Dear Colleagues,

The prevalence of diabetes mellitus (DM) in the general population is continuously increasing, and it has been estimated that the number of diabetic subjects will reach 592 million worldwide by the end of 2035. DM is a metabolic disease that causes renal failure, and renal failure increases insulin resistance.

Thus, the kidney has a major role in glucose metabolism, and the complex relationship between diabetes and the kidney has been only recently unveiled thanks to the advance of new hypoglycaemic treatments. In patients with chronic renal failure (CRF), the accumulation of uremic toxins and increased parathyroid hormone levels causes and increased need for insulin secretion. Moreover, anemia caused by CRF has an impact on insulin resistance, and the correction of anemia by erythropoietin has been shown to improve glucose metabolism and insulin sensitivity in the body. Another consequence of CRF is a reduced insulin secretion, which is due to complications of renal failure such as metabolic acidosis, elevated levels of parathyroid hormone, and decreased level of vitamin D. However, despite a reduced insulin secretion and increased insulin resistance, most non-diabetic patients with renal failure do not have hyperglycemia unless they are genetically predisposed.

The relationship between DM and the kidney changes according to the stage of renal disease, and different mechanisms intervene altering insulin and carbohydrate metabolism in advanced stages of CRF. Indeed, when the glomerular filtration rate (GFR) become less than 15ml/min, the renal clearance of insulin decreases, which is clinically important in the treatment of patients with diabetes. Thus, the decreased insulin degradation may drastically reduce the need for administration of insulin in DM patients with advanced CRF, even resolving glucose abnormalities in type 2 DM. On the other hand, this may increase the risk of hypoglycemia, rendering diabetes treatment particularly challenging in these patients.

Finally, when patients with CRF start renal replacement therapy both with hemodialysis, or peritoneal dialysis, the insulin requirements further change, mainly due to increased appetite and food intake resulting from the attenuation of uremic symptoms.

Notably, increased evidence has been recently focused on clarifying different morphological renal lesions associated with diabetes, especially the non-albuminuric phenotype. There is still an ongoing debate on the prevalence and the role of different forms of kidney disease in diabetic subjects, other than diabetic kidney disease.

Furthermore, the epidemiology of diabetic kidney disease changed overtime, mainly because of the ageing of the population and the better available therapeutic strategies, leading to a greater number of DM subjects who are at-target for glucose and blood pressure control. However, in spite of these ameliorated treatments, many DM subjects still develop renal impairment, because of the occurrence of other independent risk factors, such as atherogenic dislipidemia. To date, renal impairment represented a demanding task in diabetic patients, because of the limited therapeutic options available and the higher burden of associated complications, including cardiovascular disease. In the last decades, the appearance of new class of hypoglycaemic drugs opened new avenues for safely treating diabetes in subjects with CRF, or even preventing its occurrence and/or progression.

This Special Issue will deal with several aspects of the management of diabetes and its renal complications, as specified below. 

Prof. Dr. Domenico Santoro
Prof. Dr. Giuseppina Russo
Guest Editors

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• Diabetic kidney disease
• Microalbuminuria
• Gender
• Carbohydrate metabolism
• Low protein diet in diabetic nephropathy
• Ageing
• SGLT2 GLP1-RAs