Vasculitis and kidney involvement in pregnancy: evidence-based medicine and ethics bear upon clinical choices

Giorgina Barbara Piccoli1, Elisabetta Mezza1, Salvatore Bontempo2, Manuel Burdese1, Giorgio Soragna1, Massimo Gai1, Valentina Consiglio1, Alberto Jeantet1, Giuseppe Paolo Segoloni1, Giuseppe Piccoli1 and Tullia Todros2

1 Chair of Nephrology, Department of Internal Medicine, University of Turin and 2 Maternal-Fetal Medicine Unit, Department of Obstetrics and Gynaecology, University of Turin, Italy

Correspondence and offprint requests to: Dr Giorgina Barbara Piccoli, Department of Internal Medicine, University of Turin, Italy. Email: gbpiccoli{at}yahoo.it

Keywords: evidence-based medicine; informed consent; physician–patient relationship; pregnancy; renal disease; Wegener's granulomatosis



   Introduction
 Top
 Introduction
 Case
 Conclusion
 References
 
Wegener's granulomatosis is a rare, protean disease, with even sex distribution and higher incidence in Caucasians. Its yearly incidence is ~5–12 per 1 000 000 [1] and it displays a wide range of clinical presentations from a mild, localised lesion to widespread severe disease [2].

The age range is wide, with the peak in the 40s. Women in the childbearing age group are not spared, and pregnancy presents a critical condition both for the onset of the disease and for its flare-ups [2,3].

The decision of a patient with Wegener's granulomatosis to become pregnant presents a clinical dilemma [3]. To face it in the era of evidence-based medicine (EBM) and of patients’ right of self-determination, two tools, systematic literature search and physician–patient therapeutic alliance, were used together (as recently suggested), integrating narrative and EBM problem solving approaches [4].

To address a patient's questions, the search strategy shown in Table 1 was performed on Medline and Embase, combining terms (Mesh–Emtree and free terms) referring to Wegener's granulomatosis and those related to pregnancy.


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Table 1. Descriptive data on the pregnancies in Wegener's granulomatosis

 
In all, reports on 28 pregnancies were retrieved (Table 1); outcome data were available for 27 of those. The diagnosis of Wegener's granulomatosis occurred in pregnancy in eight out of 28 patients; 19 out of 27 pregnancies ended in live births, seven in abortions and two in maternal deaths (Table 1).

In the reviewed literature, the most common advice was to not start a pregnancy in the presence of active disease: with a clear note of caution expressed in all cases. The quality of the evidence available, however, was poor, consisting of case series and case reports, presumed to be tainted by publication biases; however, such biases affect the study and discussion of all rare diseases, especially if, as in the case of pregnancy, the condition cannot feasibly be randomized for study.

The present updating, performed after the patients decision, added only one paper to the ones retrieved by the search strategy performed at patients referral [5].



   Case
 Top
 Introduction
 Case
 Conclusion
 References
 
A 28-year-old woman was diagnosed with Wegener's granulomatosis at age 24, presenting with multisystem involvement (upper airways, ears and kidneys), a rapidly progressive course and crescentic glomerulonephritis confirmed by renal biopsy.

Her therapy initially included cyclophosphamide and steroids, and full clinical remission was obtained within 6 months. However, her renal function remained in the low normal range, with glomerular proteinuria 1–2 g/day. After 1 year in full clinical remission, she underwent a second renal biopsy, which showed 10/17 sclerotic glomeruli, with fibrotic crescents, light to moderate interstitial involvement, and no sign of active disease. She was switched to low-dose azathioprine (50 mg/day) and corticosteroids were gradually tapered and withdrawn.

When she confronted us with the clinical dilemma, she had been in full clinical remission for 2 years.

During her previous check-ups, she had mentioned her wish to become pregnant, and had asked for advice and counselling. In spring 2002, she again expressed to us a firm desire to become pregnant in the following months. At that time, her main biochemical data were as follows: serum creatinine 0.758 g/day, total protein 6.6 g/day, serum albumin 3.8 g/day, creatinine clearance 69 ml/min and proteinuria 0.758 g/day. All immunological tests, including ANCA, were negative, as they had been for a year. She was on a spontaneous low protein diet. Her nutritional status was good, blood pressure was low normal and her therapy consisted of azathioprine 50 mg/day and ramipril 2.5 mg/day.

The available data did not allow a precise quantification of the risks she faced; a rough estimate could be made of around a 70% chance of a live birth, with a non-negligible risk of death for the patient (2/27). However, no consensus exists on what risk is ‘too high’ in the case of pregnancy. In the absence of a definite prohibitive threshold, the decision would have to be based upon the patient's choice.

In the weltanshaung of our patient, becoming pregnant was fundamental. In the available literature with its above-mentioned limitations, there is no evidence that the risks decrease by the patient spending a longer time in clinical remission before conception. On the contrary, the presence of significant morphological renal damage, despite preserved renal function, alerted us to the risk of progressive renal functional impairment, which could have further adverse impact on the success of a pregnancy.

Therefore, following the patient's decision to become pregnant, strict nephrological controls were scheduled; the low dose of azathioprine was maintained, ACE inhibitors were discontinued and the patient was referred to a centre specializing in the follow-up of high risk pregnancies.

After becoming pregnant (January 2003), the patient continued her vegetarian diet. Her renal function and urinary protein were checked twice monthly (proteinuria never exceeded 1.2 g/24 h). Despite a ‘physiological’ anaemia, requiring iron supplementation, blood tests (protein, urea, uric acid and creatinine) were within their normal ranges throughout the pregnancy. Foetal growth was assessed every 4 weeks and was normal; tests of foetal wellbeing were performed weekly, starting at 32 weeks, and were always normal. In August 2003, when pregnancy had reached the lower limits of the ‘term period’, i.e. 37 weeks, labour was induced. A caesarean section had to be performed because of dystocia and a 3240 g healthy girl was delivered.

At delivery, serum creatinine was 0.6 mg/dl and proteinuria 2.5 g/day. A short course of corticosteroids was administred, and ACE inhibitors were restarted. At present, 4 months after delivery, the patient's renal functional data are as follows: serum creatinine 0.7 g/day, total proteins 6.6 g/day, serum albumin 3.7 g/day, creatinine clearance 104 ml/min and proteinuria 0.732 g/day.



   Conclusion
 Top
 Introduction
 Case
 Conclusion
 References
 
EBM is usually considered helpful in managing those common diseases for which well-coded pathways may exist. However, the EBM approach is of interest also in the case of rare diseases, to quantify experience worldwide and to provide the grounds for an informed decision, while also highlighting the grey areas of existing knowledge [25,26].

Decisions on pregnancy call for both clinical judgement (definition of risks) and an ethical approach (definition of the limits of a patient's right of self determination) [26,27]. A definition of a risk threshold, above which a pregnancy should be strongly discouraged, does not exist at the moment for Wegener's granulomatosis. A physician–patient interaction of therapeutic alliance based on knowledge and trust may help define the limits of reasonable choice and a course of action in each specific case [28].

A well coordinated, strict clinical surveillance founded on the close cooperation of the different specialists involved is indispensable in the management of high risk pregnancies [29,30].



   Acknowledgments
 
This case was prepared for presentation as part of the evidence-based medicine course for the Vth year of the Medical School of the University of Torino (San Luigi), Italy.

Conflict of interest statement. None declared.



   References
 Top
 Introduction
 Case
 Conclusion
 References
 

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Received for publication: 9. 2.04
Accepted in revised form: 15. 4.04





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