The outcome of SARS-CoV2 infection in patients who have received a kidney allograft and are being treated with immunosuppression is unclear. We describe 20 kidney transplant recipients (median age 59 ...years inter quartile range 51-64 years, median age of transplant 13 years 9-20 years, baseline eGFR 36.5 23-47.5) with SARS-CoV2 induced pneumonia. At admission, all had immunosuppression withdrawn and were started on methylprednisolone 16 mg/day, all but one was commenced on antiviral therapy and hydroxychloroquine with doses adjusted for kidney function. At baseline, all patients presented fever but only one complained of difficulty in breathing. Half of patients showed chest radiographic evidence of bilateral infiltrates while the other half showed unilateral changes or no infiltrates. During a median follow-up of seven days, 87% experienced a radiological progression and among those 73% required escalation of oxygen therapy. Six patients developed acute kidney injury with one requiring hemodialysis. Six of 12 patients were treated with tocilizumab, a humanized monoclonal antibody to the IL-6 receptor. Overall, five kidney transplant recipients died after a median period of 15 days 15-19 from symptom onset. These preliminary findings describe a rapid clinical deterioration associated with chest radiographic deterioration and escalating oxygen requirement in renal transplant recipients with SARS-Cov2 pneumonia. Thus, in this limited cohort of long-term kidney transplant patients, SARS-CoV-2 induced pneumonia is characterized by high risk of progression and significant mortality.
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Background
In patients with end stage renal disease and atrial fibrillation (AF), undergoing chronic dialysis, direct oral agents are contraindicated and warfarin does not fully prevent embolic ...events while increasing the bleeding risk. The high hemorrhagic risk represents the main problem in this population. Aim of the study was to estimate the safety and efficacy for thromboembolic prevention of left atrial appendage (LAA) occlusion in a cohort of dialysis patients with AF and high hemorrhagic risk.
Methods
Ninety-two dialysis patients with AF who underwent LAA occlusion were recruited. For comparative purposes, two cohorts of dialysis patients with AF, one taking warfarin (oral anticoagulant therapy, OAT cohort, n = 114) and the other not taking any OAT (no-therapy cohort, n = 148) were included in the study. Primary endpoints were (1) incidence of peri-procedural complications, (2) incidence of 2-year thromboembolic and hemorrhagic events, (3) mortality at 2 years. In order to evaluate the effect of the LAA occlusion on the endpoints with respect to the OAT and No-therapy cohorts, a multivariable Cox regression model was applied adjusted for possible confounding factors.
Results
The device was successfully implanted in 100% of cases. Two major peri-procedural complications were reported. No thromboembolic events occurred at 2-year follow-up. The adjusted multivariable Cox regression model showed no difference in bleeding risk in the OAT compared to the LAA occlusion cohort in the first 3 months of follow-up HR 1.65 (95% CI 0.43–6.33), when most of patients were taking two antiplatelet drugs. In the following 21 months the bleeding incidence became higher in OAT patients HR 6.48 (95% CI 1.32–31.72). Overall mortality was greater in both the OAT HR 2.76 (95% CI 1.31–5.86) and No-Therapy HR 3.09 (95% CI 1.59–5.98) cohorts compared to LAA occlusion patients.
Conclusions
The study could open the way to a non-pharmacological option for thromboembolic protection in dialysis patients with AF and high bleeding risk.
The relationship between kidneys and anticoagulation is complex, especially after introduction of the direct oral anticoagulants (DOAC). It is recently growing evidence of an anticoagulant-related ...nephropathy (ARN), a form of acute kidney injury caused by excessive anticoagulation. The pathogenesis of kidney damage in this setting is multifactorial, and nowadays, there is no established treatment. We describe a case of ARN, admitted to our Nephrology Unit with a strong suspicion of ANCA-associated vasculitis due to gross haematuria and haemoptysis; the patient was being given dabigatran. Renal biopsy excluded ANCA-associated vasculitis and diagnosed a red blood cell cast nephropathy superimposed to an underlying IgA nephropathy. Several mechanisms are possibly responsible for kidney injury in ARN: tubular obstruction, cytotoxicity of heme-containing molecules and free iron, and activation of proinflammatory/profibrotic cytokines. Therefore, the patient was given a multilevel strategy of treatment. A combination of reversal of coagulopathy (i.e., withdrawal of dabigatran and infusion of its specific antidote) along with administration of fluids, sodium bicarbonate, steroids, and mannitol resulted in conservative management of AKI and fast recovery of renal function. This observation could suggest a prospective study aiming to find the best therapy of ARN.
Introduction:
Cast nephropathy is a prevalent cause of acute kidney injury (AKI) in patients with myeloma.
Objectives:
The aim of this study is to define the outcome of a standardized supportive ...therapy for cast nephropathy.
