Increase In Effective Renal Plasma Flow Research Articles

The Impact of Nephrectomy on Living Donors – An Analysis of the Existing Literature

Introduction In kidney transplantation security for the living donor is of utmost importance. An in-depth understanding of the changes induced by donating one kidney is key to decide on the risk of donation and to define guidelines for donor selection. Robust, well-matched long-term studies on donor outcomes, especially regarding donors with medical risk factors, are missing. In addition, studies on adaptive changes in the remaining kidney are rare and the findings are not well recognized. Methods We have performed a detailed literature review of all studies that looked at outcome of living donors (LD) with a special focus on the physiological effects of donation on the remaining kidney. Here we searched and summarized findings on pre- and post-donation glomerular filtration rate (GFR), renal reserve capacity (RRC), effective renal plasma flow (ERPF) in addition to general medical risk and outcome markers. Results Overall 41 studies on LD outcomes with a special focus on physiological changes were found, covering a time period from 1956 to 2017. The primary characteristics of these studies are summarized in the attached table. The analysis shows that studies on the physiology of changes in kidney organs are rare and nearly absent in the last 10 years. They indicate an adaptive increase in ERPF and GFR in the single, remaining kidney after donation, however longer-term follow-up measurements are missing and studies on changes in ‘borderline donors’ are also needed. Recent studies have larger patients’ numbers and better controls, some identify risk groups and factors for donation but overall lack sufficient follow-up times. Conclusion To allow individual risk assessment and improve safety of living kidney donation studies on the physiology of adaptive changes, esp. in borderline donors, and long-term outcome analyses of well-matched patient cohorts are needed. Keywords living donors, kidney donation outcomes, kidney transplantation, renal reserve capacity NCCR Kidney funded by the Swiss National Science Foundation.

Editorial Comment

In this report, Funahashi et al used technetium-99m mercaptoacetyltriglycine (99mTc-MAG3) renograms to measure the changes in function after partial nephrectomy. The study is unique in that it measured tracer uptake in the regions of interest of the operated kidney unaffected by tumor excision to allow direct study of the ischemic effects. The effective renal plasma flow (ERPF) at 1 week after partial nephrectomy in the whole kidney and the regions of interest was 66% and 83%, respectively. This discrepancy suggested that ischemic injury and other factors, such as volume loss additively contributed to the functional decrease at 1 week. The ischemic duration correlated with the ERPF at 1 week. Typically, the peak creatinine level occurs 1-2 days after partial nephrectomy; thus, these data suggest that ERPF is altered well into the recovery phase. Another interesting observation was an increase in ERPF in the contralateral kidney in some patients. It is uncertain whether this was real or an artifact; however, if real, it would suggest the possibility that adult kidneys have a functional reserve. At 6 weeks, the ERPF levels of the patients with a warm ischemia time of ≤25 minutes had recovered to the preoperative ERPF levels, but those of the patients with a warm ischemia time of >25 minutes remained depressed. Their conclusion was that an ischemia time >25 minutes resulted in irreversible diffuse damage. Effect of Warm Ischemia on Renal Function During Partial Nephrectomy: Assessment With New 99mTc-Mercaptoacetyltriglycine Scintigraphy ParameterUrologyVol. 79Issue 1PreviewA decrease in renal function after partial nephrectomy caused by ischemic damage or nephron loss cannot be distinguished by conventional methods. We quantified renal function using a new 99mTc-mercaptoacetyltriglycine (99mTc-MAG3) renal scintigraphy parameter. Full-Text PDF

Hemodynamic effect of angiotensin II receptor blockade in postmenopausal women on a high-sodium diet: A double-blind, randomized, placebo-controlled study

