SARS-CoV-2-Spike Antibody and T-Cell Responses Elicited by a Homologous Third mRNA COVID-19 Dose in Hemodialysis and Kidney Transplant Recipients.

The effect of a third vaccine dose (3D) of homologous mRNA vaccine on blood levels of SARS-CoV-2-receptor binding domain (RBD)-total antibodies was assessed in 40 hemodialysis patients (HD) and 21 kidney transplant recipients (KTR) at a median of 46 days after 3D. Anti-RBD antibodies were detected in 39/40 HD and 19/21 KTR. Overall, 3D boosted anti-RBD antibody levels (median: 58-fold increase). Neutralizing antibodies (NtAb) against the Wuhan-Hu-1, Delta, and Omicron variants were detected in 14, 13, and 11 out of 14 HD patients, and in 5, 5, and 4 out of 8 KTR patients, respectively. The median fold increase in NtAb titers in HD patients was 77, 28, and 5 and 56, 37, and 9 in KTR patients for each respective variant. SARS-CoV-2-S S-IFN-γ-producing CD8+ and CD4+ T-cell responses were detected in the majority of HD (35 and 36/37, respectively) and all KTR (16/16) patients at 3D. Overall, the administration of 3D boosted T-cell levels in both population groups. In conclusion, a homologous mRNA COVID-19 vaccine 3D exerts a booster effect on anti-RBD antibodies, NtAb binding to Wuhan-Hu-1, Delta, and Omicron variants, and SARS-CoV-2-S-IFN-γ-producing T cells in both HD and KTR patients. The magnitude of the effect was more marked in HD than KTR patients.

Renal Histologic Findings in Necropsies of Type 2 Diabetes Mellitus Patients.

Background: Very few studies have analyzed early histologic lesions of diabetic nephropathy (DN) in patients without signs of clinical involvement (microalbuminuria). In this study, we analyzed renal histologic lesions in necropsies of diabetic patients with or without previous signs of DN. Methods: Histological material was analyzed from 21 autopsies of type 2 diabetes mellitus (T2DM) patients (9 with albuminuria and 12 without albuminuria) and 4 controls. Histologic lesions were evaluated according to the Tervaert classification. Results: Kidneys of diabetic patients presented significantly higher scores in most histologic indices analyzed (glomerular basal membrane thickening, mild and severe mesangial expansion, nodular sclerosis, interstitial fibrosis, and tubular atrophy) than in nondiabetic controls (p < 0.01 in all cases). In contrast, no significant differences were detected between histologic scores when comparing the 21 diabetic patients with and without albuminuria. A significant percentage of cases without albuminuria showed moderate to severe histologic lesions, particularly severe mesangial expansion and severe glomerular vascular lesions. No significant differences were found in age, blood pressure, diabetes vintage, BMI, HbA1c, cholesterol, triglycerides, or treatments between the two (albuminuric vs. nonalbuminuric) T2DM patient groups. Conclusions: Our data suggest that histologic lesions of DN are present in the early stages of the disease, even without albuminuria presence. More precise and earlier metabolic control is recommended in T2DM, and monitoring of risk factors can play a role in DN development.

Dynamics of SARS-CoV-2-Spike-reactive antibody and T-cell responses in chronic kidney disease patients within 3 months after COVID-19 full vaccination.

