference in age, gender, duration of diabetes, combined hyperlipidemia and combined hypertension between the two groups (P > 0.05); the expression of urinary NAG and serum RBP in group B was higher than that in group A, and the difference was statistically significant (P < 0.05); a multiple logistic regression model was established, and the results showed that urinary NAG and serum RBP were related to the presence or absence of injury in diabetic patients, and overexpression of urinary NAG and serum RBP may be risk factors for renal injury in T2DM patients (OR > 1, P < 0.05); receiver operating curve curve was plotted, and the results showed that the area under the curve of urinary NAG and serum RBP expression alone and in combination for predicting DN was > 0.80, and the predictive value was satisfactory; bivariate Spearman linear correlation analysis showed that there was a positive correlation between urinary NAG and serum RBP expression in patients with DN (r = 0.566, P = 0.000). CONCLUSION: The increased expression of urinary NAG and serum RBP may be the risk factors leading to the progression of T2DM to DN. The possibility of DN can be considered in patients with urinary NAG and serum RBP overexpression by examining the expression of urinary NAG and serum RBP in patients with T2DM in clinical practice.

The relationship between cadmium exposure and renal volume in inhabitants of a cadmium-polluted area of Japan.

This follow-up study was conducted over 30 years in a cadmium-polluted area of Japan. Urinary cadmium (U-Cd) concentration decreased by nearly half from 1986 to 2008 in men and women. However, it increased from 2008 to 2014 and maintained similar levels in 2016. Because renal atrophy may induce an increase in U-Cd, kidney volumes were determined using magnetic resonance imaging (MRI) scans in 2018. Based on the MRI results, we divided the participants into two groups, namely the normal group (n = 6, three men and three women) and the lesion group (n = 6, three men and three women). The level of urinary N-acetyl-ß-d-glucosaminidase/creatinine (U-NAG/Cr) in the lesion group was significantly higher than in the normal group. The level of serum alkaline phosphatase (Al-P) was positively associated with U-Cd. Age and renal cortex volumes showed significantly negative associations. However, U-Cd and renal cortex and kidney volumes showed no significant associations. These results suggest that U-NAG and serum Al-P were sensitive biomarkers to reflect renal tubular dysfunction and bone damage caused by cadmium poisoning. Individuals chronically exposed to Cd should be observed carefully, due to the increased effect of aging on renal cortex volumes.

Association between nonalbumin proteinuria and renal tubular damage of N-acetyl-ß-d-glucosaminidase and its clinical relevance in patients with type 2 diabetes without albuminuria.

AIM: Although albuminuria and urinary N-acetyl-ß-d-glucosaminidase (uNAG) are known as progression markers of diabetic kidney disease, there is limited information regarding the association between urinary nonalbumin proteinuria (NAP) and uNAG and the clinical relevance thereof in patients without albuminuria. METHODS: This cross-sectional study included samples from 244 consecutive patients with type 2 diabetes mellitus (T2D) without albuminuria. Proteinuria and albuminuria were defined according to protein-to-creatinine ratio (uPCR) and albumin-to-creatinine ratio (uACR), respectively. NAP was indirectly calculated by the difference between uPCR and uACR. RESULTS: NAP and uNAG excretion were significantly correlated (r = 0.525, P < 0.001). Individuals whose NAP levels were in the highest tertile had a longer duration of diabetes, uncontrolled hyperglycemia, and impaired insulin stimulation (all P < 0.05), although more patients in the highest NAP tertile were prescribed insulin and sulfonylurea. Multiple linear regression analyses revealed associations among uNAG, diabetes duration, and waist circumference. CONCLUSIONS: T2D patients without albuminuria excrete proteinuria and that presence of the protein in urine is associated with uNAG. NAP was positively correlated with T2D duration and waist circumference, but negatively correlated with body mass index. Lean, but centrally obese, T2D patients in late diabetes experience more tubular damage, regardless of the presence of albuminuria.

Analysis of glycosuria in okapi (Okapia johnstoni): examination of urinary N-acetyl-ß-D-glucosaminidase.

We analyzed the urinary excretion of glucose and N-acetyl-ß-D-glucosaminidase (NAG) in six okapis (Okapia johnstoni) in captivity to investigate the cause of their urinary sugar excretion. The urinary glucose-positive okapi had significantly higher urinary NAG indices than the urinary glucose-negative okapi. There was also a positive correlation between urinary glucose levels and urinary NAG indices. These results suggest that the proximal tubular function of the glycosuric okapi may have been obstructed, which impaired glucose reabsorption.