Unilateral renal artery stenosis presented with hyponatremic-hypertensive syndrome – case report and literature review

Background Renal artery stenosis is one of the secondary causes of pediatric hypertension. Cases with critical unilateral renal artery stenosis manifesting with the hyponatremic hypertensive syndrome are rare and a comprehensive description of this disorder in the pediatric population is lacking in the literature. Case presentation We describe a 4-year-old boy who presented with severe hypertension, profound hyponatremia, hypokalemia, nephrotic range proteinuria, and polyuria. Distinctly, the diagnosis of hyponatremic hypertensive syndrome secondary to unilateral renal artery stenosis was confirmed in light of laboratory and radiographic findings of severe natriuresis, elevated renin, and unilateral small kidney. Two weeks following nephrectomy, there was resolution of hyponatremia, hypokalemia, nephrotic range proteinuria and hypertension. Conclusions Findings of hyponatremia, hypokalemia, hypertension, polyuria, and unilateral renal hypoplasia can be attributed to a unifying pathology of unilateral renal artery stenosis. Electronic supplementary material The online version of this article (10.1186/s12882-019-1246-9) contains supplementary material, which is available to authorized users.


Background
Hypertension in children necessitates prompt work-up and diagnosis in order to uncover and appropriately treat secondary causes, such as coarctation of the aorta, renal parenchymal diseases, renal artery stenosis, and endocrine disorders. Concurrent hyponatremia in hypertension is most commonly caused by renin-secreting tumors, renal ischemia, and renal artery stenosis after exclusion of medication-induced hypertension [1]. The central pathomechanism that underlies hyponatremic hypertension syndrome (HHS) is the stimulation and activation of the renin-angiotensin-aldosterone (RAA) axis which consequently trigger hypertension through vasoconstriction as well as fluid and salt retention. In cases of unilateral renal artery stenosis, angiotensin II induces pressure natriuresis of the non-stenotic kidney and hence produces the unique finding of hyponatremia in conjunction with hypertension.
Hyponatremic hypertensive syndrome, a disorder of severe hypertension and hyponatremia, could result from any causes of high renin conditions. The most common etiology in children is unilateral renal artery stenosis. It could present with of conscious disturbance or seizure, polydipsia and polyuria, with the characteristics of extreme hypertension, hyponatremia, hypokalemia, and proteinuria. Due to its insidious course and potential fatality, it warrants careful investigation by an astute physician [2]. Without appropriate treatment, hypertensive encephalopathy, retinopathy, cardiomyopathy, and nephropathy can develop.
Herein, we present a 4-year-old boy with HHS, caused by unilateral renal artery stenosis, featured by hypertension, hyponatremia, polyuria, and polydipsia. After nephrectomy, he achieved full clinical recovery without sequelae.
In terms of management for this case, we began with volume repletion by normal saline administration. Subsequently, his blood pressure declined from 210/120 mmHg to 180/90 mmHg. Intravenous calcium channel blocker was used to treat his hypertensive emergency, while oral captopril was prescribed for RAA axis blockage after diagnosis of unilateral renal artery stenosis. The systolic blood pressure gradually declined to 150~160 mmHg on the 3rd day. Potassium supplement was infused for his profound hypokalemia and generalized muscle weakness. Due to the severity of left renal artery stenosis, he was not a candidate for angiographic intervention, and decision was made to proceed with left nephrectomy. Overall, electrolyte abnormalities such as hyponatremia and hypokalemia were corrected within 1 week after admission, and resolution of polyuria, polydipsia, proteinuria, and hypertension were achieved 2 weeks after nephrectomy (Additional file 1: Table S1).

