Electrochemical Skin Conductance in Diabetic Kidney Disease.

BACKGROUND: There is a need to identify patients with diabetic kidney disease (DKD) using noninvasive, cost-effective screening tests. Sudoscan®, a device using electrochemical skin conductance (ESC) to measure sweat gland dysfunction, is valuable for detecting peripheral neuropathy. ESC was tested for association with DKD (estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m(2)) in 383 type 2 diabetes mellitus (T2D)-affected patients; diagnostic thresholds were determined in 540 patients. METHODS: Relationships between ESC with eGFR and urine albumin:creatinine ratio (UACR) were assessed in 202 European Americans and 181 African Americans with T2D. RESULTS: In 92 European American DKD cases and 110 T2D non-nephropathy controls, respectively, mean (SD) ages were 69 (9.7) and 61 (10.8) years, hemoglobin A1c (HbA1c) 7.4 (1.2) and 7.4 (1.3)%, eGFR 29.6 (12.2) and 87.8 (14.2) ml/min/1.73 m(2), and UACR 1,214 (1,705) and 7.5 (5.8) mg/g. In 57 African American cases and 124 controls, respectively, mean (SD) ages were 64.0 (11.9) and 59.5 (9.7) years, HbA1c 7.4 (1.3) and 7.5 (1.7)%, eGFR 29.6 (13.3) and 90.2 (16.2) ml/min/1.73 m(2), and UACR 1,172 (1,564) and 7.8 (7.1) mg/g. Mean (SD) ESC (µS) was lower in cases than controls (European Americans: case/control hands 49.5 (18.5)/62.3 (16.2); feet 62.1 (17.9)/73.6 (13.8), both p < 1.3 × 10(-6); African Americans: case/control hands 39.8 (19.0)/48.5 (17.1); feet 53.2 (21.3)/63.5 (19.4), both p ≤ 0.01). Adjusting for age, sex, body mass index and HbA1c, hands and feet ESC associated with eGFR <60 ml/min/1.73 m(2) (p ≤ 7.2 × 10(-3)), UACR >30 mg/g (p ≤ 7.0 × 10(-3)), UACR >300 mg/g (p ≤ 8.1 × 10(-3)), and continuous traits eGFR and UACR (both p ≤ 5.0 × 10(-9)). HbA1c values were not useful for risk stratification. CONCLUSIONS: ESC measured using Sudoscan® is strongly associated with DKD in African Americans and European Americans. ESC is a useful screening test to identify DKD in patients with T2D.

Plasma FGF23 and Calcified Atherosclerotic Plaque in African Americans with Type 2 Diabetes Mellitus.

BACKGROUND: Fibroblast growth factor 23 (FGF23) is a phosphaturic hormone implicated in disorders of serum phosphorus concentration and vitamin D. The role of FGF23 in vascular calcification remains controversial. METHODS: Relationships between FGF23 and coronary artery calcified atherosclerotic plaque (CAC), aortoiliac calcified plaque (CP), carotid artery CP, volumetric bone mineral density (vBMD), albuminuria, and estimated glomerular filtration rate (eGFR) were determined in 545 African Americans with type 2 diabetes (T2D) and preserved kidney function in African American-Diabetes Heart Study participants. Generalized linear models were fitted to test associations between FGF23 and cardiovascular, bone, and renal phenotypes, and change in measurements over time, adjusting for age, gender, African ancestry proportion, body mass index, diabetes duration, hemoglobin A1c, blood pressure, renin-angiotensin-system inhibitors, statins, calcium supplements, serum calcium, and serum phosphate. RESULTS: The sample was 56.7% female with a mean (SD) age of 55.6 (9.6) years, diabetes duration of 10.3 (8.2) years, eGFR 90.9 (22.1) ml/min/1.73 m2, urine albumin:creatinine ratio (UACR) 151 (588) (median 13) mg/g, plasma FGF23 161 (157) RU/ml, and CAC 637 (1,179) mg. In fully adjusted models, FGF23 was negatively associated with eGFR (p < 0.0001) and positively associated with UACR (p < 0.0001) and CAC (p = 0.0006), but not with carotid CP or aortic CP. Baseline FGF23 concentration did not associate with changes in vBMD or CAC after a mean of 5.1 years follow-up. CONCLUSIONS: Plasma FGF23 concentrations were independently associated with subclinical coronary artery disease, albuminuria, and kidney function in the understudied African American population with T2D. Findings support relationships between FGF23 and vascular calcification, but not between FGF23 and bone mineral density, in African Americans lacking advanced nephropathy.

