A Pilot Study of the Effect of Sodium Thiosulfate on Urinary Lithogenicity and Associated Metabolic Acid Load in Non-Stone Formers and Stone Formers with Hypercalciuria

Background and Objectives

Sodium thiosulfate (STS) reduced calcium stone formation in both humans and genetic hypercalciuric stone forming (GHS) rats. We sought to measure urine chemistry changes resulting from STS administration in people.

Design, Setting, Participants & Measurements

STS was given to healthy and hypercalciuric stone forming adults. Five normal non-stone forming adults (mean age 33 years), and 5 people with idiopathic hypercalciuria and calcium kidney stones (mean age 66 years) participated. Two baseline 24-hour urine collections were performed on days 2 and 3 of 3 days of self-selected diets. Subjects then drank STS 10 mmol twice a day for 7 days and did urine collections while repeating the self-selected diet. Results were compared by non-parametric Wilcoxon signed rank test. The primary outcome was the resulting change in urine chemistry.

Results

STS administration did not cause a significant change in urinary calcium excretion in either group. In both groups, 24 hour urinary ammonium (P = 0.005) and sulfate excretion (P = 0.007) increased, and urinary pH fell (P = 0.005); citrate excretion fell (P<0.05) in hypercalciuric participants but not in non-stone formers. Among stone formers with hypercalciuria, 3 of 5 patients had measurement of serum HCO₃ concentration after the STS period: it did not change. The net effect was an increase in supersaturation of uric acid, and no change in supersaturation of calcium oxalate or calcium phosphate.

Conclusions

The basis for studies demonstrating that STS prevented stones in rats and people was not reflected by the changes in urine chemistry reported here. Although serum HCO₃ did not change, urine tests suggested an acid load in both non-stone forming and hypercalciuric stone-forming participants. The long term safety of STS needs to be determined before the drug can be tested in humans for long-term prevention of stone recurrence.     

High Dietary Sodium Intake Assessed by Estimated 24-h Urinary Sodium Excretion Is Associated with NAFLD and Hepatic Fibrosis

Background

Although high sodium intake is associated with obesity and hypertension, few studies have investigated the relationship between sodium intake and non-alcoholic fatty liver disease (NAFLD). We evaluated the association between sodium intake assessed by estimated 24-h urinary sodium excretion and NAFLD in healthy Koreans.

Methods

We analyzed data from 27,433 participants in the Korea National Health and Nutrition Examination Surveys (2008–2010). The total amount of sodium excretion in 24-h urine was estimated using Tanaka’s equations from spot urine specimens. Subjects were defined as having NAFLD when they had high scores in previously validated NAFLD prediction models such as the hepatic steatosis index (HSI) and fatty liver index (FLI). BARD scores and FIB-4 were used to define advanced fibrosis in subjects with NAFLD.

Results

The participants were classified into three groups according to estimated 24-h urinary excretion tertiles. The prevalence of NAFLD as assessed by both FLI and HSI was significantly higher in the highest estimated 24-h urinary sodium excretion tertile group. Even after adjustment for confounding factors including body fat and hypertension, the association between higher estimated 24-h urinary sodium excretion and NAFLD remained significant (Odds ratios (OR) 1.39, 95% confidence interval (CI) 1.26–1.55, in HSI; OR 1.75, CI 1.39–2.20, in FLI, both P < 0.001). Further, subjects with hepatic fibrosis as assessed by BARD score and FIB-4 in NAFLD patients had higher estimated 24-h urinary sodium values.

Conclusions

High sodium intake was independently associated with an increased risk of NAFLD and advanced liver fibrosis.     

Factors Associated with Untreated Diabetes: Analysis of Data from 20,496 Participants in the Japanese National Health and Nutrition Survey

Objective

We aimed to examine factors associated with untreated diabetes in a nationally representative sample of the Japanese population.