Background: Little is known regarding the dynamics of antibody and T-cell responses in chronic kidney disease (CKD) following coronavirus disease 2019 (COVID-19) vaccination. Methods: Prospective observational cohort study including 144 participants on haemodialysis (HD) (n = 52) or peritoneal dialysis (PD) (n = 14), those undergoing kidney transplantation (KT) (n = 30) or those with advanced CKD (ACKD) not on dialysis and healthy controls (n = 18). Anti-Spike (S) antibody and T-cell responses were assessed at 15 days (15D) and 3 months (3M) after complete vaccination schedule. HD, PD and KT patients received mRNA vaccines (mRNA-123 and BNT162b2). Most ACKD patients received BNT162b2 (n = 23), or Ad26.COV.2.S (4). Most controls received BNT162b2 (n = 12), or Ad26.COV.2.S (n = 5). Results: Anti-S antibodies at 15D and 3M were detectable in 95% (48/50)/98% (49/50) of HD patients, 93% (13/14)/100% of PD patients, 67% (17/26)/75% (21/28) of KT patients and 96% (25/26)/100% (24/24) of ACKD patients. Rates for healthy controls were 81% (13/16)/100% (17/17). Previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2-S) infection was documented in four (7.7%) HD patients, two (14.3%) PD patients, two (6.7%) KT patients, one (5.55%) healthy control and in no ACKD patient. Antibody levels decreased at 3M in HD (P = .04), PD (P = .008) and ACKD patients (P = .0009). In KT patients, levels increased (P = .04) between 15D and 3M, although they were low at both time points.T-cell responses were detected in HD patients in 37 (80%) at baseline, 35 (70%) at 15D and 41 (91%) at 3M. In PD patients, T-cell responses appeared in 8 (67%) at baseline, 13 (93%) at 15D and 9 (100%) at 3M. In KT patients, T-cell responses were detected in 12 (41%) at baseline, 22 (84%) at 15D and 25 (96%) at 3M. In ACKD patients, T-cell responses were detected in 13 (46%) at baseline, 20 (80%) at 15D and 17 (89%) at 3M. None of healthy controls showed T-cell response at baseline, 10 (67%) at 15D and 8 (89%) at 3M. Conclusions: Most HD, PD and ACKD patients develop SARS-CoV-2-S antibody responses comparable to that of healthy controls, in contrast to KT recipients. Antibody waning at 3M was faster in HD, PD and ACKD patients. No differences in SARS-CoV-2 T-cell immunity responses were noticed across study groups.

Albuminuria-Lowering Effect of Dapagliflozin, Eplerenone, and Their Combination in Patients with Chronic Kidney Disease: A Randomized Crossover Clinical Trial.

BACKGROUND: Sodium glucose cotransporter 2 (SGLT2) inhibitors and mineralocorticoid receptor antagonists (MRAs) reduce the urinary albumin-to-creatinine ratio (UACR) and confer kidney and cardiovascular protection in patients with CKD. We assessed efficacy and safety of the SGLT2 inhibitor dapagliflozin and MRA eplerenone alone and in combination in patients with CKD. METHODS: We conducted a randomized open-label crossover trial in patients with urinary albumin excretion ≥100 mg/24 hr, eGFR 30-90 ml/min per 1.73 m2, who had been receiving maximum tolerated stable doses of an ACE inhibitor (ACEi) or angiotensin receptor blocker (ARB). Patients were assigned to 4-week treatment periods with dapagliflozin 10 mg/day, eplerenone 50 mg/day, or their combination in random order, separated by 4-week washout periods. Primary outcome was the correlation in UACR changes between treatments. Secondary outcome was the percent change in 24-hour UACR from baseline. RESULTS: Of 57 patients screened, 46 were randomly assigned (mean eGFR, 58.1 ml/min per 1.73 m2; median UACR, 401 mg/g) to the three groups. Mean percentage change from baseline in UACR after 4 weeks of treatment with dapagliflozin, eplerenone, and dapagliflozin-eplerenone was -19.6% (95% confidence interval [CI], -34.3 to -1.5), -33.7% (95% CI, -46.1 to -18.5), and -53% (95% CI, -61.7 to -42.4; P<0.001 versus dapagliflozin; P=0.01 versus eplerenone). UACR change during dapagliflozin or eplerenone treatment did not correlate with UACR change during dapagliflozin-eplerenone (r=-0.13; P=0.47; r=-0.08; P=0.66, respectively). Hyperkalemia was more frequently reported with eplerenone (n=8; 17.4%) compared with dapagliflozin (n=0; 0%) or dapagliflozin-eplerenone (n=2; 4.3%; P between-groups=0.003). CONCLUSIONS: Albuminuria changes in response to dapagliflozin and eplerenone did not correlate, supporting systematic rotation of these therapies to optimize treatment. Combining dapagliflozin with eplerenone resulted in a robust additive UACR-lowering effect. A larger trial in this population is required to confirm long-term efficacy and safety of combined SGLT2 inhibitor and MRA treatment. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: European Union Clinical Trials Register, EU 2017-004641-25.

