Tubular Sodium Reabsorption Research Articles

NATRIURETIC EFFECT OF TMB‐8 IN ANAESTHETIZED DOGS

1. Effects of 8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate hydrochloride (TMB-8), an inhibitor of intracellular calcium release, on renal function were examined in anaesthetized dogs. 2. Intrarenal arterial infusion of TMB-8 (0.03 and 0.1 mg/kg per min) increased urine flow rate, urinary sodium excretion and fractional excretion of sodium without affecting blood pressure, renal blood flow or glomerular filtration rate. 3. The results suggest that TMB-8 inhibits tubular sodium reabsorption to induce natriuresis.

Chronic hydralazine treatment alters the acute pressure–natriuresis curve in young spontaneously hypertensive rats

The pressure-natriuresis relationship was studied in anesthetized, 7- to 9-week-old control spontaneously hypertensive rats (SHR) and in SHR that had been treated with hydralazine (20 mg.kg-1.day-1 in drinking water) starting at 4-5 weeks of age. To minimize reflex changes in kidney function during changes in renal artery pressure, neural and hormonal influences on the kidney were fixed by surgical renal denervation, adrenalectomy, and infusion of a hormone cocktail (330 microL.kg-1.mikn-1) containing high levels of aldosterone, arginine vasopressin, hydrocortisone, and norepinephrine dissolved in 0.9% NaCl containing 1% albumin. Changes in renal function were measured using standard clearance techniques, while renal artery pressure was varied between 136 +/- 1 and 186 +/- 2 mmHg (1 mmHg = 133.32 Pa) in control SHR (n = 10) and between 113 +/- 1 and 162 +/- 2 mmHg in treated SHR (n = 11). Mean arterial pressure (+/- SE) under Inactin anesthesia was 172 +/- 3 mmHg in control SHR and 146 +/- 3 mmHg in treated SHR (p less than 0.05). Where renal artery pressure overlapped between groups, there were no significant differences in glomerular filtration rate. Renal blood flow was also similar in both groups, although at 160 mmHg blood flow was slightly but significantly reduced in treated SHR. Urine flow and total and fractional sodium excretion increased similarly with increases in renal artery pressure in both groups, but the pressure-natriuresis curve in hydralazine-treated SHR was displaced to the left along the pressure axis. The data indicate that chronic administration of hydralazine in young SHR enhances fractional sodium excretion, suggesting that tubular reabsorption of sodium is decreased by hydralazine.

Impaired intrarenal dopamine production following intravenous sodium chloride infusion in Type 1 (insulin-dependent) diabetes mellitus

Type 1 (insulin-dependent) diabetes mellitus is characterized by impaired sodium excretion following NaCl infusion. To investigate the possible role of dopamine in the impaired natriuresis in diabetes, intrarenal sodium handling, sodium excretion and urinary dopamine output, reflecting intrarenal dopamine formation, were studied following a 2 h 0.9% NaCl infusion (25 ml/kg) in eight diabetic patients and nine control subjects. The increase in sodium excretion in response to NaCl infusion was significantly (p less than 0.01) reduced in diabetic patients (19 +/- 7%) as compared with control subjects (46 +/- 8%). Fractional proximal tubular sodium reabsorption (determined by lithium clearance) decreased in the control group (p less than 0.01) following NaCl infusion but not in the diabetic group. Fractional distal tubular reabsorption decreased similarly in both groups. In response to NaCl urinary dopamine excretion increased by approximately 15% (p less than 0.01) in the control group but did not change in the diabetic group. The mean urinary dopamine excretion above basal was significantly greater in the control group (8.4 +/- 2.1 nmol/h) than in the diabetic group (-2.2 +/- 2.1 nmol/h; p less than 0.01). The urinary sodium/dopamine excretion ratio did not differ significantly between the two groups in the basal state or following NaCl. Baseline plasma levels of atrial natriuretic peptide did not differ between control and diabetic patients. In the control group atrial natriuretic peptide levels increased significantly (p less than 0.01) in response to NaCl whereas atrial natriuretic peptide levels did not change in the diabetic group.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of a Two-Month Treatment with Low Oral Doses of Cyclosporin on Renal Function