Research Design and Methods

We pooled data from the Japanese National Health and Nutrition Survey from 2005 to 2009 (n = 20,496). Individuals aged 20 years and older were included in the analysis. We classified participants as having diabetes if they had HbA1c levels ≥6.5% (≥48 mmol/mol). People with diabetes who self-reported that they were not currently receiving diabetic treatment were considered to be untreated. We conducted a multinomial logistic regression analysis to determine factors associated with untreated diabetes relative to non-diabetic individuals.

Results

Of 20,496 participants who were included in the analysis, untreated diabetes was present in 748 (3.6%). Among participants with untreated diabetes, 48.3% were previously diagnosed with diabetes, and 46.5% had HbA1c levels ≥7.0% (≥53 mmol/mol). Participants with untreated diabetes were significantly more likely than non-diabetic participants to be male, older, and currently smoking, have lower HDL cholesterol levels and higher BMI, non-HDL cholesterol levels, and systolic blood pressure.

Conclusions

A substantial proportion of people in Japan with untreated diabetes have poor glycemic control. Targeting relevant factors for untreated diabetes in screening programs may be effective to enhance the treatment and control of diabetes.     

Comparison of 24-h Urinary Aldosterone Level and Random Urinary Aldosterone-to-Creatinine Ratio in the Diagnosis of Primary Aldosteronism

Background

Historically, urinary aldosterone level measurement was a commonly employed confirmatory test to detect primary aldosteronism (PA). However, 24-h urine collection is inconvenient and cumbersome. We hypothesized that random urinary aldosterone measurements with correction for creatinine concentration might be comparable to 24-h urinary aldosterone levels (Uald-24 h) in the diagnosis of PA.

Methods

The non-concurrent prospective study was conducted between June 2006 and March 2008 in patients admitted for confirmation of aldosteronism by salt loading test. A 24-h urine sample, which was collected during hospitalization on the day before saline infusion testing after restoration of serum hypokalemia, was collected from all subjects. Moreover, participants were asked to collect a first bladder voiding random urine sample during clinic visits. Uald-24 h and the random urinary aldosterone-to-creatinine ratio (UACR) were calculated accordingly.

Results

A total of 102 PA patients (71 patients diagnosed of aldosterone-producing adenoma, 31 with idiopathic hyperaldosteronism) and 65 patients with EH were enrolled. The receiver operating characteristic curve showed comparable areas under the curves of UACR and Uald-24 h. The Bland-Altman plot showed mean bias but no obvious heteroscedasticity between the two tests. When using random UACR >3.0 ng/mg creatinine as the cutoff value, we obtained a specificity of 90.6% to confirm PA from essential hypertension.

Conclusions

Our study reinforce that the diagnostic accuracy of random UACR was comparable to that of Uald-24 h in PA patients. With the quickness and simplicity of the UACR method and its equivalence to Uald-24 h, this assay could be a good alternative diagnostic tool for PA confirmation.     

Determinants of Brushite Stone Formation: A Case-Control Study

Purpose

The occurrence of brushite stones has increased during recent years. However, the pathogenic factors driving the development of brushite stones remain unclear.

Methods

Twenty-eight brushite stone formers and 28 age-, sex- and BMI-matched healthy individuals were enrolled in this case-control study. Anthropometric, clinical, 24 h urinary parameters and dietary intake from 7-day weighed food records were assessed.

Results

Pure brushite stones were present in 46% of patients, while calcium oxalate was the major secondary stone component. Urinary pH and oxalate excretion were significantly higher, whereas urinary citrate was lower in patients as compared to healthy controls. Despite lower dietary intake, urinary calcium excretion was significantly higher in brushite stone patients. Binary logistic regression analysis revealed pH>6.50 (OR 7.296; p = 0.035), calcium>6.40 mmol/24 h (OR 25.213; p = 0.001) and citrate excretion <2.600 mmol/24 h (OR 15.352; p = 0.005) as urinary risk factors for brushite stone formation. A total of 56% of patients exhibited distal renal tubular acidosis (dRTA). Urinary pH, calcium and citrate excretion did not significantly differ between patients with or without dRTA.

