Characteristics of ANCA-associated vasculitis with aneurysms: Case series and review of the literature.

INTRODUCTION: ANCA-associated vasculitis (AAV) is an exceptional cause of small and large vascular aneurysms. Here, we present the phenotypic characteristics of patients with AAV associated with the presence of aneurysms. METHODS: We conducted a retrospective multicenter study and a systematic review of the literature. Only AAV patients with positive ANCA results and > 1 aneurysm(s) were enrolled. Patients were recruited through a call of observations among the French Vasculitis Study Group (FVSG) and the French Internal Medicine Network. Patients with aneurysm rupture were compared to those without. RESULTS: We enrolled 51 patients in the cohort, including 31 (67%) with granulomatosis with polyangiitis. The median Birmingham Vasculitis Activity Score was 18 [6-41]. A total of 92 aneurysms were noted, 74% of which involved medium-sized arteries, particularly the renal artery. During a follow-up of 24 [6-56] months, 22 (43%) patients experienced aneurysmal rupture, 91% of which involved medium-sized vessels. Patients with aneurysmal rupture showed significantly more pulmonary infiltrates and higher creatinine levels at baseline than patients without rupture. Initial treatments did not differ between the two groups. Ten (20%) patients died during the follow-up, including three from an aneurysmal rupture. CONCLUSION: Aneurysms were more frequently observed in GPA patients and predominantly affected medium-sized vessels, especially the renal arteries. The risk of rupture was high and occurred in >40% of patients. Because of their increased mortality, further studies are required to better manage this subset of patients.

Among CMV-positive renal transplant patients receiving non-T-cell depleting induction, the absence of CMV disease prevention is a safe strategy: A retrospective cohort of 372 patients.

Cytomegalovirus (CMV) is the most common opportunistic pathogen affecting renal transplant recipients, especially in the first months. CMV-seropositive renal transplant recipients (CMV R+) are at intermediate risk for CMV disease, but this risk is enhanced among CMV R+ receiving T-cell depleting induction, compared to CMV R+ receiving non-depleting induction. In this second group, data in favor of prophylactic antiviral treatment with valganciclovir to reduce CMV disease is sparse. In this retrospective and multicentric trial, we included 372 CMV R+ transplanted between January 2012 and April 2015 and receiving non-depleting induction. During the first year following transplantation, CMV disease occurred in 5/222 patients (2.25%) in the prophylaxis group and 9/150 (6%) in the no-prophylaxis group (difference +3.7; 95% CI: 0.5-8; P = .002 for non-inferiority). The incidence of allograft rejection and other infectious diseases was similar between the two groups. Graft and patient survival were similar at the end of follow-up. In conclusion, the absence of prophylaxis did not appear to have a deleterious effect for CMV diseases among CMV R+ receiving non-depleting induction.

Drug-Induced Acute Interstitial Nephritis with Nifedipine.

Background. Acute interstitial nephritis (AIN) is a frequent cause of Acute Kidney Injury (AKI). Drug hypersensitivity is the most common etiology and the list of drugs that can induce AIN is not exhaustive yet. Case Report. Here, we describe the case of a 43-year-old man who was treated with nifedipine (Adalate®) for Raynaud's syndrome. After nifedipine introduction, serum creatininemia progressively increased from 91 to 188 µmol/L in a few months and AKI was diagnosed. Laboratory work-up results indicated the presence of tubular proteinuria and nonspecific inflammatory syndrome. Histological analysis found granulomatous interstitial nephropathy without necrosis in 20% of the kidney biopsy without immunofluorescent deposit. Nifedipine was stopped and corticosteroid treatment was started with a rapid but incomplete reduction of serum creatininemia level to 106 µmol/L. Conclusion. This is the first case of AIN caused by nifedipine.

Opinion of French nephrologists on renal replacement therapy: survey on their personal choice.

BACKGROUND: In France, like in most developed countries, peritoneal dialysis (PD) is less used than haemodialysis (HD). This is not based on medical evidence supporting HD superiority. As the practitioner's opinion is important to patients and may influence their treatment choice, we conducted a survey among French nephrologists to determine which renal replacement therapy (RRT) they would choose if they had end-stage renal disease (ESRD). METHODS: We e-mailed a self-administered questionnaire to all members of the French-speaking Nephrology Society between 19 October 2008 and 12 January 2009. We then selected from the French Renal Epidemiology and Information Network (REIN) registry a reference population of 20- to 64-year-old patients with ESRD who began RRT [HD, PD or pre-emptive transplantation, (PT)] in 2008. RESULTS: The survey response rate was 17.8%. Results showed that 59.6% of respondents chose early inscription on the transplantation waiting list in view of PT, 20.2% selected HD and 20.2% selected PD. When dialysis was the only choice, 50.2% chose HD and 49.8% chose PD. Younger nephrologists (≤44 years old) selected PD more frequently than older nephrologists (≥45 years old) (58.9 versus 40.5%; P < 0.01). Similarly, PD was chosen more often by nephrologists from regions with 'more PD' than from regions with 'less PD' (79.0 versus 48.8%; P < 0.05). The nephrologists' choices were different from the RTT distribution among the reference population: 81.7% HD, 10.1% PD and 8.2% PT. CONCLUSION: Our survey on the theoretical choice of RTT suggests that the low PD rate in France cannot be explained by a negative opinion of PD among French nephrologists.

Is home blood pressure monitoring feasible and well accepted in nephrectomized patients for renal cancer? (STAFF study).