Background: Hypertension becomes increasingly prevalent after menopause. Postmenopausal women are more responsive to salt than premenopausal women, and they have been reported to develop marked renal vasoconstriction on a high-sodium diet. Objective: The aim of this study was to assess whether angiotensin II receptor blockade can restore a normal pattern of renal response to salt in postmenopausal women on a high-sodium diet. We also assessed segmental renal sodium handling in that population. Methods: Normotensive and hypertensive postmenopausal women not receiving hormone replacement therapy were enrolled in this prospective, double-blind, placebo-controlled, crossover study. They were assigned to receive irbesartan 150 mg or placebo for 6 weeks; the sequence in which they received irbesartan or placebo was randomized. During the last week of treatment, they received a high-sodium diet (250 mmol/d). Ambulatory blood pressure (ABP), glomerular filtration rate (GFR), and effective renal plasma flow (ERPF) were measured using sinistrin and para-amino-hippurate clearances. Renal sodium handling was assessed by measuring endogenous lithium clearance on day 7 of the high-salt diet. Results: Nineteen women (mean age, 54.7 years; range, 43–72 years; 7 normotensive subjects [mean age, 53.4 years; range, 47–61 years] and 12 hypertensive subjects [mean age, 55.4 years; range, 43–72 years]) were included in the study. When the data for all 19 subjects were pooled, ABP was significantly lower with irbesartan than placebo both during the day (120 [3]/79 [2] vs 127 [3]/85 [2] mm Hg; both, P < 0.01) and at night (systolic BP, 107 [4] vs 111 [4] mm Hg [ P < 0.01] and diastolic BP, 71 [2] vs 75 [2] mm Hg [ P < 0.05]). Compared with placebo, irbesartan was not associated with a significant change in GFR in either the normotensive or the hypertensive women. When the data for all 19 subjects were pooled, irbesartan was associated with a significant increase in ERPF compared with placebo (372 [21] vs324 [18] mL/min · 1.73 m 2; P < 0.05). When the hypertensive and normotensive women were considered separately, the effect was more pronounced in the hypertensive women than in the normotensive women, but the changes did not reach statistical significance. When the data for all subjects were pooled, irbesartan was associated with a significant increase in daytime urinary sodium excretion compared with placebo (135 [13] vs 106 [13] μmol/min; P < 0.05) and a significant decrease at night (109 [13] vs 136 [19] μmol/min; P < 0.05). Fractional excretion of lithium (FELi), an inverse marker of proximal sodium reabsorption, increased significantly during the daytime with irbesartan compared with placebo (47% [6.5%] vs 35% [4.7%]; P < 0.05). At nighttime, FELi was significantly higher in the hypertensive subjects receiving irbesartan compared with placebo (43% [7.2%] vs 29% [6.5%]; P < 0.05). The fractional distal reabsorption of sodium did not change significantly with irbesartan compared with placebo. Conclusions: The results from this study suggest that angiotensin II receptor blockade had a favorable impact on BP, renal hemodynamics, and renal sodium handling in these salt-replete postmenopausal women. Blockade of the renin-angiotensin system restored the normal pattern of renal response to high sodium intake in these women.

Significance of the Renal Functional Reserve in Reflux Nephropathy: An Evaluation According to the Degree of Glomerular Damage

Objective. In the treatment of progressive reflux nephropathy (RN), the therapeutic benefit and prognosis of the renal function in RN patients appears to be influenced by the degree of renal functional reserve. We designed this study to determine the presence and characteristics of the renal functional reserve in RN patients. Materials and Methods. In the 35 RN patients with renal scars (19 males; mean age 16.1 years), an exogenous renal clearance test was performed to measure the glomerular filtration rate (GFR) and the effective renal plasma flow (ERPF). In the second half of this test, the renal functional reserve was estimated by measuring the GFR and ERPF during low-dose dopamine infusion. These measurements were then compared with the glomerular size, which had been previously determined by a renal biopsy. Results. Among the patients with a normal glomerular size (−2SD to +2SD), the GFR markedly increased after low-dose dopamine infusion (from 112.15 ± 52.51 to 182.07 ± 69.95mL/min, p < 0.0001), whereas an increase in ERPF was not significant. Among the patients with an enlarged glomerular size (+2SD to +4SD), the GFR and ERPF increased significantly over the baseline values (from 54.60 ± 32.90 to 114.00 ± 65.48 mL/min, p = 0.0076; from 281.01 ± 152.54 to 622.43 ± 392.73 mL/min, p = 0.0155, respectively). Among the patients with an extremely enlarged glomerular size (>+4SD), both the GFR and ERPF remained almost completely unchanged. Conclusion. The renal functional reserve was present even among progressive RN patients with a glomerular size ranging between +2SD and +4SD.