Conclusions

Hypercalciuria, a diminished citrate excretion and an elevated pH turned out to be the major urinary determinants of brushite stone formation. Interestingly, urinary phosphate was not associated with urolithiasis. The increased urinary oxalate excretion, possibly due to decreased calcium intake, promotes the risk of mixed stone formation with calcium oxalate. Neither dietary factors nor dRTA can account as cause for hypercalciuria, higher urinary pH and diminished citrate excretion. Further research is needed to define the role of dRTA in brushite stone formation and to evaluate the hypothesis of an acquired acidification defect.     

Chronic Kidney Disease in Non-Diabetic Older Adults: Associated Roles of the Metabolic Syndrome,Inflammation, and Insulin Resistance

Background

The aims of the study were to examine the association between CKD and the metabolic syndrome (MetS) and its components in older adults. We also explored two possible pathways linking the metabolic syndrome with CKD: inflammation as measured by high sensitivity C-Reactive Protein (hsCRP) and insulin resistance as measured by HOMA-IR.

Methods

Community-dwelling non-diabetic 70+ adults from the Einstein Aging Study participated in the study. We defined CKD as eGFR below 60mL/min/1.73m². MetS was defined according to recent guidelines from the National Cholesterol Education Program. Binary logistic regressions were used to assess the association between the metabolic syndrome, its components and CKD with adjustments for demographics, HOMA-IR and hsCRP.

Results

Of 616 participants (mean age = 79.3 years, 65.5% female), 25% had MetS and 26.5% had CKD. Participants with CKD had a significantly higher prevalence of the MetS than individuals without CKD (34.4% vs. 24.3%). Binary logistic regression models showed that CKD was associated with MetS (OR = 1.72, 95%CI = 1.13–2.61). The association was unaltered by adjustment for hsCRP but altered by adjustment for HOMA-IR. As the number of MetS components increased the relative odds of CKD also increased. None of the individual components was independently associated with CKD.

Conclusion

MetS is associated with CKD in non-diabetic older adults. Results showed that as the number of MetS components increased so did the odds for CKD. HOMA-IR seems to be in the casual pathway linking MetS to CKD.     

Association of the Estimated 24-H Urinary Sodium Excretion with Albuminuria in Adult Koreans: The 2011 Korea National Health and Nutrition Examination Survey

Background

Sodium intake and albuminuria have important roles in blood pressure and renal progression. Although their relationship has been reported, the results have not been consistent and all studies have examined small populations.

Objective

This study investigated the role of the estimated 24-h urinary sodium excretion as a marker of sodium intake and albuminuria.

Design

This investigation included 5,187 individuals age 19 years and older from a cross-sectional, nationally representative, stratified survey: The Korea National Health and Nutrition Examination Survey (KNHANES V-2), in 2011. Albuminuria was defined as a urinary albumin/creatinine ratio ≥30 mg/g. The 24-h urinary sodium excretion was estimated from a spot urine.

Results

On classifying our participants into quartiles based on the estimated 24-h urinary sodium excretion, the prevalence of albuminuria increased with the 24-h urinary sodium excretion (5.3, 5.7, 7.5, and 11.8% in the first through fourth quartiles, respectively, p for trend <0.001). Even after adjusting for age, sex, diabetes, obesity, and hypertension, the significance persisted. In a multiple logistic regression analysis, the second and third quartiles of the estimated 24-h urinary sodium excretion were not associated with the presence of albuminuria with the first quartile as a control. However, the fourth quartile was significantly associated with the presence of albuminuria (odds ratio 1.61 [95% confidence interval 1.71–2.21], p = 0.003) after adjusting for age, sex, diabetes, obesity, and hypertension.

Conclusions

These findings suggest that salt intake is associated with the presence of albuminuria in the general Korean adult population.     

A Comparison of Health Outcomes in Older versus Younger Adults following a Road Traffic Crash Injury: A Cohort Study

Background

Given the aging demographics of most developed countries, understanding the public health impact of mild/moderate road traffic crash injuries in older adults is important. We aimed to determine whether health outcomes (pain severity and quality of life measures) over 24 months differ significantly between older (65+) and younger adults (18–64).

