Clin Exp Nephrol (2002) 6:163–165
© Japanese Society of Nephrology 2002
CASE REPORT Takeki Suzuki · Masaomi Nangaku · Shinya Oku Hiroyuki Takemura · Yasuhisa Yokoyama Yuji Takahashi · Toshiro Fujita
Captopril renography in Bartter’s syndrome
Received: January 29, 2002 / Accepted: April 11, 2002
Abstract We describe a 19-year-old man who developed muscle weakness due to hypokalemia. His blood pressure on admission was considered to be relatively high, and we performed captopril renography. His baseline renogram was normal, while the results of captopril renography showed delayed patterns similar to those of renovascular hypertension. However, his blood pressure level decreased and returned to the normal range without medication 2 weeks after admission. Our final diagnosis in this patient was Barter’s syndrome. We speculate that the delayed pattern of captopril renography was due to an imbalance between the prostaglandin and the renin-angiotensin systems. The blockade of the renin-angiotensin system by captopril may cause dominant prostaglandins, produce systemic vasodilatory effects, and lead to hypoperfusion of the kidneys in patients with Bartter’s syndrome. Key words Hypertension · Hypokalemia · Renogram · Bartter’s syndrome · Renin
Introduction While both renovascular hypertension and Bartter’s syndrome are associated with hyperreninemic hyperaldoster-
T. Suzuki · M. Nangaku · H. Takemura · Y. Yokoyama · T. Fujita (*) Division of Nephrology and Endocrinology, The University of Tokyo School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan Tel. ⫹81-3-5800-9735; Fax ⫹81-3-5800-9736 e-mail: [email protected] S. Oku Department of Radiology, The University of Tokyo School of Medicine, Tokyo, Japan Y. Takahashi Division of Neurology, The University of Tokyo School of Medicine, Tokyo, Japan
onism, the presence or absence of hypertension generally makes diagnosis relatively easy. Herein we report captopril renography in a patient who suffered from transient hypertension and was finally diagnosed as having Bartter’s syndrome. The results of captopril renography showed a delayed pattern, as seen in renovascular hypertension, although the patterns were completely the same in both kidneys. To our knowledge, this is the first case of captopril renography in Bartter’s syndrome, and the results have important implications in terms of the physiology of the balance between the augmented renin-angiotensin system and compensatory vasodilatory system.
Case report A 19 year-old man was admitted to hospital because of persistent hypokalemia. He had had two episodes of weakness in his lower extremities in 1 year, which had improved within 3 days. His serum potassium level at the last episode was 2.3–2.5 mEq/l, and he was given potassium supplements. He had no history of drug abuse or of taking Chinese medicine. On admission, his general condition was good. His height was 171.2 cm and body weight was 63.8 kg. He was afebrile, with blood pressure level of 134/96 mmHg; heart rate, 80 min; and respiratory rate, 18 min. Physical examination was unremarkable. His blood chemical analysis showed hypokalemia (K, 2.5 mEq/l) and hypochloremia (Cl, 92 mEq/l). His serum sodium level was 138 mEq/l and magnesium was 2.2 mg/dl. Both blood urea nitrogen and creatinine were normal (9.0 mg/dl and 0.6 mg/dl, respectively). Analysis of arterial blood gas revealed metabolic alkalosis, with a pH of 7.532, partial pressure of carbon dioxide, 42.0 mmHg; partial pressure of oxygen, 114.5 mmHg; and bicarbonate, 34.5 mEq/l. Urine biochemistry showed urinary potassium concentration of 27.6 mEq/l, total potassium excretion of 46 mEq/day, and total calcium excretion of 0.176 g/ day. Electrocardiogram revealed normal axis and normal sinus rhythm, with a heart rate of 68 min. His blood pressure
164
level remained at 130–140/85–95 mmHg for 2 weeks and was interpreted as high, considering his age. Differential diagnoses included primary aldosteronism and renal artery stenosis. His plasma renin activity was 29.5 ng/ml per hour (range 0.3–2.9 ng/ml per h) and plasma aldosterone concentration was 516.3 pg/ml (range, 0–180.0 pg/ml). Adrenocortico-tropic hormone (ACTH) was 75.6 pg/ml (range, 9.0–52.0 pg/ml) and serum cortisol was 23.5 µg/dl (range, 4.0– 23.3 µg/dl). Computed tomography (CT) of the abdomen showed normal adrenal glands, and abdominal ultrasonography showed normal kidneys. The high plasma renin activity and plasma aldosterone concentration suggested renovascular hypertension, and we performed captopril renography. For the performance of a baseline scintigraphic study, the patient, lying prone, was placed under a dual-headed gamma camera (GCA-901HG; Toshiba, Tokyo, Japan) equipped with two low-energy general purpose collimators. Then 222 MBq of Tc-99m MAG3 was injected intravenously, immediately followed by dynamic acquisition (128 ⫻ 128 matrix, 3 s/frame, 80 frames; then 30 s/frame, 52 frames). The only difference in the captopril renal scintigraphic study from the baseline study was the oral administration of captopril (50 mg) 1 h before image acquisition. As shown in Fig. 1, his baseline renogram was normal (time to maximum
