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deterioration of the patients’ respiratory function.4 Finally, chronically infected patients who have substantial deterioration in respiratory function between courses of intravenous antibiotics despite regular treatment (including nebulised antibiotics) are considered for routine 3 monthly courses of intravenous antibiotics. Clinical judgment and extensive experience have resulted in most cystic fibrosis clinicians having a very low threshold for intravenous antibiotic treatment. In practice, many chronically infected patients receive almost regular 3 monthly courses, if not actually keeping precisely to the Danish regimen.5 Thus, in the UK and many European cystic fibrosis clinics, the standard treatment approach to P aeruginosa infection in people with cystic fibrosis is certainly not centred only on antibiotics for acute exacerbations, as your commentators state. Indeed, such a policy would now be seen as unacceptable. A high priority is accorded to prevention of infection by good hygienic measures and segregation, and if this fails, early aggressive antibiotic treatment to eradicate the infection should be used. Because the detailed recommendations for treatment of infection in UK cystic fibrosis patients are so different from those implied in the commentary, particularly relating to early treatment of P aeruginosa, UK clinicians responsible for the care of people with cystic fibrosis should ensure that they have a copy of the publication from the Cystic Fibrosis Trust.2
Cystatin C concentration and glomerular filtration rate Sir—In their report, Jaap Deinum and colleagues (Nov 11, p 1624)1 discuss the potential usefulness of serum cystatin C (sCysC) as a marker for glomerular filtration rate. However, they wonder whether sCysC dose might help clinical decisions, especially in transplant recipients, patients with diabetes, and hypertensive patients. To tentatively answer this question, we did a trial to assess the applicability of sCysC (normal values 0·5–0·96 mg/L) as a rapid estimation of glomerular filtration rate (creatinine clearance, measured by the Cockcroft and Gault formula), and analysed the sensitivity and the specificity of sCysC and serum creatinine. We included 75 patients: 27 non-haemodialysed patients with chronic renal failure (mean age 53·1 years [SD 17·9]) who had various kidney diseases (nine with diabetic nephropathies, seven with hypertensive nephroangiosclerosis, four ischaemic nephropathies, four with polycystic kidney diseases, three with interstitial nephritis) and a wide range of renal function (serum creatinine 61–721 mol/L). 17 patients who had acute renal failure, 15 who had had transplants, and 16 without renal impairment were used as controls (mean age 53·7 years [SD 10·2]). We measured serum and urine creatinine by enzymatic method, and sCysC by automated particleenhanced nephelometric immunoassay (Nephelometer System BN II, Behring 1·0
*James M Littlewood, John R W Govan *St James University Hospital, Leeds LS9 7TF, UK; and Department of Medical Microbiology, University of Edinburgh Medical School, Edinburgh (e-mail:
[email protected])
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Elusiveness of ideal approach to Pseudomonas aeruginosa infection complicating cystic fibrosis. Lancet 2000; 356: 613–14. Antibiotic treatment for cystic fibrosis. Leeds: Cystic Fibrosis Trust’s Antibiotic Group, 2000. Frederiksen B, Koch C, Hoiby N. Antibiotic treatment of initial colonization with Pseudomonas aeruginosa postpones chronic infection and prevents deterioration of pulmonary function in cystic fibrosis. Pediatr Pulmonol 1997; 23: 330–35. Ramsay BW, Pepe MS, Quan JM, et al. Intermittent administration of inhaled tobramycin in patients with cystic fibrosis. N Engl J Med 1999; 340: 23–30. Szaff M, Hoiby N, Flensborg EW. Frequent antibiotic therapy improves survival of cystic fibrosis patients with chronic Pseudomonas aeruginosa infection. Acta Paediatr Scand 1983; 72: 651–57.
