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Diabetic kidney disease (DKD) is a highly prevalent condition worldwide. It represents one of the most common complications arising from diabetes mellitus (DM) and is the leading cause of end-stage kidney disease (ESKD). Its development involves three fundamental components: the hemodynamic, metabolic, and inflammatory axes. Clinically, persistent albuminuria in association with a progressive decline in glomerular filtration rate (GFR) defines this disease. However, as these alterations are not specific to DKD, there is a need to discuss novel biomarkers arising from its pathogenesis which may aid in the diagnosis, follow-up, therapeutic response, and prognosis of the disease.

Introducción: los inhibidores del cotransportador sodio-glucosa tipo 2 (iSGLT2) son terapias innovadoras que han mostrado beneficios más allá del control glicémico. La experiencia y los estudios clínicos de reciente publicación han corroborado su utilidad para la prevención de resultados adversos renales y cardiovasculares, por ello, sus beneficios se deben extrapolar a distintas poblaciones por fuera de la diabetes mellitus tipo 2. Objetivo: presentar y describir el uso de dapagliflozina en cinco pacientes con nefropatía por IgA. Presentación del caso: se describen cinco casos de pacientes con enfermedad renal crónica no diabética, con múltiples comorbilidades cardiovasculares, diagnóstico confirmado por biopsia de nefropatía por IgA, recibiendo terapia habitual con bloqueo RAS, esteroides según criterio del caso y manejo de comorbilidades. En quienes por persistencia de albuminuria, se adicionó dapagliflozina, con la cual, se obtuvo una reducción variable en los valores de la albuminuria en el tiempo. Discusión y conclusión: el uso de dapagliflozina se asoció con una reducción en niveles de albuminuria en pacientes con nefropatía por IgA, similar a lo informado en estudios como el DAPA-CKD. No se pueden hacer comentarios con relación a evolución renal y mortalidad por el corto tiempo de seguimiento, por tal motivo, se hace necesario en nuestro medio potenciar las regulaciones y la adición a las guías de manejo de estas terapias en escenarios diferentes a diabetes mellitus.

We have read the article published by Kadowaki, et al. 1 “Semaglutide once a week in adults with overweight or obesity, with or without type 2 diabetes mellitus in an East Asian population (STEP 6): A randomized, double blind, double dummy, placebo controlled, phase 3a trial”, where the authors conclude that semaglutide at a dose of 2.4 mg, in diabetic and non-diabetic patients, reduces obesity and overweight compared to placebo in East Asian patients. These interesting results, demonstrate once again its benefits regarding overweight and obesity1,2. We consider that there should be several relevant aspects to have in mind. The study shows, once again, that semaglutide might have dose dependent effects and some that aren’t dose dependent, with weight loss being a dose-dependent effect. Regarding renal benefits, we consider that including albuminuria as a variable is of importance, given that only eGFR by CKD-EPI was included in the study. The average eGFR of the patients was 97.2 cc/min, patients with an eGFR less than 30 were excluded (eGFR less than 60 in patients receiving SGLT-2 inhibitors). We mention this since it would’ve been interesting to evaluate albuminuric vs non-albuminuric patients, hence seeing if there are any renal benefits, especially in albuminuric patients that may be dose dependent. Recently, Shaman, et al. 3 reported that liraglutide and semaglutide had renal benefits in type 2 diabetes mellitus, but their effect in albuminuria was higher in patients with 1 mg of semaglutide weekly vs 0.5 mg weekly. The latter allows to hypothesize that this effect may be dose dependent. Given this, it would be of interest to assess if higher doses bring increased renal benefits, as seen in weight loss. In summary, having in mind the renal benefits seen by semaglutide in other studies4, it would be of great importance to verify the impact of albuminuria in patients with obesity.  Hence, we hope that in the upcoming trials, albuminuria is taken into consideration, so that we can highlight not only the cardio-metabolic benefits, but renal benefits in diabetic and non-diabetic patients that are obese or overweight, and to assess if there is a dose-dependent response.

Obesity is a risk factor for the development and progression of CKD, which has been shown in numerous studies. The mechanism of how this occurs is not completely understood, but several putative mechanisms proposed via adiposity, include low adiponectin high leptin and resistin, causing inflammation, insulin resistance, RAAS activation and oxidative stress, leading to CKD; in addition, it also causes diabetes mellitus, hypertension, and cardiovascular disease. Obesity is a persistent inflammatory state, and inflammation has been shown to play an important role in the development and progression of diabetic kidney disease, hence controlling obesity has become a key component as a preventative strategy in the development of kidney disease.