Michael R. Clarkson
Cork University Hospital
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Featured researches published by Michael R. Clarkson.
Kidney International | 2010
Sinead Kinsella; Joe Coyle; Eva B. Long; Sebastian McWilliams; Michael M. Maher; Michael R. Clarkson; Joseph A. Eustace
Hemodialysis is associated with an increased risk of neoplasms which may result, at least in part, from exposure to ionizing radiation associated with frequent radiographic procedures. In order to estimate the average radiation exposure of those on hemodialysis, we conducted a retrospective study of 100 patients in a university-based dialysis unit followed for a median of 3.4 years. The number and type of radiological procedures were obtained from a central radiology database, and the cumulative effective radiation dose was calculated using standardized, procedure-specific radiation levels. The median annual radiation dose was 6.9 millisieverts (mSv) per patient-year. However, 14 patients had an annual cumulative effective radiation dose over 20 mSv, the upper averaged annual limit for occupational exposure. The median total cumulative effective radiation dose per patient over the study period was 21.7 mSv, in which 13 patients had a total cumulative effective radiation dose over 75 mSv, a value reported to be associated with a 7% increased risk of cancer-related mortality. Two-thirds of the total cumulative effective radiation dose was due to CT scanning. The average radiation exposure was significantly associated with the cause of end-stage renal disease, history of ischemic heart disease, transplant waitlist status, number of in-patient hospital days over follow-up, and death during the study period. These results highlight the substantial exposure to ionizing radiation in hemodialysis patients.
American Journal of Kidney Diseases | 2010
Ciara N. Magee; Samar Medani; Sean F. Leavey; Peter J. Conlon; Michael R. Clarkson
Rhabdomyolysis is a known complication of statin therapy and may be triggered by a pharmacokinetic interaction between a statin and a second medication. Fatal statin-induced rhabdomyolysis has an incidence of 0.15 deaths/million prescriptions. We describe 4 cases of severe rhabdomyolysis with the common feature of atorvastatin use and coadministration of fusidic acid. All cases involved long-term therapy with atorvastatin; fusidic acid was introduced for treatment of osteomyelitis or septic arthritis. Three cases occurred in the setting of diabetes mellitus, with 2 in patients with end-stage renal disease, suggesting increased susceptibility to atorvastatin-fusidic acid-induced rhabdomyolysis in these patient populations. Of the 4 patients in this series, 3 died. Fusidic acid is a unique bacteriostatic antimicrobial agent with principal antistaphylococcal activity. There have been isolated reports of rhabdomyolysis attributed to the interaction of statins and fusidic acid, the cause of which is unclear. Fusidic acid does not inhibit the cytochrome P450 3A4 isoenzyme responsible for atorvastatin metabolism; increased atorvastatin levels due to inhibition of the glucuronidation pathway may be responsible. Considering the low frequency of fusidic acid use, the appearance of 4 such cases within a short time and in a small population suggests the probability that development of this potentially fatal complication may be relatively high.
Journal of The American Society of Nephrology | 2016
Vincent P. O’Reilly; Limy Wong; Claire Kennedy; Louise A. Elliot; Shane O’Meachair; Alice M. Coughlan; Eoin C. O’Brien; Michelle Ryan; Diego Sandoval; Emma Connolly; Gerjan Dekkema; Jiaying Lau; Wayel H. Abdulahad; Jan Stephan Sanders; Peter Heeringa; Colm Buckley; Cathal P. O’Brien; Stephen Finn; Clemens D. Cohen; Maja T. Lindemeyer; Fionnuala B. Hickey; Paul V. O’Hara; C. Feighery; Sarah Moran; George Mellotte; Michael R. Clarkson; Anthony J. Dorman; Patrick T. Murray; Mark A. Little
A specific biomarker that can separate active renal vasculitis from other causes of renal dysfunction is lacking, with a kidney biopsy often being required. Soluble CD163 (sCD163), shed by monocytes and macrophages, has been reported as a potential biomarker in diseases associated with excessive macrophage activation. Thus, we hypothesized that urinary sCD163 shed by crescent macrophages correlates with active glomerular inflammation. We detected sCD163 in rat urine early in the disease course of experimental vasculitis. Moreover, microdissected glomeruli from patients with small vessel vasculitis (SVV) had markedly higher levels of CD163 mRNA than did those from patients with lupus nephritis, diabetic nephropathy, or nephrotic syndrome. Both glomeruli and interstitium of patients with SVV strongly expressed CD163 protein. In 479 individuals, including patients with SVV, disease controls, and healthy controls, serum levels of sCD163 did not differ between the groups. However, in an inception cohort, including 177 patients with SVV, patients with active renal vasculitis had markedly higher urinary sCD163 levels than did patients in remission, disease controls, or healthy controls. Analyses in both internal and external validation cohorts confirmed these results. Setting a derived optimum cutoff for urinary sCD163 of 0.3xa0ng/mmol creatinine for detection of active renal vasculitis resulted in a sensitivity of 83%, specificity of 96%, and a positive likelihood ratio of 20.8. These data indicate that urinary sCD163 level associates very tightly with active renal vasculitis, and assessing this level may be a noninvasive method for diagnosing renal flare in the setting of a known diagnosis of SVV.
