Simon Steddon

The Pan-Thames EPS study: treatment and outcomes of encapsulating peritoneal sclerosis

BACKGROUND Encapsulating peritoneal sclerosis (EPS) is a disease process that can occur as a complication of peritoneal dialysis (PD). The aim of this study was to make a general assessment of the clinical features, diagnosis, management and outcome of PD-related EPS cases from London and South-East England. METHODS Questionnaires were sent to 11 PD units in March 2007; cases were identified retrospectively. Outcome data on surviving patients were collected in March 2008. RESULTS A total of 111 patients were identified; the mean time on PD was 82 months (range 8-247). Mortality increased with length of time on PD, being 42% at <3 years (n = 12), 32% at 3-4 years (n = 19), 61% at 5-6 years (n = 31), 54% at 7-8 years (n = 24), 75% at 9-10 years (n = 8) and 59% at >10 years (n = 17). Twelve patients had no previous peritonitis episodes, 28 had one previous episode, 30 had two previous episodes and 33 had three or more previous episodes. Of the patients with PD details available, 41/63 were high (>0.81) transporters and 44/71 had ultrafiltration <1 l/24 h, but 7/63 were low average transporters (0.5-<0.65) and 27/71 had ultrafiltration >1 l/24 h and a few had significant residual renal function. Sixty-five (59%) patients had their PD discontinued prior to diagnosis (51 HD; 14 transplanted). CT scans were performed on 91 patients and laparotomy on 47 patients. Drug treatment consisted of tamoxifen, immunosuppression or both. The median survival was 15 months in patients treated with tamoxifen (n = 17), 12 months in patients treated with immunosuppression (n = 24) and 21 months in patients who received both (n = 13), against 13 months (n = 46) in patients who received no specific treatment. Adhesionolysis was performed in 5 patients, and 39 patients were given parenteral nutrition. The overall mortality was 53% with a median survival of 14 months and a median time to death of 7 months. Conclusion. This is one of the largest cohorts of patients with EPS in the literature. Long-term survival occurred in over 50%, regardless of the various treatments strategies undertaken by the centres.

Calcimimetics and calcilytics—fooling the calcium receptor

CONTEXT Just a decade after the the calcium-sensing receptor (CaR) was identified, pharmacological manipulation of the CaR is about to enter routine practice. For hyperparathyroid states, calcimimetics, which increase activation of the CaR, have been licensed in Europe and the USA. Calcilytics, which decrease CaR function and increase secretion of parathyroid hormone (PTH), might allow the anabolic effects of PTH on bone to be harnessed for the prevention and treatment of osteoporosis. STARTING POINT In a multicentre randomised double-blind placebo-controlled study, Munro Peacock and colleagues recently confirmed the efficacy of the oral calcimimetic cinacalcet for achieving long-term reductions in serum calcium and PTH concentrations in primary hyperparathyroidism (J Clin Endocrinol Metab 2005; 90: 135-41). The arrival of a non-surgical option for this common disorder is important. WHAT NEXT? Study in primary and uraemic secondary hyperparathyroidism will indicate whether the efficacy of calcimimetic agents extends into the longer term. The extracellular relation between the CaR and its ligands and the intracellular signalling cascades that modify PTH gene transcription and secretion need further study. Drugs acting on the CaR might treat other disorders of bone remodelling, including osteoporosis. CaR expression in tissues beyond those involved in mineral ion homoeostasis should remain an important focus of research.

Summary of the 5th Edition of the Renal Association Clinical Practice Guidelines (2009-2012)

Robert Mactier, Simon Davies, Chris Dudley, Paul Harden, Colin Jones, Suren Kanagasundaram, Andrew Lewington, Donald Richardson, Maarten Taal, Peter Andrews Richard Baker, Cormac Breen, Neill Duncan, Ken Farrington, Richard Fluck, Colin Geddes, David Goldsmith, Nic Hoenich, Stephen Holt, Alan Jardine, Sarah Jenkins, Mick Kumwenda, Elizabeth Lindley, Mark MacGregor, Ashraf Mikhail, Edward Sharples, Badi Shrestha, Rajesh Shrivastava, Simon Steddon, Graham Warwick, Martin Wilkie, Graham Woodrow, Mark Wright

New Prospects for the Management of Renal Bone Disease

The last decade has been a remarkably productive one in the field of bone biology. New insights into the maintenance of a normal bone microenvironment have led to significant advances in our understanding of many important skeletal disorders, including renal osteodystrophy. Novel targets for therapeutic manipulation have been exposed and encouraging progress made towards new treatments. In addition, just as clinical studies have alerted us to the potential hazards of vascular calcification, basic science has unearthed the intimate nature of the relationship between the previously separate disciplines of bone and vascular biology. The clinical nephrologist, however, may be forgiven a little cynicism at this point. If such progress has been made, why do the same proverbial difficulties confront us in day-to-day practice? Control of phosphate remains inadequate, despite a literature which constantly reaffirms its crucial importance, and parathyroid hyperplasia seems inevitable in many patients. Furthermore, even the satisfaction of successful control of serum parathyroid hormone concentration must now be tempered by disquiet regarding the skeletal and cardiovascular consequences of oversuppression. This review aims to provide an update of the latest developments in relevant skeletal research and to assess how recently acquired knowledge may improve clinical nephrological practice over the next five years.

Renal Association Clinical Practice Guideline in mineral and bone disorders in CKD.

Mineral bone disorder Renal osteodystrophy Hyperphosphat(a)emia Calcium PTH Vascular calcification Phosphate binder The search covered the period from January 2006 to November 2009. Articles not written in English were not assessed. Articles available in abstract forms; letters; case reports; editorials or review articles were also excluded. Articles were assessed for relevance to the guideline topic, eligibility for inclusion in the evidence base for that guideline and methodological quality. Articles were considered of particular relevance if they were describing:

Case report: making the CONN-ection: two cases of persistent hypertension and hypokalaemia following renal transplantation

Conn’s syndrome following renal transplantation is extremely rare. Here, we present two cases of persistent hypertension and hypokalemia, emerging after kidney transplantation, which proved resistant to medical treatment. In both patients, biochemical investigations elicited massively elevated plasma aldosterone levels and suppressed renin activity. Abdominal MRI demonstrated a 90- and 20-mm right adrenal tumour in cases 1 and 2, respectively. For both patients, curative treatment was achieved via laparoscopic right adrenalectomy.