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Diagnostics, Germany), which has within-assay and between-assay coefficients of variation of 1·47–2·86% and from 4·8–6·2%, respectively. In all patients, sCysC and serum creatinine correlated linearly with creatinine clearance, but sCysC showed greater diagnosis accuracy than serum creatinine (sensitivity 94%, specificity 95% vs 94% and 80%; figure). In agreement with other studies,2–5 sCysC offered a better clinical sensitivity than serum creatinine for discriminating between patients with normal renal function and those with mild to severe renal impairment (85·4 vs 78·4%, p=0·03) especially in albuminuric patients (diabetic and hypertensive patients). In all groups, slight variations in glomerular filtration rate was more easily detected by sCysC than by serum creatinine, since sCysC’s upper normal range of 0·96 mg/L corresponded to a creatinine clearance rate of about 87·5 mL/min per 1·73 m2, whereas serum creatinine was 92 mol/L. This finding is also obvious in the reciprocal relations between sCysC and serum creatinine with creatinine clearance. Serum CysC supplied greater sensitivity than serum creatinine in detecting variation in glomerular filtration rate, especially in the difficult range of serum creatinine of Scr (82–187 mol/L), and offered overall better diagnostic efficacy than the latter. With the advent of automated immunoephelometric assays for sCysC, evidence suggests that sCysC is better than serum creatinine as an endogenous marker for glomerular filtration rate. The factors limiting
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Non-parametric receiver operating characteristic plots for sCysC and for serum creatinine S-sensitivity; Sp=specificity.
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accuracy of serum creatinine include the influence of muscle mass, renal tubular metabolism, dietary intake, and various analytical difficulties with the widely used Jaffe colorimetric assay method for creatinine. *Pascal Meier, Céline Froidevaux, Eric Dayer, Edouard Blanc *Service of Nephrology, Hòpital Tenon (AP-HP) 75020 Paris, France; Division of Nephrology, Department of Internal Medicine, Hôpital de Sion, 1950 Sion, Switzerland; and Division of Infectious Diseases and Immunology, Institut Central des Hôpitaux Valaisans, Switzerland (E-mail:
[email protected]) 1
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Deinum J, Derkx FHM. Cystatin for estimation of glomerular filtration rate. Lancet 2000; 356: 1624–25. Meier P, Froidevaux C, Dayer E, Blanc E. Serum concentration cystatin C (␥-trace) as a rapid estimation of the renal function. J Am Soc Nephrol 1999; 10: 82A. Coll E, Botey A, Alvarez L, et al. Serum cystatin C as a new marker for noninvasive estimation of glomerular filtration rate and as a marker for early renal impairment. Am J Kidney Dis 2000; 36: 29–34. Ritsch L, Blumberg A, Huber A. Rapid and accurate assessment of glomerular filtration rate in patients with renal transplants using serum cystatin C. Nephrol Dial Transplant 1999; 14: 1991–96. Herget-Rosenthal S, Trabold S, Pietruck , Holtmann M, Philipp T, Kribben A. Cystatin C: efficacy screening test for reduced glomerular filtration rate. Am J Nephrol 2000; 20: 97–102.