American Journal of Nephrology | 2015
Mark Canney; Dearbhla Kelly; Michael R. Clarkson
Posterior reversible encephalopathy syndrome (PRES) is an uncommon clinico-radiological condition that can result in severe brain injury. The pathogenesis of cerebral vasogenic edema, the hallmark of PRES, is not fully understood. Despite its name, there is substantial heterogeneity both in terms of imaging findings and outcome. Relatively little is known about PRES in kidney disease despite the clustering of risk factors including hypertension, autoimmune disease and immunosuppression. In a retrospective observational study of incident end-stage kidney disease patients in Southwest Ireland over a ten year period, we discovered five cases of PRES representing an incidence of 0.84% in this patient population. These five cases highlight the variability in clinical presentation and the potentially life-threatening nature of this condition. We provide an in-depth review of the existing literature regarding PRES in terms of its pathogenesis and heterogeneity, as well as the experience of PRES in ESKD patients. PRES appears to be rare in the ESKD population but could be under-recognized. Marked hypertension is a cardinal risk factor in this population, associated with extracellular fluid volume expansion. Neuroimaging findings can be diverse involving both anterior and posterior circulation territories. Three of the five patients described had commenced haemodialysis within four weeks of their presentation. These patients may be particularly vulnerable to microvascular brain injury, which can be devastating. This emphasises the need for clinicians to pay meticulous attention to extracellular fluid volume control during this potentially hazardous period.
Blood Cells Molecules and Diseases | 2010
Wei Cao; Mary McMahon; Bo Wang; Rosemary O'Connor; Michael R. Clarkson
The hereditary hyperferritinemia cataract syndrome (HHCS) is an autosomal dominant disorder characterized by juvenile-onset cataracts and elevated serum ferritin levels. It is caused by mutation in the iron response element (IRE) within the 5UTR of L-ferritin gene. The mutation results in a loss of post-transcriptional negative feedback exerted by the interaction between iron regulatory proteins 1, 2 (IRP1 and IRP2) and IRE, which leads to uncontrolled expression of L-ferritin. In this paper, we describe the molecular pathogenesis of non-hereditary hyperferritinemia cataract syndrome (non-H-HCS) in a patient with typical HHCS ocular lens morphology and high ferritin levels without obvious family history. Initial sequencing of the full-length L-ferritin cloned from genomic DNA demonstrated a mutation (C33>T) in the IRE of the affected patient but not in her unaffected family members. The mutation (C/T heterozygote) was also detected in cDNA derived from her blood mononuclear cells. Structure-prediction-modeling indicates that this mutation would significantly alter the secondary structure of the IRE, resulting in a loss of the interaction between IRP and IRE. By using IRP1/IRP2-human IgG1 Fc fusion proteins, we established a novel in vitro report system (modified ELISA) to verify impaired IRE/IRP binding. Both the C33>U and A40G mutations (the first identified mutation for HHCS) showed a dramatically decreased binding to IRP1/IRP2 protein, compared to the normal IRE RNA. Surprisingly, a decrease in L-ferritin mRNA levels was observed in the affected patient compared to controls suggesting a mechanism of transcriptional negative feedback by high intracellular L-ferritin protein levels not described heretofore. Taken together, spontaneous mutation in the IRE of L-ferritin may cause non-H-HCS by the same mechanism as HHCS. In addition, under abnormal circumstances, the protein level of L-ferritin may be principally controlled by post-transcriptional regulation rather than the transcriptional regulation. The successful establishment of an ELISA report system provides an alternative method to evaluate precisely the interaction between protein and RNA.
