Proximal Sodium Reabsorption Research Articles

A pathophysiological interpretation of unresponsiveness to spironolactone in a stepped-care approach to the diuretic treatment of ascites in nonazotemic cirrhotic patients

It has been hypothesized that the magnitude of proximal sodium reabsorption affects the response to aldosterone antagonists in nonazotemic cirrhotic patients with ascites. To verify this hypothesis, we evaluated intrarenal sodium handling by lithium clearance in 51 nonazotemic ascitic cirrhotic patients and in 23 controls who were maintained on the same low-sodium diet (80 mmol/day). Seven of 51 cirrhotic patients underwent spontaneous diuresis, whereas 44 required diuretic treatment. Treatment was started with spironolactone at a dose of 150 mg once daily. The dose was increased to 300 mg and then to 500 mg once daily if no response ensued. Cirrhotic patients who did not experience ascites mobilization with 500 mg spironolactone were then treated with a combined diuretic regimen that included spironolactone at a fixed dose (500 mg once daily) and furosemide at an initial dose of 50 mg once daily. The dose was increased to 100, 150 and 200 mg once daily if no response was noticed. Response to diuretic treatment was defined as body weight loss greater than 700 gm every 3 days until ascites became clinically undetectable. Nonresponders (43%) to spironolactone showed lower sodium fractional excretion (0.34% ± 0.28% vs. 0.80% ± 0.50%; p < 0.001) because of a lower fractional sodium delivery to the distal tubule (18.2% ± 5.8% vs. 23.4% ± 7.2%; p < 0.025) than responders. Moreover, nonresponders showed lower distal sodium reabsorption, both in absolute terms (2,360 ± 723 μEq/min vs. 3,221 ± 960 μEq/min; p < 0.01) and as a percentage of filtered sodium load (17.5% ± 5.7% vs. 23.1% ± 7.6%; p < 0.01) despite higher values of plasma aldosterone (524 ± 542 pg/ml vs. 136 ± 213 pg/ml; p < 0.025). We conclude that unresponsiveness to adequate doses of spironolactone in nonazotemic ascitic cirrhotic patients is related to a pathophysiological condition in which the role of aldosterone in renal sodium retention is limited by markedly enhanced proximal sodium reabsorption. (HEPATOLOGY 1991;14:231–236.)

A pathophysiological interpretation of unresponsiveness to spironolactone in a stepped-care approach to the diuretic treatment of ascites in nonazotemic cirrhotic patients

It has been hypothesized that the magnitude of proximal sodium reabsorption affects the response to aldosterone antagonists in nonazotemic cirrhotic patients with ascites. To verify this hypothesis, we evaluated intrarenal sodium handling by lithium clearance in 51 nonazotemic ascitic cirrhotic patients and in 23 controls who were maintained on the same low-sodium diet (80 mmol/day). Seven of 51 cirrhotic patients underwent spontaneous diuresis, whereas 44 required diuretic treatment. Treatment was started with spironolactone at a dose of 150 mg once daily. The dose was increased to 300 mg and then to 500 mg once daily if no response ensued. Cirrhotic patients who did not experience ascites mobilization with 500 mg spironolactone were then treated with a combined diuretic regimen that included spironolactone at a fixed dose (500 mg once daily) and furosemide at an initial dose of 50 mg once daily. The dose was increased to 100, 150 and 200 mg once daily if no response was noticed. Response to diuretic treatment was defined as body weight loss greater than 700 gm every 3 days until ascites became clinically undetectable. Nonresponders (43%) to spironolactone showed lower sodium fractional excretion (0.34% +/- 0.28% vs. 0.80% +/- 0.50%; p less than 0.001) because of a lower fractional sodium delivery to the distal tubule (18.2% +/- 5.8% vs. 23.4% +/- 7.2%; p less than 0.025) than responders.(ABSTRACT TRUNCATED AT 250 WORDS)

Endothelin induces diuresis and natriuresis in the rat by acting on proximal tubular cells through a mechanism mediated by lipoxygenase products.

