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EGFR and renal failure associated with long term lithium use.
- James Shawcross, Dr. Mukesh Kripalani, Dr. Baxi Sinha, Prof. Joe Reilly, Prof John Main (3 September 2008)
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James Shawcross, Speciality Registrar in Renal Medicine South Tees Acute Hospitals NHS Trust, Directorate of Renal Medicine, James Cook University Hospital, Dr. Mukesh Kripalani, Dr. Baxi Sinha, Prof. Joe Reilly, Prof John Main
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james.shawcross{at}doctors.org.uk James Shawcross, et al.
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Edited version of article ID: 190/1/81-a Sir, We would like to comment on Morris and Benjamin’s recent editorial on the use of estimated glomerular filtration rate (eGFR) in long-term lithium users. The suggestion that routine reporting of eGFR might reduce renal failure induced by lithium implicitly acknowledges that current monitoring is sometimes inadequate, and a major part of that inadequacy relates to the poor correlation between serum creatinine (SCr) and true GFR. We don’t believe eGFR will have the desired benefit in lithium users – because firstly it offers very little advantage over SCr in this setting, and secondly it is not clear that the late diagnosis of progressive chronic kidney disease (CKD) in lithium users relates to the inadequacies of SCr. A detailed analysis of the limitations of eGFR is not appropriate in this journal, but we would stress the following. The major limitation of SCr is that it often does not become abnormal until about 50% of kidney function has been lost, especially in those with low muscle bulk. It would be good to have a better test that was accurate across the whole range of GFR, but eGFR is not that test. EGFR is derived from SCr and the measurement of SCr has unavoidable errors that are most marked when SCr is lowest – that is, in the very patients (with normal SCr) in whom we need a better test. Indeed the errors in eGFR when SCr is within the normal range are so significant that there is some debate as to whether eGFR should be reported when SCr is not elevated. The eGFR equation attempts to correct SCr for muscle bulk, because SCr is affected by creatinine production from muscle turnover as well as renal clearance. It does so by using the surrogates of age, gender and race, but the equation has only been verified in whites and African- Americans. As the authors point out, it may systematically underestimate GFR in elderly females, and thereby deny them the undoubted benefits of lithium. There are also problems in unstable or ill patients, and the understandable difficulties eGFR poses for non-nephrologists are highlighted by the authors incorrectly suggesting eGFR increases with muscle injury, fall or injection – the opposite is true. And of course in individual lithium-users followed sequentially fluctuations in eGFR are solely derived from SCr, as race and gender are constant and ageing uniform and predictable. The most important aspect of monitoring renal function in lithium users is change over time, and SCr and eGFR change in exact proportion to each other. Our experience of late referral of lithium users with CKD is not that SCr was being measured but misinterpreted, but either that it wasn’t being measured at all, or no-one was appreciating that it was changing. With regard to the latter, it is worth emphasising one mistake we often see when CKD is stable or only slowly progressive. From test to test, there is little rise in SCr, and even if the rise is noted, an early repeat test is falsely reassuring – i.e. if a SCr rises from 160umol/l to 190umol/l over six months, a repeat in one month of around 190umol/l is falsely assumed to show stability. The problem is compounded by the tendency of those doing the monitoring to only compare with one or two previous results. What all lithium users should have in their notes is a graph of SCr (or eGFR) against time, which hugely facilitates the interpretation of changes in renal function. Unfortunately, eGFR is not a quick fix for the problem of identifying slowly progressive CKD in a minority of lithium users. Robust local systems with clear guidelines and responsibilities, and improved liaison between psychiatry, primary care, biochemistry and renal services are needed. Authors: James Shawcross (Speciality Registrar, South Tees Acute Hospitals NHS Trust, Directorate of Renal Medicine, James Cook University Hospital, Marton Road, Middlesbrough TS4 3BW, UK) Mukesh Kripalani (Specialist Registrar, Tees, Esk and Wear Valleys NHS Foundation Trust, Liaison Psychiatry Team St Luke’s Hospital, Marton Road, Middlesbrough TS4 3AF, UK) drmukesh@doctors.org.uk Baxi Sinha (Consultant Psychiatrist, Tees, Esk and Wear Valleys NHS Foundation Trust, Affective Disorders Service, Clifton House, Stockton on Tees TS17 6SD, UK) Joe Reilly (Professor of Mental Health, Durham University, School for Medicine and Health, Wolfson Research Institute, Queen’s Campus, University Boulevard, Stockton on Tees, TS17 6BH, United Kingdom) John Main (Consultant in Renal Medicine, South Tees Acute Hospitals NHS Trust, Directorate of Renal Medicine, James Cook University Hospital, Marton Road, Middlesbrough TS4 3BW, UK) Declaration of Interest: The authors are working on an alogorithm for all professionals to follow for patients receiving lithium. |
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