Patients and Methods:
Retrospective analysis of the outcome of cast nephropathy in a University hospital for a period of five years. Data analysed; serum creatinine, estimated glomerular filtration rate (eGFR; mL/min/1.73 m
2
BSA) and need for dialysis. Standardized therapy with the aim of preventing/removing tubular casts; fluid administration and mannitol to increase urine flow, sodium bicarbonate to alkalize the urine and low dose steroid to reduce peritubular inflammation. Statistical analysis: Student’s t-test or the Mann-Whitney test according to data distribution. A two-tailed
P
value <0.05 was considered statistically significant. Survival curve was drawn according to Kaplan and Meier.
Results:
Twenty-seven cases were reviewed. Upon admission, mean serum creatinine was 7.1±4.9 mg/dL and mean eGFR 6±4 mL/min/1.73 m
2
BSA; 30% of patients had oligo-anuria. Diagnosis of cast nephropathy was presumptive in 23 patients, and renal biopsy proven in four. Hemodialysis was required by 10 (37%) patients, two of whom continued dialysis after discharge. At discharge, serum creatinine was 3.7±2.5 mg/dL and eGFR 20±13 mL/min/1.73 m
2
BSA (
P
=0.002), and after a median of 3.4 months, the values were 2.9±2.1 mg/dL and 35±32 mL/min/1.73 m
2
BSA, respectively. Patient survival was 60% after 24 months.
Conclusion:
Administration of fluid, mannitol, sodium bicarbonate and low-dose steroid may improve the outcome of cast nephropathy. Despite the fact that the study has many limitations, its findings could be the base for prospective controlled trials on cast nephropathy and could be useful in those countries where the expensive extracorporeal treatments are not available.
The SARS-CoV-2 epidemic is pressuring healthcare systems worldwide. Disease outcomes in certain subgroups of patients are still scarce, and data are needed. Therefore, we describe here the experience ...of four dialysis centers of the Brescia Renal COVID Task Force. During March 2020, within an overall population of 643 hemodialysis patients, SARS-CoV-2 RNA positivity was detected in 94 (15%). At disease diagnosis, 37 of the 94 (39%) patients (group 1) were managed on an outpatient basis, whereas the remaining 57 (61%) (group 2) required hospitalization. Choices regarding management strategy were made based on disease severity. In group 1, 41% received antivirals and 76% hydroxychloroquine. Eight percent died and 5% developed acute respiratory distress syndrome (ARDS). In group 2, 79% received antivirals and 77% hydroxychloroquine. Forty two percent died and 79% developed ARDS. Overall mortality rate for the entire cohort was 29%. History of ischemic cardiac disease, fever, older age (over age 70), and dyspnea at presentation were associated with the risk of developing ARDS, whereas fever, cough and a C-reactive protein higher than 50 mg/l at disease presentation were associated with the risk of death. Thus, in our population of hemodialysis patients with SARS-CoV-2 infection, we documented a wide range of disease severity. The risk of ARDS and death is significant for patients requiring hospital admission at disease diagnosis.
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A hyperinflammatory syndrome (HIS) may cause a life-threatening acute respiratory distress syndrome (ARDS) in patients with COVID-19 pneumonia.
A prospective series of 100 consecutive patients ...admitted to the Spedali Civili University Hospital in Brescia (Italy) between March 9th and March 20th with confirmed COVID-19 pneumonia and ARDS requiring ventilatory support was analyzed to determine whether intravenous administration of tocilizumab (TCZ), a monoclonal antibody that targets the interleukin 6 (IL-6) receptor, was associated with improved outcome. Tocilizumab was administered at a dosage of 8 mg/kg by two consecutive intravenous infusions 12 h apart. A third infusion was optional based on clinical response.
The outcome measure was an improvement in acute respiratory failure assessed by means of the Brescia COVID Respiratory Severity Score (BCRSS 0 to 8, with higher scores indicating higher severity) at 24–72 h and 10 days after tocilizumab administration.
Out of 100 treated patients (88 M, 12 F; median age: 62 years), 43 received TCZ in the intensive care unit (ICU), while 57 in the general ward as no ICU beds were available. Of these 57 patients, 37 (65%) improved and suspended noninvasive ventilation (NIV) (median BCRSS: 1 IQR 0–2), 7 (12%) patients remained stable in NIV, and 13 (23%) patients worsened (10 died, 3 were admitted to ICU). Of the 43 patients treated in the ICU, 32 (74%) improved (17 of them were taken off the ventilator and were discharged to the ward), 1 (2%) remained stable (BCRSS: 5) and 10 (24%) died (all of them had BCRSS≥7 before TCZ). Overall at 10 days, the respiratory condition was improved or stabilized in 77 (77%) patients, of whom 61 showed a significant clearing of diffuse bilateral opacities on chest x-ray and 15 were discharged from the hospital. Respiratory condition worsened in 23 (23%) patients, of whom 20 (20%) died.