The change of the split renal function before and after a nephrectomy using Tc-mercaptoacetyltriglycine (MAG3).

We examined the change in the renal function in the normal side kidney before and after a nephrectomy, by means of a newly developed diuretic renography technique utilizing Tc 99m-mercaptoacetyltriglycine (MAG3). Forty patients who underwent a nephrectomy were evaluated using MAG3 diuretic renography. We measured the effective renal plasma flow (ERPF) and Tmax time before and after a nephrectomy. The effects of the patient age and the preoperative ERPF of ill side kidney on the post operative ERPF were then assessed statistically. The ERPF increased by an average of 44.8 ml/min at 2 weeks after a nephrectomy, but it decreased by an average of 24.3 ml/min at 3 months after a nephrectomy. The Tmax time decreased by an average of 0.58 min at 2 weeks, but thereafter increased by an average of 0.58 min at 3 months after a nephrectomy. The correlation coefficient between the rate of increase in the ERPF and the patient age was 0.197. The rise of renal function in terms of ERPF and the Tmax time was observed at 2 weeks post-nephrectomy. However, this effect disappeared at 3 months post-nephrectomy. These data demonstrated that the rise in the renal function of the normal-side kidney in such patients was only temporary.

Genetic contribution to the acute effects of angiotensin II type 1 receptor blockade

Clinical observations point towards heterogeneity in patients' responses to antihypertensive drugs. As our earlier work showed that angiotensin II (AngII) sensitivity is associated with the A1166C polymorphism of the AngII type 1 receptor (AT1R) gene, we conducted the present study in which the responses to acute AT1R blockade were evaluated. After 7 days of low and high sodium diet, the hormonal as well as systemic and renal hemodynamic responses to acute AT1R blockade with EXP3174 (active metabolite of losartan) were studied in 15 AA and 14 CC essential hypertensive patients. By means of platelet-binding studies the baseline AT1R density (Bmax) and affinity (KD) was tested. During low and high salt diet, baseline Bmax and KD were comparable between both genotype groups. At baseline, during low salt diet, CC patients had significantly lower glomerular filtration rate and a trend towards lower effective renal plasma flow (ERPF) compared to AA patients. Blood pressure responses to EXP3174 during high salt were significantly blunted in CC patients compared to AA patients (mean arterial pressure: 1.8 versus 7.5%; P < 0.05). During low salt the increase in ERPF (12.9 versus 16.1%; P = 0.08), as well as the decrease in filtration fraction (9.0 versus 14.0%; P = 0.05) and renal vascular resistance (7.5 versus 15.1%; P = 0.06) were blunted in CC patients compared to AA patients. Humoral effects did not differ between the groups. This study shows that the systemic and renal hemodynamic responses to acute AT1R blockade are, at least in part, genetically determined.

Relaxin is a potent renal vasodilator in conscious rats.

The kidneys and other nonreproductive organs vasodilate during early gestation; however, the "pregnancy hormones" responsible for the profound vasodilation of the renal circulation during pregnancy are unknown. We hypothesized that the ovarian hormone relaxin (RLX) contributes. Therefore, we tested whether the administration of RLX elicits renal vasodilation and hyperfiltration in conscious adult, intact female rats. After several days of treatment with either purified porcine RLX or recombinant human RLX 2 (rhRLX), effective renal plasma flow (ERPF) and glomerular filtration rate (GFR) increased by 20%-40%. Comparable renal vasodilation and hyperfiltration was also observed in ovariectomized rats, suggesting that estrogen and progesterone are unnecessary for the renal response to rhRLX. The nitric oxide synthase inhibitor Nomega-nitro-L-arginine methyl ester completely abrogated the increase in ERPF and GFR elicited by chronic administration of purified porcine RLX. In contrast, the renal vasoconstrictory response to angiotensin II was attenuated by the RLX treatment. Short-term infusion of purified porcine RLX to conscious rats over several hours failed to increase ERPF and GFR. Plasma osmolality was consistently reduced by the chronic administration of both RLX preparations. In conclusion, the renal and osmoregulatory effects of chronic RLX administration to conscious rats resemble the physiological changes of pregnancy in several respects: (a) marked increases in ERPF and GFR with a mediatory role for nitric oxide; (b) attenuation of the renal circulatory response to angiotensin II; and (c) reduction in plasma osmolality.

