Rapid Responses to:
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Rapid Responses: Rapid Responses published:
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![[Read Rapid Response]](/icons/misc/sectionDOWN.gif)
Measuring proteinuria: albumin or total protein?
- Mark S MacGregor (5 October 2008)
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measuring proteinuria
- Charles Heatley (7 October 2008)
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NICE Guidance on CKD
- Christopher G Winearls, Richard Glassock (20 October 2008)
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Time to differentiate 'function' from 'disease'.
- Malvinder S Parmar (31 October 2008)
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Definition of Non Visible Haematuria
- Des Ling (2 December 2008)
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Mark S MacGregor, Consultant Nephrologist John Stevenson Lynch Renal Unit, NHS Ayrshire & Arran, Crosshouse Hospital, Kilmarnock, KA2 0BE
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The Scottish Intercollegiate Guidelines Network (SIGN) produced a guideline on chronic kidney disease in June 2008 (1). The recommendations are similar to the National Institute for Health and Clinical Excellence's (NICE) guideline (2) with one important difference. Both guidelines highlight the importance of formally measuring proteinuria in patients being assessed or monitored for chronic kidney disease. However, NICE recommends measuring proteinuria with an albumin:creatinine ratio in all patients, whereas SIGN recommends using albumin:creatinine ratio in patients with diabetes mellitus, and protein:creatinine ratio in non-diabetic patients. As Crowe and colleagues (3) state, in non-diabetic patients, the evidence of increased renal risk associated with proteinuria (4), and the evidence of reduced risk with interventions (5) is based on total proteinuria, not albuminuria. Protein:creatinine ratio predicts total proteinuria well, but albumin:creatinine ratio does not. The NICE guideline has extrapolated further from the evidence than the SIGN guideline. It assumes that albuminuria is a more sensitive detector of increased renal risk, but cites weak studies based on estimated glomerular filtration rate in chronic kidney disease stages 1 and 2, which did not measure total proteinuria. The NICE guideline assumes that interventions based on total proteinuria thresholds will apply equally to the albuminuria thresholds chosen, with little supporting evidence. The guideline also assumes that patients with protein:creatinine ratio >50 mg/mmol but albumin:creatinine ratio <30 mg/mmol will not benefit from intervention, again with no evidence. It is possible that these assumptions are correct but none have been adequately tested. It is also important to note that the p suffix in Scotland denotes patients with a protein-creatinine ratio >100 mg/mmol or 24-hour urinary protein >1 g/day, whereas in England it will denote a group with ACR >30 mg/day, thus identifying two different patient populations. Although important, this technical debate should not distract from the key message of both guidelines that formally measuring proteinuria identifies patients at increased risk of kidney and cardiovascular disease. 1. Scottish Intercollegiate Guidelines Network. Diagnosis and management of chronic kidney disease: a national clinical guideline. SIGN 103. SIGN, Edinburgh, June 2008. www.sign.ac.uk/guidelines/fulltext/103/index.html 2. National Institute for Health and Clnical Excellence. Chronic kidney disease: early identification and management of chronic kidney disease in adults in primary and secondary care. (Clinical guideline 73) NICE: London, Sept 2008. www.nice.org/Guidance/CG73/NiceGuidance/pdf/English 3. Crowe E, Halpin D, Stevens P. Early identification and management of chronic kidney disease: summary of NICE guidance. BMJ 2008;337:a1530. 4. Jafar TH, Stark PC, Schmid CH, Landa M, Maschio G, Marcantoni C et al. Proteinuria as a modifiable risk factor for the progression of non-diabetic renal disease. Kidney Int 2001;60:1131-40. 5. Jafar TH, Stark PC, Schmid CH, Landa M, Maschio G, de Jong PE et al. Progression of chronic kidney disease: the role of blood pressure control, proteinuria, and angiotensin-converting enzyme inhibition: a patient-level meta-analysis. Ann Intern Med 2003;139:244-52. Competing interests: I was a member of the SIGN CKD Guideline Development Group |
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Charles Heatley, GP partner Birley Health Centre S12 3BP, UK
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Talk to a bunch of GPs and you will find that CKD occupies those areas about which we claim still to know little and are easily confused. I thought I had just about cleared up the confusion regarding which test to request for proteinuria. This guideline introduces yet more uncertainty. We may think we are doing a good job when we may merely be wasting time and money asking for a lot of information we are not interpreting appropriately. Competing interests: None declared |
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Christopher G Winearls, Consultant Nephrologist Oxford Kidney Unit OX3 7LJ, Richard Glassock