To test the effects of short-term therapy with low doses (LD) of cyclosporin A (CsA) in subjects with normal renal function, seven patients receiving CsA to treat psoriasis were studied. Clearances in maximal H2O diuresis were performed to evaluate changes in GFR (CIn), RPF (CPAH) and tubular function before starting CsA (BAS), after 2 days (S1) and 1 month (S2) of oral therapy with 5 mg/kg per day CsA. The study was repeated at the withdrawal of CsA after tapering (S3) and 2 months after the withdrawal (S4). The studies were performed 12 h after the evening dose of CsA. RPF was significantly less than in BAS throughout the therapy and returned almost to basal values in S4. GFR was significantly less than in BAS both in S2 and in S3. In S4, in spite of an increase, GFR was still significantly less than in BAS. Both in S2 and in S3 proximal tubular fractional sodium reabsorption was significantly less than in BAS and, consequently, both sodium delivery to diluting segments and sodium reabsorption in diluting segments increased. Moreover, both in S2 and in S3 fractional sodium reabsorption in diluting segments and free-water generation were greater than in BAS. In S4 tubular function returned almost to basal values. Our data suggest that short-term therapy with low dose CsA impairs renal function; this impairment is not completely reversed after drug withdrawal.

A Case with Renal Tubular Damage: Differentiation of Na Reabsorption Function by Lithium Clearance.

The recovery of the renal proximal and distal tubular sodium (Na) reabsorption was evaluated by analysis of the physiological metabolism of lithium reabsorbed by the renal tubules in a patient with toxic interstitial nephropathy. Administration of glucocorticoid facilitated the rapid recovery of the proximal tubular Na reabsorption (-0.63 to 3 mmol/min for 2 wk) followed by recovery of phosphate reabsorption (51 to 82% for 2 months). Distal Na reabsorption was not altered for 2 months. Although Li clearance has been previously performed in healthy volunteers, we could differentiate the recovery of the proximal and distal renal tubular function even in a diseased patient.

Salt and the newborn kidney

Renal function differs in term infants from that in adults, with lower glomerular filtration rate (GFR) and reduced proximal tubular reabsorption of sodium (Na) and water: nevertheless, it is adequate for their needs. This is not true of very preterm infants in whom hyponatraemia is common. Animal studies have shown that Na+, K(+)-ATPase and the Na+/K+ exchanger are poorly expressed at birth with rapid postnatal rises. Cell receptors for hormones that influence tubular Na transport are less numerous in the premature infant than later in life: intracellular second messenger systems may also be immature. The low GFR is due to vasoconstriction and may be necessary to prevent water and electrolyte wasting due to tubular overload. The hyponatraemia of prematurity could, in principle, be due either to Na loss or water excess and can be prevented either by giving additional Na or by restricting water intake. Na supplementation causes relative volume expansion (VE), water restriction volume contraction (VC); this is demonstrated by the effect of the two approaches on weight gain and on the levels of vasoactive hormones in the blood. We argue that moderate VE is more physiological than VC, both in attempting to simulate intrauterine conditions and in consideration of the infant's nutritional needs. The much less common complication of hypernatraemia is usually due to abnormal water loss and should be prevented by increasing water intake appropriately. The above applies to well, preterm babies: sick preterm infants are much more variable in their Na and water requirements than well infants of comparable gestation and weight and each needs an individually tailored regimen based on frequent clinical assessment and laboratory measurement.

PATHWAYS LINKING RENAL EXCRETION AND ARTERIAL PRESSURE WITH VASCULAR STRUCTURE AND FUNCTION

1. A brief review is presented which summarizes the role of the kidney in the long-term regulation of arterial pressure and the mechanism whereby changes in body fluid volume can influence the function and structure of the systemic vasculature. 2. Studies indicate that the kidney detects changes of arterial pressure via changes of medullary blood flow which in the volume expanded state is poorly autoregulated. Elevations of renal arterial pressure raise vasa recta capillary pressure and renal interstitial fluid pressure, which in turn reduces tubular reabsorption of sodium and water. 3. The sensitivity of the pressure-diuresis relationship is controlled by renal sympathetic nerve activity and a variety of hormone and autocrine systems. 4. Evidence is also reviewed which shows that small changes of blood volume (5%) resulting from reduced renal excretion can acutely and chronically result in 25% increases of total peripheral resistance and arterial pressure. 5. Short-term increases of vascular resistance are predicted by regional autoregulatory responses while long-term elevations of vascular resistance appear to result from the structural changes of large vessel hypertrophy and microvascular rarefaction within skeletal muscle.

