Hyperaldosteronism secondary to renal agenesis: An unusual cause for hypertension in pregnancy

Abstract

Literature with regards to pregnancy related outcomes in persons with the presence of a solitary kidney of any cause is scarce. Most of the available information has been extrapolated from persons who have been renal donors. Unilateral renal agenesis affects 1 in 1500 people and can present with resistant hypertension. When a woman with a solitary kidney presents in pregnancy, it may be both a challenging diagnostic and therapeutic problem. Eplerenone, a selective aldosterone blocker has been prescribed for resistant hypertension and in the presence of pregnancy, been useful in persons with primary hyperaldosteronism and resistant hypertension due to obstructive sleep apnoea. We describe the use of Eplerenone in a patient with resistant hypertension in pregnancy, due to secondary hyperaldosteronism precipitated by renal agenesis.

1. Introduction

Unilateral renal agenesis affects 1 in 1500 people and can present as resistant hypertension [1]. Studies on patients with solitary kidneys have shown that an absent kidney on one side induces hypertrophy of the remaining renal tissue with a subsequent increase in renal plasma flow and glomerular filtration rate (GFR) per nephron. The increase in capillary pressures may lead to additional glomerular injury, proteinuria and glomerulosclerosis [2,3]. During pregnancy, there is significant increase in effective renal blood flow and GFR, which may increase the stress on a solitary kidney and induce renal impairment [4]. Pregnancies in women with solitary kidneys are at high risk for adverse outcomes. Data on pregnancy outcomes in women with a solitary kidney has been largely extrapolated from women who have been live renal donors. There has been an increased incidence of gestational hypertension and pre-eclampsia in these women. [1,5] Mineralocorticoid receptor antagonists (MRAs) have been proven to be effective in the management of resistant hypertension. [6]. We report a case of resistant hypertension in a patient with renal agenesis with secondary hyperaldosteronism managed with Eplerenone, a selective MRA.

2. Case Report

A 21-year-old primigravida was referred to our center with elevated blood pressures detected during her booking antenatal visit at 20 weeks. At presentation, she was on oral Labetalol 200 mg thrice daily and Nifedipine 10 mg once daily. She required hospitalisation at 26 weeks of gestation for optimization of control of blood pressure. Control of blood pressure was sub-optimal, despite maximum doses of four antihypertensive agents (Labetalol 400 mg four times a day, Nifedipine Retard 20 mg four times a day, Prazosin xl 5 mg-0–2.5 mg and Hydralazine 50 mg four times a day). The evaluation for secondary causes of hypertension revealed left renal agenesis as seen in Fig. 1. Biochemical evaluation revealed hypokalemia (2.8 mmol/L) due to secondary hyperaldosteronism (aldosterone > 1000 pg/ml) and elevated serum direct renin (421 mIU/ml). Her platelet count was 1,42,000/cumm, lactate dehydrogenase (LDH)was 262 U/L, aspartate aminotransferase (AST) was 20 U/l thereby ruling out Hemolysis Elevated Liver Enzymes Low Platelet (HELLP) Syndrome. Her baseline estimated GFR was 124 ml/min/1.73 sq.m. The biochemical investigations are tabulated in Table 1.

Fig. 1.

Single right kidney, MR renal angiogram- T2 weighted Image- transverse section – Yellow arrow shows right kidney on the right, blue arrow depicts the absence of the left kidney.

Table 1. Laboratory Investigation.

Parameter (units)	Value
Creatinine (mg/dl)	0.78 (0.7–1.4)
Potassium (mmol/L)	2.8 (3.5–5)
Bicarbonate (mmol/L)	22 (22–29)
Platelet count (per cu.mm)	242,000
Albumin (g/dl)	3.9 (3.5–4.5)
Renin (mIU/ml)	421
Aldosterone (pg/ml)	>1000 (25.2–392)
24-hour urine protein (mg/day)	174 (50–150) 3430 ml /24hrs

In view of resistant hypertension and hyperaldosteronism secondary to unilateral agenesis, after multidisciplinary discussion involving Obstetrics, Obstetric Medicine, Nephrology and Endocrinology, it was decided to treat her with MRAs. Eplerenone was considered over spironolactone in view of a lower affinity of eplerenone for progesterone, androgen, and glucocorticoid receptors. The addition of Eplerenone resulted in optimal blood pressure control, her potassium levels remained stable above 3.5 mmol/dl and her potassium supplementation was tapered and stopped. Her serum creatinine at our last documentation rose to 0.99 mg% from her baseline of 0.76 mg% taking her GFR to 81.7 ml/min/1.73 sq.m.

At 28 weeks of gestation, due to intermittent absent end diastolic flow to the foetus, she was taken up for an emergency LSCS. Post partum her blood pressures were well controlled on 2 anti-hypertensive agents, Nifedipine Retard 20 mg thrice daily and enalapril 5 mg twice daily, without the requirement of potassium supplements.

She delivered a boy, who was very low birth weight of 1.16 kg with an APGAR score of 4 and 8. He required prolonged stay in the Neonatal Intensive Care Unit (NICU) where he was treated for the complications of his premature birth which included respiratory distress syndrome, non-hemolytic neonatal hyperbilirubinemia, asymptomatic hypoglycemia and chronic lung disease.

3. Discussion

In 2017 Jessica Kendrick et al., in a matched cohort study, that examined pregnancy outcomes in women with renal agenesis found that, women with solitary kidneys had a higher risk of preterm delivery (OR, 2.88), delivery via caesarean section (OR 2.11), preeclampsia/eclampsia (OR 2.41) and length of inpatient stay > 3 days (OR 1.81 (5).

Eplerenone, a class B medication in pregnancy, has a low affinity for the androgen receptor and selectively binds to the mineralocorticoid receptor [7]. Eplerenone has been used in resistant hypertension in pregnancy in women with primary hyperaldosteronism and resistant hypertension due to severe OSA [6–10]. The evidence is predominantly limited to case reports and there are no large studies on their usage [7]. In all reports the doses used vary between 25 mg twice daily to a maximum of 200 mg/day. There have been no neonatal complications that have been reported based on the use of eplerenone alone. In this regard, it can be used, for patients with resistant hypertension when other therapeutic options are exhausted.

The limitations of this report may include a short duration of exposure prior to the onset of severe pre-eclampsia.

4. Conclusion

Resistant hypertension in pregnancy may induce poorer pregnancy outcomes. Although secondary hyperaldosteronism is generally managed by treating the primary cause, occasionally aldosterone antagonists may help.