Besides being a potent renal vasoconstrictor, endothelin causes diuresis and natriuresis. At which site along the nephron and how endothelin alters water and sodium handling in the tubule remain to be clarified. It was found that endothelin (75 pmol) given as an i.v. infusion in vivo to rats caused diuresis and urinary sodium excretion to double but did not affect glomerular filtration rate and renal plasma flow. On raising the dose of endothelin to 150 pmol, a further increase in diuresis and natriuresis was found, whereas glomerular filtration rate fell 33% and renal plasma flow fell 36%; 300 pmol of endothelin reduced glomerular filtration rate by 73% and renal plasma flow by 77% but did not significantly affect diuresis and absolute sodium excretion. It did, however, increase fractional sodium excretion eightfold. Lithium clearance studies of changes in tubular handling of water and sodium indicated that infusion of 150 pmol of endothelin to rats caused a reduction in absolute (pre, 84.7 +/- 5.9; post, 47.9 +/- 6.1 microEq/min/100 g) and fractional (pre, 85.7 +/- 3.0; post, 64.7 +/- 6.4%) proximal reabsorption of sodium. Endothelin infusion (150 pmol) was not associated with any significant change in plasma atrial natriuretic peptide levels, which on average remained comparable to those in rats given the vehicle alone (49.7 +/- 8.4 versus 46.3 +/- 5.6 pg/mL). In the isolated perfused rat kidney preparation, exposure to 150 pmol of endothelin significantly increased fractional sodium excretion over preinjection values (pre, 2.2 +/- 0.2; post, 7.3 +/- 1.0%) despite a marked decrease in glomerular filtration rate and renal perfusate flow. Additional in vivo experiments showed that oral administration of the specific 5-lipoxygenase inhibitor L-651,392 to rats prevented the increase in urine flow rate (pre, 5.7 +/- 0.1; post, 6.6 +/- 0.8 microL/min), and in absolute (pre, 0.33 +/- 0.04; post, 0.37 +/- 0.05 microEq/min) and fractional (pre, 0.10 +/- 0.02; post, 0.11 +/- 0.03%) sodium excretion caused by bolus i.v. infusion of endothelin (150 pmol). Similarly, a specific leukotriene C4/D4 receptor antagonist, L-649,923, also prevented the diuretic and natriuretic effect of 150 pmol of endothelin i.v. infusion. These findings show that (1) endothelin has a diuretic and natriuretic effect that is independent of its action on renal hemodynamics; (2) this effect depends on a direct action on the proximal tubules; (3) atrial natriuretic peptide does not appear to be involved in this effect; and (4) the diuretic and natriuretic responses to endothelin are mediated by 5-lipoxygenase products.

Abnormal tubular handling of sodium and water induced by atrial natriuretic peptide in essential hypertension

Atrial natriuretic peptide (ANP) was given as an intravenous bolus injection (2.0 micrograms kg-1) to 12 essential hypertensive patients (EH) and 13 normotensive control subjects (C) in order to study the effect of ANP on renal glomerular and tubular function using the lithium clearance technique. Urinary sodium excretion (EH, + 370% vs. C, + 120%; P less than 0.001) and urine volume (EH, + 137% vs. C, + 62%; P less than 0.01) increased significantly more in EH than in controls after ANP injection. Glomerular filtration rate, renal plasma flow, and plasma concentrations of angiotensin II, aldosterone and arginine vasopressin remained almost unchanged after ANP injection, whereas the filtration fraction increased to the same extent in both groups. Both proximal (EH, - 15% vs. C, - 5%; P less than 0.01) and distal fractional reabsorption (EH, - 12% vs. C, - 5%; P less than 0.01) of sodium decreased more markedly after ANP in EH than in controls. The increase in plasma cGMP and urinary excretion of cGMP was the same in the two groups. Mean blood pressure decreased and heart rate increased to the same extent in both groups. It is concluded that the increase in urinary sodium excretion and urine volume induced by ANP bolus injection is exaggerated in EH due to a more pronounced reduction in the reabsorption of sodium and water in both the proximal and the distal tubule.