Increased Proximal Tubular Reabsorption of Sodium in Childhood Diabetes Mellitus

Type 1 diabetes mellitus is associated with an increase in total exchangeable body sodium. To delineate a site of possible altered sodium handling, proximal tubular sodium reabsorption (PTRNa) was measured in 30 diabetic children, age 12.0 (range 7-16) yr, duration of diabetes 4.5 (range 0.2-12) yr, and compared with 10 non-diabetic children, age 10.0 (range 8.6-12.5) yr. PTRNa was calculated from the fractional clearance of lithium, which was determined from a single blood sample and a random untimed urine sample, taken between 0700 and 0830 h at home, fasting, before insulin therapy. PTRNa was significantly increased in the diabetic children compared with the non-diabetic children (81.6(SE 1.0) vs 74.2(2.6)%, p = 0.014). There was no relationship of PTRNa with age, duration of diabetes, metabolic control (glycosylated haemoglobin, plasma and urinary glucose, plasma lactate), or urinary protein excretion (albumin, N-acetyl-beta-D-glucosaminidase). Elevated sodium reabsorption in the proximal renal tubule may account for the high total exchangeable body sodium found in Type 1 diabetic patients.

腹水を伴う肝硬変患者における腎機能障害―ANP静注負荷およびIithium clearance法による臨床的検討―

Synthetic alpha-human atrial natriuretic peptide (alpha-hANP), 1 micrograms/kg, was intravenously given to 16 cirrhotic patients with ascites and 9 control subjects (CS) to investigate major factors responsible for sodium retention and refractory ascites. The following parameters were measured before and after alpha-hANP administration; such as lithium clearance (CLi) as an index of fluid delivery to the distal tuble, mean arterial pressure (MAP), urinary sodium excretion rate (UNaV), urine volume (V), glomerular filtration rate (GFR), effective renal plasma flow (ERPF), plasma renin activity (PRA), plasma aldosterone concentration (PAC), urinary excretion of prostaglandin (PG)E2, 6-keto-PGF1 alpha (6-k-PGF1 alpha), and thromboxane B2 (TxB2). Patients were divided following alpha-hANP administration into 2 groups as "good responders (GR)" and "poor responders (PR)", in which GR was defined as the group showing 2-fold-increase in UNaV. In contrast, PR had significant lower MAP (71.8 +/- 5.04 mmHg), GFR (21.3 +/- 3.90 ml/min), ERPF (158.0 +/- 43.8 ml/min), FELi (CLi/GFR; 12.6 +/- 1.26%), and higher PRA (8.72 +/- 0.99 ng/ml/h) and PAC (12.2 +/- 3.13 ng/dl) than GR. GR demonstrated almost same natriuretic response as CS with an increase of GFR and renal PGs synthesis, and a decrease of FELi despite reduction in blood pressure. However, alpha-hANP did not suppress PRA, PAC, and distal tubular reabsorption of sodium (FDRNa = 1-FENa/FELi) in cirrhotic patients, whereas suppressed in CS. UNaV correlated with FELi (r = 0.687, p = 0.01) and GFR (r = 0.777, p = 0.01). PRA correlated with FELi r = 0.669, p = 0.015), GFR (r = -0.634, p = 0.018), and MAP (r = 0.858, p = 0.001) only in cirrhosis. These results therefore indicated that hypotension caused by hemodynamic alteration and extremely stimulated renin release might effect on proximal tubular sodium reabsorption and GFR, leading to sodium retention and diuretic resistance in cirrhosis.

Effects of NH<sub>4</sub>CI Metabolic Acidosis on Proximal and Distal Tubular Sodium Reabsorption in Newborn Infants

The present study was undertaken to assess the influence of acute metabolic acidosis on proximal and distal tubular sodium reabsorption in a group of 7 one-week-old neonates with a mean birth weight of 2,164 g (range: 1,300-3,750 g) and a mean gestational age of 34 weeks (range: 28-40 weeks) undergoing an NH4Cl loading test. Free water clearance during water diuresis was used to estimate separately the proximal and distal sodium reabsorption. In response to NH4Cl metabolic acidosis urine flow rate (p less than 0.01) and free water clearance (p less than 0.025) increased significantly, and there was a general tendency for creatinine, osmolar and sodium clearance to increase without achieving statistical significance. The absolute amount of sodium delivered to (p less than 0.01) and reabsorbed in the distal nephron (p less than 0.01) increased significantly in spite of the constant fractional distal reabsorption. The enhanced distal sodium reabsorption during acidosis is assumed to be related to the acidosis-induced increase in aldosterone production.