Discussion and conclusions
This 4-year-old boy presented with severe hypertension and volume depletion. Comprehensive examinations excluded the possibility of coarctation of great vessels and renal parenchymal diseases and pointed towards an overactive renin-angiotensin-aldosterone axis. The presentation of natriuretic-hyponatremia, hypokalemia, polyuria, nephrotic range proteinuria, and hyperreninemic-hypertension was highly suggestive of HHS. Aside from HHS, primary neurologic diseases such as intracranial hemorrhage or malignancy may also cause hypertension and hyponatremia, secondary to the increase in intracranial pressure and inappropriate secretion of antidiuretic hormone. However, these diseases usually present with focal neurologic deficits and decreased urine output, which could be distinguished from the polyuria and volume depletion of HHS caused by the renal artery stenosis.
The main pathogenesis of HHS is renal ischemia, as shown in Fig. 2. Hypertension is induced by stimulation of unremitted renin secretion and subsequent angiotensin II-induced vasoconstriction and secondary hyperaldosteronism. Elevated circulating angiotensin II can cause glomerular hyperfiltration and subsequential pressure natriuresis of the non-stenotic kidney, which results in the clinical presentation of hyponatremia [3]. In addition, volume depletion contributes to the development of hyponatremia by stimulating the secretion of the anti-diuretic hormone. Sodium wasting and volume depletion further stimulates the renin excretion [4]. Hyperaldosteronism, secondary to hyperreninemia and volume depletion, lead to hypokalemia which is one of the leading complications of HHS. Glomerular hyperfiltration of contralateral healthy kidney, deriving from hyperreninemia-induced hypertension, could eventually result in tubulointerstitial injury from the effects of hypercalciuria and hyperuricosuria [5]. Proteinuria in cases of HHS, sometimes in nephrotic range, can result from the glomerular hyperfiltration, proteinuric effect of angiotensin II, and/or consequence of tubulointerstitial injury caused by prolonging hypercalciuria and hyperuricosuria [6].
The mainstay of treatment for renal artery stenosisassociated HHS lies in the restoration of intravascular volume, prevention of acute insult of hypertensive crisis and correction of underlying renal arterial stenosis. Volume depletion needs to be corrected first to improve systemic blood flow and prevent further injury resulting from renal ischemia [7]. After volume repletion, the prompt decline of blood pressure could be achieved by intravenous calcium channel blocker, which has been suggested to be the first line drug for severe hypertension with acute kidney injury [8]. For cases with HHS, angiotensin-converting enzyme inhibitor and angiotensin II receptor blocker should be introduced to mitigate the over-activation of the RAA system [9]. However, the use of diuretics is not recommended due to the potential deleterious effects of fluid and sodium wasting which could further activate the RAA system [10]. Lastly, correction of renal artery stenosis can be achieved surgically by percutaneous renal angioplasty, renal artery reconstruction, or nephrectomy. As shown in Table 1, all patients received anti-hypertensive agents as the first line therapy. Eleven and three cases underwent angioplasty and unilateral nephrectomy, respectively. It is important to note that HHS caused by renal artery stenosis does not always result in a favorable outcome, as five patients had residual hypertension despite aggressive treatment. Several causes of residual hypertension in cases with HHS have been proposed. A longitudinal pediatric study stated that over 40% of renal artery angioplasty would develop restenosis [11]. Also, chronic kidney disease caused by prolonging tissue hypoxia and consequence of proteinuria could lead to hypertension despite restoration of renal blood flow [12]. Finally, uncontrolled hypertension itself could cause irreversible remodeling of vascular endothelium, resulting in permanent hypertension [13].  In conclusion, HHS caused by unilateral renal artery stenosis is a potentially curable and reversible disease when promptly diagnosed and appropriate treatment is implemented. Hyperreninemic hypertension, natriuretic hyponatremia, nephrotic range proteinuria, and unilateral renal hypoplasia are clinical clues that aid in uncovering the diagnosis.

Additional file
Additional file 1: Table S1. Clinical and laboratory characteristics before and after treatment. (DOC 32 kb) Abbreviation HHS: Hyponatremic hypertension syndrome