Chris Kingswood

• MBBS MSc FRCP
• Consultant Nephrologist at Brighton and Sussex University Hospitals NHS Trust

Mechanistic target of rapamycin (mTOR) is a highly conserved serine/threonine kinase that regulates key cellular processes including cell growth, autophagy and metabolism. Hyperactivation of the mTOR pathway causes a group of rare and ultrarare genetic diseases. mTOR pathway diseases have diverse clinical manifestations that are managed by distinct...

Background Tuberous sclerosis complex (TSC) is a rare multisystem autosomal dominant genetic disorder caused by pathogenic mutations in either the TSC1 or TSC2 gene. Common manifestations of TSC have been grouped into major and minor clinical diagnostic criteria and assessed in clinical routine workup. However, case studies point towards the existe...

Background: Knowledge is increasing about TSC-Associated Neuropsychiatric Disorders (TAND), but little is known about the potentially confounding effects of intellectual ability (IA) on the rates of TAND across age, sex, and genotype. We evaluated TAND in (a) children vs. adults, (b) males vs. females, and (c) TSC1 vs. TSC2 mutations, after stratif...

Tuberous sclerosis complex (TSC) is an autosomal dominant multisystem genetic disorder characterized by benign tumors in multiple organs, including the skin, brain, kidneys, and lungs and occasional malignant tumors. Hamartomas in the brain, retina, and sometimes other organs also occur (1–3). The estimated prevalence is 1:600–1:10,000 live births...

Objective To present the baseline data of the international TuberOus SClerosis registry to increase disease Awareness (TOSCA) with emphasis on the characteristics of epilepsies associated with tuberous sclerosis complex (TSC). Methods Retrospective and prospective patients’ data on all aspects of TSC were collected from multiple countries worldwid...

Abstract Background Most evidence for TSC-associated neuropsychiatric disorders (TAND) to date have come from small studies and case reports, and very little is known about TAND in adults. We explored baseline TAND data from the large-scale international TOSCA natural history study to compare childhood and adult patterns, describe age-based pattern...

Background: Renal angiomyolipoma occurs at a high frequency in patients with tuberous sclerosis complex (TSC) and is associated with potentially life-threatening complications. Despite this frequency and severity, there are no large population-based cohort studies. Here we present baseline and follow-up data of the international TuberOus SClerosis...

Background Tuberous sclerosis complex (TSC) is a genetic disorder associated with tumour growth in various organs, including the brain, kidneys, heart, and skin. Cutaneous lesions are prevalent manifestations in TSC, occurring in up to 90% of patients. Oral mammalian target of rapamycin inhibitors, such as everolimus, are believed to be effective f...

Background Tuberous sclerosis complex (TSC) is a rare autosomal dominant genetic disorder. Many gaps remain in the understanding of TSC because of the complexity in clinical presentation. The TuberOus SClerosis registry to increase disease Awareness (TOSCA) is an international disease registry designed to address knowledge gaps in the natural histo...

Tuberous sclerosis complex (TSC) is a genetic disorder characterised by highly variable comorbid dysfunction and subsequent morbidity. The mTOR inhibitor everolimus is indicated for the treatment of adult TSC patients with renal angiomyolipomas (AMLs) and for subependymal giant astrocytoma (SEGA) in both adults and children, based on data from the...

Renal angiomyolipomata associated with tuberous sclerosis complex are often bilateral, multiple and progressive. They cause significant morbidity and mortality in older children and adults. Surveillance and pre-emptive treatment reduce this risk. Recent research suggests treatment with mammalian target of rapamycin inhibitors is better at preventin...

Renal-related disease is the most common cause of tuberous sclerosis complex (TSC)-related death in adults, and renal angiomyolipomas can lead to complications that include chronic kidney disease (CKD) and hemorrhage. International TSC guidelines recommend mammalian target of rapamycin (mTOR) inhibitors as first-line therapy for management of asymp...

Background: Tuberous sclerosis complex (TSC) is a multi-system genetic disorder characterized by the development of diverse clinical manifestations. The complexity of this disease is likely to result in substantial challenges and costs in disease management throughout the patient's lifetime. This retrospective database study aims to quantify healt...

