[Prevention of diabetic nephropathy: from bench to bedside]. / Prevenzione della nefropatia diabetica: from bench to bedside.

The early phases of diabetic nephropathy are characterized by an increase of GFR that, according to the tubular hypothesis, is secondary to alterations of proximal tubules. Experimental studies have in fact shown that hyperglycemia induces an increase in proximal re-absorption due to hypertrophy of tubular cells with consequent increment of sodium-glucose co-transport. The increased re-absorption in turn causes a reduction of the distal delivery of solutes and, through activation of tubuloglomerular feedback, an increase in single- nephron GFR. The resulting hyper-filtration has been proposed as a main risk factor for progression of diabetic renal disease. Limiting this early alteration may therefore represent a useful strategy for the prevention of diabetic nephropathy, that represents the major cause of ESRD in the western world today. Dapagliflozin, a competitive and highly selective inhibitor of sodium-glucose co-transport, reduces proximal tubular glucose re-absorption, increases renal glucose excretion, and reduces hyperglycemia in a dose-dependent manner. This singular mechanism of action may also have a limiting effect on diabetic hyper-filtration. Clinical trials are therefore warranted to evaluate the reno-protective efficacy of this drug in the long term.

[Epidemiology and prognosis of chronic kidney disease in Italy]. / Epidemiologia e prognosi della malattia renale cronica in Italia.

Because chronic kidney disease (CKD) is a major public health issue, it is important to make the available epidemiological data widely known for a proper understanding of its social impact, and to identify risk factors that can influence the prognosis of the disease. The data from the CARHES study show in the general population of Italy a prevalence of CKD (stage 1-5) of 8%, less than in other countries, a higher prevalence of proteinuria at early stages (1-2), and a cardiovascular risk profile in CKD patients characterized by metabolic syndrome. The prognosis of CKD is an essential element in clinical practice as it allows to better define the severity of the disease and to determine the most appropriate therapeutic approach. The data from the TABLE study, performed in nephrology care, show that ESRD was more frequent than death before dialysis but not in stage 3; we note that advanced age reduces the progression of renal failure and that the most important among the modifiable risk factors is proteinuria, which has a negative predictive role in stage 3-4 but not stage 5 and which interacts specifically with advanced age. No predictive role was found for hypertension, but this is only apparently surprising; in fact, there is growing evidence of the superior effectiveness of ambulatory blood pressure measurement (ABPM) over office blood pressure measurement. These data, together with the results of some trials, show the need for the more extensive use of ABPM to identify subjects with white-coat hypertension and to better control the circadian blood pressure profile by administering antihypertensive drugs also in the evening.