Sudden development of low tolerance of dialysis in a young female patient

Giorgina Piccoli1, Salvatore Bontempo2, Elisabetta Mezza1, Francesca Bermond1, Giorgio Soragna1, Carlo Umberto Preve2, Alberto Jeantet1, Giuseppe Paolo Segoloni1 and Tullia Todros1

1Chair of Nephrology, Department of Internal Medicine and 2Maternal–Fetal Medicine Unit, Department of Obstetrics and Gynaecology, University of Turin, Italy Email: gbpiccoli{at}hotmail.com

Case

A.A. is a 34-year-old woman with a presumptive diagnosis of chronic glomerulonephritis who has been on haemodialysis for 9 months. She was referred late to the Nephrologist, and dialysis was started within 2 months from referral, when she had a creatinine clearance of 9 ml/min, severe hypertension and anaemia. Low titre antinuclear antibodies and moderately depressed C3 levels also were present at referral.

At the time when she began having the problem under discussion here, A.A. was being dialysed twice weekly and in good metabolic balance, with an adequate equivalent clearance (EKRc) >11 ml/min, with a range of 14–16 ml/min [1].

Because of the increase in her residual renal clearance to 12 ml/min, she was allowed to switch to one dialysis session per week during the summer, permitting an easier organization of her vacation. Her adjunct therapy consisted of: doxazosin 4 mg/day, furosemide 125 mg twice a day, CaCO3 2 g/day, calcitriol 0.25 µg on alternate days and erythropoietin-{alpha} 4000 U/week. In the previous 3 months, she had been tested for the transplantation waiting list. No cardiovascular, pulmonary or immunological problems were detected.

One week after the first skipped dialysis session, A.A. came to the medical centre complaining of oedema, malaise, hypotension and anxiety. In the previous week, her weight had increased by 2 kg, but no signs of cardiovascular overload were present. Her blood pressure was low normal (110/70 mmHg), despite self-withdrawal of antihypertensive therapy.

Since she previously had been severely hypertensive, at first the clinical picture was attributed to relative hypotension and consequent reduction of renal function due to climatic conditions (hot early summer). The dialysis frequency was increased again but, despite a stable renal function (residual creatinine clearance 12 ml/min) and the withdrawal of antihypertensives, she tolerated dialysis poorly, with frequent intra-dialytic hypotensive episodes and cramps. She denied any changes in dietary habits that could have explained the weight gain.

Her potassium was in the normal range pre- and post-dialysis (pre-, 4.8–5.2 mM/l; post-, 3.8–4.2 mM/l). Other blood tests revealed a decrease in haemoglobin from 13 to 11.2 g/dl, with a stable iron profile; EKRc remained above the target (16–18 ml/min).

Question

What is the diagnosis and differential diagnosis?

Answer to the quiz on the preceding page

The patient was pregnant.

During the wait for the results of a long series of blood tests, including an immunological profile, antiviral tests and search for anti-erythropoeitin antibodies, she came to the medical centre in tears, because she had had a positive pregnancy test.

After discussion with her gynaecologists and other care providers, A.A. decided to terminate her pregnancy in the eighth week, mainly because of personal considerations. Within 1 month, her dialysis tolerance, dry weight, anaemia and blood pressure control returned to their usual standards.

