Nephroprotection by Hypoglycemic Agents: Do We Have Supporting Data?

Current therapy directed at delaying the progression of diabetic nephropathy includes intensive glycemic and optimal blood pressure control, renin angiotensin-aldosterone system blockade and multifactorial intervention. However, the renal protection provided by these therapeutic modalities is incomplete. There is a scarcity of studies analysing the nephroprotective effect of antihyperglycaemic drugs beyond their glucose lowering effect and improved glycaemic control on the prevention and progression of diabetic nephropathy. This article analyzes the exisiting data about older and newer drugs as well as the mechanisms associated with hypoglycemic drugs, apart from their well known blood glucose lowering effect, in the prevention and progression of diabetic nephropathy. Most of them have been tested in humans, but with varying degrees of success. Although experimental data about most of antihyperglycemic drugs has shown a beneficial effect in kidney parameters, there is a lack of clinical trials that clearly prove these beneficial effects. The key question, however, is whether antihyperglycemic drugs are able to improve renal end-points beyond their antihyperglycemic effect. Existing experimental data are post hoc studies from clinical trials, and supportive of the potential renal-protective role of some of them, especially in the cases of dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter 2 inhibitors. Dedicated and adequately powered renal trials with renal outcomes are neccessary to assess the nephrotection of antihyperglycaemic drugs beyond the control of hyperglycaemia

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

Validación de un Cuestionario Multidimensional de Adaptación a la Enfermedad para Pacientes Renales en Diálisis (CMAE-RD) diseñado a partir de un cuestionario para pacientes oncohematológicos

Objectives: The present study aims to explore the psychometric properties of a multidimensional questionnaire to assess adaptation to illness in patients with end stage renal disease under hemodialysis (CMAE-RD for its Spanish acronym). Methods: This instrument was developed to be administered by a psychologist as a semi structured interview and it was adapted from a previous questionnaire for patients with oncohaematologic diseases. A total of 113 patients receiving hemodialysis treatment were interviewed with the CMAE-RD and completed two additional questionnaires with validation purposes: the HADS (to assess anxiety and depression) and the CDRISC-2 (to assess resilience). Results: Internal consistency scores for the areas of the CMAE-RD was comprised between.53 and.70. Evidences of validity related to an external criterion and concurrent validity were obtained for the areas which assess the level of information of the patient and their emotional state. Conclusions: We conclude that the CMAE-RD shows adequate levels of reliability and validity, being a useful measurement tool from the standpoint of health care, as it allows psychologist the needs and resources of renal patients, providing guidance for psychological intervention.Objetivos: El objetivo de este trabajo es estudiar las propiedades psicométricas de un cuestionario multidimensional de adaptación a la enfermedad para pacientes con enfermedad renal en diálisis (CMAE-RD). Métodos: Esta herramienta está diseñada para ser administrada por un profesional de la psicología en forma de entrevista semiestructurada y fue diseñado a partir de un cuestionario previo para pacientes oncohematológicos. Un total de 113 pacientes en hemodiálisis fueron entrevistados mediante el CMAE-RD y completaron dos cuestionarios adicionales con propósitos de validación: el HADS (para evaluar ansiedad y depresión) y el CDRISC-2 (para evaluar resiliencia). Resultados: La consistencia interna para las áreas del CMAE-RD estuvo comprendida entre 0,53 y 0,70, y se obtuvieron evidencias de validez relacionada con un criterio externo y concurrente especialmente para las áreas que evaluaban el grado en que el paciente está informado y su estado de ánimo. Conclusiones: CMAE-RD presenta niveles adecuados de fiabilidad y validez, siendo una herramienta útil desde el punto de vista clínico, pues permite evaluar las necesidades y recursos de los pacientes, guiando la intervención psicológic

The development of anemia is associated to poor prognosis in NKF/KDOQI stage 3 chronic kidney disease