Role of Renal Nerves in Hemodynamic and Natriuretic Responses to Saline in Rabbits with Impaired Baroreflex Sensitivity

The hemodynamic and urinary Na+ excretory response to a 2.5 -fold increase in NaCl by iv infusion were assessed in conscious male rabbits with either high (BShi, salt-insensitive) or low (BSlo, salt-sensitive) cardiac baroreflex sensitivity, before, and 11–14 days after bilateral renal denervatiion. Effective renal plasma flow (ERPF) and proximal tubular Na+ reabsorption were measured by para-amino-hippumte (PAR) and Li+ clearances, respectively, before and after NaCl infused for 2 hr at a rate of 0.11 mL/kg/min. Intact BShi rabbits, showed a significant natriuresis within 30 min which was associated with an increase in ERPF and inhibition of proximal tubular reabsorption. The Na+ excretion rate was much slower in BSlo rabbits, while ERPF and proximal tubular reabsorption remained unchanged. Renal denervation reduced MAP, in-creased basal ERPF, Na+ and Li+ excretion in both groups, and abolished the difference in the renal hemodynamic re-sponse and Li+ excretion to increased NaCl, but not that in the rate of Na+ excretion. The data suggest that BSlo rabbits do not increase their ERPF and Li+ in response to saline because of an inability to bring about an inhibition of renal sympathetic nerve activity. This could be due to an impairment in the sensitivity of their cardiopulmonary baroreceptors. The difference in the rate of natriuresis in the two groups of rabbits which remained after renal denervation could involve an additional hormonal or a local renal mechanism.

Role of kinin and renal ANG II blockade in acute effects of ACE inhibitors in low-renin hypertension.

In conscious deoxycorticosterone acetate (DOCA) salt-hypertensive dogs, the angiotensin-converting enzyme (ACE) inhibitors captopril and imidaprilat significantly decreased mean arterial pressure (MAP) and significantly increased urine flow rate, effective renal plasma flow (ERPF), glomerular filtration rate, and urinary sodium excretion. However, the angiotensin type 1 (AT1) receptor antagonist losartan caused a significant increase only in urinary sodium excretion without significant changes in MAP, urine flow rate, ERPF, and glomerular filtration rate. Simultaneous infusion of a bradykinin receptor antagonist inhibited the ACE inhibitor-induced reduction in MAP and increase in ERPF. DOCA salt treatment markedly suppressed plasma angiotensin II (ANG II) concentration (P < 0.001), although it decreased renal ANG II content only slightly (P < 0.05). Comparison of the expression of renal AT1 receptor mRNA in control kidneys with that in DOCA salt-hypertensive kidneys revealed no significant change. These results suggest that, in low-renin hypertension, inhibition of the relatively maintained ANG II production in the kidney participates in the natriuretic action of ACE inhibitors. However, hypotensive and other renal effects are mainly due to the action of bradykinin.

Partial ureteric obstruction: a study of Doppler ultrasonography and diuretic renography in different grades and durations of obstruction.