All the patients presented with lymphopenia and high levels of C-reactive protein (CRP), fibrinogen, ferritin and IL-6 indicating a HIS. During the 10-day follow-up, three cases of severe adverse events were recorded: two patients developed septic shock and died, one had gastrointestinal perforation requiring urgent surgery and was alive at day 10.
In conclusion, our series showed that COVID-19 pneumonia with ARDS was characterized by HIS. The response to TCZ was rapid, sustained, and associated with significant clinical improvement.
The outcome of kidney transplant patients with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection is still unclear. Here we describe the clinical characteristics, disease outcome, ...and risk factors for acute respiratory distress syndrome (ARDS) and death of a cohort of 53 kidney transplant patients with coronavirus disease 2019 (COVID‐19). Eight of 53 have been handled as outpatients because of mild disease, on average with immunosuppression reduction and the addition of hydroxychloroquine and azithromycin; no patients required admission, developed ARDS, or died. Because of severe symptoms, 45/53 required admission: this cohort has been managed with immunosuppression withdrawal, methylprednisolone 16 mg/d, hydroxychloroquine, and antiviral drugs. Dexamethasone and tocilizumab were considered in case of ARDS. About 33% of the patients developed acute kidney injury, 60% ARDS, and 33% died. In this group, thrombocytopenia was associated to ARDS whereas lymphopenia at the baseline, higher D‐dimer, and lack of C‐reactive protein reduction were associated with risk of death. In the overall population, dyspnea was associated with the risk of ARDS and age older than 60 years and dyspnea were associated with the risk of death with only a trend toward an increased risk of death for patients on tacrolimus. In conclusion, SARS‐CoV‐2 infection may have a variable outcome in renal transplant patients, with higher risk of ARDS and death in the ones requiring admission.
Findings from an Italian cohort of kidney transplant patients with COVID‐19 support heterogenous disease courses with higher risks of acute respiratory distress syndrome and death in the subgroup with severe disease.
Abstract
Background and Aims
The recent decades have witnessed significant changes in the epidemiology and clinical course of infection-related glomerulonephritis (IRGN). We analyzed the ...clinicopathological features and long-term outcome of adult patients with biopsy-proven IRGN followed in a large Italian referral centre.
Method
We included patients with biopsy-proven IRGN diagnosed from 2000 to 2018. Clinical and laboratory findings, histological features, possible risk factors and therapy were assessed for both renal and patient outcome.
Results
Forty-one patients met the inclusion criteria (male:female ratio 3:1, mean age 61±16 years). Smoke habit (47.2%), alcoholism (30.6%), and diabetes (27.5%) were the most common risk factors. The most frequently identified sites of infection were skin, lung and heart (Table 1). Staphylococci spp. accounted for 76.5% of positive cultures (Figure 1). Hypocomplementaemia emerged in 48.5% of cases. The most frequent histologic patterns were diffuse proliferative (56.0%) and membranoproliferative (29.3%) glomerulonephritis. Haemodialysis was required by 22.5% of patients at inception. Two thirds of patients developed chronic kidney disease; half of them reached end-stage renal disease (ESRD). By multivariate analysis ESRD was associated with diabetes (HR 13.7; 95% CI, 1.6-121.0; p=0.018), crescents (HR 25.2; 95% CI, 2.7-235.7; p=0.005), and interstitial fibrosis (HR 31.0; 95% CI, 3.3-287.3; p=0.003). Male gender (HR 12.7; 95% CI, 10.8-14.6; p=0.008) hypertension (HR 40.8; 95% CI, 38.6-43.1; p=0.001), gross haematuria (HR 11.8; 95% CI, 9.4-14.2; p=0.047), need for haemodialysis at onset (HR 16.3; 95% CI, 14.7-17.8; p<0.0001), and interstitial infiltrate (HR 13.3; 95% CI, 11.6-15.0; p=0.003) significantly affected survival. Corticosteroids did not affect prognosis.
Conclusion
While traditionally considered a “benign” disease with a favorable course in children, IRGN is a potentially severe disease in adults, particularly when a background of major comorbidities and older age are present. A significant proportion of patients does not recover renal function, with a remarkable risk of ESRD.
Table 1.
Sites of infection. Three patients (11.5%) presented multiple infections
N°/ TOT
%
Pneumonia
9/26
34.6
Skin infection
7/26
26.9
Endocarditis
6/26
23.1
Bone infection
3/26
11.5
Pharyngitis
1/26
3.8
Cholangitis
1/26
3.8
Prosthetic aortic graft infection
1/26
3.8
Urinary tract infection
1/26
3.8
Granulomatous rhinitis overinfection
1/26
3.8
Figure 1.
Results from microbiological tests.
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