• Pattern of change in renal function following radical nephrectomy for renal cell carcinoma

      Coyle, D; Quinlan, MR; D’Arcy, FT; Kelly, BD; Corcoran, O; Durkan, GC; Jaffry, S; Walsh, K; Rogers, E (2015-09)
      Radical nephrectomy (RN) is an independent risk factor for the development of chronic kidney disease (CKD) in those with renal cell carcinoma (RCC). We aimed to examine the pattern of change in post-operative renal function in patients who underwent RN for RCC over a 3 year period at our institution. We performed a retrospective review of histological and biochemical findings in patients undergoing RN for RCC over a 38 month period. Estimated glomerular filtration rate (eGFR) was recorded pre- and post-operatively and at follow-up. We analysed data on 131 patients (median follow-up 24 months). The proportion of patients with advanced CKD increased significantly at follow-up with 48 (85.7%) patients, classified as having stage 2 CKD pre-operatively, being re-classified as stage 3-5. Mean eGFR was significantly lower pre-operatively (76.6 mL/min/1.73 m2) compared to hospital discharge (61 mL/ min/1.73 m2, p<0.001) and follow-up (55.5 mL/min/1.73 m2, p<0.001). Those with pT1 tumours sustained a significantly greater decline in eGFR compared to other stages. In conclusion, patients with pT1a and pT1b tumours sustain a disproportionate decline in renal function and may benefit the most from NSS.
    • Targeting the Pim kinases in multiple myeloma.

      Keane, N A; Reidy, M; Natoni, A; Raab, M S; O'Dwyer, M (Nature Publishing Group, 2015-07-17)
      Multiple myeloma (MM) is a plasma cell malignancy that remains incurable. Novel treatment strategies to improve survival are urgently required. The Pims are a small family of serine/threonine kinases with increased expression across the hematological malignancies. Pim-2 shows highest expression in MM and constitutes a promising therapeutic target. It is upregulated by the bone marrow microenvironment to mediate proliferation and promote MM survival. Pim-2 also has a key role in the bone destruction typically seen in MM. Additional putative roles of the Pim kinases in MM include trafficking of malignant cells, promoting oncogenic signaling in the hypoxic bone marrow microenvironment and mediating resistance to therapy. A number of Pim inhibitors are now under development with lead compounds entering the clinic. The ATP-competitive Pim inhibitor LGH447 has recently been reported to have single agent activity in MM. It is anticipated that Pim inhibition will be of clinical benefit in combination with standard treatments and/or with novel drugs targeting other survival pathways in MM.