RAAS blockers

In the presence of albuminuria or proteinuria, RAAS blockers should be prescribed to reduce not only the overactivity of the system but also the sympathetic overactivity, HTN, insulin resistance, and low-grade inflammation. The most important effect is to reduce the filtration fraction and consequently albuminuria; however, in CKD patients the reduction in eGFR should be monitored after starting treatment.

Antiobese-drugs

Of the drugs approved for treatment of obesity, Phentermine-Topiramate, GLP-1 receptor agonist, and Bupropion-Naltresone, mainly data about the impact on renal function is available for the GLP1 agonist. This class of drug has been tested for renal protection in diabetic patients. Liraglutide, a GLP1 agonist, introduced initially as a glucose-lowering drug with impact in body-weight, is able to reduce weight and in a recent trial, LEADER, demonstrated reduction in CV risk [95]. A significant decrease in albuminuria, new onset of persistent proteinuria, and no progression of eGFR decline have been reported in diabetic patients. SUSTAIN-6 with semaglutide [96], another member of the GLP1 agonist class, reduces the risk of composite renal outcome largely driven by persistent proteinuria. However, Dulaglutide in the AWARD-7 [97] did not find differences in the reduction of albuminuria. Topiramate in one study did not demonstrate a beneficial impact on re-

nal outcomes in Type 2 diabetes. Lorcaserin, a selective serotonin 2C receptor, in high cardiovascular risk patients, offered a reduced rate of renal impairment in comparison with placebo [98]. The beneficial impact of GLP1 is that it may protect the kidney from progression to CKD and/or ESKD.

Sodium-glucose cotransporter 2 inhibitors

Sodium-glucose cotransporter 2 inhibitor (SGLT2i) is a class of drug released in the last years with a mechanism that produces various beneficial effects in patients with diabetes, obesity, and cardio and renal protection. Inhibition of glucose reabsorption in the proximal tubule produce glucosuria, reducing the caloric burden and the sodium content with reduction of blood volume, and increasing the sodium arrival to the yuxtaglomerular corpus, inhibiting the hyperactivity of the renal angiotensin system and reducing the filtration fraction, giving protection to the kidney [99]. As a consequence, slightly reduced weight, reduced BP, and the GFR that results can protect of renal function at large. Additional mechanisms in NH3, sympathetic activity, and oxidative stress with beneficial effects complete a frame of a very useful drug. Several outcome trials supported the beneficial impact of the drug in the cardiovascular and renal outcomes [100–103]. The last European of Society of Cardiology and the European Society of Diabetes (ESC/EASD) recommended introduction of SGLT2i in the first step of diabetic patients with very high risk or previous cardiovascular events [104]. In patients with obesity associated diabetes, it may be a good choice in order to protect renal function. The same applies in obese subjects with increased urinary albumin excretion or proteinuria. However, in patients with reduced GFR the efficacy of the drug is reduced and the impact on protection is diminished. As GFR < 45 mL/min/1.73 m<sup>2</sup> is almost negligible, it is a challenge to their use. The beneficial impact observed in patients with GFR between 30–45 mL/min/1.73 m2 in trials and the absence of side effect point to their use off-label [105].
