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Could Cystatin C improve the detection of Pre-eclampsia ?
- Prof. Enrique J. Sánchez-Delgado MD (16 April 2008)
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Proteinuria in Pregnancy
- Muthukrishnan Jayaraman (7 May 2008)
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Proteinuria in pregnancy; not always pre-eclampsia
- Clara J Day, Graham W Lipkin, Consultant Nephrologist (8 May 2008)
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Optimal cut-off point for protein:creatinine ratio
- Shehnaaz Jivraj, Dilly Anumba, Consultant Obstetrician and Senior Lecturer, Jessop Wing, Tree Root Walk, Sheffield, S10 2SF (19 May 2008)
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Prof. Enrique J. Sánchez-Delgado MD, Director of Medical Education.Internal Medicine-Clinical Pharmacology Hospital Metropolitano Vivian Pellas, Managua, Nicaragua
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The excellent review by Côté et. al. is based on urinary spot protein:creatinine ratio for proteinuria in hypertensive pregnant women to improve the diagnostic accuracy. The negative likelihood ratio permits to rule out significant proteinuria. We still need a more sensitive and specific test to detect Pre- eclampsia, besides Hypertension and Proteinuria. Serum Cystatin C has been widely studied and confirmed to be more sensitive and specific than Creatinine. Recently it was reported that early kidney impairment might play a role in the pathogenesis of essential hypertension, and that each 15 nmol/l increase in cystatin C was associated with a statistically significant 15% greater incidence of hypertension (1) Could the use of serum Cystatin C, combined with spot proteinuria (or, if possible,not known to me yet, a urinary spot protein:cystatin C ratio) plus hypertension, permit an earlier and improved detection of Pre- eclampsia ? Prof. Enrique Sánchez-Delgado MD Ref.1. Bryan Kestenbaum et. al.Ann Intern Med 2008; 148: 501-508 Competing interests: None declared |
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Muthukrishnan Jayaraman, SR Endocrinology Medwin Hospital, Hyderabad, India-500001
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Urinary tract infection and inflammation is a common occurence in Pregnancy. This may vitiate the urinary albumin concentration estimation. It is recommended that a routine urinalysis to rule out urinary tract infection should precede estimation of proteinuria with urine albumin - creatinine ratio in women. This will help reduce false positive results and improve the specificity of this spot test. Competing interests: None declared |
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Clara J Day, Specialist registrar in Nephrology University Hospital Birmingham NHS Foundation Trust, Edgbaston, Birmingham B15 2TH, Graham W Lipkin, Consultant Nephrologist
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Dear Editor, We welcome the systematic review by Côté et al assessing the use of spot protein:creatinine (PCR) or albumin:creatinine ratios (ACR) for the measurement of proteinuria in pregnancy. These are valuable investigatory tools when compared to the imprecise measure provided by urine dipstick analysis or time-consuming and often inaccurate 24 hour urine collections. We agree that the detection of low grade proteinuria in pregnancy in the context of hypertension is useful for the diagnosis of pre-eclampsia but emphasise, as do the authors, that pre-eclampsia may occur in the absence of proteinuria. Moreover, proteinuria in pregnancy can indicate renal disease unrelated to pre-eclampsia. Urinary tract infection may cause a transient rise in proteinuria (certainly above the 30mg/mmol described) and should always be ruled out. In addition, parenchymal renal disease may be diagnosed for the first time in pregnancy by the detection of proteinuria on routine screening and is often accompanied by hypertension[1]. This should present earlier in pregnancy than pre- eclampsia but may be amplified by the physiological increase in proteinuria seen in the second trimester. As patients with such primary renal disease are more at risk of developing pre-eclampsia, diagnosis and management is often complex. After exclusion of infection we recommend that all women presenting with significant proteinuria, as judged by elevated PCR or ACR before 20 weeks should be discussed with a nephrologist. Ante-natal screening procedures ensure that pregnancy provides a valuable diagnostic window for unidentified renal disease. 1. Day C, Hewins P, Hildebrand S, Sheikh L, Taylor G, Kilby M, Lipkin G. The role of renal biopsy in women with kidney disease identified in pregnancy. Nephrol Dial Transplant. 2008 Jan;23(1):201-6. Competing interests: None declared |
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Shehnaaz Jivraj, SpR Obstetrics & Gynaecology Jessop Wing, Tree Root Walk, Sheffield, S10 2SF, Dilly Anumba, Consultant Obstetrician and Senior Lecturer, Jessop Wing, Tree Root Walk, Sheffield, S10 2SF
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Published guidelines have suggested using a protein:creatinine ratio (PCR) cut-off point of 30mg/mmol for diagnosing significant proteinuria. Cote et al (2008) have demonstrated that this cut-off point is a reasonable rule-out test for proteinuria of 0.3g/day or more.1 At present, PCR is not employed in the majority of maternity units in the UK. Instead a 24-hour quantitation of proteinuria is done. While the latter is the gold standard diagnostic test for significant proteinuria in pre-eclampsia, many women are still admitted to hospital to have this done. This has substantial resource and economic implications and poses the added problems of incomplete collection and poor timing of return of specimens for analysis.2 We therefore agree with the authors that the use of protein:creatinine ratios may facilitate the diagnosis of new significant proteinuria by enabling results the same day the patient first attends the hospital.
However based on a small sample of women in our local hospital we advocate a protein: creatinine ratio cut-off level of ≥20 mg/mmol for instigating 24 hour collection. Our small data set comparing cut-off values of 30mg/mmol to20 mg/mmol are shown in the table below. Although a cut-off value of 30mg/mmol appears to give better likelihood ratios for significant proteinuria, 20mg/mmol has higher sensitivity although consequentially, a lower specificity. Employing the latter threshold, the additional resource implications of performing a few more 24 hour urine protein estimations may be obviated by the potential risk of missing women with established pre-eclampsia who may be sent home at the risk of complications in an unattended setting. It is on this basis that we recommend using 20mg/mmol as cut-off threshold for performing 24-hour collections. However we accept that further studies from both clinical and economic standpoints are required to determine the best cut-off values for routine clinical practice
References: 1. Cote A-M, Brown MA, Lam E et al. Diagnostic accuracy of urinary spot protein:creatinine ratio for proteinuria in hypertensive pregnant women: systematic review. BMJ 2008;336:1003-1006 2. Kyle, P.M., Fielder, J.N., Pullar, B., Horwood, L.J., and Moore, M.P. Comparison of methods to identify significant proteinuria in pregnancy in the outpatient setting. BJOG 2008;115:523-527.
Shehnaaz Jivraj SpR Obstetrics & Gynaecology
Dilly Anumba Consultant Obstetrician and Subsepcialist Feto-Maternal Medicine Competing interests: None declared |
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