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder that affects multiple organ systems and is caused by loss-of-function mutations in one of two genes: TSC1 or TSC2. The disorder can affect both adults and children. First described in depth by Bourneville in 1880, it is now estimated that nearly 2 million people are affected by the...

Tuberous sclerosis complex (TSC) is a genetic disorder arising from mutations in the TSC1 or TSC2 genes. The resulting over-activation of the mammalian target of rapamycin (mTOR) signalling pathway leaves patients with TSC susceptible to the growth of non-malignant tumours in multiple organs. Previously, surgery was the main therapeutic option for...

Background: Tuberous Sclerosis Complex (TSC) is a multi-system genetic disorder characterised by the development of benign growths and diverse clinical manifestations, varying in severity, age at onset and with high clinical burden. Aims: This longitudinal study aims to describe the broad spectrum of clinical manifestation profiles in a large, r...

Aim: The purpose is to determine the exposure-response relationship of everolimus in patients with angiomyolipoma from the EXIST-2 trial and to analyze the correlation between exposure and plasma concentrations of angiogenic biomarkers in these patients. Methods: 118 patients with angiomyolipoma associated with tuberous sclerosis complex (TSC) o...

Introduction La sclérose tubéreuse de Bourneville (STB) est une maladie génétique rare qui se manifeste par le développement de tumeurs bénignes dans de nombreux organes. La cohorte TOSCA est la plus grande cohorte qui permettra de décrire son histoire naturelle : les manifestations cliniques, leurs évolutions, l’efficacité des traitements. Nous pr...

Mammalian target of rapamycin (mTOR) inhibitors are recommended as first-line treatment of renal angiomyolipoma associated with tuberous sclerosis complex (TSC) or sporadic lymphangioleiomyomatosis (sporadic LAM), but follow-up is limited. Longer term efficacy and tolerability data from a Phase 3, double-blind, placebo-controlled trial are presente...

Tuberous sclerosis complex (TSC) is a multisystem, genetic disorder associated with an enormous range of physical and neuropsychiatric manifestations. Over the last few decades' significant progress has been made in understanding the molecular biology of the disorder, and TSC is now one of the first genetic conditions with molecularly targeted trea...

La STB est une maladie genetique rare qui affecte de nombreux organes. TuberOus SClerosis registry to increase disease Awareness (TOSCA) est une cohorte internationale qui a pour but de decrire les manifestations de la STB, dont la lymphangioleiomyomatose (LAM), d’identifier les manifestations rares et comorbidites, de recueillir les traitements et...

Background: Tuberous sclerosis complex (TSC) is a rare, multisystem, genetic disorder with an estimated prevalence between 1/6800 and 1/15000. Although recent years have seen huge progress in understanding the pathophysiology and in the management of TSC, several questions remain unanswered. A disease registry could be an effective tool to gain mo...

Introduction and Aims: According to classical nephrology practice, pure microscopic hematuria [MH] in early life is not considered a serious problem and up to date diagnostic studies are not always carried out. Family urine studies to confirm or rule out a familial disease should always be carried out early and if positive, molecular genetics shoul...

Tuberous sclerosis complex (TSC) is characterized by benign tumours in multiple organs, including the brain, kidneys, skin, lungs and heart. Our objective was to evaluate everolimus, an mTOR inhibitor, in the treatment of angiomyolipoma in patients with subependymal giant cell astrocytoma (SEGA) associated with TSC. EXamining everolimus In a Study...

Tuberous sclerosis complex is a genetic disorder affecting every organ system, but disease manifestations vary significantly among affected individuals. The diverse and varied presentations and progression can be life-threatening with significant impact on cost and quality of life. Current surveillance and management practices are highly variable a...

Background: Angiomyolipomas are slow-growing tumours associated with constitutive activation of mammalian target of rapamycin (mTOR), and are common in patients with tuberous sclerosis complex and sporadic lymphangioleiomyomatosis. The insidious growth of these tumours predisposes patients to serious complications including retroperitoneal haemorr...

