Immunosuppression minimization in kidney transplant recipients hospitalized for COVID-19

Background. Immunosuppressed patients such as kidney transplant recipients (KTs) have increased mortality risk in the setting of coronavirus disease 2019 (COVID-19). The role and management of chronic immunosuppressive therapies during COVID-19 must be characterized. Methods. Herein, we report the follow-up of a cohort of 47 KTs admitted at two Spanish Kidney Transplant Units, who survived COVID-19. The impact of the management of immunosuppression during COVID-19 on graft function and immunologic events was evaluated. Results. At least one immunosuppressive agent was withdrawn in 83% of patients, with antimetabolites being the most frequent. Steroids were generally not stopped and the dose was even increased in 15% of patients as part of the treatment of COVID-19. Although immunosuppressive drugs were suspended during a median time of 17 days, no rejection episodes or de novo donorspecific antibodies were observed up to 3 months after discharge, and no significant changes occurred in calculated panel reactive antibodies. Acute graft dysfunction was common (55%) and the severity was related to tacrolimus trough levels, which were higher in patients receiving antivirals. At the end of follow-up, all patients recovered baseline kidney function. Conclusions. Our observational study suggests that immunosuppression in KTs hospitalized due to COVID-19 could be safely minimized

Eficacia de dos tecnicas de bloqueo del nervio dentario inferior "Técnica de los tres tiempos y técnica de Akinosi" en exodoncias de primeras y segundas molares inferiores en las Clínicas Odontológicas del Centro de Salud Pedro Altamirano, Managua-Nicaragua en el periodo comprendido enero marzo 2010

Tesis (Dr. Cirujano Dentista)-Universidad Nacional Autónoma de Nicaragua, León.UNAN-Leó

Novel Insights in the Physiopathology and Management of Obesity-Related Kidney Disease

Obesity is recognized as an independent risk factor for the development of kidney disease, which has led to the designation of obesity-related glomerulopathy (ORG). Common renal features observed in this condition include glomerular hypertrophy, glomerulosclerosis, haemodynamic changes and glomerular filtration barrier defects. Additionally, and although less studied, obesity-related kidney disease also involves alterations in renal tubules, including tubule hypertrophy, lipid deposition and tubulointerstitial fibrosis. Although not completely understood, the harmful effects of obesity on the kidney may be mediated by different mechanisms, with alterations in adipose tissue probably playing an important role. An increase in visceral adipose tissue has classically been associated with the development of kidney damage, however, recent studies point to adipose tissue surrounding the kidney, and specifically to the fat within the renal sinus, as potentially involved in the development of ORG. In addition, new strategies for the treatment of patients with obesity-related kidney disease are focusing on the management of obesity. In this regard, some non-invasive options, such as glucagon-like peptide-1 (GLP-1) receptor agonists or sodium–glucose cotransporter-2 (SGLT2) inhibitors, are being considered for application in the clinic, not only for patients with diabetic kidney disease but as a novel pharmacological strategy for patients with ORG. In addition, bariatric surgery stands as one of the most effective options, not only for weight loss but also for the improvement of kidney outcomes in obese patients with chronic kidney disease

Table_1_Rational use of eculizumab in secondary atypical hemolytic uremic syndrome.docx

BackgroundSecondary atypical hemolytic uremic syndrome (secondary aHUS) is a heterogeneous group of thrombotic microangiopathies (TMA) associated with various underlying conditions. Unlike primary aHUS, there is still no hard evidence on the efficacy of complement blockade in secondary aHUS, since the two main series that investigated this subject showed discrepant results. Our work aims to reassess the efficacy of eculizumab in treating secondary aHUS.MethodsObservational, retrospective, single-center study, in which we analyzed the hematological and renal evolution of 23 patients diagnosed with secondary aHUS who received treatment with eculizumab and compared them with a control cohort of 14 patients. Complete renal response was defined as the recovery of renal function before the event, partial renal response as a recovery of 50% of lost glomerular filtration rate, and hematological response as normalization of hemoglobin and platelets.ResultsWe found no statistically significant differences in baseline characteristics or disease severity between both groups. After a median of 5 doses of eculizumab, the group of patients who received complement blockade presented a significant difference in renal response (complete in 52.3% of patients and partial in 23.8%) compared to the control cohort (complete response 14.3% and partial of 14.3%). Rates of hematological remission were similar in both groups (90.9% in the eculizumab cohort and 85.7% in the control cohort).ConclusionEarly and short-term use of eculizumab in patients with secondary aHUS could be an effective and safe therapeutic option, assuring better renal recovery compared to patients who do not receive complement blockade.</p

Hemodialysis-Associated Immune Dysregulation in SARS-CoV-2-Infected End-Stage Renal Disease Patients