Methods

Prospective cohort study of 364, 284 and 252 participants with mild/moderate injury following a vehicle collision at baseline, 12 and 24 months, respectively. A telephone-administered questionnaire obtained information on socio-economic, pre- and post-injury psychological and heath characteristics.

Results

At baseline, there were 55 (15.1%) and 309 (84.9%) participants aged ≥65 and 18–64 years, respectively. At 12- and 24-month follow-up, older compared to younger participants who had sustained a mild/moderate musculoskeletal injury had lower physical functioning (3.9-units lower Short Form-12 Physical Composite Score, multivariable-adjusted p = 0.03 at both examinations). After multivariable adjustment, older (n = 45) versus younger (n = 207) participants had lower self-perceived health status (8.1-units lower European Quality of Life-5 Dimensions Visual Acuity Scale scores at 24 months, p = 0.03), 24 months later.

Conclusions

Older compared to younger participants who sustained a mild/moderate injury following a road-traffic crash demonstrated poorer physical functioning and general health at 24 months.     

Periostin as a Tissue and Urinary Biomarker of Renal Injury in Type 2 Diabetes Mellitus

Background

Improving the early detection of diabetic nephropathy remains a great challenge in disease management. Periostin is a marker of renal tubular injury and related to progressive kidney injury in animal models of chronic kidney disease. The clinical implications of urinary periostin activities in patients with type 2 diabetes have not been evaluated.

Methods

Urine samples were obtained from 30 healthy volunteers and 328 type 2 diabetic patients with normoalbuminuria (n=114), microalbuminuria (n=100) and macroalbuminuria (n=114). The excretion levels of urinary periostin were quantified with enzyme-linked immunosorbent assay. Immunohistochemical periostin expression was determined in kidney tissues from overt diabetic nephropathy.

Results

Increased periostin expression in glomeruli and tubular epithelium in diabetic renal pathology was observed. Urinary periostin levels were significantly elevated in the patients of the normoalbuminuria [3.06 (IQR: 1.12, 6.77) ng/mgCr], microalbuminuria [8.71 (IQR: 5.09, 19.29) ng/mgCr] and macroalbuminuria [13.58 (IQR: 3.99, 16.19) ng/mgCr] compared with healthy controls [1.15 (IQR: 0.60, 1.63) ng/mgCr] (P<0.01).Increased urine periostin level significantly correlated with aging, high albuminuria and decline of GFR. Urine periostin ELISA also demonstrated high performance for the diagnosis of established normoalbuminuric, microalbuminuric and macroalbuminuric type 2 diabetes (AUC 0.78 (95%CI, 0.71 to 0.86), 0.99 (95%CI, 0.98 to 1.00) and 0.95 (95%CI, 0.91 to 0.98), respectively).

Conclusion

The study indicates that increased urine periostin levels can be detected in patients with type 2 diabetes before the onset of significant albuminuria. Urinary periostin is an associated renal derangement in patients with established diabetic nephropathy and it may be used as an early marker of diabetic renal injury.     

Insulin Resistance Is Associated with Prevalence of Physician-Diagnosed Urinary Incontinence in Postmenopausal Non-Diabetic Adult Women: Data from the Fourth Korea National Health and Nutrition Examination Survey

Objective

To investigate the association between insulin resistance (IR) and urinary incontinence in Korean adult women by analyzing the data from the Korea National Health and Nutrition Examination Survey IV (KNHANES) 2007–2009

Methods

A nationally representative sample of 5318 non-diabetic Korean women ≥19-years-of-age (3043 premenopausal and 2275 postmenopausal women) was included from KNHANES 2008–2010. IR was measured using the homeostasis model assessment of IR (HOMA-IR). Participants in the highest and lowest quartile of HOMA-IR were defined as insulin-resistant and insulin-sensitive respectively. Women who have current physician-diagnosed urinary incontinence were classified as having urinary incontinence.