Abstract BACKGROUND: Angiomyolipomas are slow-growing tumours associated with constitutive activation of mammalian target of rapamycin (mTOR), and are common in patients with tuberous sclerosis complex and sporadic lymphangioleiomyomatosis. The insidious growth of these tumours predisposes patients to serious complications including retroperitoneal...

(Named collaborator on this multi-centre study)

Purpose: Renal angiomyolipomas are a frequent manifestation of tuberous sclerosis and sporadic lymphangioleiomyomatosis (LAM). These disorders are associated with mutations of TSC1 or TSC2 that lead to overactivation of mTOR complex 1 (mTORC1), suggesting an opportunity for targeted therapy by using mTORC1 inhibitors. This study investigated the ef...

Tuberous sclerosis complex (TSC) is a genetic condition characterized by the growth of benign tumours in multiple organs, including the brain and kidneys, alongside intellectual disability and seizures. Identification of a causative mutation in TSC1 or TSC2 is important for accurate genetic counselling in affected families, but it is not always cle...

Lymphangioleiomyomatosis (LAM) is a rare lung disease, which occurs sporadically or in association with the genetic disease tuberous sclerosis complex (TSC) 1, 2. Sporadic LAM affects ∼1 in 400,000 adult females; in TSC, LAM occurs in 30–40% of adult females 3, 4 and exceptionally in males and children 5, 6. Patients with LAM usually develop progr...

To examine the presentation, management and outcomes of patients with renal angiomyolipoma (AML) over a period of 10 years, at St George's Hospital, London, UK. We assessed retrospectively 102 patients (median follow-up 4 years) at our centre; 70 had tuberous sclerosis complex (TSC; median tumour size 3.5 cm) and the other 32 were sporadic (median...

To the Editor: Tuberous sclerosis is an autosomal dominant disorder characterized by hamartomatous growths in many organs and caused by inherited mutations of the TSC1 or TSC2 gene. Acquired (somatic) mutations of either gene occur within pathologic cells in patients with sporadic lymphangioleiomyomatosis. Renal angiomyolipomas occur in both disord...

To study the radiological characteristics of renal masses in individuals with tuberous sclerosis complex (TSC) using serial CT, and to examine how renal cell carcinoma (RCC) may be differentiated from indeterminate cysts or masses. This was a retrospective study of 12 cases of TSC in which dedicated renal CT followed after US had demonstrated cysti...

Renal angiomyolipomata can exist as an imaging curiosity or represent a life-threatening condition. There are likely over 10 million people world-wide who have a renal angiomyolipomata and approximately one tenth of these people also have tuberous sclerosis complex. The optimum treatment of angiomyolipomata is focused on sparing renal tissue and ha...

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To report anterior ischemic optic neuropathy associated with systemic hypotension in a patient undergoing continuous ambulatory peritoneal dialysis. Case report. A 58-year-old man undergoing continuous ambulatory peritoneal dialysis developed painless blurred vision in both eyes and bilateral optic disk swelling with an altitudinal field defect in...

Tuberous sclerosis (TSC) is a multisystem disorder encompassing a wide spectrum of pathological renal lesions. Renal involvement is commonly asymptomatic but can result in significant morbidity, and renal failure has been reported. The risk of renal failure in patients with TSC in the UK has not been defined. A survey of the 170 members of the Euro...

Abnormalities (reduction in/absence of) in diurnal bp rhythm are much more commonly seen in patients with chronic uremia than in patients with primary hypertension or in normal subjects. Target-organ damage is greater in these patients. However, the extent to which these diurnal bp rhythm changes are consistent or variable is untested. We retrospec...

The physico-chemical properties of cefpirome (low protein binding, high water solubility and low molecular weight) suggest that it may be lost readily from the extracorporeal circulation of intensive care unit patients during continuous renal replacement therapy. In order to make informed dosage recommendations for patients receiving artificial ren...

Hypertensive non-diabetic patients who lack the normal nocturnal decline in blood pressure ('non-dippers') have an increased incidence of cardiovascular complications. Poor blood pressure control is known to exacerbate the decline in glomerular filtration rate in patients with diabetic nephropathy. The aim of this study was to assess the contributi...