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Crowe et al have provided a succinct summary of NICE guidance on early identification and management of CKD. 1 We raise two issues with them. 1. The recommendations for early detection are sensible, offering testing for those at risk. The test is an estimate of GFR. Unfortunately, the mandatory reporting of eGFR means that the test is often available before the identification of risk. A single laboratory test is then translated not only into a diagnosis but also a stage of a chronic disease. This is opportunistic screening.2 The error is compounded by the fact that the MDRD formula for estimating GFR is only moderately reliable for quantifying the “true” GFR in patients with unequivocally reduced kidney function but quite unreliable for defining normal renal function 3. 2. They also describe the recommended modifications to the current version of the CKD Staging System. Any modification is to be welcomed 4 Former attempts have been rejected on the grounds that the present system is at least simple. 5 Stage 3 is to be subdivided into A and B by GFR 30-44 vs. 45-59ml/min/1.73m2 , and for each stage the presence or of proteinuria defines a subcategory. If this modification is accepted there will be twelve categories instead of five and 2 suffixes. Where is the evidence that patients in each of these twelve stages are qualitatively different from one another? What is more perplexing is the loyalty to perpetuating Stages 1 and 2. Stage 1 is currently defined as the presence of renal disease with a “normal or increased” GFR (>90ml/min/1.73m2). Population studies of the distribution of eGFR show that the majority of normal subjects have an eGFR of <90ml/min/1.73m2. 6,7 Moreover, the MDRD formula cannot reliably predict GFR in the 60-120/ml/min/1.73m2 range. It would be more logical to define Stage 1 as the presence of renal disease diagnosed by histology, imaging or abnormalities in the urine, but with renal function preserved within the normal range (95% CI) for age and gender. 7 It would have been helpful if NICE, having started to modify the Staging System, had completed a much needed task. Christopher G Winearls, Consultant Nephrologist, Oxford Radcliffe Hospitals NHS Trust Richard Glassock, Emeritus Professor of Medicine, David Geffen School of Medicine, UCLA Competing interests: None 1. Crowe E, Halpin D, Stevens, P- On behalf of the Guideline Development Group. Guidelines. Early identification of and management of chronic kidney disease: a summary of NICE guidance. BMJ 2008;337:612-815 2 Glassock R and Winearls C. Screening for CKD with eGFR: doubts and dangers. Clin J Am Soc Nephrol 2008;3:1563-8. 3. Froissart M, Rossert J, Jacquot C, Paillard M, Houllier. Predictive performance of the Modification of Diet in Renal Disease and the Cockcroft -Gault equations for estimating renal function. J Am Soc Nephrol 2005; 16:763-773 4. Bauer C, Melamed ML and Hostetter TH. Staging of Chronic Kidney Disease: Time for a course correction. J Am Soc Nephrol 2008; 19:844-6 5. Eknoyan G. Chronic kidney disease definition and classification: the quest for refinements. Kidney Int 2007;72:1183-1185 6 de Lusignan S, Chan T, Stevens P, O'Donoghue D, Hague N, Dzregah B, Van Vlymen J, Walker M, Hilton S. Identifying patients with chronic kidney disease from general practice computer records. Fam Pract. 2005 22:234-41 7. Wetzels JFM, Kiemency LALM, Swinkels DW, Willems HL, den Heijer M. Age -and gender specific reference values of estimated GFR in Caucasians: The Nijmegen Biochemical Study. Kidney Int 2007; 72:632-637 Competing interests: None declared |
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Malvinder S Parmar, Associate professor, Northern Ontario School of Medicine 640 Ross Ave. East, Suite E, Timmins, ON. P4N 8P2, Canada
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Let’s not confuse ‘function’ with ‘disease’. Kidney function (KF) is similar to left ventricular function (LVEF) – a number with prognostic implications irrespective of the underling disease process. As some healthy persons may have Grade 2 LV function without heart disease, similarly many healthy elderly persons may have stage 3 kidney function (KF) without kidney disease. In both circumstances, there may be increased risk of cardiovascular mortality (as shown in various epidemiological studies – although these studies suggested increased CV risk with stage 3 CKD but none clearly established that all patients with decreased estimated glomerular filtration rate (eGFR) really had kidney disease, my understanding is, that it is stage 3 KF rather than 'true' stage 3 CKD) and we should all recognize this without undermining the importance of these implications. The estimated eGFR gives a number that in this circumstance describes nothing else than the ‘kidney function.’ It is important to recognize that decreased function doesn’t mean disease and disease doesn't mean decreased kidney function. I can understand the confusion created by the current guidelines among the promary care providers and non-nephrologists, when there is not a consensus among nephrologists and concerns about the current guidelines are being published rapidly. The so called ‘epidemic of CKD’ is created by ballooning of stage 3, where many healthy elderly persons with low normal eGFR have been classified as having a disease and undergoing unnecessary investigations, nephrology consultations and wasting resources. I fully agree with division of stage 3 kidney function into 2 stages – stage 3A and stage 3B, as proposed by NICE. “Kidney disease” and “Kidney function” are separate and doesn’t always correlate, although