isotope activity [Tmax], 3.85 and 3.65 min, left and right kidney, respectively), while the results of captopril renography showed delayed patterns compatible with renovascular hypertension with captopril-induced hypotension (Tmax, 13.80 and 11.80 min, left and right kidney, respectively). However, the patterns were quite similar for the right and left kidneys. Furthermore, his blood pressure level decreased and returned to the normal range without medication 2 weeks after admission, and 24-h blood pressure monitoring showed average systolic blood pressure of 117 mmHg and average diastolic blood pressure of 68 mmHg. The normalization of blood pressure revealed Bartter’s syndrome and Gitelman syndrome as potential differential diagnoses. To confirm the presence or absence of renovascular hypertension, renal angiography was performed, which showed normal renal arteries. To differentiate Bartter’s syndrome from Gitelman syndrome, we measured his serum magnesium, which was 2.2 mg/dl, and his urinary calcium excretion, which was 0.176 g/day. These results led us to make the final diagnosis of Bartter’s syndrome. Treatment with indomethacin (100 mg/day for 3 days) increased his serum potassium level to 3.2 mEq/l with no change in blood pressure, while it resulted in a decrease of plasma renin activity from 22.2 ng/ml per hour to 6.6 ng/ml per hour and decreased plasma prostaglandin E2 level, from 8.1 pg/ml (normal, ⬍8.4) to 5.5 pg/ml. The result of renography after the treatment with indomethacin showed delayed patterns that were more severe than those of the captopril renography (data not shown). The patient gave informed consent for all these studies. He was discharged from hospital with potassium supplements and spironolactone.
Discussion
Fig. 1. A Baseline renogram shows a normal pattern. B After administration of captopril, both kidneys demonstrated a delayed pattern. L, left; R, right; KCPM, kilo counts per minute; MAG, mercaptoacetyltriglycine
Relative hypovolemia and enhanced activity of the reninangiotensin-aldosterone system are cardinal features of Bartter’s syndrome and Gitelman syndrome. Clinical manifestations include renal potassium wasting and hypokalemia.1–3 Muscle weakness due to hypokalemia, as well in this patient, is one of the main symptoms. While both renovascular hypertension and Bartter’s syndrome are associated with hyperreninemic hyperaldosteronism, the presence or absence of hypertension generally makes diagnosis easy. In our patient, sustained high blood pressure led us to suspect renovascular hypertension. Indeed, captopril renography showed a delayed pattern compatible with renovascular hypertension in this patient. However, it is rare that two kidneys show the same delayed pattern in cases of renovascular hypertension. Furthermore, the blood pressure levels of this patient returned to normal 2 weeks after his admission. Renal angiography ruled out renovascular hypertension, and we made the diagnosis of Bartter’s syndrome. The cause of the transient hypertension in this patient remains unknown. Angiotensin-converting enzyme inhibitor (ACEI) renography is highly accurate in patients with normal renal
165
function and suspected renovascular hypertension. In this patient population, the sensitivity and specificity of ACEI renography for renal artery stenosis are both approximately 90%.4 We speculate that the delayed pattern of captopril renography in our patient was due to an imbalance between the prostaglandin and the renin-angiotensin systems. Enhanced prostaglandin E2 secretion and resistance to the pressor effects of infused angiotensin II and catecholamines are associated with generalized reduction in vascular tone and low-normal systemic blood pressure in Bartter’s syndrome.5 The blockade of the renin-angiotensin system by captopril may cause dominant prostaglandins, produce systemic vasodilatory effects, and lead to hypoperfusion of the kidneys in patients with Bartter’s syndrome. Indeed, the diagnosis of Bartter’s syndrome is supported by the additional finding that the treatment with indomethacin in our patient, which inhibited both the prostaglandin and the renin-angiotensin systems, as previously reported,6–8 aggravated the delayed pattern of renography as compared with the treatment of captopril alone.