Renal response to blood volume expansion in Brattleboro rats after acute treatment with vasopressin

The renal response to iso-oncotic blood volume expansion with bovine serum albumin was studied in anaesthetized homozygous Brattleboro (DI) rats after acute (1 day) pretreatment with 1 U arginine-vasopressin (AVP) compared to heterozygous controls. In AVP-treated DI (DI + AVP) rats, basal urine flow as well as urinary sodium, chloride, and potassium excretion, were not different from controls. Diuresis and kaliuresis induced by volume expansion were blunted in DI + AVP rats. However, natriuresis and chloruresis were exaggerated in DI + AVP rats. They increased faster, reached a higher maximum, but declined earlier, compared to controls. The blunted diuresis resulted in a positive volume balance by the end of the experiment in DI + AVP rats, whereas the controls showed restoration of normal balance. Significant retention of sodium and chloride was observed in controls, but not in DI + AVP rats, over the time of the experiment. DI + AVP rats lost significantly less potassium than controls during the experiment. As judged from the lithium clearance method, the exaggerated saluresis in DI + AVP rats was mainly due to a reduced proximal sodium reabsorption. Plasma immunoreactivity of atrial natriuretic peptide (ANP) rose during blood volume expansion and fell in the recovery period. It was not different between AVP-treated DI rats and controls at any time of the experiment. Inulin clearance was slightly, but not significantly, lower in DI + AVP rats and increased after blood volume expansion in DI + AVP rats only.(ABSTRACT TRUNCATED AT 250 WORDS)

THE SYNDROME OF HYPERTENSION AND HYPERKALAEMIA WITH NORMAL GLOMERULAR FILTRATION RATE: IS THERE A DEFICIENCY IN VASODILATOR PROSTAGLANDINS?

1. In Gordon's syndrome (GS; a syndrome of hypertension and hyperkalaemia with normal glomerular filtration rate), excessive proximal sodium reabsorption leads to suppression of renin and aldosterone, hyperkalaemia and hyperchloraemic acidosis. 2. Low urinary levels of vasodilator prostaglandins (PG) have been reported in GS, suggesting renal hypoprostaglandinism as a pathophysiological mechanism. 3. In four cases of GS, levels of vasodilator prostaglandins PGE2 and 6-keto-PGF1 alpha were low. 4. In one case of GS, low PGE2 levels were normalized by dietary salt restriction or diuretic therapy.

Effects of endothelin on renal haemodynamics and segmental sodium handling in conscious rats

The effects of endothelin (100 and 600 pmol/kg) on renal plasma flow (RPF), glomerular filtration rate (GFR), sodium excretion (UNa V) and segmental sodium handling were investigated in conscious rats. Low-dose endothelin decreased renal plasma flow by 26% without affecting glomerular filtration rate and sodium excretion. High-dose endothelin reduced renal plasma flow, glomerular filtration rate, sodium excretion and lithium clearance by 57, 45, 38 and 52%, respectively. The fall in sodium excretion was not due to a direct effect of endothelin on tubular sodium transport since sodium excretion corrected by glomerular filtration rate and fractional proximal and distal sodium reabsorption did not change throughout the study. These results indicate that the impairment in renal perfusion is responsible for the antinatriuretic effect of endothelin in conscious rats.

Decreased Renal Clearance of Sodium in Cystic Fibrosis

In 10 patients with cystic fibrosis (CF) and 10 controls of similar age quantitative segmental handling of sodium was estimated by lithium clearance. In the CF group, there was a tendency for an increased glomerular filtration rate (GFR) and increased absolute proximal sodium reabsorption. The fractional distal sodium reabsorption was significantly (p = 0.015) increased and sodium clearance was significantly (p less than 0.01) decreased in CF.

