Critical bilateral renal arterial stenosis presenting as cardio-renal syndrome: isolated ultrafiltration preceding percutaneous transluminal revascularization.

Bilateral, severe renal artery stenosis stimulates the renin-angiotensin-aldosterone system and, as it reduces the physiologic natriuretic response, it may lead to fluid overload, renovascular hypertension, heart failure, and impaired renal function. Known as cardio-renal syndrome, the condition is treated mainly by percutaneous transluminal angioplasty.1–8 No uniform definition of cardio-renal syndrome has yet been established.9 Based on the established studies3–7 and our case report we have attempted to elaborate on the definition of cardio-renal syndrome. We report on a patient with impaired kidney function, refractory hypertension, extreme fluid overload, and high renin and aldosterone levels due to bilateral renal artery stenosis. Treatment with isolated ultrafiltration followed by bilateral percutaneous transluminal angioplasty resulted in remission of hypertension and edema and normalization of kidney function. This report is, to our knowledge, one of the first reports of treatment of severe, refractory fluid overload (+47% baseline body weight) with isolated ultrafiltration as a preparation to the percutaneous transluminal angioplasty. A 53-year-old male smoker in renal failure and hypertensive crisis without previous medical history was admitted to an outside hospital. The patient was dyspneic at rest and had massive peripheral edema, hepatomegaly, ascites, and hydrothorax. His heart rate was 88 beats per minute and blood pressure was 260/150 mm Hg. He presented with a serum creatinine level of 206.8 μmol/L (normal range, 60–130 μmol/L); blood urea of 30.5 mmol/L (normal range, 2.5–6.7 mmol/L); sodium of 128 mmol/L (normal range, 135–145 mmol/L); potassium of 3.7 mmol/L (normal range, 3.5–5.5 mmol/L); alkaline phosphatase of 332 U/L (normal range, 100–290 U/L); and γ-glutamyl-transpeptidase level of 47 U/L (normal range, 9–43 U/L). His hemoglobin was 104 g/L. Chest radiographic results demonstrated enlargement of the cardiac silhouette and enlarged hilar vessels and right hydrothorax. Abdominal ultrasonography showed ascites, hepatomegaly, kidney asymmetry (right kidney: 10.4×4.6 cm, left kidney: 7.0×5.1 cm). Transthoracic echocardiographic results revealed enlargement of all heart chambers with normal diastolic and systolic function (left ventricular ejection fraction, 64%), mild tricuspid regurgitation, and pulmonary hypertension features. During the subsequent few days the patient was treated with intravenous furosemide, his renal function worsened, oliguria developed (400 mL urine output per day), peripheral edema and ascites increased, and he developed dyspnea at rest. He was transferred to our hospital with general edema, ascites, hepatomegaly and high arterial pressure (200/100 mm Hg), a heart rate of 120 beats per minute, and a central venous blood pressure of 14 cm H2O. Auscultation revealed widespread crepitant rales. Laboratory examination revealed a serum creatinine of 315.5 μmol/L, blood urea nitrogen of 30.7 mmol/L, sodium of 124 mmol/L, and a normal serum potassium level (3.8 mmol/L). Urine examination showed only mild proteinuria. Plasma renin activity at rest and serum aldosterone levels were elevated at 18.38 ng/mL/h (normal range, 0.2–2.8 ng/mL/h) and 721.3 pg/mL (normal range, 10–105 pg/mL), respectively. Ultrasonography confirmed kidney asymmetry, with the left kidney being smaller and the presence of fluid in the pleural and peritoneal cavities. Furosemide therapy was stopped and a β-blocker (metoprolol) with a calcium channel blocker (nitrendipine) were administered to control blood pressure. Spirolactone was added at 200 mg/d with a slight diuretic effect. Due to worsening renal failure, 2 hemodialysis procedures were carried out, followed by daily isolated ultrafiltration via a central venous catheter. This treatment resulted in gradual symptomatic recovery and massive body weight reduction (from 103.8 kg to 71.0 kg), with improvement of renal function. Spontaneous diuresis of more than 2000 mL/d ensued. A renal artery angiography showed critical (95%) stenosis of the left renal artery and 75% stenosis of the right renal artery. A stent was placed into the left renal artery enabling complete recanalization, while revascularization of the right renal artery was planned for another time. (1-3). Aortography before implantation of a stent into the renal arteries. Left renal artery before stenting. Right renal artery before stenting. Six months later physical examination showed no abnormalities. Laboratory examination showed a moderate increase in creatinine (132.6 μmol/L) and urea level (5.9 mmol/L). A 24-hour blood pressure monitoring showed the average blood pressure to be 144/91 mm Hg. Control plasma renin activity and aldosterone level were 1.72 ng/mL/h and 173.3 pg/mL, respectively. At that time, a control angiography was performed and a stent was placed in the stenotic right renal artery (Figure 4). After 6 months, kidney function remained normal and blood pressure normalized. Aortonephrography after stenting of right and left renal arteries. The relationship between heart failure and bilateral renal artery stenosis