Renal angiomyolipomas (AML) are usual manifestations of tuberous sclerosis complex (TSC) that may cause aneurism-related haemorrhages and renal impairment. Everolimus has emerged as an alternative to surgery/embolization. We provide further insight into everolimus safety and efficacy for TSC-related AML. This was a Spanish expanded access trial including patients aged ≥18 years with TSC-related AML. They received 10 mg everolimus once daily until AML progression, unacceptable toxicity, death/withdrawal, commercialisation for TSC-related AML, or 1 year after first patient enrolment. The primary outcome was dose-limiting safety according to grade 3/4 adverse events, serious adverse events, or adverse events leading to treatment modification. Secondary outcomes included overall safety and efficacy. Nineteen patients were enrolled and received everolimus for a median of 6.6 (5.3–10.9) months. Eleven (57.9 %) remained on 10 mg/day throughout the study and eight (42.1 %) required treatment modifications due to adverse events; none permanently discontinued treatment. Adverse events were overall grade 1/2 and most frequently included aphthous stomatitis/mucosal inflammation, hypercholesterolaemia/hypertriglyceridaemia, urinary tract infection, hypertension, dermatitis acneiform, and insomnia. Four (21.1 %) patients experienced grade 3 adverse events, none was grade 4, and only one (5.3 %) was serious (pneumonia). AML volume was reduced ≥30 % in 11 (57.9 %) patients and ≥50 % in 9 (47.4 %); none progressed. Right and left kidney sizes decreased in 16 and 14 patients, respectively. These findings support the benefit of everolimus for renal AML due to a manageable safety profile accompanied by reduced AML and kidney volumes. EudraCT number 2012-005397-63 ; date of registration 22 Nov 2012.

Recombinant human erythropoietin (rHuEPO) is a sialoglycoprotein hormone that appears to be immunologically and biologically equivalent to the endogenous compound, enhancing erythropoiesis dose-proportionally. The recombinant product is structurally very similar, if not identical, to native human erythropoietin, being a 193-amino acid peptide from which a 27-amino acid leader sequence is cleaved. Evidence indicates that the arginyl residue at the carboxyl terminus is also removed. The 165-amino acid mature protein contains two disulfide bonds, and one O-linked and three N-linked carbohydrate chains. The major carbohydrate units are sialated tetraantennary saccharides, which are required for stability in vivo ( 1). Two different rHuEPO products have been developed, alpha and beta, with differences in carbohydrate structure (glycoforms). In spite of the fact that rHuEPO is produced in mammalian cell lines and despite its widespread use, relatively little information is available regarding its immunogenic character. To date, few reports have been published on the development of anti-rHuEPO antibodies ( 2)( 3)( 4)( 5).

Background: Autosomal dominant polycystic kidney disease (ADPKD) and neurofibromatosis type 1 (NF1) are both autosomal dominant disorders with a high rate of novel mutations. However, the two disorders have distinct and well‐delineated genetic, biochemical, and clinical findings. Only a few cases of coexistence of ADPKD and NF1 in a single individual have been reported, but the possible implications of this association are unknown.Methods: We report an ADPKD male belonging to a family of several affected members in three generations associated with NF1 and optic pathway gliomas. The clinical diagnosis of ADPKD and NF1 was performed by several image techniques.Results: Linkage analysis of ADPKD family was consistent to the PKD2 locus by a nonsense mutation, yielding a truncated polycystin‐2 by means of next‐generation sequencing. The diagnosis of NF1 was confirmed by mutational analysis of this gene showing a 4‐bp deletion, resulting in a truncated neurofibromin, as well. The impact of this association was investigated by analyzing putative genetic interactions and by comparing the evolution of renal size and function in the proband with his older brother with ADPKD without NF1 and with ADPKD cohorts.Conclusion: Despite the presence of both conditions there was not additive effect of NF1 and PKD2 in terms of the severity of tumor development and/or ADPKD progression.

We report for the first time a family with type 1 ADPKD in which the marriage between affected non-consanguinous individuals resulted in two live-born heterozygous offspring and two fetuses lost in mid-pregnancy. Given a 25% chance for mutant compound heterozygosity in the offspring of this family, our findings suggest that compound heterozygosity of PKD1 mutations in humans may be embryonically lethal.