Intravitreal Injection of Anti-VEGF Antibody Induces Glomerular Endothelial Cells Injury.

INTRODUCTION: Antiangiogenic agents that inhibit vascular endothelial growth factor have emerged as important tools in cancer therapy and ocular diseases. Their systemic use can induce renal limited microangiopathy. Local use of anti-VEGF agent is supposed to be safe. We report here a unique case of early endothelial cells injury induced by intravitreal injection of bevacizumab. CASE PRESENTATION: A 72-year-old man was addressed for acute kidney injury with proteinuria. He was under treatment with intravitreal injections of bevacizumab for glaucoma. Kidney biopsy was performed and electron microscopy showed signs of early stages of glomerular microangiopathy. Bevacizumab was discontinued resulting in the improvement of renal function and albuminuria. DISCUSSION: Bevacizumab, a humanized monoclonal antibody to VEGF is an approved therapy for metastatic cancer. Systemic adverse events including thrombotic microangiopathy have been mainly reported after its systemic injection. Podocytes produce VEGF that interacts with endothelial cells VEGF receptor-2 maintaining glomerular basement membrane integrity. Bevacizumab induce the detachment of endothelial cells from glomerular basement membrane leading to the proteinuria and renal function decline. Intravitreal bevacizumab is generally supposed to be safe. However, glomerular injury with microangiopathy features, even after intravitreal injection is possible. CONCLUSION: We report the electron microscopy evidence that intravitreal injection of anti-VEGF induces glomerular endothelial cells injury. Nephrologists and ophthalmologists should be aware of this complication.

[Recurrent episodes of brushite nephrolithiasis revealing primary hyperparathyroidism]. / Néphrolithiases récurrentes de brushite révélant une hyperparathyroïdie primaire.

INTRODUCTION: Nephrolithiasis is a frequent disease observed in 1 to 20 % of the general population. This disease predominates in male patients (2:1) and is characterized by a high rate of recurrences (about 50 %). CASE REPORT: We report the case of a 45-year old male patient who experienced during about ten years recurrent bilateral renal colic episodes due to brushite lithiasis. These stones were treated with multiple extracorporeal shock wave lithotripsy sessions. A pyeloureteral junction syndrome predisposing to bulky stones formation has been put in evidence and required a pyeloplasty. After more than ten years of disease activity, a biochemical screening diagnosed primary hyperparathyroidism (PHPT). Radiological assessment identified a parathyroid gland adenoma. Successful surgical removal of this lesion was followed by resolution of the symptomatic kidney stones formation. DISCUSSION: PHPT is associated with kidney stones in about 20 % of the patients. Hypercalciuria is the main risk factor of stones formation but other predisposing factors are also probably involved. Patients carrying a polymorphism located in the coding sequence of the calcium-sensing receptor gene or in the regulatory region of this gene seem to experience an increased occurrence of urinary lithiasis. CONCLUSION: The present case stresses the importance of a metabolic assessment in all patients with recurrent nephrolithiasis, especially in case of bilateral episodes.

[Anti-NEP and anti-PLA2R antibodies in membranous nephropathy: an update]. / Anticorps anti-EPN et anti-PLA2R dans les glomerulopathies extramembraneuses: le point en 2014.

Membranous nephropathy (MN) is the most common cause for nephrotic syndrome in adults and occurs as an idiopathic (primary) or secondary disease. Since the early 2000's, substantial advances have been made in the understanding of the molecular bases of MN. The neutral endopeptidase (NEP) and the receptor for secretory phospholipase A2 (PLA2R) have been identified as target antigens for circulating and deposited antibodies in allo-immune neonatal and adult " idiopathic " MN, respectively. These antibodies recognize specific antigens of podocytes, precipitate as subepithelial immune complexes and activate complement leading to proteinuria. Anti-PLA2R antibodies are of particular clinical importance. Indeed, they are detected in approximately 70% of primary MN in adults, demonstrating that MN actually is an autoimmune condition specific to the kidney. In Europeans, genome-wide studies have shown an association between alleles of PLA2R1 and HLA DQA1 (class II genes of tissue histocompatibility complex) genes and idiopathic MN. Newly developed diagnostic tests detecting circulating anti-PLA2R antibody and PLA2R antigen in glomerular deposits have induced a change in paradigm in the diagnostic approach of idiopathic MN. Measurement of circulating anti-PLA2R antibody is also very useful for the monitoring of MN activity. However, the mechanisms responsible for the formation of anti-PLA2R antibodies as well as those involved in the progression of MN to end-stage renal disease remain to be defined.