To study the changes in renal resistive index (RI) and renal function with time during different grades of partial unilateral ureteric obstruction, and to determine the correlation between the ultrasonographic and renographic findings. Ten dogs underwent right partial ureteric obstruction: grade 1 (mild) obstruction was applied in five dogs (group A) and grade 3 (moderate and severe) obstruction in the other five (group B). All dogs were assessed using excretory urography, diuretic renography with the calculation of half-time drainage (T 1/2) and bilateral renal Doppler ultrasonography before the experiment began, after one week of obstruction, and every 2 weeks during 8 weeks of obstruction. In both groups, after the induction of right ureteric obstruction, there was a progressive decrease of effective renal plasma flow (ERPF) and a progressive increase of the RI of the right kidney at the end of the first and second weeks of obstruction, with an almost stable value thereafter. The decrease of ERPF and the increase of RI in the right kidney were correlated with the degree of obstruction. There was also a dramatic increase of T 1/2 of the right kidney that correlated with the degree of obstruction. Concomitantly, there was a significant compensatory increase of ERPF and a significant decrease of the RI of the left kidney in both groups. The compensatory increase in CRPF limited the loss in total ERPF in both groups. The contribution of obstructed kidney to the total ERPF was significantly reduced in both groups. At the end of the eighth week, taking all kidneys together, there was a statistically significant negative correlation between the ERPF and RI, and between ERPF and T 1/2 and a positive correlation between T 1/2 and RI. Unilateral partial ureteric obstruction increased the RI and T 1/2 and decreased the ERPF of the corresponding kidney, together with a decrease of RI and an increase in ERPF of the contralateral kidney. The more severe the obstruction, the greater the increase in RI and T 1/2 and the decrease in ERPF. After the obstruction stabilized, RI and T 1/2 were positively correlated.

Role of adenosine in the renal responses to contrast medium

Despite the development of non-ionic radiographic contrast media (CM), CM-induced nephropathy is a clinically important problem in patients with pre-existing renal insufficiency. We examined the effects of non-ionic CM (iohexol) on renal function in conscious dogs with and without renal insufficiency, and evaluated the effects of a non-selective (theophylline), an A1 selective (KW-3902), and an A2 selective adenosine antagonist (KF17837) on the renal responses to CM. In sham-operated group, iohexol (2 ml/kg/min for 3 min) increased effective renal plasma flow (ERPF) and glomerular filtration rate (GFR), whereas in renal insufficiency group (with subtotal nephrectomy), following transient increases in ERPF and GFR, CM markedly decreased ERPF (-46.5 +/- 6.7%) and GFR (-51.2 +/- 7.1%). In sham-operated group, theophylline and KF17837 markedly attenuated CM-induced increases in ERPF and GFR, while KW-3902 had no effects on CM-induced increases in ERPF or GFR. In renal insufficiency group, initial increases in ERPF and GFR were blunted by theophylline and KF17837. In contrast, the subsequent decreases in ERPF and GFR were attenuated by theophylline (% delta ERPF, -12.2 +/- 3.2% vs. -46.6 +/- 6.7%, P < 0.01; % delta GFR, 4.3 +/- 2.5% vs. -51.0 +/- 7.1%, P < 0.01), and were completely prevented by KW-3902 (% delta ERPF, 10.8 +/- 2.9%; % delta GFR, 23.8 +/- 4.4%), whereas KF17837 aggravated ERPF (-73.3 +/- 5.3%) and GFR (-78.4 +/- 5.3%). These data indicate that in normal renal function, iohexol elicits renal vasodilation by activating mainly the adenosine A2 receptors. In contrast, in impaired renal function, CM induces both A2 and A1 activation; the former is associated with the initial renal vasodilation, while the latter is responsible for the sustained aggravation of renal hemodynamics.

