Kidney Renin-Angiotensin System: Lost in a RAS Cascade.

Renin was discovered more than a century ago. Since then, the functions of the renin-angiotensin system in the kidney have been the focus of intensive research revealing its importance in regulation of renal physiology and in the pathogenesis of heart, vascular, and kidney diseases. Inhibitors of renin-angiotensin system components are now foundational therapies for a range of kidney and cardiovascular diseases from hypertension to heart failure to diabetic nephropathy. Despite years of voluminous research, emerging studies continue to reveal new complexities of the regulation of the renin-angiotensin system within the kidney and identification of nonclassical components of the system like the prorenin receptor (PRR) and ACE2 (angiotensin-converting enzyme 2), with powerful renal effects that ultimately impact the broader cardiovascular system. With the emergence of a range of novel therapies for cardiovascular and kidney diseases, the importance of a detailed understanding of the renin-angiotensin system in the kidney will allow for the development of informed complementary approaches for combinations of treatments that will optimally promote health and longevity over the century ahead.

[Reninoma: a rare but curable cause of high blood pressure, a case report]. / Réninome: une cause rare mais curable d'HTA. A propos d'un cas.

We report a case of a renin secreting tumor, which is a very rare cause of secondary high blood pressure. A 22-year-old woman was hospitalised for exploration of high blood pressure (160/110 mmHg) with severe hypokaliemia (2,7 mmol/l) and secondary hyperaldosteronism. Physical examination was normal except the high blood pressure. Bioassays show increased kaliuresis (66 mmol/24h), plasma renin (89 pg/ml in clinostastism--108 pg/ml in orthostatism), pro-renin (1207 pg/ml in clinostastism--1412 pg/ml in orthostatism) and aldosterone (210 pg/ml in clinostastism--566 pg/ml in orthostatism). The rest of the endocrine tests were normal (cortisol and ACTH at 8:00 am, urinary free cortisol, overnight 1 mg dexamethasone suppression test). Doppler ultrasound method, performed by an experienced radiologist, did not show renal artery stenosis. Abdominal computerized tomography showed a nodular formation at the upper pole of the right kidney, isodense to renal medullary. The size tumor was 15 mm. The renal vein sampling shows high values of renin on both sides whereas, for the pro-renin, the values were higher on the tumor side. In spite of treatment with CEI (Converting Enzyme Inhibitors) and calcium antagonists, the blood pressure was not controlled. Hypokaliemia persisted (3 mmol/l) in spite of high daily potassium intake (64 mmol/l of potassium chloride). After tumor resection, reninoma was diagnosed by the pathology examination and blood pressure, plasma rennin, plasma aldosterone level returned to normal.

Avaliaçäo hormonal e de reflexos cardiovasculares em portadora de falência autonômica pura / Hormonal and cardiovascular reflex assessment in a female patient with pure autonomic failure

We report the case of a 72-year-old female with pure autonomic failure, a rare entity, whose diagnosis of autonomic dysfunction was determined with a series of complementary tests. For approximately 2 years, the patient has been experiencing dizziness and a tendency to fall, a significant weight loss, generalized weakness, dysphagia, intestinal constipation, blurred vision, dry mouth, and changes in her voice. She underwent clinical assessment and laboratory tests (biochemical tests, chest X-ray, digestive endoscopy, colonoscopy, chest computed tomography, abdomen and pelvis computed tomography, abdominal ultrasound, and ambulatory blood pressure monitoring). Measurements of catecholamine and plasmatic renin activity were performed at rest and after physical exercise. Finally the patient underwent physiological and pharmacological autonomic tests that better diagnosed dysautonomia.

[Assessment of active renin instead of plasma renin activity in the renin captopril test]. / Oznaczanie aktywnej reniny w miejsce aktywnosci reninowej osocza w reninowym tescie kaptoprylowym.

In the study usefulness of active renin (AR) measurement instead of plasma renin activity (PRA) in the diagnosis of reno-vascular hypertension(RVH) was evaluated. 42 patients with arterial hypertension (17F, 25M; mean age 45 + 12 years) and suspicion on RVH on the ground of the abnormal result of the preliminary renal angioscintigraphy were qualified to the study. Angioscintigraphic (SCT) and simultaneously renin captopril test (RCT) followed by renal arteriography or Doppler ultrasonography of renal arteries were performed in every case Haemodynamic significant stenosis of renal artery was revealed in 5 cases. The results of the examination in this group were as follows: in 3 patients positive RCT with PRA, in 4 patients positive RCT with R and in 2 patients positive SCT were found. The false positive results of RCT using PRA were obtained in 5 patients and only in 2 patients if using AR. There were no false positive results of SCT. The introduction of AR instead of PRA in RCT resulted in simplification and shortening of the diagnostic procedure. Furthermore, this modification increased detection of hemodynamically significant stenosis of renal artery from 2 cases revealed with SCT and 3 cases with PRAin RCT to 4 cases with AR. The successful preliminary results let us to introduce this modification of RCT to routine out-patients screening for RVH.