Results

Incontinence was found in 9.18% of the total population, 8.51% of the premenopausal population, and 10.86% of the postmenopausal population. The prevalence of incontinence increased with age, reaching a peak at 60-69-years-of-age. The prevalence of urinary incontinence increased significantly with higher HOMA-IR quartiles in pre- and post-menopausal women (p for linear association = 0.0458 and 0.0009 respectively). Among post-menopausal women, those in the highest quartile of HOMA-IR were significantly more likely to have urinary incontinence compared to those in the lowest quartile [adjusted odds ratio, 1.72; 95% confidence interval, 1.07–2.77]. However premenopausal population exhibited no association between incontinence and HOMA-IR quartiles

Conclusion

Our results suggest that the prevalence of incontinence increased across HOMA-IR in non-diabetic adult women, and especially, IR might be a risk factor for incontinence in postmenopausal non-diabetic women.     

Two Urinary Peptides Associated Closely With Type 2 Diabetes Mellitus

Objective

To monitor of type 2 diabetes more simply, conveniently and noninvasively, we are trying to identify the potential urinary peptides that associated with different stages of glucose control in type 2 diabetes mellitus.

Methods

Firstly, we collected urine samples from type 2 diabetic patients and normal controls. These type 2 diabetic patients were divided into two groups according to fasting plasma glucose (FPG) and hemoglobin A1c% (HbA1c), respectively. Magnetic beads based weak cation exchange chromatography (MB-WCX) was used to condense urinary peptides. The eluates were then analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). Subsequently, ClinProt was used to profile and screen the polypeptide patterns based on different methods of grouping in diabetic patients and normal controls. Finally, the amino acid sequences of differentially expressed peptides were identified by nano-liquid chromatography-tandem mass spectrometry and the protein sources of the corresponding peptide were matched in IPI Human database.

Results

Proteomics analysis found two up-regulated peptide (m/z 2756.1 and m/z 3223.2) representations in diabetic subjects, and the two peptides increased with increases in the amount of glycosylated hemoglobin. Further, the parallelism between m/z 3223.2 and glycosylated hemoglobin was better than the parallelism between m/z 2756.1 and glycosylated hemoglobin. Area under the receiver operating characteristic of the two peptides was 0.722 and 0.661, respectively. The above-mentioned peptide m/z 2756.1 was further identified as fragment of fibrinogen alpha chain precursor and m/z 3223.2 was fragment of prothrombin precursor.

Conclusion

These results suggested the two urinary biomarkers enable monitor of type 2 diabetes patients with different stages of glucose control.     

Trends in Cardiovascular Disease Risk Factors in People with and without Diabetes Mellitus: A Middle Eastern Cohort Study

Aims/Hypothesis

To investigate secular trends in cardiovascular disease (CVD) risk factors during a decade of follow-up in a Middle Eastern cohort, and to compare observed trends between diabetic and non-diabetic populations.

Methods

In a population of 6181 participants (2622 males and 3559 females), diabetes status and CVD risk factors were evaluated in 4 study phases from 1999–2011. 1045 subjects had type 2 diabetes mellitus at baseline and 5136 participants were diabetes-free. To examine the trends of CVD risk factors, generalized estimation equation models were constructed. The interaction between the diabetes status and each phase of the study was checked in a separate model.

Results

During the follow-up period diabetic females significantly gained better control of their blood pressure, serum low density lipoprotein cholesterol and general and central obesity measures compared to non-diabetic counterparts, although 60% of them had high BP and 64% had high serum LDL-C levels till the end of the study. Diabetic males however, experienced significantly better control on their serum LDL-C and general and central obesity measures compared to their non-diabetic controls; but 24% of them were still smoker, 63% had high BP and 60% had high serum LDL-C levels at the end of the follow-up (all Ps _interaction <0.05). Use of lipid-lowering and antihypertensive medications increased consistently in both diabetic and non-diabetic populations.