Effects of NH&lt;sub&gt;4&lt;/sub&gt;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.

Atrial natriuretic peptide and renal adaptation to contralateral nephrectomy in healthy man

Atrial natriuretic peptide (ANP), angiotensin II (AII), aldosterone (Aldo) and arginine vasopressin (AVP) in plasma were determined in 12 healthy renal transplant donors before and 5, 12, 26, 54 days after uninephrectomy (Nx) in order to study the possible role of these hormones in functional adaptation to acute reduction in renal mass. Glomerular and tubular function was studied by measurements of the clearances of 51Cr-EDTA, lithium, sodium, potassium, and albumin. ANP was 7.4 +/- 3.1 pmol l-1 (mean +/- SD) before Nx and 8.7 +/- 6.1 pmol l-1 at 5 days after Nx and remained at this level through the observation period. Aldo showed a non-significant transient fall at 5 days after Nx. AII and AVP remained normal after Nx. At 5 days after Nx glomerular filtration rate (GFR) of the remaining kidney had risen from 45 +/- 7 ml min-1 before Nx to 57 +/- 8 ml min-1 (p less than 0.01), lithium clearance had risen from 13 +/- 2 ml min-1 before Nx to 20 +/- 7 ml min-1 (p less than 0.01), and sodium and water balance was normal. To conclude, plasma ANP, AII, Aldo and AVP do not appear to be responsible for the hyperfiltration and depression of fractional proximal sodium and water reabsorption observed in recently uninephrectomized man with normal sodium and water balance.

Effects of Isradipine on Renal Function in Cydosporin-Treated Renal Transplanted Patients

The renal effects of the calcium-channel antagonist isradipine were evaluated in cyclosporin A (CsA)-treated renal allografted patients more than 5 months after transplantation. Twelve patients with stable renal function were given placebo for 2 weeks and then isradipine 1.25 mg x 2 for 1 week and 2.5 mg x 2 for the next 3 weeks in an open trial. The CsA dose was unchanged during the study. Isradipine did not interfere with the pharmacokinetics of CsA as both whole blood trough and peak levels were unchanged. Isradipine reduced mean arterial blood pressure (MAP) from 117.0 +/- 1.8 to 106.3 +/- 1.9 mmHg (P less than 0.01). The renal effects were studied during water diuresis 1-3 h after drug intake. Para-aminohippurate clearance (CPAH) increased from 256.4 +/- 21.5 to 291.5 +/- 26.3 ml/min (P less than 0.05), renal vascular resistance was reduced by 21.5% (P less than 0.01) and inulin clearance (CIn) was unchanged. Fractional proximal reabsorption, calculated from lithium clearance (CLi), was reduced by 11.9% (P less than 0.01) by isradipine. Isradipine also reduced proximal reabsorption of sodium (APRNa) and increased distal sodium delivery (DDNa). Distal sodium reabsorption (ADRNa) and free-water clearance (CH2O) were significantly increased. Urinary excretion of enzymes and proteins was unchanged by isradipine.

Effect of Angiotensin II on Proximal Tubular Reabsorption in Normal Humans

The effects of angiotensin II (AII) on proximal tubular reabsorption have been evaluated in 6 healthy volunteers under normal salt and water balance. One-hour clearance periods were performed before, during and after the infusion of pressor doses of AII; in 3 of the 6 subjects, the study was repeated with lower doses of AII. Glomerular filtration rate (GFR) and renal plasma flow (RPF) were determined by the clearances of inulin and PAH, and the fractional excretion of lithium (FELi) was considered as an index of proximal sodium reabsorption. The effects of AII on the fractional excretion of beta 2 microglobulin (FE beta 2M) were also studied. Both doses of AII decreased GFR and RPF and increased the filtration fraction (FF); the modifications of these parameters, as well as the reduction of FELi and the fractional excretion of sodium (FENa) and the increase of plasma aldosterone and of plasma atrial natriuretic peptide (ANP), were more evident with pressor doses of AII, which increased the blood pressure from 129/83 to 142/95 mm Hg (p less than 0.01). AII did not modify FE beta 2M in either study. During AII, FELi decreased less than FENa and both were closely and inversely related to the variations of FF, whilst no relationship was present between FE beta 2M and FF. These results suggest that, in normal humans, the AII-induced rise of FF may be an important factor, even if not the only one, in enhancing the proximal reabsorption of lithium and thus of sodium, whilst it does not affect the absorption of beta 2M.

