An unusual cause of nephrotic syndrome and hypertension in a young woman

(Section Editor: K. Kühn)

Luis Álvarez1, Elisa Ortega2, Natalia Rocamora1, Ana Tormo1, Carmen María Gil1, Miguel Trigueros2 and Francisco Rivera3,

1 Servicio de Nefrología and 2 Servicio de Anatomía Patológica, Hospital General Universitario de Alicante, Departamento de Medicina Clínica, Facultad de Medicina, Universidad Miguel Hernández, Elche, Alicante and 3 Sección de Nefrología, Hospital Alarcos, Ciudad Real, Spain

Keywords: hydatidiform mole; hypertension; nephrotic syndrome; pre-eclamptic nephropathy

Introduction

The most common causes of adult nephrotic syndrome in our country are focal glomerulosclerosis, membranous nephropathy and minimal-change disease [1]. There are, however, less common causes to be considered [28].

We describe a 15-year-old Spanish woman with nephrotic syndrome secondary to pre-eclamptic nephropathy in association with a total hydatidiform mole, in whom pregnancy was not initially considered.

Case

A 15-year-old Spanish woman was admitted to our hospital because of a 4-week history of asthenia, anorexia, and progressive oedema of her face, hands, and lower extremities. Two weeks before admission she had developed acute back pain without urinary or digestive symptoms. After an unsuccessful trial of non-steroidal anti-inflammatory drugs, she was brought to our hospital. At admission she had vaginal bleeding, which was interpreted as normal menstruation, starting a few days earlier. The patient had a 2-year history of bronchial asthma, intermittently treated with inhaled bronchodilators, and ferropenic anaemia, treated with oral ferrous sulphate. She denied drug abuse. Her obstetric history was unremarkable, with menarche at 12 years of age and regular menstruation.

Physical examination on admission revealed a supine blood pressure of 170/110 mmHg and mucocutaneous pallor. Abdominal palpation revealed a non-tender mass in the hypogastrium, but no hepatosplenomegaly. There was generalized oedema. The remainder of the examination was normal.

Laboratory studies showed: haemoglobin 8.4 g/dl, haematocrit 25%, white cell count 7910/µl, platelet count 126300/µl, serum glucose 69 mg/dl, serum creatinine 0.8 mg/dl, albumin 21 g/l, cholesterol 253 mg/dl. Serum bilirubin, alanine and aspartate transaminase and alkaline phosphatase were normal. Antinuclear antibodies, c-ANCA, p-ANCA and anti-GBM were absent. Tests for serum antibodies to hepatitis C virus, hepatitis B surface antigen and anti-HIV were also negative. Serum levels of complements C3 and C4, serum immunoglobulins and TSH were normal. Twenty-four-hour urine protein was 7.7 g/day, and urinary sediment contained no abnormalities.

Renal ultrasonography revealed normal kidneys and a multi-vesicular mass of 20 mm diameter, which was also seen on computed tomography (CT) (Figure 1Go).



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Fig. 1.  Abdominal CT. 20x21 cm heterogeneous mass with cystic and solid areas within and a thick capsule (thick arrow), probably of ovarian origin (thin arrow).

 
Fine-needle aspiration from the mass and a percutaneous renal biopsy were performed simultaneously. Cytology from the mass showed atypical cells suggestive of ovarian carcinoma (Figure 2Go).



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Fig. 2.  Fine-needle aspiration for cytology of the abdominal mass obtained giant cells with hyperchromic and pleomorphic nuclei, irregular nuclear membranes, and wide cytoplasm.

 
Some days later the patient developed profuse vaginal bleeding, acute abdominal pain and decreased serum haemoglobin that required transfusion with several units of blood. Gynaecological examination showed a dilated cervix with active bleeding. A pregnancy test, which had not been performed previously, was positive, and beta-human chorionic gonadotrophin (ß-hCG) concentrations were greatly elevated at 101400 mU/ml. The uterus was evacuated by the Crede manoeuvre, and a mass suggested of a trophoblastic disease was obtained. An aspiration and intracavitary evacuation under echographic control were performed. Thereafter, the uterus involuted normally and vaginal bleeding reduced progressively.

Grossly, the uterine content was a mass of 18x18x5 cm and 670 g with a grape-like appearance. Fetal parts were not present (Figure 3Go).



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Fig. 3.  Macroscopic aspect of the complete hydatidiform mole.

 
Histopathological analysis showed diffusely hydropic chorionic villi, with diffuse hyperplastic trophoblastic cells and cellular atypia consistent with a complete hydatidiform mole (Figure 4Go). Re-evaluation of the findings obtained from the initial fine-needle aspiration resulted in the conclusion that hydatidiform mole was the correct diagnosis.



