Background. The mammalian target of rapamycin (mTOR) inhibitor, rapamycin, has been shown to inhibit the progression of murine lupus nephritis by virtue of its potent immunosuppressive properties. The phosphoinositol-3-kinase (PI3K)/Akt pathway is a major upstream activator of mTOR and has been implicated in the propagation of cancer and autoimmunity. However, the activation status of the PI3K/Akt/mTOR pathway in lupus nephritis has not been studied so far.

Background. In the general population, accumulating data support a link between low testosterone levels and mortality by all causes, but especially by cardiovascular disease (CVD). Also, accelerated arterial stiffness has been recognized as an important cardiovascular risk factor. Here, we explored the association between testosterone levels and risk of death in male haemodialysis (HD) patients, whose arterial system is characterized by generalized stiffening. Methods. In this three-centre prospective observational study, 111 male HD patients after completion of baseline assessment, including measurement of male sex hormones and pulse wave velocity (PWV), were followed up for CVD and all-cause mortality. Results. Of the 111 patients studied, 54 were found with and 57 without testosterone deficiency, defined as testosterone levels <8 nmol/L. During a median follow-up period of 37 months, 49 deaths occurred, 28 (57%) of which were caused by CVD. Testosterone deficiency patients had increased CVD and all-cause mortality {crude hazard ratio: 3.14 [95% confidence interval (CI), 1.21–8.16] and 3.09 (95% CI, 1.53–6.25), respectively}, even after adjustment for age, body mass index, serum albumin and C-reactive protein, prevalent CVD and HD vintage. The association of testosterone with CVD mortality, but not with all-cause mortality, was lost after adjusting for PWV, an index of arterial stiffness. Testosterone levels were inversely related to PWV (r = −0.441; P < 0.001). Conclusion. We showed that testosterone deficiency in male HD patients is associated with increased CVD and all-cause mortality and that increased arterial stiffness may be a possible mechanism explaining this association.

The AKT-mTOR pathway is activated in diabetic nephropathy. Renin-angiotensin system modulators exert beneficial effects on the diabetic kidney. We explored the action of losartan on AKT-mTOR phosphorylation in glomeruli and podocytes. Diabetes mellitus was induced to Sprague-Dawley rats by streptozotocin. Five months later, the rats were commenced on losartan and euthanized 2 months later. Kidneys were processed for immunofluorescence studies. Glomeruli were isolated for Western blot analysis. Diabetes increased activated forms of AKT and mTOR both in glomeruli and podocytes. In diabetic rats, losartan decreased phosphorylated/activated forms of AKT (Thr308) and mTOR (Ser2448) in glomeruli but decreased only activated mTOR in podocytes. However, in both glomeruli and podocytes of healthy animals, an inverse pattern was evident. In conclusion, a new body of evidence indicates the differential activation of AKT-mTOR in glomeruli and podocytes of healthy and diabetic animals in response to losartan.

Background: Acromegaly is almost always caused by a pituitary adenoma and is associated with high morbidity and mortality when uncontrolled. Trans-sphenoidal removal of the adenoma is the mainstay of therapy, but fails to control the disease in a significant number of patients who require further treatment. Somatostatin analogues (SSAs) as monotherapy or in combination with growth hormone (GH)-receptor antagonists and/or dopamine agonists are used either alone or in combination following surgical failure to achieve disease control. The use of specific biomarkers may help to individualize the therapeutic plan after surgical failure and direct towards a more personalized approach. Methods: We report a 41-year-old man with acromegaly and residual disease after repeated surgery that was resistant to first-generation SSAs. Results: Biochemical and tumor control were achieved following the administration of a second-generation SSA, pasireotide, combined with pegvisomant, both at maximal doses and along with cabergoline. Histology specimens showed a sparsely-granulated GH-immunostaining pituitary adenoma with intense positivity for somatostatin receptors 2 and 5 and low levels of E-cadherin. Conclusion: Personalized medical therapy guided by currently available biomarkers, such as immunohistochemically-characterized receptor profiling or adhesion molecules, resulted in controlled insulin-like growth factor-1 (IGF-1) and GH levels and symptom alleviation following the combination of three drug-classes.

Light-chain deposition disease (LCDD) is caused by an underlying clonal plasma cell dyscrasia in which monoclonal immunoglobulin light chains (LCs) are deposited in tissues, resulting in varying degrees of organ dysfunction. Autologous stem cell transplantation (ASCT) has been reported to stabilize renal function in patients with LCDD, but currently, no evidence of histopathologic resolution of LC deposition after ASCT exists. We present a patient, with severe renal dysfunction due to LCDD, who was treated with high-dose melphalan and ASCT that resulted in a significant and extended period of improved renal function. Four years after the initial improvement, the patient developed nephrotic range proteinuria, without any evidence of relapse of the plasma cell dyscrasia. At that time, a repeat renal biopsy showed complete resolution of LC depositions and development of extensive glomerulosclerosis, thus explaining proteinuria. To the best of our knowledge, this is the first report of a biopsy-proven resolution of renal LCDD following ASCT. A timely application of ASCT should be considered in LCDD to prevent deterioration of renal function in the long run.