The effect of spironolactone on calcineurin inhibitor induced nephrotoxicity: a multicenter randomized, double-blind, clinical trial (the SPIREN trial).

BACKGROUND: Calcineurin inhibitor induced nephrotoxicity contributes to late allograft failure in kidney transplant patients. Evidence points towards aldosterone to play a role in the development of fibrosis in multiple organs. Animal studies have indicated a beneficial effect of mineralocorticoid receptor antagonists preventing calcineurin inhibitor induced nephrotoxicity. Only few studies have explored this effect in humans. The objective of this study is to evaluate the effect of spironolactone on glomerular filtration rate and fibrosis in kidney transplant patients. METHOD: Prospective, double-blind, randomized, clinical trial including 170 prevalent kidney transplant patients. Patients are randomized to spironolactone 25-50 mg/day or placebo for three years. Primary outcome is glomerular filtration rate evaluated by chrome-EDTA clearance. Secondary outcomes are 24-h protein excretion, amount of interstitial fibrosis in renal allograft biopsies, and cardiovascular events. As an exploratory outcome, we aim to identify markers of fibrosis in blood and urine. DISCUSSION: Long term allograft survival remains a key issue in renal transplantation, partly due to calcineurin inhibitor induced nephrotoxicity. Evidence from animal- and small human studies indicate a beneficial effect of mineralocorticoid receptor antagonism on renal function and fibrosis. This study aims to test this hypothesis in a sufficiently powered randomized clinical trial. Results might influence the future management of long term allograft survival in renal transplantation. TRIAL REGISTRATION: ClinicalTrials.gov identifier (05/17/2012): NCT01602861 . EudraCT number (05/31/2011): 2011-002243-98.

Parapharyngeal abscess is frequently associated with concomitant peritonsillar abscess.

To characterize patients with parapharyngeal abscess admitted to a Danish tertiary care centre and evaluate our management. This is a retrospective chart review. All records of patients with parapharyngeal abscess admitted to the Ear-Nose-Throat Department at Aarhus University Hospital, Denmark, from January 2001 through December 2011 were reviewed. In total, 63 patients (41 males), aged 4-89 years (median, 45 years) were included in the study. The mean annual incidence of parapharyngeal abscess was 0.9 cases/100,000 population. Thirty-three (52%) patients had concomitant peritonsillar abscess. In two patients the parapharyngeal abscess was accompanied by necrotizing fasciitis. The most frequent surgical approach used was intrapharyngeal incision in combination with tonsillectomy. The most commonly used antibiotic regimen was benzylpenicillin plus metronidazole. Seven (13%) patients returned to the operating theatre due to post-tonsillectomy haemorrhage or insufficient abscess drainage. Tonsillectomy and internal incision of the abscess in combination with a narrow-spectrum intravenous penicillin and metronidazole is a safe and efficient approach for managing parapharyngeal abscesses. This approach, however, carries a relatively high complication rate, requiring close surveillance in the early post-operative period. This is especially true for parapharyngeal abscess patients without peritonsillar abscess. In our series, these patients were more ill, more likely to experience complications, require intensive care, intubation, and tracheotomy, than parapharyngeal abscess patients with concurrent peritonsillar abscess. The frequent co-existence of parapharyngeal abscess and peritonsillar abscess favours careful consideration of addition of tonsillectomy to intrapharyngeal incision.

Influenza virus vaccination and kidney graft rejection: causality or coincidence.

Influenza can cause significant morbidity and mortality in renal transplant recipients especially with a high rate of lower respiratory disease. Annual influenza vaccination is therefore recommended to renal transplant recipients. We report the first three cases of acute kidney injury in renal transplant recipients following influenza vaccination that all led to graft loss. They all had different native diseases and were all vaccinated in the same season of 2009-10. The time span from vaccination to decline of kidney function is shorter than the time to diagnosis since the three patients only had blood tests every 3 months or when symptoms became severe. These reports do not justify a change of current recommendations regarding influenza vaccination in renal transplant recipients, but they support the continued attention and registration of vaccinations to monitor side effects.