[Contribution of clinical biology in the etiological exploration and follow-up of urolithiasis]. / Apport de la biologie clinique dans l'exploration étiologique et le suivi de l'urolithiase.

Urolithiasis is a frequent pathology with a constantly increasing prevalence in industrial countries. The relapse frequency is around 50 % with a risk of complications. The laboratory input is essential in the determination of the etiology and in the therapeutic monitoring. The morphoconstitutional analysis of the stone is the most important element. It comprises the examination of the stone with binocular loupes and the simultaneous analysis of its crystalline composition. This can be done by different techniques but infrared spectrophotometry is the most powerful. The chemical analysis should be definitely proscribed. The analysis of crystalluria includes the search, the identification and the counting of crystals in fresh morning urines. It is useful for the diagnosis and for the patient follow-up. Finally, the biochemical analyses in urine and serum, in first line or on the basis of the stone composition, are an important part of the etiological exploration and therapeutic monitoring.

[Acute kidney injury and drug-induced nephropathies]. / Insuffisance (atteinte) rénale aiguë et néphrotoxicité médicamenteuse.

All types of acute kidney injury (AKI) (functional /pre-renal, parenchymal/intra-renal, obstructive/post-renal) result in a sharp drop of the glomerular filtration rate, with variable reversibility according to the initial cause. In one case out of five, drug intake can be related to the onset of AKI. Antibiotics, analgesics and nonsteroidal anti-inflammatory drugs, angiotensin converting enzyme inhibitors and angiotensin II receptor antagonists are the agents mostly involved, as well as iodinated radio-contrast agents. Mechanisms are often complex: toxic cellular effect directed on a nephron segment (tubular necrosis) associated or not with intraglomerular hemodynamic changes, or immune process leading to acute tubule-interstitial nephritis. Each underlying risk factor (age > 60 year, cardiac or hepatic failure, hypertension, diabetes, intra-vascular volume depletion, preexisting or unknown chronic kidney disease) must be taken into consideration by the prescribing physician because it reduces the chance of functional recovery and worsens the renal and the overall prognosis. A pre-renal additional component is often present and avoidable thanks to a strict hemodynamic monitoring. The present article summarizes some recent physiopathological aspects of AKI and makes the link between clinical situations and currently prescribed drugs. Lessons from the radio-contrast induced nephropathy are examined by taking into account prevention aspects and risk factors screening. An effective collaboration between the general practitioner and the nephrologist would benefit in optimizing the treatment of difficult cases.

[Experimental nephrology unit: overview and research projects]. / Unité de néphrologie expérimentale facultaire: etat des lieux et projets d'avenir.

After a short historical background of the Laboratory, the main research topics--renal toxicology, physiopathology of renal interstitial fibrosis and hormonology--are described in the perspective of a partnership between research clinicians and full time scientists. National as well as international scientific collaborations underline the need of combining expertises, stimulating also the training of youngest colleagues to the experimental approach of their future discipline.

Aristolochic acid induces proximal tubule apoptosis and epithelial to mesenchymal transformation.

Aristolochic acid contamination in herbal remedies leads to interstitial fibrosis, tubular atrophy, and renal failure in humans. To study the cellular mechanisms contributing to the pathophysiology of this renal disease, we studied Wistar rats treated with aristolochic acid and measured tubular and interstitial cell proliferation, epithelial/mesenchymal cell marker expression, tubular membrane integrity, myofibroblast accumulation, oxidative stress, mitochondrial damage, tubular apoptosis, and fibrosis. Oxidative stress, a loss of cadherin concomitant with vimentin expression, basement membrane denudation with active caspase-3 expression, and mitochondrial injury within tubular cells were evident within 5 days of administration of the toxin. During the chronic phase, interstitial mesenchymal cells accumulated in areas of collagen deposits. Impaired regeneration and apoptosis of proximal tubular cells resulted in tubule atrophy with a near absence of dedifferentiated cell transmembrane migration. We suggest that resident fibroblast activation plays a critical role in the process of renal fibrosis during aristolochic acid toxicity.