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Background: Peripheral artery disease (PAD) is a complication of type 2 diabetes that leads to critical limb ischemia and amputation. We tested whether absent or diminished pedal pulses (ADPPs) predicts subsequent renal functional decline in patients with diabetic chronic kidney disease (CKD). We also examined the association between urinary biomarkers and ADPP as well as worsening CKD. Methods: Using a prospective longitudinal design, we studied 91 patients with type 2 diabetes and estimated glomerular filtration rate (eGFR) from 7 to 146 mL/min/1.73 m2. Baseline pedal pulses were assessed by standardized history and physical examination. The primary endpoint was decline in eGFR >30%. Potential confounders of the relationship between pedal pulses and eGFR were assessed by multivariable logistic regression. Results: Of 91 participants (median age 58 (range 30–83); median eGFR 72.4 ± 33.4 mL/min/1.73 m2), 43% had at least one ADPP. Baseline ADPP associated with increased risk of greater than 30% decline in eGFR (OR= 3.67, p =.004). This association remained significant (OR = 3.09, p =.029) after adjustment for traditional risk factors of renal function decline in diabetic kidney disease (DKD). In addition, urinary endothelin-1 (ET-1) was higher among patients with ADPP (p =.0006) and associated with eGFR decline greater than 30% (adjusted OR = 1.81, p =.035). Conclusions: ADPP is a strong predictor of decline in renal function in type 2 diabetes. Patients with type 2 diabetes and abnormal pedal pulses should be screened for DKD and monitored closely for progression of CKD. [ABSTRACT FROM AUTHOR]

Background: Endothelin-1 (ET-1) is associated with progression of renal disease, acting as a vasoconstrictor and growth factor for mesangial cells. ET-1 and endothelin A receptor (ET-RA) might have a role in the development of diabetic nephropathy (DN). The aims of this study were to determine ET-1 and ET-RA expressions in patients with DN and to correlate these expressions with renal function and proteinuria. Materials and methods: This is a cross-sectional study comprising 13 patients with type 2 diabetes mellitus and DN, 10 patients with proteinuric IgA nephropathy, and 13 samples of normal kidney from tumor nephrectomies. Demographic and selected data were collected from medical charts. The distribution and intensity of ET-1 and ET-RA immunostaining in renal biopsies were determined by immunohistochemistry and these correlated with the estimated glomerular filtration rate (eGFR) and proteinuria. Results: Patients with DN and IgA nephropathy on biopsy had markedly increased staining for ET-1 in endothelial cells of glomerular and peritubular capillaries when compared with controls ( p < 0.001). ET-RA staining was also more intense and more diffuse in DN and IgA nephropathy than in controls ( p == 0.019) and was restricted to tubular epithelial cells. A positive correlation was observed between ET-1 expression and proteinuria ( r == 0.634, p == 0.027), but both ET-1 and ET-RA expressions did not correlate with eGFR. Conclusion: In this preliminary report, the higher expressions of ET-1 and ET-RA found in both DN and IgA nephropathy suggest a potential role for the endothelin system in DN as well as in other nondiabetic glomerular diseases. [ABSTRACT FROM AUTHOR]

In patients on chronic hemodialysis the prevalence of atherosclerosis is increased and is by far the leading cause of morbidity and mortality. Endothelin-1, an endothelium-derived peptide with vasoconstrictive and mitogenic effects on vascular smooth muscles, is involved in the pathogenesis of atherosclerosis. The aim of the present study was to investigate the time course of plasma endothelin-1 levels during a hemodialysis session and to explore the influence of preexisting type 2 diabetes mellitus. Forty-five clinically stable hemodialysis patients (21 females, 24 males; mean age 62 ± 12 years) were evaluated. Patients with type 2 diabetes (n = 11) were compared with the group of patients without diabetes (n = 34). Relative blood volume (BV) changes (hemoglobinometry) and blood pressure (BP) was measured. Samples were taken before, every hour during, and after hemodialysis. Plasma endothelin-1 levels were measured by enzyme-linked immunoassay (ELISA) and results were corrected according to hemoconcentration. Hemodialysis with an ultrafiltration of 2215 ± 952 mL was performed. Total BV at the end of hemodialysis was 89.3% ± 8.3% of the pretreatment volume. Plasma endothelin-1 was enhanced in hemodialysis patients compared to normal subjects and increased from 1.28 ± 0.47 before to 1.44 ± 0.54 pg/mL (ref. 0.3–0.9) at the end of hemodialysis ( p [ABSTRACT FROM AUTHOR]