Diabetic kidney disease: new clinical and therapeutic issues. Joint position statement of the Italian Diabetes Society and the Italian Society of Nephrology on “The natural history of diabetic kidney disease and treatment of hyperglycemia in patients with type 2 diabetes and impaired renal function”

Abstract

Aims This joint document of the Italian Diabetes Society and the Italian Society of Nephrology reviews the natural history of diabetic kidney disease (DKD) in the light of the recent epidemiological literature and provides updated recommendations on anti-hyperglycemic treatment with non-insulin agents. Data Synthesis Recent epidemiological studies have disclosed a wide heterogeneity of DKD. In addition to the classical albuminuric phenotype, two new albuminuria-independent phenotypes have emerged, i.e., "nonalbuminuric renal impairment" and "progressive renal decline", suggesting that DKD progression toward end-stage kidney disease (ESKD) may occur through two distinct pathways, albuminuric and nonalbuminuric. Several biomarkers have been associated with decline of estimated glomerular filtration rate (eGFR) independent of albuminuria and other clinical variables, thus possibly improving ESKD prediction. However, the pathogenesis and anatomical correlates of these phenotypes are still unclear. Also the management of hyperglycemia in patients with type 2 diabetes and impaired renal function has profoundly changed during the last two decades. New anti-hyperglycemic drugs, which do not cause hypoglycemia and weight gain and, in some cases, seem to provide cardiorenal protection, have become available for treatment of these individuals. In addition, the lowest eGFR safety thresholds for some of the old agents, particularly metformin and insulin secretagogues, have been reconsidered. Conclusions The heterogeneity in the clinical presentation and course of DKD has important implications for the diagnosis, prognosis, and possibly treatment of this complication. The therapeutic options for patients with type 2 diabetes and impaired renal function have substantially increased, thus allowing a better management of these individuals.

Targeting Inflammation in Diabetic Kidney Disease: Is There a Role for Pentoxifylline?

“…In subsequent cross-sectional analyses of the NHANES data, higher adjusted prevalence rates (~ 50%) for the non-albuminuric phenotype among individuals with reduced eGFR were observed [8]. Similar findings have been observed in cohorts of type 2 DM patients outside the U.S. and in those enrolled in multicenter multinational interventional studies [16].…”

“…It is not known whether RAAS blockers have similar benefits in these patients. Concern has been raised that RAAS blockers, by preventing constriction of the efferent arteriole, may actually increase susceptibility to acute kidney injury (AKI) in non-albuminuric patients [16]. With respect to SGLT2 inhibitors, in a posthoc analysis of data from the CANVAS program, canagliflozin slowed the annual loss of kidney function across albuminuria subgroups, suggesting that SGLT2 inhibitors may also be beneficial in nonalbuminuric patients, though there was a greater absolute benefit in participants with severely increased albuminuria [17].…”

“…Non-albuminuric DKD is thought to be predominantly due to vascular and tubulo-interstitial lesions, and decline in renal function in such patients may be at least in part due to ongoing inflammation not entirely remediated by current therapies [16]. Therefore, there is much interest in the development of anti-inflammatory agents for the treatment of DKD.…”

The future of diabetic kidney disease management: what to expect from the experimental studies?

“…Progressive accumulation of extracellular matrix components (ECM) in both the mesangium and the tubulointerstitium plays a key role in renal function decline, eventually resulting in ESRD [1]. Besides the classical albuminuric phenotype, a new "non-albuminuric" phenotype characterized by eGFR decline without albuminuria has emerged in the last decades, indicating that DKD progression toward ESRD may occur through distinct albuminuric and non-albuminuric pathways [2]. Nevertheless, higher albuminuria still remains the major risk factor for progressive DKD [3,4].…”

Сахарный Диабет 2-Го Типа И Хроническая Болезнь Почек: Современные Возможности Сахароснижающей Терапии

“…Дискусії й дослідження щодо можливості, переваг та недоліків застосування цих препаратів у хворих із ІІІА ст. ХХН тривають, результати є неоднозначними, тому потребують подальшого вивчення [23][24][25][26].…”