AIMS: Few studies have looked at blood pressure (BP) evolution after nephrectomy, except for in living kidney donors with no clinical relevant modifications. STAFF is a pilot, open-label, observational study to evaluate the feasibility of following BP by home blood pressure monitoring (HBPM) after nephrectomy for cancer. MAJOR FINDINGS: 56 patients (66.1% previously treated for hypertension) were included between November 1, 2011, and December 31, 2012; 95.8% of the patients realized five of six primary end-points in HBPM, but the last monitoring session at 6 months was often lacking (60%) probably because of a lack of understanding. When BP was controlled before surgery, 36% of the patients underwent new hypertension or hypertension dysregulation, without any correlating factor found; 33% of the patients presented the presence of proteinuria or an increase during the follow-up. Previous hypertension or high body mass index were risk factors for proteinuria increase (p = 0.036 and 0.032) but not treatment by an renin-angiotensin system blocker. There was no statistical link between HTA control and proteinuria. CONCLUSION: Our study shows that most patients undergoing nephrectomy for cancer are able to follow HBPM. It should be encouraged for detecting high BP or proteinuria, especially if antiangiogenic therapies are envisaged because of the supplementary risk of hypertension and proteinuria induced by these treatments.

[Prospective study of drug-induced interstitial nephritis in eleven French nephrology units]. / Médicaments à l'origine d'insuffisances rénales aiguës allergiques en France en 2013.

OBJECTIVE: Certain medications have been associated with drug-induced acute interstitial nephritis (AIN), but few prospective studies have been published. This prospective observational study aims to record and assess incidents of drug-induced AIN observed over a period of one year in nephrology units in France. The goal is to determine which medications are involved in AIN and to expound the clinical and biological presentation, management, and evolution of AIN. METHODS: Between April 2012 and April 2013, drug-associated cases of AIN were prospectively recorded in 24 patients registered in 11 nephrology units that belong to the Société de Néphrologie de l'Ouest (SNO). Data sheets, including suspected and concomitant drug(s), kidney function assessment, biological disturbances, clinical signs, histological data, management, and evolution, were collected by the Rennes Regional Pharmacovigilance Center and recorded in the French pharmacovigilance database. RESULTS: In order, the most frequently involved medications in the AIN cases were: vitamin K antagonists (33.3% of the cases, almost exclusively fluindione), antibiotics (20.8% of cases) non-steroidal anti-inflammatory drugs (20.8% of cases), and proton pump inhibitors (16.7% of cases). The mean delay of onset to AIN was 8.3 weeks. At the time of diagnosis, mean serum creatinine was 366 µM, higher for vitamin K antagonists (VKAs), except in the case of warfarin. During the course of an AIN event, 70% of patients had complete blood count and/or urine analysis abnormalities, 55% had clinical signs of systemic hypersensitivity, and 13% of patients had hepatic disorders. Renal biopsies were performed in 54% of patients; however, only 37% of patients requiring therapeutic anticoagulation underwent a biopsy. Suspected drugs were discontinued in all patients and the majority was treated with oral corticosteroids. Renal function often continued to be impaired after an AIN event. At baseline, 25% of patients had chronic kidney disease (CKD); after an AIN event, 67% of patients were noted to have CKD. CONCLUSION: Physicians need to be aware of the possibility of drug-induced acute interstitial nephritis as a common cause of acute kidney injury (AKI). This study supports increased vigilance when prescribing three therapeutic classes frequently associated with AIN: antibiotics, NSAIDs and PPIs (especially in instances of polypharmacy), which were associated with two thirds of the AIN cases in this study. Fluindione, an oral anticoagulant exclusively marketed in Luxembourg and France where it constitutes the vast majority of VKA prescriptions, was associated with one third of the AIN cases alone, making it a common possible culprit of drug-induced AIN, warranting particular attention.

All anti-vascular endothelial growth factor drugs can induce 'pre-eclampsia-like syndrome': a RARe study.

BACKGROUND: Specific therapies that target vascular endothelial growth factor (VEGF) and its receptors have improved the survival of patients with metastatic cancers, but can induce side effects. Renal side effects (proteinuria, hypertension and renal failure) are underestimated. METHODS: The French RARe (Reins sous traitement Anti-VEGF Registre) study collects data on patients with cancer who had a renal biopsy because of major renal side effects during treatment with anti-VEGF drugs. RESULTS: We collected 22 renal biopsies performed 16.2±10.6 months after the beginning of treatment; of which 21 had hypertension, mean proteinuria was 2.97±2.00 g/day and mean serum creatinine, 134±117 µmol/L. Thrombotic microangiopathy (TMA) was observed in 21 biopsy specimens, sometimes associated with acute tubular necrosis (ATN; n=4). TMA histological lesions were more important than the biological signs of TMA could suggest. Patients with ATN of >20% had higher serum creatinine levels than those with only TMA (231 versus 95 µmol/L). Nephrin, podocin and synaptopodin were variably down-regulated in all renal biopsies. VEGF was down-regulated in all glomeruli. CONCLUSION: This study underlines the importance of regular clinical and biological cardiovascular and renal checking during all anti-VEGF therapies for cancer for early detection of renal dysfunction. Collaboration between oncologists and nephrologists is essential. In such cases, renal biopsy might help in appreciating the severity of the renal lesions and after multidisciplinary discussion whether or not it is safe to continue the treatment.

Three kidneys, two diseases, one antibody?

Anti-factor H antibody has been recently described as responsible for thrombotic microangiopathies (TMA) as well as membranoproliferative glomerulonephritis (MPGN). We report here, for the first time, the case of a woman with an anti-factor H antibody, who developed MPGN on native kidney, rapid recurrence on first graft, and TMA on second graft despite immunosuppressive therapy and plasma exchanges. This case supports the hypothesis that MPGN and TMA are closely linked by common pathogenic mechanisms and the need for complete exploration of complement pathway including factor H activity and autoantibody in front of any MPGN.