Kimio Tomita

Immunohistochemical localization of V2 vasopressin receptor along the nephron and functional role of luminal V2 receptor in terminal inner medullary collecting ducts.

We investigated immunohistochemical localization of V2 vasopressin receptor along the nephron using a specific polyclonal antibody. Staining was observed in some of thick ascending limbs and all of principal and inner medullary collecting duct (IMCD) cells. Not only basolateral but also luminal membrane was stained in collecting ducts, especially in terminal IMCD (tIMCD). To learn the functional role of luminal V2 receptor in tIMCD, we studied the luminal effects of arginine vasopressin (AVP) on osmotic water permeability (Pf), urea permeability (Pu), and cAMP accumulation using isolated perfused rat tIMCD. In the absence of bath AVP, luminal AVP caused a small increase in cAMP accumulation, Pf and Pu, confirming the presence of V2 receptor in the lumen of tIMCD. In contrast, luminal AVP inhibited Pf and Pu by 30-65% in the presence of bath AVP by decreasing cAMP accumulation via V1a or oxytocin receptors and by an unknown mechanism via V2 receptors in the luminal membrane of tIMCD. These data show that V2 receptors are localized not only in the basolateral membrane but also in the luminal membrane of the distal nephron. Luminal AVP acts as a negative feedback system upon the basolateral action of AVP in tIMCD.

mRNA distribution and membrane localization of the OAT-K1 organic anion transporter in rat renal tubules

OAT‐K1, a renal organic anion transporter, which mediates methotrexate uptake, was analyzed for mRNA distribution along microdissected nephron segments and the immunolocalization in isolated plasma membranes from rat kidney. By using a reverse transcription‐coupled PCR, OAT‐K1 mRNA was detected predominantly in the superficial and juxtamedullary proximal straight tubules. Western blotting with antiserum for OAT‐K1 revealed that the transporter protein with the apparent molecular mass of 40 kDa was expressed exclusively in the brush‐border membranes from rat kidney. These findings suggest that the OAT‐K1 is localized in the brush‐border membranes of the renal proximal straight tubules.

USE OF AUTOANALYSER TO EXAMINE URINARY-RED-CELL MORPHOLOGY IN THE DIAGNOSIS OF GLOMERULAR HAEMATURIA

Nouvelle technique pour le diagnostic rapide et clair grâce a un «autoanalyseur» donnant une courbe de distribution des hematies de differentes morphologies

Role of Urinary Arginine Vasopressin in the Sodium Excretion in Patients With Chronic Renal Failure

Patients with chronic renal failure show almost equal levels of sodium excreted in the urine as healthy subjects through an increase of the fractional excretion sodium (FE(Na)). The mechanisms of this adaptation, however, are unknown. Recently, urinary arginine vasopressin (AVP) has been shown to inhibit the antidiuretic action of plasma AVP in the collecting ducts of rabbits and rats. In this article, the roles of plasma and urinary AVP are examined with other hormones in the sodium excretion of 57 patients with chronic renal disease. The fractional excretion of AVP, plasma atrial natriuretic peptide (ANP) and endothelin-1 (ET-1), urinary ET-1, and FE(ET-1) correlated with the decrease of creatinine clearance (Ccr). Multiple and stepwise regression analyses showed that FE(AVP) is the major dependent determinant for FE(Na) (adjusted r2 = 0.78). These results suggest that the increase of AVP excretion per remaining nephron could be a cause of the increase of FE(Na) in patients with renal failure. Although plasma AVP works as an antidiuretic hormone, urinary AVP serves as an intrinsic diuretic, especially in patients with chronic renal failure.

