Estimating glomerular filtration rate in kidney transplantation:Still searching for the best marker

Kidney transplantation is the treatment of choice for endstage renal disease.The evaluation of graft function is mandatory in the management of renal transplant recipients.Glomerular filtration rate(GFR),is generally considered the best index of graft function and also a predictor of graft and patient survival.However GFR measurement using inulin clearance,the gold standard for its measurement and exogenous markers such as radiolabeled isotopes(51Cr EDTA,99 mTc DTPA or 125 I Iothalamate) and non-radioactive contrast agents(Iothalamate or Iohexol),is laborious as well as expensive,being rarely used in clinical practice.Therefore,endogenous markers,such as serum creatinine or cystatin C,are used to estimate kidney function,and equations using these markers adjusted to other variables,mainly demographic,are an attempt to improve accuracy in estimation of GFR(e GFR).Nevertheless,there is some concern about the inability of the available e GFR equations to accurately identify changes in GFR,in kidney transplant recipients.This article will review and discuss the performance and limitations of these endogenous markers and their equations as estimators of GFR in the kidney transplant recipients,and their ability in predicting significant clinical outcomes.     

Vemurafenib

Oral vemurafenib (Zelboraf^®) is a first-in-class, small molecule BRAF^V600E inhibitor indicated for the treatment of unresectable or metastatic melanoma in BRAF ^V600 mutation-positive patients (EU) or BRAF ^V600E mutation-positive patients (USA). Compared with intravenous dacarbazine, vemurafenib significantly improved overall survival and progression-free survival in patients with unresectable, previously untreated, BRAF ^V600E mutation-positive, stage IIIC or IV melanoma. Oral vemurafenib was generally well tolerated, with cutaneous adverse events among the most commonly occurring adverse events.     

Vemurafenib: an unusual UVA‐induced photosensitivity

Vemurafenib is a new‐targeted therapy approved for the treatment of patients with V600E BRAF‐mutant metastatic melanoma. Among the cutaneous adverse events reported, the photosensitivity is frequently experienced. We aimed to characterize more deeply the mechanism leading to this photosensitivity as well as the corresponding UV spectrum. Phototests showed that the phototoxicity was UVA‐dependent since from normal value prior to vemurafenib treatment, the UVA‐minimal erythema dose decreased in 17 of 18 patients (94.4%) while the minimal erythema dose remained unchanged. Furthermore, a vemurafenib‐induced erythema appeared quickly during the UVA exposure contrarily to what is observed with a conventional drug‐induced phototoxicity showing an erythema 12–24 h after the phototesting. Vitamin PP concentration decreased, and porphyrin level significantly increased after 2 months of vemurafenib. Our study confirms the high risk of vemurafenib‐induced photosensitivity and indicates that it is possibly vitamin PP‐ and porphyrin dependent.     

Lysine acetylsalicylate decreases proliferation and extracellular matrix gene expression rate in keloid fibroblasts in vitro

BACKGROUND: In genetically predisposed individuals keloids are formed as benign collagenous tumors. OBJECTIVE: The purpose of this study was to investigate whether the proliferation and matrix gene expression of keloid fibroblasts is differently influenced by the anti-inflammatory active drug lysine acetylsalicylate (LAS) when compared to normal skin fibroblasts in vitro. METHODS: Normal skin and keloid fibroblasts derived from human donors were compared. RESULTS: Excessive scarring and the formation of keloids are (at least in part) due to an overproduction of collagen types I and III. The results show a significant dose-dependent anti-proliferative effect of lysine acetylsalicylate. At the level of gene expression we observed a pronounced inhibitory effect of LAS on procollagen I and III mRNA synthesis, whereas matrix metalloproteinase 1 and tissue inhibitor of metalloproteinases 1 were not altered. CONCLUSIONS: Further clinical studies are planned to evaluate these effects of a high-dose treatment of keloids with LAS.     

Bumps in the Road: Panniculitis in Children and Adolescents Treated with Vemurafenib

Vemurafenib is increasingly being used to treat nonmelanoma tumors that are positive for the BRAF V600E mutation. We report three children who presented with panniculitis induced by vemurafenib while undergoing treatment for central nervous system tumors and review the literature.     

Vemurafenib and cobimetinib‐induced toxic epidermal necrolysis in a patient with metastatic melanoma

Combination therapy in the treatment of metastatic melanoma has been associated with more durable response rate compared to monotherapy. However, previous studies have shown that combined target therapy commonly causes a wide spectrum of adverse events. These adverse reactions are usually manageable, however, it is always necessary to compare drug efficacy with its potential adverse effects. Toxic epidermal necrolysis represents severe mucocutaneous reaction, usually triggered by medications and characterized by extensive necrosis and detachment of the epidermis. Here we present a first case of toxic epidermal necrolysis induced by combined target therapy (vemurafenib plus cobimetinib). The case was observed in a young patient with BRAF mutant melanoma who was started on first‐line metastatic immunotherapy with pembrolisumab.     

Pathogenesis of glomerular haematuria

Haematuria was known as a benign hallmark of some glomerular diseases, but over the last decade, new evidences pointed its negative implications on kidney disease progression. Cytotoxic effects of oxidative stress induced by hemoglobin, heme, or iron released from red blood cells may account for the tubular injury observed in human biopsy specimens. However, the precise mechanisms responsible for haematuria remain unclear. The presence of red blood cells(RBCs) with irregular contours and shape in the urine indicates RBCs egression from the glomerular capillary into the urinary space. Therefore glomerular haematuria may be a marker of glomerular filtration barrier dysfunction or damage. In this review we describe some key issues regarding epidemiology and pathogenesis of haematuric diseases as well as their renal morphological findings.