Re-evaluation of this case revealed at least four elements that could have pointed to an unexpected pregnancy as the cause of increased dialysis tolerance, anaemia, hypotension and malaise. (i) She was a young woman of childbearing age, with very good metabolic control, high residual renal clearance, and more than adequately dialysed. Menses were regular and gynaecological examinations, performed in preparation for the transplant waiting list, were normal. (ii) She showed an unexpected sudden decrease in blood pressure. In the absence of cardiac disease, this pattern is unusual during immunological flare-ups. However, decreased blood pressure is an early physiological feature of pregnancy, as is the tendency to gain weight due to interstitial pooling of sodium and water. (iii) Her residual clearance increased (from 9 to 12–14 ml/min). Again, this is unusual in immunological, viral or other systemic problems, but it could be a physiological response to pregnancy, despite the severe renal failure. (iv) Despite a normal iron profile and an increase in the EKRc, her haemoglobin decreased, due to the increased residual clearances. The differential diagnosis took into account an immunological reactivation or the rare event of red blood cell aplasia; however, the increased renal clearances and the sudden onset of the problem were less supportive of these explanations. A greater erythropoietin requirement has been described [2,3] as a hallmark of pregnancy in dialysis patients, and the optimization of erythropoeitin therapy has been suggested as a means to achieve a successful pregnancy [3,4].

Discussion

This case is both complex and trivial: although pregnancy is a common physiological condition which causes non-specific symptoms in young women, it is rare in dialysis patients [5].

Uraemia is an example of clinical mimicry, i.e. its protean effects can suggest a vast array of diseases and conditions. This case may be emblematic in this regard: when a young woman complains of malaise, weight gain and hypotension, pregnancy should be suspected. Our patient, however, was subjected to an extensive series of tests in a search for rare diseases, including red cell aplasia, while the simple explanation of pregnancy was not taken into account initially.

The patient self-diagnosed pregnancy. Her story and our approach underline two major points: first, as care providers, we look at uraemia as a very unphysiological condition, despite the continuous advances in dialysis and in support therapy; and physiological situations are often, possibly all too often, relegated outside our usual scenarios for intervention. The second point, partly related to the first, is our reluctance to discuss ‘private issues’, such as birth control, with our young dialysis patients unless specifically required [6].

We retrieved 143 relevant abstracts (from >1571 titles) in a systematic review of the literature on EMBASE and MEDLINE, using a wide search strategy that combined terms related to dialysis (free text: dialys$; hemodialys$; haemodialys$; keywords: exp renal dialysis; exp peritoneal dialysis; exp hemodiafiltration; exp hemodialysis; home) with those related to pregnancy (free text: pregnan$; childbear$; childbirth$; keywords: exp childbirth; exp multiple pregnancy). The first report was from Italy in 1971 [7], and a few cases were published in the 1970s when anything concerning life with chronic dialysis was new and worthy of attention. However, most of the retrieved reports are from the 1990s when the standard dose of dialysis had increased. In keeping with the contribution of dialysis efficiency, several reports are from Asian countries, where the dialysis dose generally is higher, taking into account the average body size of women there [8,9].

Our search strategy retrieved >600 cases of pregnancies in dialysis patients. Allowing for presumable duplications and triplications, it may be estimated that >300 pregnancies in women on dialysis were reported, including twin pregnancies and repeated pregnancies in long-term dialysis patients [10,11]. While few reports address the probability of pregnancy (which ranges from ~8% in countries where contraception is forbidden for religious reasons to <1% in the USA [5]), the overall success rate among dialysis patients who become pregnant currently is >50% [12].

These data could logically lead to a review of our policies towards birth control counselling in our dialysis patients. Few of the 143 papers dealing with pregnancy on dialysis addressed birth control in dialysis patients, a fact which underlines the need for further discussion of this topic [6,13]. In some cultural settings (such as ours in Italy), sexual activity seldom is discussed during routine dialysis follow-up unless the patient requires counselling. Indeed, the widespread opinion that pregnancy is almost impossible to achieve by those on dialysis may be misleading, as it was in this case.

If the current trend of increasing dialysis doses continues, we probably will encounter this situation more frequently, which is at the same time beautiful (because it involves the regaining of full metabolic balance) and potentially complicated (because of the psychological effects of an unwanted and unexpected pregnancy).

Conflict of interest statement. None declared.

References

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  13. Gipson D, Katz LA, Stehman-Breen C. Principles of dialysis: special issues in women. Semin Nephrol 1999; 19: 140–147[ISI][Medline]




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