References 1. Bartter FC, Pronove P, Gill J Jr, MacCardle RC. Hyperplasia of the juxtaglomerular complex with hyperaldosteronism and hypokalemic alkalosis. Am J Med 1962;33:811–28. 2. Stein JH. The pathogenetic spectrum of Bartter’s syndrome. Kidney Int 1985;28:85–93. 3. Kurtz I. Molecular pathogenesis of Bartter’s and Gitelman’s syndromes. Kidney Int 1998;54:1396–410. 4. Taylor A. Functional testing: ACEI renography. Semin Nephrol 2000;20:437–44. 5. Fujita T, Ando K, Sato Y, Yamashita K, Nomura M, Fukui T. Independent roles of prostaglandins and the renin-angiotensin system in abnormal vascular reactivity in Bartter’s syndrome. Am J Med 1982;73:71–5. 6. Frolich JC, Hollifield JW, Dormois JC, Frolich BL, Seyberth H, Michelakis AM, et al. Suppression of plasma renin activity by indomethacin in man. Circ Res 1976;39:447–52. 7. Gerber JG, Olson RD, Nies AS. Interrelationship between prostaglandins and renin release. Kidney Int 1981;19:816–21. 8. Henrich WL. Role of prostaglandins in renin secretion. Kidney Int 1981;19:822–30.
© Japanese Society of Nephrology 2002
CASE REPORT Takeki Suzuki · Masaomi Nangaku · Shinya Oku Hiroyuki Takemura · Yasuhisa Yokoyama Yuji Takahashi · Toshiro Fujita
Captopril renography in Bartter’s syndrome
Received: January 29, 2002 / Accepted: April 11, 2002
Abstract We describe a 19-year-old man who developed muscle weakness due to hypokalemia. His blood pressure on admission was considered to be relatively high, and we performed captopril renography. His baseline renogram was normal, while the results of captopril renography showed delayed patterns similar to those of renovascular hypertension. However, his blood pressure level decreased and returned to the normal range without medication 2 weeks after admission. Our final diagnosis in this patient was Barter’s syndrome. We speculate that the delayed pattern of captopril renography was due to an imbalance between the prostaglandin and the renin-angiotensin systems. The blockade of the renin-angiotensin system by captopril may cause dominant prostaglandins, produce systemic vasodilatory effects, and lead to hypoperfusion of the kidneys in patients with Bartter’s syndrome. Key words Hypertension · Hypokalemia · Renogram · Bartter’s syndrome · Renin
Introduction While both renovascular hypertension and Bartter’s syndrome are associated with hyperreninemic hyperaldoster-
T. Suzuki · M. Nangaku · H. Takemura · Y. Yokoyama · T. Fujita (*) Division of Nephrology and Endocrinology, The University of Tokyo School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan Tel. ⫹81-3-5800-9735; Fax ⫹81-3-5800-9736 e-mail: [email protected] S. Oku Department of Radiology, The University of Tokyo School of Medicine, Tokyo, Japan Y. Takahashi Division of Neurology, The University of Tokyo School of Medicine, Tokyo, Japan
onism, the presence or absence of hypertension generally makes diagnosis relatively easy. Herein we report captopril renography in a patient who suffered from transient hypertension and was finally diagnosed as having Bartter’s syndrome. The results of captopril renography showed a delayed pattern, as seen in renovascular hypertension, although the patterns were completely the same in both kidneys. To our knowledge, this is the first case of captopril renography in Bartter’s syndrome, and the results have important implications in terms of the physiology of the balance between the augmented renin-angiotensin system and compensatory vasodilatory system.