Effects of ACE Inhibition on Renal Haemodynamics in Essential Hypertension and Hypertension Associated with Chronic Renal Failure

Angiotensin II has many actions in the kidney, including regulation and distribution of renal circulation and glomerular filtration, as well as effects on mesangial contraction and on the filtration coefficient. The reduction in circulating and intrarenal angiotensin II by angiotensin converting enzyme (ACE) inhibitors in essential hypertension is associated with a significant increase in renal blood flow and a decrease in filtration fraction, without changes in glomerular filtration rate. In addition, administration of ACE inhibitors can reduce proximal sodium reabsorption via changes in peritubular hydrostatic and oncotic forces resulting from the fall in postglomerular capillary resistance. In severe hypertension the state of the renal vasculature does not allow ACE inhibition to induce similar haemodynamic changes and, therefore, it cannot contribute to renal sodium handling that requires the recruitment of alternate mechanisms. In spite of this, ACE inhibitors may exert a protective effect on the renal function of patients with severe hypertension as well as in those with renal impairment, by lowering systemic and, probably, intraglomerular pressure, reducing proteinuria and slowing the progression of renal failure.

Nephron Sites of the Natriuretic Effect of Intrarenal Infusion of Atrial Natriuretic Peptide in the Rat

Since renal mechanisms by which ANP induces a natriuresis remain unclear, the effects of the infusion of 0.03 micrograms/min/kg body weight of rANP 1-28 into the right renal artery (via a very thin catheter inserted into the suprarenal artery) were studied in anesthetized rats using lithium clearance to monitor proximal tubular function. Intrarenal ANP did not cause changes in arterial pressure and hematocrit, nor in contralateral kidney handling of sodium. Its natriuretic effect on the right kidney resulted from an increase in the filtered load of sodium and from a decrease in reabsorption in the distal segments of the nephron. Proximal tubule sodium reabsorption increased in proportion to the filtered load.

Renal sodium and water handling in hypothyroid patients

The mechanism responsible for renal tubular abnormalities in sodium and water excretion in hypothyroid patients is poorly understood. To evaluate the possible contribution of the reduced glomerular filtration rate of hypothyroidism to these abnormalities, tubular function in hypothyroid patients was compared with that in patients with chronic renal failure and in normal subjects. The lithium clearance method and oral water loading were used to evaluate parameters of tubular sodium and water handling, respectively. The hypothyroid and the chronic renal failure patients were selected to have similar reductions in glomerular filtration rate. As compared to the normal subjects, the hypothyroid and chronic renal failure patients had a decrease in proximal sodium reabsorption and an increase in distal sodium reabsorption. The changes in tubular handling of sodium were not different in the hypothyroid and the chronic renal failure patients. Maximal urinary flow rate and free water clearances were similarly reduced in the hypothyroid patients and the chronic renal failure patients. For all subjects studied, proximal sodium reabsorption and maximal urinary volume were directly correlated with the glomerular filtration rate, and distal nephron sodium reabsorption was proportionate to delivery of sodium from the proximal tubule. The results suggest that the abnormalities in tubular sodium and water handling in hypothyroid patients are comparable to those present in other patients with a similar degree of renal insufficiency. Thus, the tubular abnormalities in hypothyroidism may be a consequence of the associated decrease in glomerular filtration rate.

