In recent years, following the publication of results from several RCTs, first on cardiovascular and more recently on renal outcomes, SGLT2is have become the standard of care to prevent diabetic kidney disease and slow its progression. This narrative review focuses on biological mechanisms, both renal and extrarenal, underlying kidney protection with SGLT2is. Furthermore, data from cardiovascular as well as renal outcome trials, mostly conducted in diabetic patients, are presented and discussed to provide an overview of current uses as well as the future therapeutic potential of these drugs.

Arterial hypertension (AH) is a global challenge that greatly impacts cardiovascular morbidity and mortality worldwide. AH is a major risk factor for the development and progression of kidney disease. Several antihypertensive treatment options are already available to counteract the progression of kidney disease. Despite the implementation of the clinical use of renin–angiotensin aldosterone system (RAAS) inhibitors, gliflozins, endothelin receptor antagonists, and their combination, the kidney damage associated with AH is far from being resolved. Fortunately, recent studies on the molecular mechanisms of AH-induced kidney damage have identified novel potential therapeutic targets. Several pathophysiologic pathways have been shown to play a key role in AH-induced kidney damage, including inappropriate tissue activation of the RAAS and immunity system, leading to oxidative stress and inflammation. Moreover, the intracellular effects of increased uric acid and cell phenotype transition showed their link with changes in kidney structure in the early phase of AH. Emerging therapies targeting novel disease mechanisms could provide powerful approaches for hypertensive nephropathy management in the future. In this review, we would like to focus on the interactions of pathways linking the molecular consequences of AH to kidney damage, suggesting how old and new therapies could aim to protect the kidney.

There is no specific therapy for polyoma BK virus nephropathy (BKVN) in kidney transplant recipients, a condition associated with poor outcomes. Everolimus showed promising antiviral effects, but data from prospective studies are limited. Therefore, we converted ten consecutive kidney transplant recipients with biopsy-proven BKVN from standard exposure Calcineurin inhibitors and Mycophenolate to Everolimus and reduced exposure Calcineurin inhibitors. Ten patients not administered Everolimus, on reduced exposure Calcineurin inhibitor and halved MPA doses served as controls. All kidney transplant recipients continued steroid therapy. Each patient underwent kidney graft biopsy, BKV replication by PCR, and de novo DSA determination. During a 3-year follow-up no graft loss occurred in kidney transplant recipients on Everolimus but it was observed in 5/10 controls (P = 0.032). eGFR improved on Everolimus and worsened in controls (between group difference + 25.6 ml/min/1.73 m², 95% CI 10.5–40.7, P = 0.002). BKV replication declined in the Everolimus group alone (from 6.4 ± 0.8 to 3.6 ± 1.6 Log 10 genomic copies, P = 0.0001), and we found a significant inverse relationship between eGFR and BKV genomic copy changes (P = 0.022). Average Calcineurin inhibitors trough levels did not differ between the two study groups during follow-up. By multivariable Cox regression analysis, Everolimus treatment resulted the only significant predictor of survival free of a combined endpoint of graft loss and 57% eGFR reduction (P = 0.02). Kidney transplant recipients on Everolimus had a higher survival free of adverse graft outcome (log-rank test, P = 0.009). In conclusion an Everolimus-based immunosuppressive protocol with minimization of Calcineurin inhibitors and antimetabolite discontinuation effectively treated BKVN in kidney transplant recipients.

Background: The predictive role of blood pressure variability for all‐cause mortality and fatal and nonfatal cardiovascular events has been described in the general population and in patients with diabetes, independently of mean BP. Although systolic blood pressure variability has been proposed as an informative measure for predicting clinical outcomes in patients with chronic kidney disease, its role in kidney transplant recipients is still debatable. Methods and Results: We performed a retrospective, observational, monocentric analysis of all kidney transplant recipients in follow‐up at the outpatient Nephrology Clinic of San Martino Hospital from January 1, 2016 to December 31, 2016, who underwent kidney transplantation >12 months. The primary outcome was a fatal or nonfatal cardiovascular event (myocardial infarction, unstable angina, stroke, and hospitalization for heart failure). Visit‐to‐visit systolic blood pressure variability was expressed as the SD of systolic blood pressure values recorded at baseline and 3 months up to 18 months. Among the 272 patients (mean age, 64±13; 63% men) included in the present analyses, for each increase of 2.7 mm Hg in systolic blood pressure SD, the risk for events increased 3‐fold (hazard ratio [HR], 3.1 [95% CI, 1.19–7.88]; P =0.02), and patients in the highest tertile of systolic blood pressure SD showed a 4‐fold increased risk (HR, 4.1 [95% CI, 1.34–12.43]; P =0.01). This relationship was maintained even after incremental adjustment for time‐averaged pulse pressure, age, diabetes, and prior cardiovascular event (HR, 3.2 [95% CI, 1.1–10.0]; P =0.04). Conclusions: Long‐term blood pressure variability represents a risk factor for cardiovascular events in kidney transplant recipients, even independently by several confounding factors including blood pressure load.