A case report of a 50-year-old woman who has been treated with peritoneal dialysis for 9 years, with a short period off dialysis following transplantation. The patient had long-standing secondary hyperparathyroidism and had declined parathyroidectomy, she had had two episodes of peritonitis in the preceding eight years. She presented with blood-sta...

Ambulatory blood pressure recordings have been shown to correlate better with target organ damage than have isolated clinic blood pressure readings. There have been some small studies demonstrating that abnormal blood pressure diurnal rhythm is common in uraemia and in patients on renal replacement therapy. Abnormal blood pressure diurnal rhythm it...

A 56-year-old man who received a live-related renal transplant in 1988 was started in 1995 on the selective angiotensin II antagonist losartan (Dupont-Merke) to treat worsening hypertension. Two months later because of pulmonary oedema, loop diuretics were started. Within two weeks, serum creatinine had increased from 245 to 571 mumol/l, and the pa...

Patients with renal insufficiency commonly require the administration of an opioid analgesic to provide adequate pain relief. The handling of morphine, pethidine (meperidine) and dextropropoxyphene in patients with renal insufficiency is complicated by the potential accumulation of metabolites. While morphine itself remains largely unaffected by re...

To describe a case involving the removal of quinine by continuous venovenous hemofiltration (CVVH) in a patient with malaria and acute renal failure and to present recommendations on the dosing of quinine in such patients. A 50-year-old white man developed Plasmodium falciparum malaria following a visit to Nigeria. Although he received intravenous...

Nine cases of hereditary stomatocytosis (HSt) are presented which show documented thrombotic complications after splenectomy. In three cases, patients became severely ill with pulmonary hypertension and a fourth developed portal hypertension. One unsplenectomized affected adult relative had suspected but unconfirmed thrombotic pathology; the six ot...

Hypertension complicates the treatment of anaemia of chronic renal failure with recombinant human erythropoietin (EPO) in some patients. We conducted a prospective study measuring changes in cardiac index (CI) and systemic vascular resistance index (SVRI) in 29 patients from before commencement of EPO to attainment of target haemoglobin concentrati...

Although both continuous haemofiltration and continuous haemodialysis are techniques routinely employed in the management of critically ill patients, deciding on a drug dosing regimen is often difficult. This article highlights the factors influencing drug removal by both processes, the difficulties associated with the interpretation of research in...

Hypertension is the most common side-effect of treatment with recombinant human erythropoietin (EPO) for the anemia of chronic renal failure. To elucidate why this occurs in some patients we measured changes in blood volumes and diurnal blood pressure (BP) variation during treatment. Isotope labelled measurements of red cell and plasma volume (RCV...

Aims - To compare ambulatory blood pressure (ABP) and single, sphygmanometric (clinic) blood pressure in long-term dialysis patients and to ascertain if measures of hypertensive end organ damage correlate with ABP and clinic blood pressure. Patients and methods - clinic blood pressure was compared with ambulatory blood pressure in 11 haemodialysis...

β2-microglobulin (β2M) amyloidosis is a frequent and disabling complication of long-term dialysis. It has a predilection for periarticular and synovial deposition and the carpal tunnel is the most common site. There is no specific treatment but the symptoms of carpal tunnel syndrome often improve symptomatically and rapidly after transplantation, a...

We compared 10 patients treated with overnight APD in their homes with a parallel group of 30 patients having CAPD (Freeline II) over two years 1990 and 1991. Our aim was to discover if APD was an efficient and cost effective alternative to CAPD. The average amount of dialysate used per day in APD patients was 11 litres (range 9 to 14 litres) compa...

Conventional haemodialysis is not available on all intensive care units (ICUs) and there are relatively few renally trained nurses able to run haemodialysis machines. Continuous arteriovenous haemodialysis provides effective renal replacement therapy for critically ill patients in the ICU. Unlike continuous arteriovenous haemofiltration it provides...

The effect of Nadolol treatment on lipid subfractions in a group of 23 hyperthyroid patients was assessed in a randomised double-blind placebo controlled trial lasting six weeks, carbimazole being given to both groups from weeks 2 to 6. Clinical and biochemical euthyroidism was seen in both groups at 6 weeks; no effect of nadolol on peripheral mono...