Renal sodium handling and sodium transport inhibitor in salt-sensitive essential hypertension

To investigate the mechanism whereby blood pressure rises with NaCl loading in salt-sensitive essential hypertension, salt-sensitivity index was determined along with sodium and lithium clearances, plasma Na+,K(+)-ATPase inhibitor and intra-erythrocyte sodium and potassium concentrations. Salt-sensitivity index was defined as the percentage of change in mean blood pressure when NaCl intake was changed from low (34 mmol/day) to high (342 mmol/day). Salt-sensitivity index was inversely correlated with fractional excretion of lithium both on the low and high NaCl diets (r = -0.721, P less than 0.01 and r = -0.591, P less than 0.02, respectively; n = 16), but not with fractional excretion of sodium. The change of plasma Na+,K(+)-ATPase inhibition with NaCl loading had a direct correlation with salt-sensitivity index (r = 0.704, P less than 0.01; n = 16). Either intra-erythrocyte sodium and potassium concentrations or the ratio of these two values did not change significantly with an increase of dietary NaCl intake. These results suggest that an enhancement of proximal tubular sodium reabsorption stimulates secretion of plasma Na+,K(+)-ATPase inhibitor which may be involved in a rise in blood pressure with sodium loading. They also suggest that lithium clearance is a determinant which can predict salt sensitivity without actual NaCl loading.

Postnatal Changes in Proximal and Distal Tubular Sodium Reabsorption in Healthy Very-Low-Birth-Weight Infants

We studied 7 healthy very-low-birth-weight male infants with a mean birth weight of 1,195 g and a gestational age of 29.0 weeks, from birth to 6 weeks. The filtered Na load increased fivefold but urine Na excretion decreased from 3.4 to 0.1% of the filtered Na load. The efficiency of Na reabsorption increased 8% in the proximal tubule compared with 66% in the distal tubule. Because greater than 90% of Na reabsorption always occurred proximally, the smaller percentage increase in efficiency of the proximal tubule contributed as much as the larger percentage increase in efficiency of the distal tubule to the postnatal improvement in renal Na conservation.

Renal sodium handling and sodium transport inhibitor in salt-sensitive essential hypertension

To investigate the mechanism whereby blood pressure rises with NaCl loading in salt-sensitive essential hypertension, salt-sensitivity index was determined along with sodium and lithium clearances, plasma Na+,K(+)-ATPase inhibitor and intra-erythrocyte sodium and potassium concentrations. Salt-sensitivity index was defined as the percentage of change in mean blood pressure when NaCl intake was changed from low (34 mmol/day) to high (342 mmol/day). Salt-sensitivity index was inversely correlated with fractional excretion of lithium both on the low and high NaCl diets (r = -0.721, P less than 0.01 and r = -0.591, P less than 0.02, respectively; n = 16), but not with fractional excretion of sodium. The change of plasma Na+,K(+)-ATPase inhibition with NaCl loading had a direct correlation with salt-sensitivity index (r = 0.704, P less than 0.01; n = 16). Either intra-erythrocyte sodium and potassium concentrations or the ratio of these two values did not change significantly with an increase of dietary NaCl intake. These results suggest that an enhancement of proximal tubular sodium reabsorption stimulates secretion of plasma Na+,K(+)-ATPase inhibitor which may be involved in a rise in blood pressure with sodium loading. They also suggest that lithium clearance is a determinant which can predict salt sensitivity without actual NaCl loading.

US 4,943,391 Stabilizers BASF

The renin-angiotensin system (RAS) is a widely studied hormonal system that comprises substrate-enzyme interactions, the end result of which is production of the active peptide angiotensin II (Ang II). Because Ang II affects blood pressure control, sodium and water homeostasis, and cardiovascular function and structure, a great deal of research effort has been directed toward blocking the RAS. Angiotensin II may also be involved in end-organ damage in hypertension, heart failure, and vascular disease. At least two subtypes of angiotensin II receptors have been identified: AT1 and AT2. The AT1 mediates all of the known actions of Ang II on blood pressure control. Additionally, research has indicated that the AT1 receptor modulates cardiac contractility and glomerular filtration, and increases renal tubular sodium reabsorption, and cardiac and vascular hypertrophy. Less is known regarding the function of the AT2 receptor. Evidence suggests that the AT2 receptor inhibits cell proliferation and reverses AT1-induced hypertrophy. Indeed, these receptors are thought to exert opposing effects.Angiotensin II AT1 receptor antagonists (AT1RA) inhibit the RAS at the receptor level by specifically blocking the AT1 receptor subtype. These drugs induce a dose-dependent blockade of Ang II effects, resulting in reduced blood pressure, urinary protein, and glomerular sclerosis. It is postulated that AT1RA may provide end-organ protection by blocking Ang II effects via the AT1 receptor, yet leaving the AT2 receptor unopposed. Consequently, these agents may reduce the morbidity and mortality that result from myocardial infarction (MI) and other conditions resulting from structural alterations in the heart, kidney, and vasculature.