Case report A 19 year-old man was admitted to hospital because of persistent hypokalemia. He had had two episodes of weakness in his lower extremities in 1 year, which had improved within 3 days. His serum potassium level at the last episode was 2.3–2.5 mEq/l, and he was given potassium supplements. He had no history of drug abuse or of taking Chinese medicine. On admission, his general condition was good. His height was 171.2 cm and body weight was 63.8 kg. He was afebrile, with blood pressure level of 134/96 mmHg; heart rate, 80 min; and respiratory rate, 18 min. Physical examination was unremarkable. His blood chemical analysis showed hypokalemia (K, 2.5 mEq/l) and hypochloremia (Cl, 92 mEq/l). His serum sodium level was 138 mEq/l and magnesium was 2.2 mg/dl. Both blood urea nitrogen and creatinine were normal (9.0 mg/dl and 0.6 mg/dl, respectively). Analysis of arterial blood gas revealed metabolic alkalosis, with a pH of 7.532, partial pressure of carbon dioxide, 42.0 mmHg; partial pressure of oxygen, 114.5 mmHg; and bicarbonate, 34.5 mEq/l. Urine biochemistry showed urinary potassium concentration of 27.6 mEq/l, total potassium excretion of 46 mEq/day, and total calcium excretion of 0.176 g/ day. Electrocardiogram revealed normal axis and normal sinus rhythm, with a heart rate of 68 min. His blood pressure
164
level remained at 130–140/85–95 mmHg for 2 weeks and was interpreted as high, considering his age. Differential diagnoses included primary aldosteronism and renal artery stenosis. His plasma renin activity was 29.5 ng/ml per hour (range 0.3–2.9 ng/ml per h) and plasma aldosterone concentration was 516.3 pg/ml (range, 0–180.0 pg/ml). Adrenocortico-tropic hormone (ACTH) was 75.6 pg/ml (range, 9.0–52.0 pg/ml) and serum cortisol was 23.5 µg/dl (range, 4.0– 23.3 µg/dl). Computed tomography (CT) of the abdomen showed normal adrenal glands, and abdominal ultrasonography showed normal kidneys. The high plasma renin activity and plasma aldosterone concentration suggested renovascular hypertension, and we performed captopril renography. For the performance of a baseline scintigraphic study, the patient, lying prone, was placed under a dual-headed gamma camera (GCA-901HG; Toshiba, Tokyo, Japan) equipped with two low-energy general purpose collimators. Then 222 MBq of Tc-99m MAG3 was injected intravenously, immediately followed by dynamic acquisition (128 ⫻ 128 matrix, 3 s/frame, 80 frames; then 30 s/frame, 52 frames). The only difference in the captopril renal scintigraphic study from the baseline study was the oral administration of captopril (50 mg) 1 h before image acquisition. As shown in Fig. 1, his baseline renogram was normal (time to maximum
isotope activity [Tmax], 3.85 and 3.65 min, left and right kidney, respectively), while the results of captopril renography showed delayed patterns compatible with renovascular hypertension with captopril-induced hypotension (Tmax, 13.80 and 11.80 min, left and right kidney, respectively). However, the patterns were quite similar for the right and left kidneys. Furthermore, his blood pressure level decreased and returned to the normal range without medication 2 weeks after admission, and 24-h blood pressure monitoring showed average systolic blood pressure of 117 mmHg and average diastolic blood pressure of 68 mmHg. The normalization of blood pressure revealed Bartter’s syndrome and Gitelman syndrome as potential differential diagnoses. To confirm the presence or absence of renovascular hypertension, renal angiography was performed, which showed normal renal arteries. To differentiate Bartter’s syndrome from Gitelman syndrome, we measured his serum magnesium, which was 2.2 mg/dl, and his urinary calcium excretion, which was 0.176 g/day. These results led us to make the final diagnosis of Bartter’s syndrome. Treatment with indomethacin (100 mg/day for 3 days) increased his serum potassium level to 3.2 mEq/l with no change in blood pressure, while it resulted in a decrease of plasma renin activity from 22.2 ng/ml per hour to 6.6 ng/ml per hour and decreased plasma prostaglandin E2 level, from 8.1 pg/ml (normal, ⬍8.4) to 5.5 pg/ml. The result of renography after the treatment with indomethacin showed delayed patterns that were more severe than those of the captopril renography (data not shown). The patient gave informed consent for all these studies. He was discharged from hospital with potassium supplements and spironolactone.
