Intravenous administration of radiographic contrast agents is an important cause of acute renal failure, accounting for one third of the cases of hospital-acquired acute renal failure in patients with native kidneys. The safety of intravenous contrast has not been studied in renal allograft recipients since the availability of cyclosporine as a maintenance immunosuppressive therapy. As patients with renal transplantation may be at a higher risk of contrast-induced nephrotoxicity (CIN) due to concomitant use of cyclosporine and higher prevalence of diabetes and renal insufficiency, we retrospectively studied development of CIN in these patients.We identified 44 patients (1988 1997) with functioning renal allograft who underwent different intravenous or intraarterial contrast studies (ICS). Pre- and post-ICS renal function tests were done in 35 of these patients. The following were the various ICS done in these patients: coronary angiogram (6), CT scan with intravenous contrast ( 11), angiogram for evaluation of peripheral vascular disease (11), allograft angiogram with angioplasty (5), pulmonary angiogram (1) and intravenous pyelogram (1). The mean age of the patients was 42 +/- 2.1 years and the mean serum creatinine was 2.3 +/- 0.25 mg/dl (mean +/- SEM). Fourty percent of patients (14 of 35) had diabetes, and 25.7% (9 of 35) had chronic rejection. Ninety four percent (33 of 35) of the patients were taking cyclosporine at the time of ICS.Nine patients had > or = 25% increase in serum creatinine from baseline after ICS. Two of these patients were excluded from the analysis as renal functions in these patients had deteriorated prior to ICS and renal failure was attributed to sepsis. Of the remaining 7 patients, 5 had diabetes and 2 had chronic rejection. Only 4 of these 7 patients with CIN received prophylaxis (I/V hydration) prior to ICS. The baseline serum creatinines were not different in patients who had no change in renal function to those who developed CIN (1.97 +/- 0.20 vs 1.54 +/- 0.17 mg/dl, p = 1.5, mean +/- SEM). More than 50% increase in baseline serum creatinine was seen in only 3 of these 7 patients, 2 of these patients had diabetes and third had chronic rejection and congestive heart failure. None of these patients received prophylaxis for CIN. Dialysis was not required in any patient. Three patients also had a > 25% decrease in baseline serum creatinine after ICS, and all of them had allograft angiography with angioplasty for renal artery stenosis.In our retrospective study, the incidence of CIN in renal allograft recipients applying a broader classification of > or = 25% increase in baseline serum creatinine was 21.2% (7 of 33 patients). The incidence of CIN was lower 15.3% (4 of 26) in patients who received intravenous hydration compared to 42.8% (3 of 7) in patients who received no prophylaxis prior to ICS.
Background: Bivalirudin is a direct thrombin inhibitor (DTI), used with antiplatelets during percutaneous coronary intervention (PCI).1 A rare, but potentially fatal complication of antithrombotic therapy is diffuse alveolar hemorrhage (DAH).Aims: We report a case of DAH secondary to bivalirudin.Methods: A 79-year-old hypertensive woman underwent PCI to the ramus and left circumflex coronary arteries for an acute myocardial infarction.She received aspirin, clopidogrel, and bivalirudin at a dose of 1.75 mg/kg/hr which was continued for 4 hours.Her pulmonary capillary wedge pressure (PCWP) was elevated at 35 mmHg.She developed hemoptysis and hypoxic respiratory failure requiring intubation.A chest computed tomography (CT) scan revealed multilobular opacities consistent with hemorrhage (Figure 1).Bivalirudin was discontinued and she improved, with extubation 24 hours later.