COVID-19 Vaccination Improved Psychological Distress (Anxiety and Depression Scores) in Chronic Kidney Disease Patients: A Prospective Study.

The purpose of the study is to analyze the impact of vaccination against SARS-CoV-2 on anxiety and depression scores in patients with different modalities of chronic kidney disease. One hundred and seventeen renal patients (50 hemodialysis patients, 13 peritoneal dialysis patients, 32 kidney transplants, and 22 advanced chronic kidney disease patients at pre-dialysis care) were evaluated for depression, anxiety, health-related quality of life (HRQOL), and perceived fears and resources with standardized (Hospital Anxiety and Depression Scale (HADS)) and self-reported questionnaires. The measure points were before vaccination and 15 days after vaccination. The main finding of the study was that there was a decrease in the global mean of normal scores for anxiety and depression symptoms in chronic kidney disease patients post-vaccination. We did not find statistically significant differences in depression or anxiety scores, nor any HRQOL differences between the treatment groups. The three main fears reported by the participants at baseline were those of adverse effects, not getting the vaccine, and lack of information. These findings highlight the potential interest of assessing psychological variables related to the impact of vaccination against SARS-CoV-2. New studies will be required to assess the impact of comprehensive vaccine coverage and its psychological impact.

Long-term mortality and trajectory of potassium measurements following an episode of acute severe hyperkalaemia.

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.

Oxidative Stress in Non-Dialysis-Dependent Chronic Kidney Disease Patients.

BACKGROUND: Cardiovascular complications are the leading cause of morbidity and mortality at any stage of chronic kidney disease (CKD). Moreover, the high rate of cardiovascular mortality observed in these patients is associated with an accelerated atherosclerosis process that likely starts at the early stages of CKD. Thus, traditional and non-traditional or uremic-related factors represent a link between CKD and cardiovascular risk. Among non-conventional risk factors, particular focus has been placed on anaemia, mineral and bone disorders, inflammation, malnutrition and oxidative stress and, in this regard, connections have been reported between oxidative stress and cardiovascular disease in dialysis patients. METHODS: We evaluated the oxidation process in different molecular lines (proteins, lipids and genetic material) in 155 non-dialysis patients at different stages of CKD and 45 healthy controls. To assess oxidative stress status, we analyzed oxidized glutathione (GSSG), reduced glutathione (GSH) and the oxidized/reduced glutathione ratio (GSSG/GSH) and other oxidation indicators, including malondialdehyde (MDA) and 8-oxo-2'-deoxyguanosine (8-oxo-dG). RESULTS: An active grade of oxidative stress was found from the early stages of CKD onwards, which affected all of the molecular lines studied. We observed a heightened oxidative state (indicated by a higher level of oxidized molecules together with decreased levels of antioxidant molecules) as kidney function declined. Furthermore, oxidative stress-related alterations were significantly greater in CKD patients than in the control group. CONCLUSIONS: CKD patients exhibit significantly higher oxidative stress than healthy individuals, and these alterations intensify as eGFR declines, showing significant differences between CKD stages. Thus, future research is warranted to provide clearer results in this area.

SARS-CoV-2 vs. Hepatitis Virus Infection Risk in the Hemodialysis Population: What Should We Expect?

Since the dramatic rise of the coronavirus infection disease 2019 (COVID-19) pandemic, patients receiving dialysis have emerged as especially susceptible to this infection because of their impaired immunologic state, chronic inflammation and the high incidence of comorbidities. Although several strategies have thus been implemented to minimize the risk of transmission and acquisition in this population worldwide, the reported severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seroprevalence varies across studies but is higher than in the general population. On the contrary, the screening for hepatitis viruses (HBV and HCV) has seen significant improvements in recent years, with vaccination in the case of HBV and effective viral infection treatment for HCV. In this sense, a universal SARS-CoV-2 screening and contact precaution appear to be effective in preventing further transmission. Finally, regarding the progress, an international consensus with updated protocols that prioritize between old and new indicators would seem a reasonable tool to address these unexpended changes for the nephrology community.