Discussion
Fig. 1. A Baseline renogram shows a normal pattern. B After administration of captopril, both kidneys demonstrated a delayed pattern. L, left; R, right; KCPM, kilo counts per minute; MAG, mercaptoacetyltriglycine
Relative hypovolemia and enhanced activity of the reninangiotensin-aldosterone system are cardinal features of Bartter’s syndrome and Gitelman syndrome. Clinical manifestations include renal potassium wasting and hypokalemia.1–3 Muscle weakness due to hypokalemia, as well in this patient, is one of the main symptoms. While both renovascular hypertension and Bartter’s syndrome are associated with hyperreninemic hyperaldosteronism, the presence or absence of hypertension generally makes diagnosis easy. In our patient, sustained high blood pressure led us to suspect renovascular hypertension. Indeed, captopril renography showed a delayed pattern compatible with renovascular hypertension in this patient. However, it is rare that two kidneys show the same delayed pattern in cases of renovascular hypertension. Furthermore, the blood pressure levels of this patient returned to normal 2 weeks after his admission. Renal angiography ruled out renovascular hypertension, and we made the diagnosis of Bartter’s syndrome. The cause of the transient hypertension in this patient remains unknown. Angiotensin-converting enzyme inhibitor (ACEI) renography is highly accurate in patients with normal renal
165
function and suspected renovascular hypertension. In this patient population, the sensitivity and specificity of ACEI renography for renal artery stenosis are both approximately 90%.4 We speculate that the delayed pattern of captopril renography in our patient was due to an imbalance between the prostaglandin and the renin-angiotensin systems. Enhanced prostaglandin E2 secretion and resistance to the pressor effects of infused angiotensin II and catecholamines are associated with generalized reduction in vascular tone and low-normal systemic blood pressure in Bartter’s syndrome.5 The blockade of the renin-angiotensin system by captopril may cause dominant prostaglandins, produce systemic vasodilatory effects, and lead to hypoperfusion of the kidneys in patients with Bartter’s syndrome. Indeed, the diagnosis of Bartter’s syndrome is supported by the additional finding that the treatment with indomethacin in our patient, which inhibited both the prostaglandin and the renin-angiotensin systems, as previously reported,6–8 aggravated the delayed pattern of renography as compared with the treatment of captopril alone.
References 1. Bartter FC, Pronove P, Gill J Jr, MacCardle RC. Hyperplasia of the juxtaglomerular complex with hyperaldosteronism and hypokalemic alkalosis. Am J Med 1962;33:811–28. 2. Stein JH. The pathogenetic spectrum of Bartter’s syndrome. Kidney Int 1985;28:85–93. 3. Kurtz I. Molecular pathogenesis of Bartter’s and Gitelman’s syndromes. Kidney Int 1998;54:1396–410. 4. Taylor A. Functional testing: ACEI renography. Semin Nephrol 2000;20:437–44. 5. Fujita T, Ando K, Sato Y, Yamashita K, Nomura M, Fukui T. Independent roles of prostaglandins and the renin-angiotensin system in abnormal vascular reactivity in Bartter’s syndrome. Am J Med 1982;73:71–5. 6. Frolich JC, Hollifield JW, Dormois JC, Frolich BL, Seyberth H, Michelakis AM, et al. Suppression of plasma renin activity by indomethacin in man. Circ Res 1976;39:447–52. 7. Gerber JG, Olson RD, Nies AS. Interrelationship between prostaglandins and renin release. Kidney Int 1981;19:816–21. 8. Henrich WL. Role of prostaglandins in renin secretion. Kidney Int 1981;19:822–30.