Summary. The impact of hepatitis C virus (HCV) and other comorbid conditions upon survival is not well quantified in patients on dialysis. We identified HCV‐infected and uninfected persons in the USRDS using claims data in 1997–1998 and followed until September 22, 2002 or death. We used Gray's time‐varying coefficients model to examine factors associated with survival. Subjects with a renal transplant were excluded. A total of 5737 HCV‐infected and 11 228 HCV‐uninfected persons were identified. HCV‐infected subjects were younger (mean age 57.8 vs 65.3 years), more likely to be male (57.6% vs 49.6%) and black (54.0% vs 36.4%). They were more likely to have a diagnosis of drug (16.5% vs 4.6%) and alcohol use (14.0% vs 3.1%), and to be human immunodeficiency virus (HIV) co‐infected (7.4% vs 1.8%) (all comparisons, P < 0.0005). In an adjusted Gray's time‐varying coefficient model, HCV was associated with an increased risk of mortality ( P < 0.0005). The hazards were highest at the time of HCV diagnosis and decreased to a stable level 2 years after diagnosis. Other factors associated with increased risk of mortality were ( P < 0.0005 unless stated) HIV coinfection; diagnosis of drug use ( P = 0.001); coronary artery disease ( P = 0.006); stroke; diabetes as the primary cause for renal failure; peripheral vascular disease; depression and presence of anaemia. HCV was associated with higher risk of death in patients on dialysis, even after adjusting for concurrent comorbidities. The risk was highest at the time of HCV diagnosis and stabilized over time. Clinical trials of HCV screening and treatment to reduce mortality in this population are warranted.
Abstract In vitro, ACE2 translocates to the nucleus to induce SARS-CoV-2 replication. Here, using digital spatial profiling of lung tissues from SARS-CoV-2-infected golden Syrian hamsters, we show that a specific and selective peptide inhibitor of nuclear ACE2 (NACE2i) inhibits viral replication two days after SARS-CoV-2 infection. Moreover, the peptide also prevents inflammation and macrophage infiltration, and increases NK cell infiltration in bronchioles. NACE2i treatment increases the levels of the active histone mark, H3K27ac, restores host translation in infected hamster bronchiolar cells, and leads to an enrichment in methylated ACE2 in hamster bronchioles and lung macrophages, a signature associated with virus protection. In addition, ACE2 methylation is increased in myeloid cells from vaccinated patients and associated with reduced SARS-CoV-2 spike protein expression in monocytes from individuals who have recovered from infection. This protective epigenetic scarring of ACE2 is associated with a reduced latent viral reservoir in monocytes/macrophages and enhanced immune protection against SARS-CoV-2. Nuclear ACE2 may represent a therapeutic target independent of the variant and strain of viruses that use the ACE2 receptor for host cell entry.
Plasma viral load has become an important test in predicting the progress of HIV-1 infected patients. The higher the viral load the faster is the progression to AIDS. As HIV-1 infected hemodialysis (HD) patients have higher mortality and morbidity than HIV-1 infected non-dialysis patients, and as all the blood tests in the HD patients are drawn during HD, we measured the effect of HD and antiretroviral therapy on viral load in HIV-1 infected HD patients.We measured plasma viral load pre-dialysis and post-dialysis in 10 HIV-1 infected HD patients. The viral load was measured using an in vitro quantitative nucleic acid amplification test. We also compared viral load in 8 HIV-1 infected HD patients on one antiretroviral drug with 8 HIV-1 patients on two (6) or three (2) antiretroviral drugs.There was a small reduction in plasma viral load postdialysis in all HIV-1 infected HD patients (45% +/- 5.4, 0.3 log +/- 0.05, p < 0.0004). However, HIV-1 RNA could not be detected in the ultrafiltrate. The patients who were on two or three antiretroviral drugs had lower viral load (8915 +/- 3702 vs. 351440 +/- 101237, p < 0.004) and higher CD4 count (355 +/- 81 vs 82 +/- 39, p < 0.009) than patients on only one antiretroviral drug.We conclude that there is a small reduction in plasma viral load in HIV-1 infected hemodialysis patients post-dialysis. As no viral RNA could be detected in the ultrafiltrate, the reduction could be due to nonspecific adsorption of the viral RNA to the dialysis membrane. HIV-1 infected hemodialysis patients who are on two or three antiretroviral drugs had significantly lower viral load and higher CD4 count than patients on only single antiretroviral drug. Therefore a single antiretroviral drug should not be used in treating HIV-1 infected HD patients.
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