Sodium and Water Excretion in Nephrotic Patients: Effects of Changes in Renal Haemodynamics

1. Eight nephrotic patients were studied in order to evaluate the effects of acute changes in renal plasma flow and glomerular filtration rate on renal solute and water handling, in the absence of plasma volume expansion. 2. The subjects were studied first after the administration of captopril, a manoeuvre that increased renal plasma flow without a significant change in glomerular filtration rate, and a second time after receiving combined therapy with captopril and ibuprofen, a manoeuvre that decreased glomerular filtration rate without a significant change in renal plasma flow. 3. After captopril therapy, despite the increase in renal plasma flow, there was no significant change in proximal sodium reabsorption (as estimated from fractional lithium reabsorption), urine volume or urine osmolality. 4. The decrease in glomerular filtration rate observed after the administration of captopril plus ibuprofen was associated with decreases in fractional excretion of sodium and urine volume, and an increase in urine osmolality. The changes in these parameters of tubular function were proportionate to the changes in glomerular filtration rate. Fractional proximal sodium reabsorption increased substantially. 5. These observations suggest that, in the absence of plasma volume expansion, an increase in renal plasma flow does not increase sodium or water excretion by the nephrotic kidney. Moreover, during acute decreases in glomerular filtration rate, glomerulotubular balance appears to be disrupted, resulting in disproportionately high rates of proximal tubule sodium reabsorption.

GLOMERULOTUBULAR FUNCTION IN LONG-TERM RENAL ALLOGRAFT RECIPIENTS

Glomerular and tubular function were assessed, using a lithium clearance technique, in two groups of renal allograft recipients at least one year after transplantation. Group 1 comprised 14 patients receiving low-dose prednisolone and cyclosporine, and group 2, 14 patients receiving low-dose prednisolone and azathioprine. There were no significant differences in creatinine clearances between the two groups, although the clearances of lithium (which is absorbed almost exclusively from the proximal tubule) and sodium were significantly lower in the cyclosporine-treated group. Fractional lithium excretion was also significantly lower in group 1 than in group 2, but there was no significant difference in fractional sodium excretion. The absolute proximal reabsorption of sodium and water did not differ between the groups, although the fractional proximal reabsorption of sodium and water was significantly higher in group 1. In contrast, the distal reabsorption of sodium and of water was significantly lower in the cyclosporine-treated patients than in the azathioprine-treated patients; there were, however, no significant differences in the distal fractional reabsorptions of sodium and water between the two groups. In addition there was no correlation in group 1 between whole-blood cyclosporine levels or time since transplantation and any of the assessed parameters of renal function. These results indicate that tubular concentrating abnormalities in cyclosporine-treated renal allograft recipients are similar to those observed in rodent models of cyclosporine nephrotoxicity. They suggest that the pathogenesis of cyclosporine nephrotoxicity may be similar in renal allograft recipients to that in experimental models.

Tubular sodium handling in cirrhotic patients with ascites as analysed by the renal lithium clearance method

The proximal and distal sodium reabsorption were calculated from lithium clearance in 21 healthy controls and 24 cirrhotic patients with ascites after 4 days under a sodium-restricted diet. The values of fractional lithium clearance were lower in patients than in controls (7.37 +/- 0.87 vs. 18.13 +/- 1.76%, P less than 0.001). Fractional proximal sodium reabsorption was increased in patients compared with controls (92.8 +/- 1.1 vs. 81.8 +/- 1.7%, P less than 0.001). No differences were found in fractional distal sodium reabsorption between controls and patients (96.9 +/- 0.8 vs. 98.6 +/- 0.1%). When patients were separated into two subgroups according to their sodium balance, it was found that fractional distal sodium reabsorption was increased in patients whose balance remained positive, compared with patients on a negative sodium balance (98.99 +/- 0.26 vs. 94.11 +/- 1.50%, P less than 0.05). In addition, the natriuretic response to a specific dose of spironolactone was higher in patients on positive sodium balance compared with patients on negative sodium balance (per cent increase in natriuresis after spironolactone 300 mg day-1: 355.24 +/- 73.98 vs. 84.21 +/- 15.8%, P less than 0.01). We conclude that proximal sodium reabsorption is increased in cirrhotics with ascites. In addition, distal sodium reabsorption is enhanced only in those patients which exhibit avid sodium retention.