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Fig. 4.  Histopathological analysis of hydatidiform mole. Chorionic villi with hydropic degeneration, trophoblastic hyperplasia, and marked atypical cells are seen.

 
Renal biopsy showed endothelial cell swelling, capillary obliteration and mesangial cell proliferation. The interstitium, tubules and arterioles were not affected. Immunofluorescence was negative. The histology of the renal changes was compatible with pre-eclamptic nephropathy (Figure 5Go).



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Fig. 5.  Renal histology. Swelling of endothelial cells with capillary obliteration and mesangial proliferation.

 
Seven days later the patient left hospital after complete remission of the nephrotic syndrome and normalization of blood pressure, haemoglobin and serum levels of ß-hCG (Figure 6Go).



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Fig. 6.  Evolution of serum levels of ß-hCG.

 

Discussion

We report a transient nephrotic syndrome in a young woman with pre-eclamptic nephropathy secondary to molar pregnancy. This association is well described in the literature [37,9,10] but the interest of our case is based on two points: the need to (i) rule out the possibility of pregnancy in a young woman with glomerular disease, and (ii) to review the clinical manifestations of hydatidiform mole.

In this case, the lack of a complete history delayed the consideration of a complicated pregnancy. The patient denied or was unaware of her pregnancy, and the vaginal bleeding, thought to be normal menstruation, justified in part the initial diagnosis. Thus, our case was initially misdiagnosed as an abdominal mass produced by an ovarian or germinal tumour with a paraneoplasic nephrotic syndrome. A pregnancy test, not considered in the primary evaluation, would have been the diagnostic key.

Hydatidiform mole is a form of gestational trophoblastic disease. Its classic symptoms include vaginal bleeding, increased uterine size, anaemia, hyperemesis, hyperthyroidism, vaginal passage of hydropic vesicles and, as we observed in our patient, early pre-eclampsia [11]. Most of the clinical manifestations are secondary to marked elevations in serum ß-hCG, which often exceeds 100000 mU/ml [12,13]. The diagnosis of complete mole is based upon characteristic ultrasound findings: no fetal or embryonic tissue, no amniotic fluid, a central heterogeneous mass with anechoic spaces, which corresponds to the hydropic vesicular changes of the trophoblast that has typically a grapelike appearance, and thecally lutein cysts. In our patient, the retrospective analysis of clinical, laboratory, and radiological data was indicative of a complete molar pregnancy.

There is some variation in the incidence of moles throughout the world. In Japan, which has the highest incidence of gestational trophoblastic disease, hydatidiform moles complicate two of every 1000 pregnancies. The rate in the United States is about one per 1000 pregnancies. Choriocarcinoma is much less common in the United States, but in Africa it is one of the leading malignant tumours in women. Differences in diet, in particular, deficiencies in carotene and animal fat, may contribute to these variations. Moreover, the risk is significantly higher in those over the age of 35 years. Nevertheless, more cases occur in women under age 35 because of the greater number of pregnancies among younger women [12,13]. The pathogenesis of hydatidiform mole is unknown. The chromosomes in a 46,XY complete mole appear to be entirely of paternal origin and probably result from dispermy; their mitochondrial DNA, however, is of maternal origin [13]. Histopathological analyses of hydatidiform moles show oedematous chorionic villi, circumferential trophoblastic proliferation and, in several non-malignant transformations, cytological atypia [1214]. In our case, cytological studies of aspirations revealed atypical cells and the echographic findings were misinterpreted as a gynaecological malignant mass.

It is well known that pre-eclampsia affects the kidney both functionally and morphologically. The reactive changes, termed ‘glomerular capillary endotheliosis’, seem to be fully reversible and without long-term cardiorenal complications [15]. Indeed, the renal complications of hydatidiform mole are the same as those appearing in pre-eclampsia unrelated to trophoblastic diseases. It is possible that the placenta releases trophoblastic cells with cytotoxic characteristics and the capacity to cause secondary glomerular endothelial damage [16]. Other authors have speculated about the role of intravascular coagulation [2,6] or immunological mechanisms [5,9]. In our case, however, coagulation was normal and renal immunofluorescence negative.

Teaching points

(i)  In the initial evaluation of nephrotic syndrome in fertile women, an occult or complicated pregnancy should be considered.
(ii) Hydatidiform mole can present as nephrotic syndrome with hypertension, simulating severe pre-eclampsia.
(iii) The evacuation of the mole normally results in the complete remission of all renal manifestations.

Acknowledgments

We gratefully acknowledge the technical assistance of Marcial García-Rojo.

Notes

Correspondence and offprint requests to: Dr Francisco Rivera Hernández, Sección de Nefrología. Hospital Alarcos, Avenida Pío XII, s/n, 13002 Ciudad Real, Spain. Email: francisco.rivera{at}wanadoo.es Back

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