Effect of Natriuretic Agents, Vasoactive Agents and of the Inhibition of Metabolism on Sodium Handling in the Isolated Perfused Kidney of the Nephrotic Rat

1. The kidney taken from a rat rendered nephrotic by exposure to puromycin aminonucleoside retains sodium abnormally when perfused in isolation and has an abnormally low vascular resistance (J. D. Firth et al., Clin. Sci. 1989; 76, 387-95). In this study the relation of oxygen consumption to sodium reabsorption has been examined in the isolated nephrotic organ, which has also been exposed to a variety of natriuretic agents and to the effect of inhibition of metabolism by cooling, in an attempt to discern the transport process, or processes, responsible for abnormal tubular handling of sodium. In addition, the effects of three endogenous vasoconstrictors, noradrenaline, angiotensin II and endothelin, on the function of the isolated nephrotic kidney have been examined. 2. The ratio of mol of sodium reabsorbed by the tubules of the isolated nephrotic kidney to mol of oxygen consumed was reduced in comparison with the control kidney (means +/- SEM): 9.22 +/- 0.97 versus 15.43 +/- 1.55 (P less than 0.002). 3. In the presence of ouabain (1 mmol/l), acetazolamide (1 mmol/l), frusemide (200 mumol/l), the combination of these three agents together, hydroflumethiazide (100 mumol/l), benzamil (100 nmol/l) or atrial natriuretic peptide (1000 pmol/l), a lesser increment in sodium excretion was induced in the isolated nephrotic kidney than in the control kidney and the nephrotic organ continued to excrete less sodium in both absolute and fractional terms. 4. This suggests that enhanced tubular sodium reabsorption in the isolated nephrotic kidney does not depend upon abnormally increased activity of the Na+/K(+)-adenosine triphosphatase, bicarbonate-dependent sodium transport, Na+/K+/2Cl- co-transport, electrically neutral proportionate reabsorption of sodium and chloride (distal tubule), epithelial sodium channel (distal tubule) or atrial natriuretic peptide-sensitive sodium transport processes. 5. When isolated nephrotic kidneys and normal kidneys were cooled to 8-10 degrees C the handling of sodium became virtually identical in the two groups. On re-warming to 37 degrees C, the original differences in sodium handling between nephrotic and control kidneys were restored. This implies that the mechanism responsible for the abnormal tendency to retain sodium is temperature-sensitive; as yet it remains otherwise undefined. 6. The sensitivity of the renal vessels to noradrenaline, angiotension II and endothelin, as judged by the percentage reduction in perfusate flow rate produced by a given concentration of any of these agents, was not substantially altered in the nephrotic kidney compared with the control kidney. Increase in vascular tone was not associated with amelioration of the tendency of the isolated nephrotic organ to retain sodium. Increasing concentrations of angiotensin II caused the filtration rate to increase in the nephrotic kidney. This effect was unexpected: in the control preparation, as anticipated, angiotensin II caused the filtration rate to decrease.

Renal function in obstructive jaundice in man: Cholangiocarcinoma model

Renal function with respect to water clearance and renal hemodynamics was studied in 15 patients with obstructive jaundice due to cholangiocarcinoma. The results were compared with those of the control normal subjects. There was no change in renal function in the patients with mild to moderate jaundice, with total serum bilirubin from 8.0 to 15.1 mg/dl. Increased urinary sodium excretion and decreased free water and negative water clearances were observed in the patients with severe jaundice with total serum bilirubin from 27.0 to 40.4 mg/dl and normal serum albumin. Renal blood flow was normal, but creatinine clearance was decreased. In severely jaundiced patients with serum bilirubin from 30.5 to 40.1 mg/dl and hypoalbuminemia urinary sodium excretion, free water clearance, negative water clearance, renal blood flow and creatinine clearance were decreased. There was salt and water retention in this group. The findings suggest that in severe jaundice there is inhibition of sodium chloride reabsorption in the thick ascending limb of Henle's loop. ADH and increased hydraulic conductivity of the collecting tubules possibly contribute to decreased free water clearance. In severely jaundiced patients with hypoalbuminemia this salt losing effect is converted to salt retention by increased proximal tubular reabsorption of sodium.

