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 COVID19 mortality is 15-25% for haemodialysis patients even when not developing pneumonia

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

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

SGLT2i and GLP-1RA in cardiometabolic and renal diseases : from glycemic control to adipose tissue inflammation and senescence

Background. Over the last few years, the use of sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP-1RA) has increased substantially in medical practice due to their documented benefits in cardiorenal and metabolic health. In this sense, and in addition to being used for glycemic control in diabetic patients, these drugs also have other favorable effects such as weight loss and lowering blood pressure, and more recently, they have been shown to have cardio and renoprotective effects with anti-inflammatory properties. Concerning the latter, the individual or associated use of these antihyperglycemic agents has been linked with a decrease in proinflammatory cytokines and with an improvement in the inflammatory profile in chronic endocrine-metabolic diseases. Hence, these drugs have been positioned as first-line therapy in the management of diabetes and its multiple comorbidities, such as obesity, which has been associated with persistent inflammatory states that induce dysfunction of the adipose tissue. Moreover, other frequent comorbidities in long-standing diabetic patients are chronic complications such as diabetic kidney disease, whose progression can be slowed by SGLT2i and/or GLP-1RA. The neuroendocrine and immunometabolism mechanisms underlying adipose tissue inflammation in individuals with diabetes and cardiometabolic and renal diseases are complex and not fully understood. Summary. This review intends to expose the probable molecular mechanisms and compile evidence of the synergistic or additive anti-inflammatory effects of SGLT2i and GLP-1RA and their potential impact on the management of patients with obesity and cardiorenal compromise

The sick adipose tissue : new insights into defective signaling and crosstalk with the myocardium

Adipose tissue (AT) biology is linked to cardiovascular health since obesity is associated with cardiovascular disease (CVD) and positively correlated with excessive visceral fat accumulation. AT signaling to myocardial cells through soluble factors known as adipokines, cardiokines, branched-chain amino acids and small molecules like microRNAs, undoubtedly influence myocardial cells and AT function via the endocrine-paracrine mechanisms of action. Unfortunately, abnormal total and visceral adiposity can alter this harmonious signaling network, resulting in tissue hypoxia and monocyte/macrophage adipose infiltration occurring alongside expanded intra-abdominal and epicardial fat depots seen in the human obese phenotype. These processes promote an abnormal adipocyte proteomic reprogramming, whereby these cells become a source of abnormal signals, affecting vascular and myocardial tissues, leading to meta-inflammation, atrial fibrillation, coronary artery disease, heart hypertrophy, heart failure and myocardial infarction. This review first discusses the pathophysiology and consequences of adipose tissue expansion, particularly their association with meta-inflammation and microbiota dysbiosis. We also explore the precise mechanisms involved in metabolic reprogramming in AT that represent plausible causative factors for CVD. Finally, we clarify how lifestyle changes could promote improvement in myocardiocyte function in the context of changes in AT proteomics and a better gut microbiome profile to develop effective, non-pharmacologic approaches to CVD

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

IgA-Dominant Infection-Associated Glomerulonephritis Following SARS-CoV-2 Infection

The renal involvement of severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) has been reported. The etiology of kidney injury appears to be tubular, mainly due to the expression of angiotensin-converting enzyme 2, the key joint receptor for SARS-CoV-2; however, cases with glomerular implication have also been documented. The multifactorial origin of this renal involvement could include virus-mediated injury, cytokine storm, angiotensin II pathway activation, complement dysregulation, hyper-coagulation, and microangiopathy. We present the renal histological findings from a patient who developed acute kidney injury and de novo nephrotic syndrome, highly suggestive of acute IgA-dominant infection-associated glomerulonephritis (IgADIAGN) after SARS-CoV-2 infection, as evidenced by the presence of this virus detected in the renal tissue of the patient via immunohistochemistry assay. In summary, we document the first case of IgA-DIAGN associated to SARS-CoV-2. Thus, SARS-CoV-2 S may act as a super antigen driving the development of multisystem inflammatory syndrome as well as cytokine storm in patients affected by COVID-19, reaching the glomerulus and leading to the development of this novel IgA-DIAGN

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

Long-term mortality and trajectory of potassium easurements following an episode of acute severe hyperkalemia

Background: Hyperkalaemia is a common condition in patients with comorbidities such as chronic kidney disease (CKD) or congestive heart failure (HF). Moreover, severe hyperkalaemia is a potentially life-threatening condition that is associated with a higher risk of adverse clinical events such as ventricular arrhythmias and sudden cardiac death. Currently, data regarding the prognostic implications of chronic hyperkalaemia are available; however, information about the long-term clinical consequences after an episode of severe hyperkalaemia remains scarce. The objective of this study was to evaluate the association between the trajectory of potassium measurements in patients with acute hyperkalaemia and long-term all-cause mortality. Methods: This is a retrospective observational study that included patients with acute severe hyperkalaemia [potassium (K) >6 mEq/L] without haemolysis in the emergency room of Dr Peset University Hospital in Valencia, Spain searching the lab database from January 2016 to March 2017. The multivariable-adjusted association of serum potassium with mortality was assessed by using comprehensive state-of-the-art regression methods that can accommodate time-dependent exposure modelling. Results: We found 172 episodes of acute hyperkalaemia in 160 patients in the emergency room. The mean ± standard deviation age of the sample was 77 ± 12 years and 60.5% were males. The most frequent comorbidities were CKD (71.2%), HF (35%) and diabetes mellitus (56.9%). Only 11.9% of the patients were on chronic dialysis. A quarter of the patients did not have previous CKD, making hyperkalaemia an unpredictable life-threatening complication. During the acute episode, mean potassium and estimated glomerular filtration rate (eGFR) were 6.6 ± 0.6 (range 6.1-9.2) mEq/L and 23 ± 16 (range 2-84) mL/min/1.73 m2, respectively. After a median (interquartile range) follow-up of 17.3 (2.2-23.7) months, 68 patients died (42.5%). Recurrences of hyperkalaemia (K >5.5 mEq/L) were detected in 39.5% of the patients who were monitored during follow-up. We found that previous potassium levels during an acute severe hyperkalaemia episode were not predictors of mortality. Conversely, the post-discharge longitudinal trajectories of potassium were able to predict all-cause mortality (overall P = 0.0015). The effect of transitioning from hyperkalaemia to normokalaemia (K >5.5 mEq/L to K ≤5.5 mEq/L) after the acute episode was significant, and inversely associated with the risk of mortality. Conclusions: Potassium levels prior to a severe hyperkalaemic event do not predict mortality. Conversely, following an episode of acute severe hyperkalaemia, serial kinetics of potassium trajectories predict the risk of death. Further evidence is needed to confirm these findings and clarify the optimal long-term management of these patients