Angiotensin II release from rabbit intrarenal arteries: a critical assessment.

A microdissected rabbit intrarenal arterial network (IAN) perfused at constant flow with Krebs-bicarbonate solution was employed to determine whether this network, which has a high renin content, releases angiotensin II (AII) either spontaneously or during beta-adrenergic stimulation. Six groups of experiments were conducted in which samples of the vascular effluent were collected on Sep Paks before and during intraluminal infusion of L-isoproterenol (1.1 to 11 microg/min). Separation and assay of AII were by combined HPLC and RIA. For an accurate estimation of the quantity of AII released, it was important to subtract the Krebs and isoproterenol blanks, 19 and 23 pg, respectively, from the basal and isoproterenol-induced AII release. In Groups 1 and 2, AII release was determined before and during isoproterenol infusion (5.5 microg/min). Basal release of AII was insignificant in Groups 1 to 5. In Group 1, infusion of isoproterenol caused AII release from IAN before and after removal of glomeruli (glomerulectomy), but with variability between experiments. An even higher infusion rate of isoproterenol (11 microg/min) in Group 2 caused no significant AII release. Similarly, in Group 3, in which a longer collection period was imposed, isoproterenol (5.5 microg/min) failed to cause significant AII release. In Groups 4 and 5, Goldblatt hypertensive and salt-restricted rabbits, respectively, isoproterenol caused AII release, but the effect was statistically significant only in Group 4. Supplying renin substrate in Group 6 caused only a small spontaneous AII release. We conclude that under these conditions of complete isolation from the intact circulation, the IAN despite a high renin content, releases little locally generated AII.

[Radiographic appearances of a renin secreting renal tumor. A rare cause of hypertension (author's transl)]. / Aspects radiologiques de la "tumeur à rénine". Cause rare d'hypertension artérielle (H.T.A.).

Eleven cases of hypertension due to a renin secreting renal tumor have been reported since 1967. Here we are dealing with another case which appeared as hypertension and cerebro vascular accident in a thirty - year old woman an I.V. Pyélogram and a renal angiogram showed a tumor in the upper pole of the left kidney. Renal veins renin dosage showed hypersecretion on the side of the tumor. The tumorectomy was followed by a normalization of blood pressure. The microscopic study confirmed the diagnosis of renin secreting juxta-glomerular cell tumor.

Electrolyte economy and its hormonal regulation in congenital chloride diarrhea.

The economy of Cl-, K+, and Mg++, extracellular volume (ECV) and plasma volume, and the role of hyperreninemia and hyperaldosteronism were explored in 22 patients with congenital chloride diarrhea. Stool volume was in significant correlation with its Cl-, Na+ and K+ content, the correlation being significantly better with Cl- content than with the Na+ content. Low fecal Cl- concentrations were seen in chronic hypochloremic contraction, but acute episodes did not cause reduction of fecal Cl- concentration from the basal level of 140--150 mmol/liter. The adequate condition (defined as normal serum electrolyte concentrations and bl;od pH, and presence of Cl- in urine) was associated with high total exchangeable Cl- and ECV. This excess Cl- and ECV roughly equalled the high daily fecal amount of Cl- and volume. Reduced ECV was accompanied by high renin activities and hyperaldosteronism, but in the adequate condition these were normal. Hyperaldosteronism caused a decrease in urinary Na+-K+ ratio and, after the age of 2--6 months, in the fecal Na+-K+ ratio. Total exchangeable K+ was normal in the adequate condition. No Mg++ depletion was present, although the patients lack Mg++ substitution. The adequate condition could be maintained with an oral supplement of NaCl, KCl and water.

Prostaglandins and renin release: II. Assessment of renin secretion following infusion of PGI2,E2 and D2 into the renal artery of anesthetized dogs.

The influence of intra-renal infusions of prostaglandin (PG) I2, PGE2 and PGD2 on renin secretion and renal blood flow was investigated in renally denervated, beta-adrenergic blocked, indomethacin treated dogs with unilateral nephrectomy. All three prostaglandins when infused at doses of 10(-8) g/kg/min and 10(-7) g/kg/min resulted in marked renal vasodilation. Renin secretory rates increased significantly with both PGI2 and PGE2 at the 10(-8) g/kg/min and 10(-7) g/kg/min infusion rates in a dose dependent manner. However, PGD2 was inactive. At 10(-7) g/kg/min, PGI2 infusions resulted in systemic hypotension indicated recirculation of this prostaglandin. These findings suggest that PGI2 should be included among the cyclooxygenase derived metabolites of arachidonic acid to be considered as possible mediators of renin release.