The use of a single non-timed urine collection in the calculation of fractional lithium clearance

The fractional clearance of lithium (CLLi/CLCR) calculated in 15 normal healthy adults from a single morning urine aliquot collection, together with a single venous blood sample (FQ) was compared with the average CLLi/CLCR obtained from three timed consecutive urine collections with mid-point blood sampling (FABC). Lithium had been ingested 15-18 h prior to the collection of these samples. Mean CLLi/CLCR was similar (FQ, 0.186, FABC, 0.177), with a highly significant correlation in each individual of CLLi/CLCR measured by either method (r = 0.97, P less than 0.0001). Proximal tubular reabsorption of sodium using lithium clearance may be calculated from a single urine and blood sample.

Mineral Excretion by Low Birth Weight Infants

The preterm, low or very low birth weight (VLBW) infant has several inadequate homeostatic mechanisms, among which renal immaturity is prominent. Maximal renal concentrating ability in the VLBW infant is often less than twice the osmolality of plasma, compared to a fourfold increase in the mature infant. Equally important is the VLBW infant's limited proximal tubular reabsorption of sodium. The mature infant's response to sodium restriction results in over 99.5% of filtered sodium being reabsorbed; in the case of the VLBW infant, sodium reabsorption may be only 97% to 98% from days 4 through 14 of life. As a result of these two important limits, the VLBW infant has a higher water requirement than the full-term infant.

Role of microfilaments in maintenance of proximal tubule structural and functional integrity

To determine the selective effect of microfilament disruption on both cellular structure and function, microfilament-specific doses of cytochalasin D (10 microM) were used in an isolated perfused kidney system. Structurally, cytochalasin D resulted in extensive disruption of the apical surface with blebbing, vacuolization, and patchy loss and fusion of microvilli. Functionally, cytochalasin D resulted in an initial decrease in glomerular filtration rate (300.8 +/- 29.9 vs. 541.6 +/- 51 microliters.min-1.g-1, P less than 0.05) with subsequent stabilization throughout the duration of the perfusion. In contrast, the tubular reabsorption of sodium decreased significantly in a linear fashion from 97.1 +/- 0.7 to 64.3 +/- 7.0% over the duration of the perfusion. Similarly, the tubular reabsorption of lithium decreased linearly from 74.8 +/- 2.6%, before the addition of cytochalasin, to 33.6 +/- 6.8% by the end of the perfusion. Correlation of the decrements in percent tubular reabsorption of sodium and lithium for individual kidneys was 0.87 (P less than 0.01), suggesting the effect of microfilament disruption on tubular reabsorption of sodium was localized primarily to the proximal tubule. Because ischemic injury is characterized by time-dependent structural alterations in the apical membrane of proximal tubule cells, we set out to determine whether microfilament disruption occurs during ischemic acute renal failure. Utilizing indirect immunofluorescence with an anti-actin antibody, control kidneys demonstrated intact circumferential apical immunofluorescence representing brush-border and terminal web actin staining. Fifteen minutes of ischemia resulted in multiple large gaps in the terminal web, and 50 min of ischemia caused diffuse redistribution of actin immunofluorescence throughout the cytoplasm.(ABSTRACT TRUNCATED AT 250 WORDS)

Renal tubular reabsorption of calcium and sodium in primary hyperparathyroidism

Nine patients with primary hyperparathyroidism were studied to investigate the renal tubular reabsorption of calcium and sodium. Fasting serum and urine samples were analysed, and the glomerular filtration rate and the renal plasma clearance of lithium were determined simultaneously. Comparison was made with 9 age- and sex-matched normocalcemic controls. In the proximal tubule, there was a significantly higher absolute reabsorption of calcium in patients than in controls, whereas the fractional reabsorption rate of calcium did not differ between the two groups. In the distal tubule, the absolute calcium reabsorption rate was significantly higher in the patients, whereas the fractional reabsorption rate of calcium was significantly lower than in controls. In the patient group there was a significantly positive linear correlation between the increased tubular capacity for calcium reabsorption and the absolute proximal calcium reabsorption rate, but not between the increased capacity and the absolute distal calcium reabsorption rate. No significant differences were found in the renal tubular handling of sodium between patients and controls. Our results suggest that the increased capacity for tubular calcium reabsorption in primary hyperparathyroidism mainly is localized in the proximal tubule, and that the renal tubular handling of calcium and sodium in this disease differs from that in familial hypocalciuric hypercalcemia.