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.

Cardiorenal Fat: A Cardiovascular Risk Factor With Implications in Chronic Kidney Disease.

There is a growing interest in the potential role of adipose tissues in cardiac and renal pathophysiology, and determining the mechanisms by which fat compartments around the heart and kidneys influence cardiovascular disease is of clinical importance in both general and high-risk populations. Epicardial fat and perirenal fat have been associated with adverse outcomes in chronic kidney disease (CKD) patients. Epicardial fat is a rich source of free fatty acids and is capable of secreting inflammatory and pro-atherogenic cytokines that promote atherosclerosis through a local paracrine effect. Recent evidence has demonstrated that perirenal fat has a closer correlation with kidney diseases than other visceral fat deposits in obesity or metabolic disturbances. Moreover, perirenal fat has been reported as an independent risk factor for CKD progression and even associated with cardiorenal dysfunction. Accordingly, these forms of organ-specific fat deposits may act as a connecter between vascular and cardiorenal disease. This review explores the possible links between epicardial and perirenal fat and its significant role as a modulator of cardiorenal dysfunction in CKD patients.

Cardiovascular risk factors and the impact on prognosis in patients with chronic kidney disease secondary to autosomal dominant polycystic kidney disease.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is the most frequent hereditary renal disease. There is an increased rate of cardiovascular disease (CVD) in ADPKD. In this study, we evaluate the prevalence of cardiovascular risk factors, the achievement rates for treatment goals and cardiovascular events (CVE) in ADPKD and their relations with asymptomatic CVD in CKD from other etiologies (CKDoe) and controls. METHODS: We evaluated 2445 CKD patients (2010-2012). The information collected was: clinical, anthropometric and analytical parameters, treatments and CVD evaluation (intima-media thickness (IMT), atheromatous plaque presence and ankle-brachial index (ABI)). Laboratory, vital status, CVE and hospitalizations were collected for 4 years. RESULTS: ADPKD patients had a worse renal function and worst achievement of blood pressure, higher parathormone levels but lower proteinuria compared to CKDoe. ADPKD patients presented lower IMT values than other groups, however, an intermediate rate of pathologic ABI and atheromatous plaque was present. More than half of the patients received statins, achieving LDL-c levels < 100 only in 50 and 39.8% of them (ADPKD and CKDoe respectively). The number of CVE during the follow-up period was low. In adjusted Cox regression model, ADPDK had the lowest occurrence of CVE of all three groups (HR:0.422, 95%CI 0.221-0.808, p = 0.009). CONCLUSION: ADPKD patients show intermediate control rates of CVD. A better control of CVD risk seems to be related with a lower load of CVD compared to other groups, which may lead in the long term to a better prognosis. Further investigation is necessary to determine cardiovascular prognosis in ADPKD.

Iron replacement therapy in the management of anaemia in non-dialysis chronic renal failure patients: Perspective of the Spanish Nephrology Society Anaemia Group. / Ferroterapia en el manejo de la anemia en la enfermedad renal crónica no en diálisis: perspectiva del grupo de anemia de la S.E.N.