Background: Anemia is a common condition in CKD that has been identified as a cardiovascular (CV) risk factor in end-stage renal disease, constituting a predictor of low survival. The aim of this study was to define the onset of anemia of renal origin and its association with the evolution of kidney disease and clinical outcomes in stage 3 CKD (CKD-3). Methods: This epidemiological, prospective, multicenter, 3-year study included 439 CKD-3 patients. The origin of nephropathy and comorbidity (Charlson score: 3.2) were recorded. The clinical characteristics of patients that developed anemia according to EBPG guidelines were compared with those that did not, followed by multivariate logistic regression, Kaplan-Meier curves and ROC curves to investigate factors associated with the development of renal anemia. Results: During the 36-month follow-up period, 50% reached CKD-4 or 5, and approximately 35% were diagnosed with anemia (85% of renal origin). The probability of developing renal anemia was 0.12, 0.20 and 0.25 at 1, 2 and 3 years, respectively. Patients that developed anemia were mainly men (72% anemic vs. 69% non-anemic). The mean age was 68 vs. 65.5 years and baseline proteinuria was 0.94 vs. 0.62 g/24h (anemic vs. non anemic, respectively). Baseline MDRD values were 36 vs. 40 mL/min and albumin 4.1 vs. 4.3 g/dL; reduction in MDRD was greater in those that developed anemia (6.8 vs. 1.6 mL/min/1.73 m(2)/3 years). These patients progressed earlier to CKD-4 or 5 (18 vs. 28 months), with a higher proportion of hospitalizations (31 vs. 16%), major CV events (16 vs. 7%), and higher mortality (10 vs. 6.6%) than those without anemia. Multivariate logistic regression indicated a significant association between baseline hemoglobin (OR=0.35; 95% CI: 0.24-0.28), glomerular filtration rate (OR=0.96; 95% CI: 0.93-0.99), female (OR=0.19; 95% CI: 0.10-0.40) and the development of renal anemia. Conclusions: Renal anemia is associated with a more rapid evolution to CKD-4, and a higher risk of CV events and hospitalization in non-dialysis-dependent CKD patients. This suggests that special attention should be paid to anemic CKD-3 patients

Exploring Sodium Glucose Co-Transporter-2 (SGLT2) Inhibitors for Organ Protection in COVID-19

Hospital admissions and mortality from the Coronavirus disease 2019 (COVID-19) pandemic are spreading throughout the world, and second and third waves are thought to be likely. Risk factors for severe COVID-19 include diabetes, chronic kidney disease and cardiovascular disease. Currently, there is no vaccine and no approved therapy. Therapeutic approaches are aimed at preventing viral replication and spread, limiting the impact of the inflammatory overdrive (cytokine storm), preventing thromboembolic complications and replacing or supporting organ function. However, despite organ support, mortality is currently 65% for those receiving advanced respiratory support and 78% for those requiring renal replacement therapies. Thus, efforts should be made to provide adjuvant organ protection therapy. This may imply novel therapies in clinical development (e.g., the Fas ligand trap asunercept), but uptake of repurposed drugs already in clinical use may be faster. In this regard, sodium glucose co-transporter-2 (SGLT2) inhibitors were recently shown to protect the heart and kidney both within and outside of a diabetic milieu context. Further, preclinical data support a beneficial effect for the lung. We now discuss the potential benefits and risks of SGLT2 inhibitors in COVID-19 and an ongoing clinical trial testing the impact of dapagliflozin on outcomes in COVID-19 patients with respiratory failure

Coronavirus disease 2019 in chronic kidney disease

The clinical spectrum of coronavirus disease 2019 (COVID-19) infection ranges from asymptomatic infection to severe pneumonia with respiratory failure and even death. More severe cases with higher mortality have been reported in older patients and in those with chronic illness such as hypertension, diabetes or cardiovascular diseases. In this regard, patients with chronic kidney disease (CKD) have a higher rate of all-type infections and cardiovascular disease than the general population. A markedly altered immune system and immunosuppressed state may predispose CKD patients to infectious complications. Likewise, they have a state of chronic systemic inflammation that may increase their morbidity and mortality. In this review we discuss the chronic immunologic changes observed in CKD patients, the risk of COVID-19 infections and the clinical implications for and specific COVID-19 therapy in CKD patients. Indeed, the risk for severe COVID-19 is 3-fold higher in CKD than in non-CKD patients; CKD is 12-fold more frequent in intensive care unit than in non-hospitalized COVID-19 patients, and this ratio is higher than for diabetes or cardiovascular disease; and acute COVID-19 mortality is 15-25% for haemodialysis patients even when not developing pneumonia

Cost of Type 2 Diabetes Patients with Chronic Kidney Disease Based on Real-World Data: An Observational Population-Based Study in Spain