Clinical Journal of The American Society of Nephrology | 2016
Mark Canney; Paul V. O’Hara; Caitriona M. McEvoy; Samar Medani; Dervla M. Connaughton; Ahad A. Abdalla; Ross Doyle; Austin G. Stack; Conall M. O’Seaghdha; Michael R. Clarkson; Matthew D. Griffin; John Holian; Anthony Dorman; Aileen Niland; Mary T. Keogan; Eleanor Wallace; Niall Conlon; Cathal Walsh; Alan Kelly; Mark A. Little
BACKGROUND AND OBJECTIVESnAn environmental trigger has been proposed as an inciting factor in the development of anti-GBM disease. This multicenter, observational study sought to define the national incidence of anti-GBM disease during an 11-year period (2003-2014) in Ireland, investigate clustering of cases in time and space, and assess the effect of spatial variability in incidence on outcome.nnnDESIGN, SETTING, PARTICIPANTS, & MEASUREMENTSnWe ascertained cases by screening immunology laboratories for instances of positivity for anti-GBM antibody and the national renal histopathology registry for biopsy-proven cases. The population at risk was defined from national census data. We used a variable-window scan statistic to detect temporal clustering. A Bayesian spatial model was used to calculate standardized incidence ratios (SIRs) for each of the 26 counties.nnnRESULTSnSeventy-nine cases were included. National incidence was 1.64 (95% confidence interval [95% CI], 0.82 to 3.35) per million population per year. A temporal cluster (n=10) was identified during a 3-month period; six cases were resident in four rural counties in the southeast. Spatial analysis revealed wide regional variation in SIRs and a cluster (n=7) in the northwest (SIR, 1.71; 95% CI, 1.02 to 3.06). There were 29 deaths and 57 cases of ESRD during a mean follow-up of 2.9 years. Greater distance from diagnosis site to treating center, stratified by median distance traveled, did not significantly affect patient (hazard ratio, 1.80; 95% CI, 0.87 to 3.77) or renal (hazard ratio, 0.76; 95% CI, 0.40 to 1.13) survival.nnnCONCLUSIONSnTo our knowledge, this is the first study to report national incidence rates of anti-GBM disease and formally investigate patterns of incidence. Clustering of cases in time and space supports the hypothesis of an environmental trigger for disease onset. The substantial variability in regional incidence highlights the need for comprehensive country-wide studies to improve our understanding of the etiology of anti-GBM disease.
American Journal of Nephrology | 2012
Donal J. Sexton; Michael R. Clarkson; M.J. Mazur; W.D. Plant; Joseph A. Eustace
Background: The nephrotic syndrome is associated with an increased risk of venous and arterial thrombosis. There are little published data on the distribution, interpretation or determinants of serum D-dimer levels in patients with the nephrotic syndrome. We aimed to describe this relationship. Methods: This was a cross-sectional study of 100 patients with the nephrotic syndrome. Multivariate linear regression was used to evaluate for independent predictors of elevated D-dimer levels. Patients were observed for a period of 2 years after the baseline measurement of D-dimer level to assess for subsequent clinically evident thrombosis. Results: On univariate linear regression, D-dimer elevation was associated with age in years β (95% CI) 0.02 (0.016, 0.03), log-transformed urinary protein:creatinine ratio in g/g 0.439 (0.32, 0.558) and inversely with serum albumin in g/l –0.05 (–0.073, –0.035) and estimated glomerular filtration rate (eGFR) in ml/min/1.73 m2 –0.01 (–0.016, –0.003). On multivariate linear regression, age in years β (95% CI) 0.019 (0.012, 0.026), serum albumin in g/l –0.023 (–0.043, –0.003), and log-transformed urinary protein:creatinine ratio in g/g 0.266 (0.124, 0.408) were independently associated with elevated D-dimer levels. Conclusion: D-dimer levels are commonly raised in the nephrotic syndrome in the absence of clinically evident thrombosis, and are independently associated with age, degree of proteinuria and serum albumin, but not with eGFR. Baseline levels of D-dimer did not predict subsequent episodes of clinically evident thrombosis after 2 years of follow-up.
Practical Neurology | 2017
Dearbhla Kelly; Michael R. Clarkson; Simon Cronin
Neurological symptoms commonly occur in chronic kidney disease and may result from its treatments and complications. Impaired renal function also influences treatments for other neurological conditions, requiring various cautions, dose adjustments and timing considerations, particularly in the context of renal replacement therapy. In this review, we present six illustrative clinical vignettes to highlight these challenges.
Ndt Plus | 2011
Donal J. Sexton; Kara M. Vaughan; Carthage Moran; William D. Plant; Michael R. Clarkson; Joseph A. Eustace
Spina bifida (SB) is associated with chronic kidney disease as a result of vesicoureteric reflux. A proportion of patients progress to end-stage kidney disease (ESKD). Haemodialysis (HD) is probably the most common modality in ESKD, as intra-abdominal malformations and previous surgery can make peritoneal dialysis more challenging. The Chiari malformations also frequently occur in these patients. We report a case of recurrent syncope induced by HD in a patient with SB and the Chiari II malformation. Sparse data exist on the complications of HD in this patient population and on the approach to the management of dialysis-induced syncope in these individuals.
Nephrology Dialysis Transplantation | 2015
Yvelynne P Kelly; Sarah Moran; Dearbhla M Kelly; Limy Wong; Mark A. Little; Michael R. Clarkson