majority of persons with decreased kidney function – stage 3b, 4 and 5 have kidney disease. I believe that current staging based on eGFR [understanding that it only defines a function] is reasonable but requires modification and should consider classifying as stages of kidney function (KF) than stages of disease (CKD), as patients with normal function may have disease and similarly person with decreased eGFR may not have the disease. I agree with Bauer et al[1] that reporting eGFR with all serum creatinine levels is valuable in recognizing reduced kidney function, irrespective of whether the individual has kidney disease or not, that would improve drug dosing and reduce nephrotoxin exposure in such individuals. The kidney disease should be labeled as an individual diagnosis and the term ‘CKD’ should be reserved for persons with ill-defined kidney disease. A patient with IgA nephritis with eGFR of 55 ml/min/1.73 m2 should be classified as, “IgA nephritis stage 3 KF” than “IgA nephritis stage 3 CKD”. An elderly person with no underlying kidney disease may then be classified as, “no evidence of kidney disease, stage 3 KF” or “ Stage 3 KF, possibly age-related” and a person with chronically scarred kidneys with eGFR of 55 ml/min/1.73 m2 may then be classified as, “CKD, stage 3 KF”. Lumping together several diseases into a single large group “CKD” based on eGFR potentially may results in failure of diagnosis in some patients2. The recommendation that all patients with diabetic kidney disease should undergo albumin:creatinine ratio (ACR) monitoring is NOT CORRECT and would cause MORE confusion among the practitioners as one has already alluded to in the rapid responses. If this recommendation is not modified, wait when nephrologists are going to be flooded with calls about ACR of 1000 or higher on emergent basis, especially in patients with known overt nephropathy and nephrotic range proteinuria. ACR is a screening test and should be used for screening purposes, when patients have low grade proteinuria or albuminuria, however, once urine protein excretion is over 0.5g/d, the urine dipstick is often positive for protein and when the urine dipstick is persistently positive for protein, then use of urine protein:creatinine ratio (UPR) is reasonable, a test to monitor disease progression and effectiveness of therapy. Let’s make guidelines simple that are easy to follow by primary care providers – the frontline of healthcare in all regions around the world. My simplified approach in assessing for kidney disease, irrespective of if patient has diabetes or not, is: 1. First, do simple urinalysis or urine dipstick for protein and measure of kidney function – serum creatinine and estimation of eGFR 2. If urinalysis is negative for protein or weakly positive for protein, then do ACR 3. If urinalysis is 2+ or higher for urine protein, then do UPR, than performing ACR. 4. Define underlying kidney disease process – may require referral to nephrologist 5. Determine stage of Kidney function, as per current guidelines and guide therapy and monitoring for complications of kidney disease. References: 1. Bauer C, Melamed M, Hostetter TH. Staging of Chronic Kidney Disease: Time for a course correction. J Am Soc Nephrol 2008; 19:844-6. 2. Glassock RJ, Winearls C. An epidemic of chronic kidney disease: fact or fiction? Nephrol Dial Transplant 2008; 23:1117-21. Competing interests: None declared |
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Des Ling, General Practitioner Queens Avenue Surgery, Dorchester
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Recent guidelines have suggested using dipstick urine testing to define non visible haematuria rather than microscopy on the basis that “community based urine samples sent for microscopy have a significant false negative rate; the procedure is more labour intensive, and adds little to establishing the diagnosis of haematuria”. 1,2 However abnormal red cell counts are frequently reported on samples sent for culture in cases of suspected UTI. Recently our local microbiology laboratory has changed from using direct microscopy to flow cytometry. This has led to a great increase in the number of samples being reported positive for red cells– a survey in my practice revealed from 17% to 33% borderline and from 3% to 27% abnormal. Flow cytometry red cell count NORMAL < 50 12 40% BORDERLINE 50-100 10 33% ABNORMAL > 100 8 27% ________ TOTAL 30 100% Direct microscopy red cell count NORMAL >10 24 80% BORDERLINE 10-50 5 17% ABNORMAL 50-200 0 ABNORMAL >200 1 3% ________ TOTAL 30 100% In addition, poor correlation between urine dipstick testing and flow cytometry red cell counts has been documented.3 Whilst the guidelines deal well with haematuria found on dipstick testing, primary care practitioners need guidance on how to manage abnormal red cell counts found incidentally on samples sent for culture, particularly with flow cytometry results. Des Ling general practitioner, Queens Avenue Surgery, Dorchester DT1
2EW 1.http://www.bauslibrary.co.uk/PDFS/BAUS/haematuria_consensus_guidelines_July_2008.pdf 2. http://www.nice.org.uk/nicemedia/pdf/CG073FullGuideline.pdf 3. Michel R. Langlois, Joris R. Delanghe, Sophia R. Steyaert, Karel C. Everaert, and Marc L. De Buyzere Automated Flow Cytometry Compared with an Automated Dipstick Reader for Urinalysis Clin Chem 1999; 45: 118-122 Competing interests: None declared |
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