This work presents an update on the management of iron deficiency in patients with chronic renal failure (CRF), either with or without anaemia. A review is made of the recommendations of the guidelines for the treatment of iron deficiency in CRF. It also presents new studies on iron deficiency in patients with CRF, as well as new findings about iron deficiency and its impact on clinical outcomes. Anaemia is a common complication of CRF, and is associated with a decrease in the quality of life of the patients, as well as an increase in morbidity and mortality. Iron deficiency (absolute or functional) is common in non-dialysis chronic renal failure patients, and may cause anaemia or a low response to erythropoiesis-stimulating agents. For this reason, the clinical guidelines for the treatment of the anaemia in Nephrology advise the correction of the deficiency in the presence of anaemia. Iron replacement therapy is indicated in patients with CRF and anaemia (Hb < 12 g/dL) in accordance with the guidelines. There is no unanimity in the indication of iron replacement therapy in patients with Hb>12 g/dL, regardless of whether they have an absolute or functional iron deficiency. Intravenous iron replacement therapy is safe, more efficient and rapid than oral therapy for achieving an increase haemoglobin levels and reducing the dose of erythropoiesis-stimulating agents. For the administration of intravenous iron in non-dialysis chronic renal failure patients a strategy of high doses and low frequency would be preferred on being more convenient for the patient, better conserving of the venous tree, and on being safe and cost-effective. Iron plays an essential role in energy metabolism and other body functions beyond the synthesis of haemoglobin synthesis, for which the iron deficiency, even in the absence of anaemia, could have a harmful effect in patients with CRF. The correction of the iron deficiency, in the absence of anaemia is associated with functional improvement in patients with heart failure, and in muscle function or fatigue in patients without CRF. Despite the evidence of benefits in the correction of iron deficiency in patients with CRF, more studies are required to evaluate the impact of the correction of the iron deficiency in the absence of anaemia on morbidity and mortality, quality of life and physical capacity, as well as the long-term effect of oral and intravenous iron replacement therapy in this population.

Finerenone: A Potential Treatment for Patients with Chronic Kidney Disease and Type 2 Diabetes Mellitus.

Type 2 diabetes mellitus (T2DM) affects an estimated 463 million people worldwide, equivalent to 1 in 11 adults. Moreover, the rapid growth of this disease has resulted in a high incidence of diabetic kidney disease (DKD), which, together with hypertension, is the main cause of chronic kidney disease (CKD). Hyperglycaemia, low-grade inflammation, altered lipid metabolism and hyperactivation of the renin-angiotensin-aldosterone system (RAAS) seem to be interrelated mechanisms contributing to both T2DM and microvascular complications. The introduction of drugs such as sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide 1 receptor agonists has improved the ability to slow the progression of DKD, and has also demonstrated benefits in cardiovascular disease. Beyond the effects of these novel antidiabetic drugs, a body of evidence suggests that the overactivation of the mineralocorticoid receptor also contributes to CKD progression. Moreover, new and ongoing trials have demonstrated that the selective nonsteroidal mineralocorticoid receptor antagonist (MRA) finerenone improves the risk of CKD progression and cardiovascular events in patients with CKD and T2DM and optimized RAAS blockade. We review the rationale for the development and use of MRA drugs to slow CKD progression in patients with DKD, as well as other pleiotropic effects, and highlight the warnings associated with these agents.

Iron replacement therapy in the management of anaemia in non-dialysis Chronic kidney disease patients: Perspective of the Spanish Nephrology Society Anaemia Group.

This work presents an update on the management of iron deficiency in patients with chronic kidney disease (CKD), either with or without anaemia. A review is made of the recommendations of the guidelines for the treatment of iron deficiency in CKD. It also presents new studies on iron deficiency in patients with CKD, as well as new findings about iron therapy and its impact on clinical outcomes. Anaemia is a common complication of CRF, and is associated with a decrease in the quality of life of the patients, as well as an increase in morbidity and mortality. Iron deficiency (absolute or functional) is common in non-dialysis chronic kidney disease patients, and may cause anaemia or a low response to erythropoiesis-stimulating agents. For this reason, the clinical guidelines for the treatment of the anaemia in Nephrology indicate the correction of the deficiency in the presence of anaemia. Iron replacement therapy is indicated in patients with CKD and anaemia (Hb < 12 g/dl) in accordance with the guidelines. There is no unanimity in the indication of iron replacement therapy in patients with Hb > 12 g/dl, regardless of whether they have an absolute or functional iron deficiency. Intravenous iron replacement therapy is safe, more efficient and rapid than oral therapy for achieving an increase haemoglobin lels and reducing the dose of erythropoiesis-stimulating agents. For the administration of intravenous iron in non-dialysis chronic renal failure patients a strategy of high doses and low frequency would be preferred on being more convenient for the patient, preserves better the venous capital, and is safe and cost-effective. Iron plays an essential role in energy metabolism and other body functions beyond the synthesis of haemoglobin, for which the iron deficiency, even in the absence of anaemia, could have harmful effects in patients with CKD. The correction of the iron deficiency, in the absence of anaemia is associated with functional improvement in patients with heart failure, and in muscle function or fatigue in patients without CKD. Despite the evidence of benefits in the correction of iron deficiency in patients with CKD, more studies are required to evaluate the impact of the correction of the iron deficiency in the absence of anaemia on morbidity and mortality, quality of life and physical capacity, as well as the long-term effect of oral and intravenous iron replacement therapy in this population.