Primary role of hyperkalemia in the acidosis of hyporeninemic hypoaldosteronism

A 65-year-old woman with mild renal insufficiency had persistent hyperkalemia and hyperchloremic acidosis. Her plasma aldosterone level was relatively low for her hyperkalemia, and her urine pH was low. Fludrocortisone acetate administration corrected both hyperkalemia and acidosis by increasing urinary excretion of potassium and net acid, implicating deficient mineralocorticoid activity in the distal renal tubule in this patient. During this medication urinary ammonium excretion increased, but urine pH remained low, so that urinary titratable acid excretion did not decrease. On the other hand, correction of hyperkalemia by administration of a potassium-calcium exchange resin alone also resolved the acidosis by increasing urinary ammonium excretion. This increment exceeded the decrement of urinary titratable acid excretion, which was caused by raised urine pH secondary to increased urinary ammonium excretion, and resulted in increase of net acid excretion. Thus, in this patient, hyperkalemia appears to be a decisive causative factor in the acidosis, with deficient mineralocorticoid effect only contributing in part to the reduction of net acid excretion and the acidosis.

Renin-Angiotensin-Aldosterone System in Mild Diabetic Nephropathy

The mechanism of lowered renin-aldosterone system was investigated in 17 patients with diabetic nephropathy (serum Cr less than 3 mg/100 ml) with concomitant control of the blood sugar level. The response of plasma renin activity (PRA) to upright stimulation was lower in the low renin group (group I) than in the normal to high renin group (group II) and in the control group. The PRA response to theophylline was delayed in group I. The percentage of the luminal area of the arteriole in the biopsy specimens was larger in group I and the control group than in group II. Plasma aldosterone concentration (PAC) was not increased by angiotensin II in group I. Low PRA in diabetic nephropathy with slightly to moderately impaired renal function may not be due to hyaline destruction of the arteriolar walls, but to other factors such as sympathetic nervous dysfunction. The adrenal responses of PAC to angiotensin II may also be impaired.

Decreased Lithium Clearance in Patients with Hyperthyroidism

Lithium clearance was studied to investigate proximal tubular function in patients with hyperthyroidism (n = 10) and control subjects (n = 7). Patients with hyperthyroidism showed significantly reduced fractional excretion of lithium (FELi) compared with control subjects (15.0 +/- 1.5%, n = 10, vs. 23.7 +/- 0.6%, n = 7, means +/- SE, p < 0.001). The reduced FELi of the hyperthyroid state was reversed toward control values with treatment by antithyroid drugs (12.6 +/- 2.6 toward 26.8 +/- 2.5% for 5 patients, means +/- SE). Tubular reabsorption of phosphate (TRP) was significantly increased in hyperthyroid patients compared with control subjects (96.1 +/- 0.7 vs. 87.5 +/- 0.7%, p < 0.001), and it returned to control values after the treatment. Our data demonstrate that lithium clearance is decreased and TRP is increased in patients with hyperthyroidism, which suggests that proximal tubular reabsorption of sodium and TRP is increased in hyperthyroidism.

Increased Urinary Kallikrein-Like Activity in the Syndrome of Inappropriate Secretion of Antidiuretic Hormone

The role of the kallikrein system in the natriuresis of SIADH was studied in 3 patients. Following free water intake, serum Na decreased. Urinary Na excretion, urinary aldosterone excretion and urinar

Unilateral Renal Agenesis Associated with Various Metabolic Disorders in Three Siblings

Unilateral renal agenesis with impaired renal function was found in all 3 siblings of a single family, in association with various metabolic disorders such as diabetes mellitus, hyperuricemia and hyperbilirubinemia with gallstones. The present report suggests that unilateral renal agenesis could occur as a manifestation of a genetic disorder.

Angiotensin-Converting Enzyme Activity as a Prognostic Factor in Acute Renal Failure

We evaluated serum angiotensin-converting enzyme (ACE) activity and thyroid function to determine the importance as prognostic factors in acute renal failure (ARF). Among 37 ARF patients, 24 survived (recovered group) and 13 died (lethal group). Both serum thyroxine (T4) level and ACE activity were lower in ARF as a whole group (n = 37) than normal control group (n = 27, p less than 0.01). Both serum T4 level and ACE activity in lethal group (n = 13) were significantly lower than those of the recovered group (n = 24, p less than 0.01). Serum ACE activity but not serum T4 level was significantly related to the prognosis of ARF (p less than 0.02, Mantel-Haenszel analysis). This suggests that lowered serum T4 levels are not a specific indicator of ARF, but lowered ACE activity is significantly related to the prognosis of the patient in ARF. Serum ACE activity seems to be one of several clinically useful prognostic indicators in ARF.