[EN] This study analyzed the prevalence, costs and economic impact of chronic kidney disease CKD in patients with T2D in a Spanish Health District using real-world data. Observational cross-sectional study in adult patients with T2D was through data extracted from the information systems of the Valencia Clinico-La Malvarrosa Health District in the year 2015. Patients were stratified with the KDIGO classification for CKD. Additionally, patients were assigned to Clinical Risk Groups (CRGs) according to multimorbidity. Direct costs of primary and specialized care, and medication were estimated. The prevalence of T2D in the database population (n = 28,345) was 10.8% (mean age (SD) = 67.8 years (13.9); 51.5% male). Up to 14.935 patients (52.6%) had data on kidney function. According to the KDIGO classification, 66.2% of the patients were at low risk of CKD, 20.6% at moderately increased risk, 7.9% at high risk, and 5.2% at very high risk. The average healthcare costs associated with these four risk groups were EUR 3437, EUR 4936, EUR 5899 and EUR 7389, respectively. The large number of T2D patients with CKD in the early stages of the disease generated a significant increase in direct healthcare costs. The economic impact could be mitigated by early and comprehensive therapeutic approaches.This research was funded by Boehringer-Ingelheim Espana, S.A.Usó-Talamantes, R.; González-De Julián, S.; Díaz-Carnicero, J.; Saurí-Ferrer, I.; Trillo-Mata, JL.; Carrasco-Pérez, M.; Navarro-Pérez, J.... (2021). Cost of Type 2 Diabetes Patients with Chronic Kidney Disease Based on Real-World Data: An Observational Population-Based Study in Spain. International Journal of Environmental research and Public Health (Online). 18(18):1-14. https://doi.org/10.3390/ijerph18189853S114181

Optimizing the timing of nephrology referral for patients with diabetic kidney disease

Diabetis mellitus; Malaltia renal diabètica; Atenció multidisciplinàriaDiabetes mellitus; Diabetic kidney disease; Multidisciplinary careDiabetes mellitus; Enfermedad renal diabética; Atención multidisciplinariaAge-standardized rates of diabetes mellitus (DM)-related complications, such as acute myocardial infarction, stroke or amputations, have decreased in recent years, but this was not associated with a clear reduction of the incidence of advanced chronic kidney disease (CKD) requiring renal replacement therapy. The early detection of diabetic kidney disease (DKD) is a key to reduce complications, morbidity and mortality. Consensus documents and clinical practice guidelines recommend referral of DM patients to nephrology when the estimated glomerular filtration rate falls below 30 mL/min/1.73 m2 or when albuminuria exceeds 300 mg/g urinary creatinine. Conceptually, it strikes as odd that patients with CKD are referred to the specialist caring for the prevention and treatment of CKD only when >70% of the functioning kidney mass has been lost. The increasing global health burden of CKD, driven in large part by DKD, the suboptimal impact of routine care on DKD outcomes as compared with other DM complications, the realization that successful therapy of CKD requires early diagnosis and intervention, the advances in earlier diagnosis of kidney injury and the recent availability of antidiabetic drugs with a renal mechanism of action and lack of hypoglycaemia risk, which additionally are cardio- and nephroprotective, all point towards a paradigm shift in the care for DM patients in which they should be referred earlier to nephrology as part of a coordinated and integrated care approach.Sources of support: FIS/Fondos FEDER PI18/01386, PI19/00588, PI19/00815, DTS18/00032, ERA-PerMed-JTC2018 (KIDNEY ATTACK AC18/00064 and PERSTIGAN AC18/00071, ISCIII-RETIC REDinREN RD016/0009), Sociedad Española de Nefrología, FRIAT, Comunidad de Madrid en Biomedicina B2017/BMD-3686 CIFRA2-CM

Sodium-glucose cotransporter 2 inhibition: towards an indication to treat diabetic kidney disease

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have clearly demonstrated their beneficial effect in diabetic kidney disease (DKD) on top of the standard of care [blood glucose control, renin-angiotensin system blockade, smoking cessation and blood pressure (BP) control], even in patients with overt DKD. However, the indication of this drug class is still blood glucose lowering in type 2 diabetic patients with estimated glomerular filtration rate >45mL/min/1.73m(2). Based on the new evidence, several scientific societies have emphasized the preferential prescription of SGLT2i for patients at risk of heart failure or kidney disease, but still within the limits set by health authorities. A rapid positioning of both the European Medicines Agency and the US Food and Drug Administration will allow patients with overt DKD to benefit from SGLT2i. Clinical experience suggests that SGLT2i safety management may in part mirror renin-angiotensin blockade safety management in patients with overt DKD. This review focuses on the rationale for an indication of SGTL2i in DKD. We further propose clinical steps for maximizing the safety of SGLT2i in DKD patients on other antidiabetic, BP or diuretic medication