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.

Prevalence of Vertebral Fractures and Their Prognostic Significance in the Survival in Patients with Chronic Kidney Disease Stages 3‒5 Not on Dialysis.

Background: The prevalence of vertebral fractures (VF) and their association with clinical risk factors and outcomes are poorly documented in chronic kidney disease (CKD) cohorts. The aim of the study was to evaluate the prevalence of VF in patients with non-dialysis dependent CKD (NDD-CKD), their value in predicting mortality and its correlation with parameters of bone mineral metabolism and vascular calcification. Materials and Methods: 612 NDD 3‒5 stage CKD patients participating in the OSERCE-2 study, a prospective, multicenter, cohort study, were prospectively evaluated and categorized into two groups according to presence or absence of VF at enrollment. VF were assessed with lateral radiographs and Genant semi-quantitative method was applied. Three radiologists specialized in musculoskeletal radiology performed consensual reading of individual images obtained using a Raim DICOM Viewer and a Canon EOS 350 camera to measure with Java Image software in those who had traditional acetate X-ray. Factors related to VF were assessed by logistic regression analysis. Association between VF and death over a 3-year follow-up was assessed by Kaplan-Meier survival curves and Cox-proportional hazard models. Results: VF were detected in 110 patients (18%). Serum phosphate levels (OR 0.719, 95% CI 0.532 to 0.972, p = 0.032), ankle-brachial index < 0.9 (OR 1.694, 95% CI 1.056‒2.717, p = 0.029) and treatment with bisphosphonates (OR 5.636, 95% CI 1.876‒16.930, p = 0.002) were independently related to the presence of VF. After a median follow-up of 35 months (IQR: 17‒37 months), 62 patients (10%) died. The causes of death were cardiovascular (n = 21, 34%) and infectious (n = 11, 18%). In the crude analysis, fractured patients group had poorer survival (log-rank test, p = 0.02). After multivariate adjustment for age, MDRD, albumin, diabetes mellitus, comorbidity, Adragao Score > 3 and serum phosphate, the presence of VF (HR 1.983, 95% CI 1.009‒3.898, p = 0.047) were an independent predictor of all-cause mortality. Conclusions: In our study 18% of patients with NDD-CKD have VF. Factors associated with VF were age, low serum phosphate levels and peripheral vascular disease. The presence of VF was an independent risk factor for mortality in stages 3‒5 NDD-CKD patients. Clinical trials are needed to confirm whether this relationship is causal and reversible with treatment for osteoporosis.

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.

Epicardial Adipose Tissue, Adiponectin and Leptin: A Potential Source of Cardiovascular Risk in Chronic Kidney Disease.

The importance of cardiometabolic factors in the inception and progression of atherosclerotic cardiovascular disease is increasingly being recognized. Beyond diabetes mellitus and metabolic syndrome, other factors may be responsible in patients with chronic kidney disease (CKD) for the high prevalence of cardiovascular disease, which is estimated to be 5- to 20-fold higher than in the general population. Although undefined uremic toxins are often blamed for part of the increased risk, visceral adipose tissue, and in particular epicardial adipose tissue (EAT), have been the focus of intense research in the past two decades. In fact, several lines of evidence suggest their involvement in atherosclerosis development and its complications. EAT may promote atherosclerosis through paracrine and endocrine pathways exerted via the secretion of adipocytokines such as adiponectin and leptin. In this article we review the current knowledge of the impact of EAT on cardiovascular outcomes in the general population and in patients with CKD. Special reference will be made to adiponectin and leptin as possible mediators of the increased cardiovascular risk linked with EAT.