Conclusions/Interpretation

Although CVD risk factors have been controlled to some extent among diabetic population in Iran, still high numbers of people with diabetes have uncontrolled CVD risk factors that prompt more attention.     

Comparison of Plasma and Urine Biomarker Performance in Acute Kidney Injury

Background

New renal biomarkers measured in urine promise to increase specificity for risk stratification and early diagnosis of acute kidney injury (AKI) but concomitantly may be altered by urine concentration effects and chronic renal insufficiency. This study therefore directly compared the performance of AKI biomarkers in urine and plasma.

Methods

This single-center, prospective cohort study included 110 unselected adults undergoing cardiac surgery with cardiopulmonary bypass between 2009 and 2010. Plasma and/or urine concentrations of creatinine, cystatin C, neutrophil gelatinase-associated lipocalin (NGAL), liver fatty acid-binding protein (L-FABP), kidney injury molecule 1 (KIM1), and albumin as well as 15 additional biomarkers in plasma and urine were measured during the perioperative period. The primary outcome was AKI defined by AKIN serum creatinine criteria within 72 hours after surgery.

Results

Biomarkers in plasma showed markedly better discriminative performance for preoperative risk stratification and early postoperative (within 24h after surgery) detection of AKI than urine biomarkers. Discriminative power of urine biomarkers improved when concentrations were normalized to urinary creatinine, but urine biomarkers had still lower AUC values than plasma biomarkers. Best diagnostic performance 4h after surgery had plasma NGAL (AUC 0.83), cystatin C (0.76), MIG (0.74), and L-FAPB (0.73). Combinations of multiple biomarkers did not improve their diagnostic power. Preoperative clinical scoring systems (EuroSCORE and Cleveland Clinic Foundation Score) predicted the risk for AKI (AUC 0.76 and 0.71) and were not inferior to biomarkers. Preexisting chronic kidney disease limited the diagnostic performance of both plasma and urine biomarkers.

Conclusions

In our cohort plasma biomarkers had higher discriminative power for risk stratification and early diagnosis of AKI than urine biomarkers. For preoperative risk stratification of AKI clinical models showed similar discriminative performance to biomarkers. The discriminative performance of both plasma and urine biomarkers was reduced by preexisting chronic kidney disease.     

The Diagnostic Accuracy of Urine Lipoarabinomannan Test for Tuberculosis Screening in a South African Correctional Facility

Background

We evaluated the diagnostic accuracy of the urine lipoarabinomannan (LAM) antigen detection assay (Clearview TB-ELISA) to screen for tuberculosis in a South African correctional facility.

Methods

Between September 2009 and October 2010, male offenders were screened for tuberculosis (symptoms, chest radiograph, two spot sputum specimens for microscopy and culture), and urine tested for LAM. Sensitivity, specificity and predictive values of LAM were calculated using definite and probable tuberculosis combined as our gold standard.

Findings

33/871 (3.8%) participants (26% HIV-positive) had tuberculosis. Amongst HIV-positive vs. HIV-negative offenders the sensitivity and specificity of LAM was 7.1% vs. 0% and 98.5% vs. 99.8% respectively.

Conclusion

Urine LAM ELISA has inadequate sensitivity for TB screening in this population.     

Type 2 Diabetes Mellitus and Kidney Cancer Risk: A Retrospective Cohort Analysis of the National Health Insurance

Purpose

To evaluate the association between incidence of any kidney cancer and type 2 diabetes mellitus.

Methods

A random sample of 1,000,000 subjects covered by the National Health Insurance was recruited. A total of 998728 people (115655 diabetes and 883073 non-diabetes) without kidney cancer at recruitment were followed from 2003 to 2005. The cumulative incidence of kidney cancer from 2003 to 2005 in diabetic patients and non-diabetic people in all ages and in age <40, 40–64, 65–74 and ≥75 years were calculated in the diabetic patients and the non-diabetic people, respectively. Logistic regression was used to estimate the odds ratios comparing diabetic patients to non-diabetic people in the respective age groups. Multivariable-adjusted odds ratios for kidney cancer with regards to diabetes status and diabetes duration (as a continuous variable or categorized into subgroups of non-diabetes, diabetes duration <1 year, 1–2.9 years, 3–4.9 years and ≥5 years) were estimated after multivariable adjustment. The multivariable-adjusted odds ratios for all baseline variables were also estimated for diabetic patients and non-diabetic people, respectively.