Response of superficial proximal convoluted tubule to decreased and increased renal perfusion pressure. In vivo microperfusion study in rats.

Although urinary sodium excretion is positively influenced by acute changes in renal perfusion pressure, micropuncture studies show highly conflicting results concerning the response of superficial proximal tubule sodium reabsorption to changes in renal perfusion pressure. In the present study, the changes of superficial proximal reabsorption to decreased and increased renal perfusion pressure were determined in rats by an in vivo microperfusion method. In vivo microperfusion was selected as the method to determine the proximal sodium reabsorption because this method made it possible to deliver a constant fluid and electrolyte load to the proximal tubule without the influence of possible changes of glomerular filtration rate. Renal perfusion pressure was decreased from normal pressure by inflating a suprarenal aortic cuff and was increased from the normal level by the occlusion of celiac and mesenteric arteries and the infrarenal aorta. Although fractional excretion of sodium (FENa) in the urine was decreased from 1.24 +/- 0.23% to 0.45 +/- 0.11% (n = 7, p less than 0.01) when renal perfusion pressure was decreased from 125 +/- 6 to 99 +/- 3 mm Hg, absolute tubular reabsorption by the superficial proximal convoluted tubules was not increased (from 4.4 +/- 0.5 to 4.2 +/- 0.3 nl/min/mm, n = 22). When the renal perfusion pressure was elevated from 126 +/- 4 to 149 +/- 4 mm Hg, tubular reabsorption by the superficial proximal tubules was decreased from 4.1 +/- 0.3 to 2.5 +/- 0.3 nl/min/mm (n = 36, p less than 0.01) with an accompanying increase in FENa (from 1.28 +/- 0.24% to 2.29 +/- 0.37%, n = 9, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Renal hemodynamics and segmental tubular reabsorption in early type 1 diabetes

To investigate mechanisms underlying GFR control in diabetes mellitus, renal hemodynamics and segmental tubular handling of sodium, using lithium clearance, were assessed in 41 insulin-dependent diabetics (IDD) treated by insulin for 11 +/- 8 days, and in 19 normal controls. Average GFR and effective renal plasma flow (ERPF) were slightly but not significantly higher (136 +/- 22 vs. 123 +/- 16 ml/min.1.73 m2) in IDD than in normal subjects. GFR and ERPF were positively and strongly correlated in controls (r = 0.61, P less than 0.001) and in diabetics (r = 0.72, P less than 0.0001) indicating the marked flow dependency of GFR in both populations. After adjustment for ERPF, GFR was significantly higher in diabetics, suggesting a role of increased glomerular capillary pressure and ultrafiltration coefficient in the subset of "hyperfiltering" patients. Both fractional (FPRNa) and absolute (APRNa) proximal sodium reabsorption were significantly higher in IDD and significantly correlated with GFR. The ensuing decrease in sodium distal delivery could deactivate the tubuloglomerular feedback response and thus favor sustained vasodilation and high GFR in some diabetics. The renal effects of acute administration of drugs acting predominantly at either the pre- or the postglomerular resistance using nicardipine (N = 16) or captopril (N = 25) were further evaluated in IDD. The renal response to captopril or nicardipine was different in IDD. Whereas both drugs induced a marked decrease in renal vascular resistance, GFR was slightly decreased by captopril and was unchanged after nicardipine; these results are similar to those observed in normotensive non-diabetic subjects.(ABSTRACT TRUNCATED AT 250 WORDS)