Kidney disease and cognitive function: African American-diabetes heart study MIND.

AIMS: Albuminuria and reduced estimated glomerular filtration rate (eGFR) are linked with poorer cognitive performance in European-ancestry populations with advanced nephropathy; relationships in African Americans (AAs) with type 2 diabetes (T2D) are less clear. Tests of cognitive performance, urine albumin:creatinine ratio (UACR), and CKD-EPI eGFR were performed in unrelated AAs with T2D to determine relationships. METHODS: Cross-sectional analysis of 263 unrelated AAs with T2D recruited in the African American-Diabetes Heart Study (AA-DHS) MIND. Global cognitive function (mini-mental state exam [3MSE] and Montreal Cognitive Assessment [MoCA]), memory (Rey Auditory Verbal Learning Test [RAVLT]), executive function (Stroop, verbal fluency for animals, and Digit Symbol Copy [DSC]), UACR, and eGFR were determined. Relationships between cognitive tests and renal parameters were assessed using multivariate models, adjusted for age, gender, body mass index, hemoglobin A1c, level of education, hypertension, and LDL cholesterol. RESULTS: Participants had a mean ± SD age of 60.2 ± 9.7 years, 62.7% were female, T2D duration was 14.3 ± 8.9 years, eGFR 86.0 ± 23.2 ml/min/1.73 m(2), and UACR 155.8 ± 542.1 (median 8.1) mg/g. In adjusted models, higher UACR was associated with worse 3MSE (p = 0.014), MoCA (p = 0.0089), DSC (p = 0.0004), Stroop performance time (p = 0.003), Stroop errors (p = 0.032), and Stroop interference (p = 0.026). Higher eGFR was associated with better performance on DSC (p = 0.0071). CONCLUSIONS: In AAs with T2D, albuminuria and eGFR were associated with cognitive function, even in mild kidney disease. These data stress the need for interventions to prevent cognitive decline well before the late stages of kidney disease.

Relationships between electrochemical skin conductance and kidney disease in Type 2 diabetes.

BACKGROUND: SUDOSCAN® non-invasively measures peripheral small fiber and autonomic nerve activity using electrochemical skin conductance. Since neuropathy and nephropathy are microvascular Type 2 diabetes (T2D) complications, relationships between skin conductance, estimated glomerular filtration rate (eGFR), and urine albumin:creatinine ratio (UACR) were assessed. METHODS: Two hundred five African Americans (AA) with T2D, 93 AA non-diabetic controls, 185 European Americans (EA) with T2D, and 73 EA non-diabetic controls were evaluated. Linear models were fitted stratified by population ancestry and T2D, adjusted for covariates. RESULTS: Relative to EA, AA had lower skin conductance (T2D cases p<0.0001; controls p<0.0001). Skin conductance was also lower in T2D cases vs. controls in each population (p<0.0001, AA and EA). Global skin conductance was significantly associated with eGFR in AA and EA with T2D; adjusting for age, gender, BMI, and HbA1c, positive association was detected between skin conductance and eGFR in AA T2D cases (parameter estimate 3.38, standard error 1.2; p=5.2E(-3)), without association in EA T2D cases (p=0.22). CONCLUSIONS: Noninvasive measurement of skin conductance strongly associated with eGFR in AA with T2D, replicating results in Hong Kong Chinese. SUDOSCAN® may prove useful as a low cost, non-invasive screening tool to detect undiagnosed diabetic kidney disease in populations of African ancestry.