Angiotensin II Local Hyperreactivity in the Progression of IgA Nephropathy

Immunologic and hemodynamic factors are likely to work in synergism in the progression of immunoglobulin A nephropathy (IgAN) toward sclerosis. The local activation of the renin-angiotensin system may be one of the most relevant mechanisms. We investigated the hemodynamic effects of the acute administration of angiotensin-converting enzyme inhibitor (ACEI) (captopril 50 mg). The glomerular filtration rate (GFR) and the effective renal plasma flow (ERPF) were measured by 51Cr-EDTA and 125I hippurate clearances. The correspondent filtration fractions (FFs) in basal conditions and after administration of ACEI were calculated, then the changes in FF (ΔFF and %ΔFF) were determined. We studied 27 IgAN patients. Eighteen patients had normal renal function (GFR, 112 ± 19 mL/min/1.73 m2) and nine had moderate renal impairment (GFR, 54 ± 13 mL/min/1.73 m2). Sixteen patients had proteinuria≥ 0.5 g/d. In addition, 12 glomerulonephritis control cases and eight healthy subjects were investigated. After the administration of ACEI in healthy subjects we observed slight modifications in the GFR, a significant increase in the ERPF (P < 0.005), and a significant decrease in FF (P < 0.04). Similarly, in IgAN patients with normal renal function the GFR increased slightly, the ERPF increased significantly (P <0.01), and there was a decrease in FF (P <0.01). The ΔFF and %ΔFF values were not significantly different from those found in the controls. In patients with initial renal failure GFR remained unchanged, ERPF increased significantly (P <0.005), and FF significantly decreased (P <0.004). However, the changes in ΔFF and %ΔFF were significantly greater than those found in healthy controls (P <0.01) and in IgAN patients with normal renal function (P <0.001). IgAN patients with proteinuria levels ≥ 0.5 g/d showed greater changes in ΔFF and %ΔFF after the administration of ACEI than patients with proteinuria levels lower than 0.5 g/d (P <0.003 and P <0.04, respectively) or proteinuric control cases (P <0.05 and P <0.01, respectively). This different response in proteinuric and nonproteinuric patients was evident even when the analysis was limited to the subgroup of IgAN patients with normal renal function. The decrease in FF consequent to an increase in the ERPF after the administration of ACEI suggests a local hyperactivity of the renin-angiotensin system in some cases of IgAN. The relevance of this finding in patients with initial renal failure and in those with overt proteinuria suggests that angiotensin II plays a role in the progressive forms of IgAN.

Fenoldopam Reverses Cyclosporine-Induced Renal Vasoconstriction in Kidney Transplant Recipients

Cyclosporine causes renal vasoconstriction and reduced renal blood flow that may contribute to chronic nephrotoxicity. This effect has not been consistently reversed by available pharmacologic agents. The efficacy of orally administered fenoldopam, a dopamine-1 (DA-1) agonist with renal vasodilator properties, was evaluated in six patients whose condition was stable 3 to 6 months following renal transplantation. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured by inulin and p-aminohippurate (PAH) clearances, respectively, at baseline, after the acute oral administration of 100 mg of fenoldopam, and following 3 weeks of chronic oral fenoldopam therapy (100 mg thrice daily). Mean ERPF increased from 3.15 ± 0.17 mL/s/1.73 m2 (189 ± 10 mL/min/1.73 m2) at baseline to 3.48 ± 0.17 mL/s/1.73 m2 (209 ± 10 mL/min/1.73 m2) 4 hours after acute administration of fenoldopam (P = 0.04). Urine flow rate and fractional excretion of sodium also increased after acute administration, but not significantly. Mean systolic (SBP) and diastolic blood pressure (DBP) decreased maximally by 18 and 6 mm Hg, respectively, and mean pulse rate increased maximally by 8 bpm between 75 and 90 minutes after both acute and chronic administration. GFR was unchanged following both acute and chronic administration. The increase in ERPF was not maintained to the end of the dosing interval during chronic administration, probably due to the short half-life of fenoldopam, However, the renal vasodilatory response was still observed 3 to 4 hours after readministration of the drug following 3 weeks of oral dosing. Thus, fenoldopam significantly reverses the renal vasoconstriction caused by cyclosporine in renal transplant recipients. Further evaluation of fenoldopam in preventing cyclosporine-induced nephrotoxicity appears warranted.