Results

The 3-year cumulative incidence of kidney cancer in the diabetic patients and the non-diabetic people was 166.9 and 33.1 per 100,000 person-years, respectively. The incidence increased with regards to increasing age in both the diabetic patients and the non-diabetic people, but a higher risk of kidney cancer for the diabetic patients compared to the non-diabetic people was consistently observed in different age groups. After multivariable adjustment, the odds ratio for diabetic patients versus non-diabetic people was 1.7 (95% confidence interval: 1.3–2.1, P<0.01). While compared to the non-diabetic people, the odds ratio (95% confidence interval) for diabetes duration <1, 1–2.9 years, 3–4.9 years and ≥5 years was 1.5 (0.8–2.7), 1.6 (1.0–2.4), 1.6 (1.1–2.4) and 1.7 (1.3–2.3), respectively (P-trend <0.01). Analyses conducted in the diabetic patients and the non-diabetic people, respectively, consistently showed age, nephropathy and end-stage renal disease as significant risk factors of kidney cancer. Additionally, living in metropolitan Taipei region might also be associated with a higher risk of kidney cancer in the non-diabetic people, indicating a potential link between kidney cancer and some factors related to urbanization.

Conclusions

Patients with type 2 diabetes mellitus have a significantly higher risk of kidney cancer.     

Biological Monitoring of Human Exposure to Neonicotinoids Using Urine Samples,and Neonicotinoid Excretion Kinetics

Background

Neonicotinoids, which are novel pesticides, have entered into usage around the world because they are selectively toxic to arthropods and relatively non-toxic to vertebrates. It has been suggested that several neonicotinoids cause neurodevelopmental toxicity in mammals. The aim was to establish the relationship between oral intake and urinary excretion of neonicotinoids by humans to facilitate biological monitoring, and to estimate dietary neonicotinoid intakes by Japanese adults.

Methodology/Principal Findings

Deuterium-labeled neonicotinoid (acetamiprid, clothianidin, dinotefuran, and imidacloprid) microdoses were orally ingested by nine healthy adults, and 24 h pooled urine samples were collected for 4 consecutive days after dosing. The excretion kinetics were modeled using one- and two-compartment models, then validated in a non-deuterium-labeled neonicotinoid microdose study involving 12 healthy adults. Increased urinary concentrations of labeled neonicotinoids were observed after dosing. Clothianidin was recovered unchanged within 3 days, and most dinotefuran was recovered unchanged within 1 day. Around 10% of the imidacloprid dose was excreted unchanged. Most of the acetamiprid was metabolized to desmethyl-acetamiprid. Spot urine samples from 373 Japanese adults were analyzed for neonicotinoids, and daily intakes were estimated. The estimated average daily intake of these neonicotinoids was 0.53–3.66 μg/day. The highest intake of any of the neonicotinoids in the study population was 64.5 μg/day for dinotefuran, and this was <1% of the acceptable daily intake.     

Is Urinary Lipoarabinomannan the Result of Renal Tuberculosis? Assessment of the Renal Histology in an Autopsy Cohort of Ugandan HIV-Infected Adults

Objective

The detection of urinary lipoarabinomannan (LAM), a mycobacterial cell wall component, is used to diagnose tuberculosis (TB). How LAM enters the urine is not known. To investigate if urinary LAM-positivity is the result of renal TB infection we correlated the outcomes of urinary LAM-antigen testing to renal histology in an autopsy cohort of hospitalized, Ugandan, HIV-infected adults.

Methods

We performed a complete autopsy, including renal sampling, in HIV-infected adults that died during hospitalization after written informed consent was obtained from the next of kin. Urine was collected postmortem through post-mortem catheterisation or by bladder puncture and tested for LAM with both a lateral flow assay (LFA) and an ELISA assay. Two pathologists assessed the kidney histology. We correlated the LAM-assay results and the histology findings.

