Diabetic kidney disease: from physiology to therapeutics.

Diabetic kidney disease (DKD) defines the functional, structural and clinical abnormalities of the kidneys that are caused by diabetes. This complication has become the single most frequent cause of end-stage renal disease. The pathophysiology of DKD comprises the interaction of both genetic and environmental determinants that trigger a complex network of pathophysiological events, which leads to the damage of the glomerular filtration barrier, a highly specialized structure formed by the fenestrated endothelium, the glomerular basement membrane and the epithelial podocytes, that permits a highly selective ultrafiltration of the blood plasma. DKD evolves gradually over years through five progressive stages. Briefly they are: reversible glomerular hyperfiltration, normal glomerular filtration and normoalbuminuria, normal glomerular filtration and microalbuminuria, macroalbuminuria, and renal failure. Approximately 20-40% of diabetic patients develop microalbuminuria within 10-15 years of the diagnosis of diabetes, and about 80-90% of those with microalbuminuria progress to more advanced stages. Thus, after 15-20 years, macroalbuminuria occurs approximately in 20-40% of patients, and around half of them will present renal insufficiency within 5 years. The screening and early diagnosis of DKD is based on the measurement of urinary albumin excretion and the detection of microalbuminuria, the first clinical sign of DKD. The management of DKD is based on the general recommendations in the treatment of patients with diabetes, including optimal glycaemic and blood pressure control, adequate lipid management and abolishing smoking, in addition to the lowering of albuminuria.

Anti-inflammatory profile of paricalcitol in hemodialysis patients: a prospective, open-label, pilot study.

Inflammation is a strong predictor of increased morbidity and mortality in hemodialysis (HD) patients. Paricalcitol, a selective vitamin D receptor activator used for prevention and treatment of secondary hyperparathyroidism, has shown anti-inflammatory properties in experimental studies, although clinical data are scarce. In an open-label, prospective, single center, pilot study, 25 stable HD patients, previously receiving calcitriol, completed 12 weeks of therapy with oral paricalcitol. Serum and peripheral blood mononuclear cell (PBMC) expression profiles of inflammatory cytokines were analyzed. Serum interleukin (IL)-1, IL-10, and IL-18 did not change, unlike high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α), and IL-6, which experienced a significant mean percent decrease of 14.3%, 4.7%, and 5%, respectively. There was a significant reduction in the TNF-α/IL-10 and the IL-6/IL-10 ratios (P < .05). Serum intact parathyroid hormone concentration experienced a mild but significant reduction. In addition, expression levels of TNF-α and IL-6 decreased by 19.1% (P < .01) and 17.5% (P < .001), respectively, whereas expression of IL-10 increased by 17.7% (P < .01) after treatment. In conclusion, paricalcitol administration to HD patients is associated with a beneficial effect on the inflammatory cytokine serum and gene expression profile of PBMC. This effect may contribute to the survival benefits of paricalcitol observed in clinical studies.

A simple clinical score for type 2 diabetes mellitus screening in the Canary Islands.

AIM: To develop a straightforward risk score for type 2 diabetes (DM2) screening to use in clinical practice. METHODS: A sample of 6237 adult inhabitants of the Canary Islands (Spain) was randomly divided into two subgroups: one yielded data used to develop the instrument, and the other yielded data used for validation testing. Performance of the instrument was compared in persons with clinically diagnosed DM2 and undiagnosed diabetes. The risk score, calculated by multivariate logistic regression, included the potential risk variables that yielded the highest odds ratio in the univariate analysis. A cut-off point for screening purposes was established at a 99% negative predictive value. RESULTS: In men, variables included in the risk score were age, waist/height ratio, familial antecedents of diabetes, and systolic blood pressure (ROC curve 0.837, 95% CI: 0.803-0.871). In women, the risk score contained the same variables plus gestational diabetes history (ROC curve 0.874, 95% CI: 0.847-0901). Excluding systolic blood pressure from the score had no significant effect on the area under the curve. This instrument resulted valid only for people aged less than 55 years. CONCLUSIONS: This simple risk score for DM2 would be easy to apply in clinical practice.