leading to hypertension development was first discussed in 1988 and has appeared in several reports since.3–8 As mentioned in the introduction, the uniform definition of cardio-renal syndrome is lacking. In light of several studies,3–8 however, simultaneous occurrence of heart and renal failure is one of the established features of this syndrome. Cardio-renal syndrome can be diagnosed in the following conditions: hypervolemia in advanced renal failure, co-occurrence of heart and kidney failure (eg, ischemic heart disease and obstructive arterial disease), malignant hypertension leading to the development of simultaneous heart and kidney failure, and bilateral renal artery stenosis or unilateral renal artery stenosis of the only kidney. Clinical and laboratory symptoms of cardio-renal syndrome include progressive heart and kidney failure with refractory hypertension and vascular disease, difference in size of the kidneys by more than 1.5 cm, and reversible creatinine level increase caused by angiotensin convertase inhibitors.10 Renal artery atherosclerotic stenosis is a major cause of renovascular hypertension.11 Ischemic nephropathy (due to renal artery stenosis) leads to refractory hypertension and renal dysfunction.12 There are many case reports on severe hypertension with recurring refractory congestive heart failure (as manifested with pulmonary edema) in patients with renal artery stenosis (unilateral or bilateral).5,13 Invasive treatment—such as renal artery percutaneous transluminal angioplasty with stent placement or surgery—proved beneficial to patients with renal artery stenosis.4 An association between heart and renal failure and bilateral renal artery stenosis needs to be promptly established. Appropriate early treatment prevents end-stage renal disease development and reduces the risk of death associated with pulmonary edema. It also, in some cases, allows to fully reverse cardio-renal syndrome manifestations. One of the studies showed that 19% of patients who underwent renal artery stent placement experienced from at least 1 episode of pulmonary edema and/or congestive heart failure.14 According to other studies, “flash” pulmonary edema (defined as sudden left ventricular failure in patients who have no previous cardiac history and good cardiac function) may be seen in up to 10% of patients with atherosclerotic renovascular disease15 and it is a cardio-renal syndrome feature. There was no pulmonary edema in the discussed patient, even though symptoms of congestive heart failure were observed. One possible explanation for this is relatively high heart ejection fraction (65%). A number of studies have shown that only invasive treatment (percutaneous angioplasty with stent placement or surgery) may effectively reduce high blood pressure and thus prevent renal failure development in cardio-renal syndrome.16,17 Most studies carried out so far show that revascularization-based treatment of renal artery stenosis improves heart function rather than renal function. A few studies have demonstrated, however, the impact that the treatment has on the serum creatinine level. Gray and colleagues14 have shown improved blood pressure after revascularization in 82% of patients. Renal function was better for a number of patients, including patients with the initial serum creatinine level of 353 μmol/L. This contrasts with findings of previous studies showing that revascularization does not positively influence renal function in advanced renal failure.18 Indeed, the fact that revascularization does not lead to improvement of renal function in each and every case can be accounted for by other pathomechanisms, such as hypertensive nephrosclerosis and atheroembolic disease.8,19 Success in restoring heart function is due to the transient and, most often, short-term nature of cardio-renal syndrome. Although, according to some reports, one third of patients undergoing revascularization had a history of hypertension, their high blood pressure most commonly resulted from reversible hypervolemia and not from irreversible vascular disorders. Similarly, symptoms of congestive heart failure were due to acute/subacute sodium and water retention due to kidney ischemia, rather than irreversible myocardium remodelling. This emphasizes the role of early diagnosis and etiologic treatment in the acute, renin-dependent phase of renovascular hypertension. Only timely and appropriate treatment can lastingly improve renal and heart function. This case report demonstrates the effectiveness of isolated ultrafiltration as a preparatory procedure for revascularization of stenotic renal arteries. Ultrafiltration can be used in patient with severe, diuretic-resistant congestive heart failure due to poor left ventricular function.20,21 In contrast, the objective of ultrafiltration in our patient was to reduce volemia and restore the natriuretic response as well as to provide conditions for angiography and revascularization. The extreme hypervolemia, resulting from high renin-angiotensin-aldosterone system activity and deficient natriuresis was relatively well tolerated by our patient due to his good baseline cardiac status. One final remark is that unexplained cardio-renal syndrome should be presumed due to renal artery stenosis and treated early.