The effect of uninephrectomy on osteocalcin metabolism in sheep: a direct evaluation of renal osteocalcin clearance

Indirect evidence has suggested that the kidney is a major organ of clearance for osteocalcin, a circulating marker of osteoblast function. The objectives of the present study were (1) to confirm the role of the kidney in osteocalcin clearance (2) to quantify the contribution of extrarenal sites and (3) to investigate the renal mechanism(s) of osteocalcin clearance. Plasma osteocalcin levels, osteocalcin plasma clearance rate (PCR) and plasma production rate (PPR) were determined in oophorectomized (OX) and uninephrectomized oophorectomized (UOX) sheep. The osteocalcin renal extraction efficiency (REE) and the effective renal plasma flow (ERPF) were measured, and the osteocalcin renal clearance rate (RCR) was calculated. The osteocalcin PCR was reduced significantly in UOX compared with OX sheep (2.0 +/- 0.1 (n = 9) vs 2.5 +/- 0.1 litres/h (n = 44); P less than 0.0005). In UOX sheep with plasma creatinine levels less than or equal to 130 mumol/l, the osteocalcin REE was 9 +/- 1.3% and the osteocalcin RCR was 50-91% of osteocalcin PCR (n = 4). In UOX sheep with plasma creatinine levels in the range 100-440 mumol/l, there was a linear relationship between osteocalcin PCR and ERPF; the osteocalcin RCR was related to the osteocalcin PCR (RCR = 0.9 x PCR - 0.50). Intravenous infusion of the synthetic glucocorticoid triamcinolone acetonide (TA) in UOX sheep led to marked decrements in plasma osteocalcin levels and the osteocalcin PPR, and a significant increase in the osteocalcin PCR. These changes were accompanied by a 44% increase in ERPF.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of Blood Pressure in the Natriuretic Response to Acute Calcium Channel Blockade in Humans

Glomerular filtration rate (GFR), effective renal plasma flow (ERPF), and renal excretion of sodium and lithium were measured before and after acute oral administration of 20 mg nifedipine in 19 essential hypertensive patients. In 10 of them, with a diastolic pressure less than 105 mm Hg, nifedipine resulted in a decrease in mean blood pressure toward normal (109 +/- 2 to 97 +/- 2, p less than 0.001), a 27% increase in ERPF (p less than 0.001), no change in GFR, and an increase in fractional sodium excretion (28%, p less than 0.001). In nine subjects with a diastolic pressure greater than or equal to 105 mm Hg, nifedipine produced a decrease in mean blood pressure (133 +/- 6 to 117 +/- 4, p less than 0.001), which however remained higher than in mild hypertensives (p less than 0.001). ERPF rose by 29% (p less than 0.001), GFR remained unchanged, and fractional sodium excretion definitely increased more than in mild hypertensives (126%, p less than 0.001), as did fractional lithium excretion, used as an estimate of proximal tubular sodium handling. Acute nifedipine produces renal vasodilation in hypertensives, but with a greater natriuretic response in those subjects whose blood pressure remains elevated. Thus, acute natriuresis following nifedipine administration is largely dependent on the interaction between changes in arterial pressure and renal hemodynamics.

Renal hemodynamics and prostaglandin E2 excretion in a nonhuman primate model of septic shock

The mechanisms responsible for renal insufficiency in septic shock (SS) have not been well characterized. We therefore investigated renal hemodynamics and the renal excretion of prostaglandin E2 (PGE2) in a nonhuman primate model of severe, low systemic vascular resistance (SVR) SS. In 18 cynomolgus monkeys, SS was induced by an infusion of 3 x 10(10) live Escherichia coli per kg; five saline-treated animals served as nonseptic controls. Systemic and renal hemodynamics, and urine PGE2 concentrations were determined over the 3 h after the induction of sepsis. The septic group demonstrated a significant (p less than .001) and sustained depression in both mean arterial pressure and SVR. Septic animals also had significantly lower effective renal plasma flow (ERPF) (p less than .01) and glomerular filtration rate (GFR) (p less than .01) compared to controls. Furthermore, the renal hemodynamic response to SS was biphasic, with significant increases in ERPF and GFR in the second hour postsepsis, followed by a pronounced decrease in the third postseptic hour. The septic group also demonstrated an increase in the renal excretion of PGE2 (p less than .001) that was temporally associated with the transient recovery in renal hemodynamics during the second postseptic hour. These sepsis-induced renal alterations may be important in the pathogenesis of renal insufficiency complicating clinical SS.