Results

Of the 13/36 (36%) patients with a positive urinary LAM ELISA and/or LFA, 8/13 (62%) had renal TB. The remaining 5 LAM-positive patients had disseminated TB without renal involvement. Of the 23 LAM-negative patients, 3 had disseminated TB without renal involvement. The remaining LAM-negative patients had no TB infection and died mostly of fungal and bacterial infections. LAM LFA had a sensitivity of 81% and specificity of 100% to diagnose TB at any location, and the LAM ELISA a sensitivity of 63% and a specificity of 100%. 54% (7/13) LAM LFA-positive patients were not on anti-TB treatment at the time of death.

Conclusion

Renal TB infection explained LAM-positivity in the majority of patients. Patients with disseminated TB without renal involvement can also be diagnosed with LAM. This suggests that other mechanisms that lead to urinary LAM-positivity exist in a minority of patients.     

Urine/Plasma Neutrophil Gelatinase Associated Lipocalin Ratio Is a Sensitive and Specific Marker of Subclinical Acute Kidney Injury in Mice

Background

Detection of acute kidney injury (AKI) is still a challenge if conventional markers of kidney function are within reference range. We studied the sensitivity and specificity of NGAL as an AKI marker at different degrees of renal ischemia.

Methods

Male C57BL/6J mice were subjected to 10-, 20- or 30-min unilateral renal ischemia, to control operation or no operation, and AKI was evaluated 1 day later by histology, immunohistochemistry, BUN, creatinine, NGAL (plasma and urine) and renal NGAL mRNA expression.

Results

A short (10-min) ischemia did not alter BUN or kidney histology, but elevated plasma and urinary NGAL level and renal NGAL mRNA expression although to a much smaller extent than longer ischemia. Surprisingly, control operation elevated plasma NGAL and renal NGAL mRNA expression to a similar extent as 10-min ischemia. Further, the ratio of urine to plasma NGAL was the best parameter to differentiate a 10-min ischemic injury from control operation, while it was similar in the non and control-operated groups.

Conclusions

These results suggest that urinary NGAL excretion and especially ratio of urine to plasma NGAL are sensitive and specific markers of subclinical acute kidney injury in mice.     

Dose- and Time-Dependent Association of Smoking and Its Cessation with Glycemic Control and Insulin Resistance in Male Patients with Type 2 Diabetes Mellitus: The Fukuoka Diabetes Registry

Objective

Cigarette smoking is an important modifiable risk factor for cardiovascular diseases. However, the effect of smoking and its cessation on glycemic control in diabetic patients has not been fully examined yet. The aim of the present study was to examine the association of smoking status with glycemic level and markers of insulin resistance and secretion in patients with type 2 diabetes mellitus.

Research Design and Methods

A total of 2,490 Japanese male patients with type 2 diabetes mellitus aged ≥20 years were divided according to smoking status, amount of cigarettes smoked and years since quitting. The associations with glycemic level and markers of insulin resistance and secretion were examined cross-sectionally.

Results

HbA_1c levels increased progressively with increases in both number of cigarettes per day and pack-years of cigarette smoking compared with never smokers (P for trend = 0.001 and <0.001, respectively), whereas fasting plasma glucose did not. On the other hand, HbA_1c, but not fasting plasma glucose, decreased linearly with increase in years after smoking cessation (P for trend <0.001). These graded relationships persisted significantly after controlling for the confounders, including total energy intake, current drinking, regular exercise, depressive symptoms, and BMI. In addition, a homeostasis model assessment of insulin resistance and high-sensitivity C-reactive protein also showed similar trends.

Conclusions

Smoking and its cessation showed dose- and time-dependent relationship with glycemic control and insulin resistance in patients with type 2 diabetes mellitus. These findings may highlight the importance of smoking cessation in the clinical management of diabetes mellitus.