Sir—In their Nov 11 commentary, J Deinum and F H M Derkx1 question the usefulness of cystatin C for detecting slight impairment of glomerular filtration rate. We did a study to detect short-term alterations in renal function in 15 patients with kidney stones undergoing extracorporeal shock-wave lithotropsy (ESWL). All patients had normal serum creatinine, normal creatinineclearance, and normal cystatin C concentrations. Before ESWL, we 120
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measured glomerular filtration rate2 and calculated clearance.3 We also measured serum creatinine, cystatin C, and sinistrin clearance immediately after ESWL, and on the day after the procedure. Mean creatinine was similar before and immediately after ESWL, as was cystatin C, but concentrations of both substances rose the day after the procedure. Clearances estimated by concentrations of creatinine (CockcroftGault’s method) and cystatin C (based on linear regression of 1/cystatin C on sinistrin clearance similarly to CockroftGault’s method) showed no acute changes in renal function because of shock waves. By contrast, glomerular filtration rate of sinistrin decreased significantly immediately after ESWL and recovered the day after the procedure in 13 participants (figure). The remaining two had small increases in glomerular filtration rate of 4 and 5 mL/min, respectively. Cystatin C is a stable endogenousrenal function marker since it is not dependent on inflammation, malignant disease, muscle mass, sex, or age,4 as are creatinine and other endogenous kidney markers, but it may not indicate slight, short-lasting, acute alterations of kidney function. Compartmental analysis of kinetic clearance experiments seems more useful to detect acute changes.5 We speculate that expected acute increases of the concentration of endogenous markers due to acute impairment of renal function are masked by increased distribution of the marker into the peripheral body compartments while plasma concentration remains constant. Thus, compartmental analysis gives full information of temporal concentration profiles. Sabine Zitta, Marco Auprich, Herwig Holzer, *Gilbert Reibnegger Nephrology Division, Department of Internal Medicine, University of Graz; and *Institute for Medical Chemistry and Pregl-Laboratory, University of Graz, A-8010 Graz, Austria 1
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Deinum J, Derkx FHM. Cystatin for estimation of glomerular filtration rate? Lancet 2000; 356: 1624–25. Estelberger W, Petek W, Zitta S, et al. Determination of the glomerular filtration rate by identification of sinistrin kinetics. Eur J Clin Chem Clin Biochem 1995; 33: 201–09. Zitta S, Stoschitzky K, Zweiker R, et al. Determination or renal reserve capacity by identification of kinetic systems. Math Mod Syst 2000; 6: 190–207. Randers E, Erlandsen EJ. Serum cystatin C as an endogenous marker of the renal function: a review. Clin Chem Lab Med 1999; 73: 389–95. Zitta S, Stoschitzky K, Zweiker R, et al. Dynamic renal function testing by compartmental analysis: assessment of renal functional reserve in essential hypertension. Nephrol Dial Transpl 2000; 15: 1162–69.
Why choose caesarean section? Sir—Marsden Wagner (Nov 11, p 1677)1 questions the right of women to choose caesarean section. It is important that we understand why they might want to choose to give birth this way. We interviewed 53 women who had reported postnatally that the issue of caesarean section arose during their recent pregnancy or birth; 30 underwent the procedure. Preliminary analysis suggests that women have to balance two opposing views of vaginal birth: as natural and desirable, or as natural and hazardous.2 Hazards ascribed to vaginal birth included risks to the baby (eg, getting stuck and being damaged) and to themselves (eg, urinary incontinence and the long-term consequences of perineal damage). However, caesarean section is generally described as safe. The increasing frequency of the operation appears to reinforce this belief. Women may use the term major operation and many realise they will be debilitated after surgery. When asked, most women said that they were not told of any risks1 from caesarean section to themselves or to their babies. Conversely, obstetricians and midwives interviewed as part of our study report that they do inform women of the risks. Since the aim of most women is to give birth to a healthy baby, they may be choosing caesarean section in the false belief that it is safer than vaginal birth. A reduction in the caesarean section rate may depend partly on ensuring that women understand that although the benefits of caesarean section outweigh the risks for a small proportion of births with known complications, this benefit will not apply to the majority. Until the RCOG audit of caesarean section is completed, we do not know the risk/ benefit for most of the operations being undertaken. Our continuing study is funded by the Nuffield Foundation.
*Helen Statham, Jane Weaver, Martin Richards Centre for Family Research, Social and Political Sciences Faculty, Free School Lane, Cambridge CB2 3RF, UK 1 2
Wagner M. Choosing caesarean section. Lancet 2000; 356: 1677–80. Weaver J. Talking about caesarean section. MIDIRS Midwifery Digest 2000; 10: 487–90.
Sir—The increase in caesarean-section rates addressed by Marsden Wagner1 is of concern. In Australia, at least, the
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