Insulin withdrawal in diabetic kidney disease : What are we waiting for?

The prevalence of type 2 diabetes mellitus worldwide stands at nearly 9.3% and it is estimated that 20-40% of these patients will develop diabetic kidney disease (DKD). DKD is the leading cause of chronic kidney disease (CKD), and these patients often present high morbidity and mortality rates, particularly in those patients with poorly controlled risk factors. Furthermore, many are overweight or obese, due primarily to insulin compensation resulting from insulin resistance. In the last decade, treatment with sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP1-RA) have been shown to be beneficial in renal and cardiovascular targets; however, in patients with CKD, the previous guidelines recommended the use of drugs such as repaglinide or dipeptidyl peptidase-4 inhibitors (DPP-4 inhibitors), plus insulin therapy. However, new guidelines have paved the way for new treatments, such as SGLT2i or GLP1-RA in patients with CKD. Currently, the new evidence supports the use of GLP1-RA in patients with an estimated glomerular filtration rate (eGFR) of up to 15 mL/min/1.73 m2 and an SGLT2i should be started with an eGFR > 60 mL/min/1.73 m2. Regarding those patients in advanced stages of CKD, the usual approach is to switch to insulin. Thus, the add-on of GLP1-RA and/or SGLT2i to insulin therapy can reduce the dose of insulin, or even allow for its withdrawal, as well as achieve a good glycaemic control with no weight gain and reduced risk of hypoglycaemia, with the added advantage of cardiorenal benefits

GLP-1 Receptor Agonists and Diabetic Kidney Disease: A Call of Attention to Nephrologists

Type 2 diabetes mellitus (T2DM) represents the main cause of chronic kidney disease (CKD) and end-stage renal disease (ESKD), and diabetic kidney disease (DKD) is a major cause of morbidity and mortality in diabetes. Despite advances in the nephroprotective treatment of T2DM, DKD remains the most common complication, driving the need for renal replacement therapies (RRT) worldwide, and its incidence is increasing. Until recently, prevention of DKD progression was based around strict blood pressure (BP) control, using renin-angiotensin system blockers that simultaneously reduce BP and proteinuria, adequate glycemic control and control of cardiovascular risk factors. Glucagon-like peptide-1 receptor agonists (GLP-1RA) are a new class of anti-hyperglycemic drugs shown to improve cardiovascular and renal events in DKD. In this regard, GLP-1RA offer the potential for adequate glycemic control in multiple stages of DKD without an increased risk of hypoglycemia, preventing the onset of macroalbuminuria and slowing the decline of glomerular filtration rate (GFR) in diabetic patients, also bringing additional benefit in weight reduction, cardiovascular and other kidney outcomes. Results from ongoing trials are pending to assess the impact of GLP-1RA treatments on primary kidney endpoints in DKD

Renal pathophysiology and pharmacological mechanisms of nephroprotection

Son varios los factores de riesgo que pueden afectar la progresión de la enfermedad renal crónica (ERC). La hipertensión arterial, la proteinuria, la obesidad, la hipertensión intraglomerular, el tabaco y el control metabólico en la diabetes mellitus son los principales factores de riesgo de progresión modificables. En la progresión de la ERC participan muchos procesos celulares que se originan en compartimentos específicos del ri˜nón, compartimento vascular con nefroangioesclerosis y compartimento tubulointersticial con fibrosis y atrofia tubulointersticial, pudiendo haber imbricación entre ambos mecanismos. Dada la implicación de tantos factores de riesgo y tantas vías patogénicas en la progresión de la ERC, la mejor esperanza para retrasar o prevenir la progresión de la ERC reside en un enfoque terapéutico combinado y multidisciplinar, basado en las evidencias existentes y que actúe sobre todos estos procesos y vías desde el punto mecanístico, y sobre un proceso global que es el riesgo cardiovascular y renal para mejorar el pronóstico de los pacientes.Several risk factors may affect the progression of chronic kidney disease (CKD). Arterial hypertension, proteinuria, obesity, intraglomerular hypertension, smoking and metabolic control in diabetes mellitus are the main modifiable risk factors for progression. The progression of CKD involves many cellular processes that originate in specific compartments of the kidney, the vascular compartment with nephroangiosclerosis and the tubulointerstitial compartment with fibrosis and tubulointerstitial atrophy, and there may be overlap between both mechanisms

COVID-19 and cardiovascular and kidney disease: Where are we? Where are we going?

La pandemia SARS-CoV-2 es una emergencia sanitaria global y necesitamos conocer más sobre ella. Los pacientes con riesgo cardiovascular y renal previo se han identificado como especialmente vulnerables para una mayor morbimortalidad cuando sufren la COVID-19, y una proporción considerable de pacientes pueden desarrollar una lesión vascular en el contexto de la enfermedad que conlleva una mayor letalidad. Las complicaciones cardiovasculares y renales representan un problema, y es probable que en un futuro próximo puedan suponer una amenaza para los pacientes que han sobrevivido a la COVID-19. Como médicos no podemos olvidar que durante una epidemia como esta otras enfermedades ----crónicas---- siguen presentes, y los pacientes continúan precisando atención. Estamos obligados a vigilar de una forma incluso más intensa sus tratamientos y el grado de control. Además, no debemos olvidar que las situaciones urgentes siguen presentándose en esta situación de pandemia y precisan atención rápida; en esta situación actual es muy probable que muchos pacientes, por miedo, no hayan buscado atención médica. La situación durante la epidemia y la incertidumbre de la época post COVID-19 exige la intensificación en el control y seguimiento de la enfermedad cardiovascular y renal de nuestros pacientes. La atención primaria constituye un nivel asistencial clave para el cuidado de la población con enfermedad cardiovascular. Del mismo modo, y ante este nuevo escenario sanitario, necesitamos impulsar las medidas de prevención y control que emanen de los estudios actualmente en desarrollo. Ahora más que nunca necesitamos la investigación, crucial para mejorar el pronóstico cardiovascular y renal de nuestros pacientes.The SARS-CoV-2 pandemic is a global health emergency and we need to know more about it. Patients with cardiovascular risk and previous kidney risk have been identified as especially vulnerable for greater morbidity and mortality when they suffer from COVID-19. A considerable proportion of patients can develop a vascular lesion in the context of the disease that entails a greater lethality. Cardiovascular and renal complications represent a problem and, probably in the near future, may pose a threat to patients who have survived COVID-19. As physicians, we cannot forget that during an epidemic like this, other chronic diseases are present, and patients continue to require care. We are obliged to monitor even more intensely their treatments and control degree. Furthermore, we must not forget that urgent situations continue to arise in this pandemic situation and require prompt attention. In this current situation, it is very likely that many patients, out of fear, have not sought medical attention. The situation during the epidemic and the uncertainty of the post-COVID-19 period, requires intensification in the control and monitoring of cardiovascular and kidney disease in our patients. Primary care constitutes a key level of care for the care of the population with cardiovascular disease. Likewise, and in the face of this new health scenario, we need to promote the prevention and control measures that emanate from the studies currently underway. Now, more than ever, we need research, crucial to improve the cardiovascular and renal prognosis of our patients