Patients on hemodialysis show dysregulated immunity, basal hyperinflammation and a marked vulnerability to COVID-19. We evaluated the immune profile in COVID-19 hemodialysis patients and the changes associated with clinical deterioration after the hemodialysis session. Recruited patients included eight hemodialysis subjects with active, PCR-confirmed SARS-CoV-2 infection, five uninfected hemodialysis patients and five healthy controls. In SARS-CoV-2-infected hemodialysis patients TNF-α, IL-6 and IL-8 were particularly increased. Lymphopenia was mostly due to reduction in CD4+ T, B and central memory CD8+ T cells. There was a predominance of classical and intermediate monocytes with reduced HLA-DR expression and enhanced production of pro-inflammatory molecules. Immune parameters were analysed pre- and post-hemodialysis in three patients with COVID-19 symptoms worsening after the hemodialysis session. There was a higher than 2.5-fold increase in GM-CSF, IFN-γ, IL-1β, IL-2, IL-6, IL-17A and IL-21 in serum, and augmentation of monocytes-derived TNF-α, IL-1β and IL-8 and CXCL10 (p < 0.05). In conclusion, COVID-19 in hemodialysis patients associates with alteration of lymphocyte subsets, increasing of pro-inflammatory cytokines and monocyte activation. The observed worsening during the hemodialysis session in some patients was accompanied by augmentation of particular inflammatory cytokines, which might suggest biomarkers and therapeutic targets to prevent or mitigate the hemodialysis-related deterioration during SARS-CoV-2 infection

Galectin-3 and its relation with the risk of mortality and repeated readmissions due to cardiovascular causes.

<p>Gal-3 was modelled linearly with the gradient of risk, and centered at a threshold of risk of 17.8 ng/ml. A) Gal-3 and the risk of cardiovascular mortality in patients with CA125 >67 U/ml. B) Gal-3 and the risk of cardiovascular mortality in patients with CA125 ≤67 U/ml. C) Gal-3 and the risk of cardiovascular rehospitalization in patients with CA125 >67 U/ml. D) Gal-3 and the risk of cardiovascular rehospitalization in patients with CA125 ≤67 U/ml. Estimates for cardiovascular mortality adjusted for age, etiology, prior admission for acute heart failure, left ventricular ejection fraction<50%, glomerular filtration rate, NT-pro brain natriuretic peptide, treatment with beta blocker and treatment with angiotensin converting enzyme inhibitor. Estimates for cardiovascular rehospitalization adjusted for age, etiology, prior admission for acute heart failure, left ventricular ejection fraction, pleural effusion, prior stroke, prior myocardial infarction, implantable cardiac defibrillator, blood urea nitrogen, NT-pro brain natriuretic peptide, and treatment with beta blocker. Gal-3: galectin-3; CA125: antigen carbohydrate 125.</p

IgA Nephropathy Is the Most Common Underlying Disease in Patients With Anticoagulant-Related Nephropathy.

Anticoagulant-related nephropathy (ARN) is a relatively novel recognized entity characterized by hematuria-associated acute kidney injury (AKI) in the context of overanticoagulation. Preexisting or underlying kidney disease seems to be a predisposing factor; however, few studies have described histologic findings in patients with ARN. We aimed to evaluate underlying kidney pathology in patients on oral anticoagulation who presented an episode of AKI with hematuria in whom a kidney biopsy was performed. Retrospective observational multicenter case study in patients treated with oral anticoagulants who developed macroscopic or intense hematuria followed by AKI. Only patients with available kidney biopsy specimens were included. Histologic findings and clinical data throughout follow-up were analyzed. A total of 26 patients were included with a median age of 75 years (62-80) and a follow-up period of 10.1 months. Of the patients, 80% were male, and most cases (92%) were on anticoagulation with vitamin K antagonists (VKAs). At admission, median serum creatinine (SCr) level was 4.2 mg/dl (2.8-8.2), median international normalized ratio (INR) 2.4 (1.5-3.4), and 11 patients (42%) required acute dialysis during hospitalization. Kidney biopsy results revealed that all patients except 1 had an underlying nephropathy: IgA nephropathy (IgAN) in 19, probable IgAN in 1, diabetic nephropathy in 3, nephrosclerosis in 1, and idiopathic nodular glomerulosclerosis in 1. At 12 weeks after discharge, only 6 subjects (24%) attained complete kidney recovery whereas 7 (28%) remained on chronic dialysis. IgAN was the most common underlying kidney disease in our biopsy-proven series of ARN, in which a significant percentage of patients did not achieve kidney function recovery

CA125/Gal-3 categories and risk of adverse events.

<p>CA125: carbohydrate antigen 125; Gal-3: galectin-3; HR; hazard ratio; IRR: incident rate ratio.</p><p>CA125/Gal-3 categories and risk of adverse events.</p

Galectin-3 and its relation with the risk of all-cause mortality expressed as adjusted hazard ratios.

<p>Gal-3 was modelled linearly with the gradient of risk, and centred at a threshold of risk of 17.8 ng/ml. A) Gal-3 and the risk of all-cause mortality in patients with CA125 >67 U/ml; B) Gal-3 and the risk of all-cause mortality in patients with CA125 ≤67 U/ml. CA125: antigen carbohydrate 125; Gal-3: galectin-3.</p