Antigravity suit inflation: kidney function and cardiovascular and hormonal responses in men.

To investigate the effects of lower body positive pressure (LBPP) on kidney function while controlling certain cardiovascular and endocrine responses, seven men [35 +/- 2 (SE) yr] underwent 30 min of sitting and then 4.5 h of 70 degrees head-up tilt. An antigravity suit was applied (60 Torr legs, 30 Torr abdomen) during the last 3 h of tilt. A similar noninflation experiment was conducted where the suited subjects were tilted for 3.5 h. To provide adequate urine flow, the subjects were hydrated during the course of both experiments. Immediately after inflation, mean arterial pressure increased by 8 +/- 3 Torr and pulse rate decreased by 16 +/- 3 beats/min. Plasma renin activity and aldosterone were maximally suppressed (P less than 0.05) after 2.5 h of inflation. Plasma vasopressin decreased by 40-50% (P less than 0.05) and plasma sodium and potassium remained unchanged during both experiments. Glomerular filtration rate was not increased significantly by inflation, whereas inflation induced marked increases (P less than 0.05) in effective renal plasma flow (ERPF), urine flow, osmolar and free water clearances, and total and fractional sodium excretion. No such changes occurred during control. Thus, LBPP induces 1) a significant increase in ERPF and 2) significant changes in kidney excretory patterns similar to those observed during water immersion or the early phase of bed rest, situations that also result in central vascular volume expansion.

Role of renal hemodynamics in the exaggerated natriuresis of essential hypertension

Extracellular fluid volume expansion is known to produce exaggerated natriuresis in essential hypertension. In order to assess the role of hemodynamic and intrarenal physical factors upon natriuretic response to central volume expansion, two hour water immersion (WI) experiments were made in six uncomplicated essential hypertensives and six normotensive healthy controls. Before and during WI we measured mean arterial pressure (MAP), urine flow (V/min), sodium (UNaV) and potassium (UKV) excretion, glomerular filtration rate (GFR), effective renal plasma flow (ERPF) and intrarenal (wedged) venous pressure (IRVP). In comparison with normotensive controls, the exaggerated natriuretic response in hypertensives (P less than 0.05 for UNaV during WI) was associated with an enhanced vasodilating response as demonstrated by a greater increase in ERPF (P less than 0.05) and by a more pronounced fall in calculated renal precapillary resistances (P less than 0.05). A more significant increase in IRVP was found in hypertensive group (P less than 0.05). Glomerular filtration rate (GFR) did not change in either group during WI. MAP, unchanged in normotensives, was significantly reduced in hypertensives (P less than 0.05), while remaining in the hypertensive range. These findings suggest that intrarenal physical factors play a major role in determining the exaggerated natriuresis during WI in hypertensive man.

Renal Effects of a Vasodilator: 2-[N-Methyl-Piperidyl-(4)]-3-Amino-5-(4'-Pyridyl)-Pyrazole HCL (Ciba 31-531 Ba)

Acetylcholine (Ach), when infused directly into the renal artery of a kidney, causes unilateral vasodilatation and increased salt excretion. Ciba 31-531 Ba, a nonspecific vasodilator, was infused both directly into the renal artery and given systemically, and the effects were compared to Ach. Infusion of Ach at 0.1 μg./kg./min. into the left renal artery (LRA) of an anesthetized dog effected a unilaterally increased salt excretion and increased effective renal plasma flow (ERPF) and urine volume, but no demonstrable change in glomerular filtration rate (GFR) or blood pressure. Infusion of Ciba 31-531 Ba (LRA) at 0.1 mg./kg./min. resulted in a similar unilateral saluresis of approximately 50% increase over Ach with an increase in ERPF and urine volume but no change in GFR or blood pressure. The right kidney served as an internal control. When Ach and Ciba 31-531 Ba were given systemically, at higher doses there was a drop in blood pressure, decreased solute excretion, and decreased ERPF and GFR for both drugs. The effects of Ach were reversed with atropine. The effects of Ciba 31-531 Ba were not reversed by atropine or propranolol. The authors believe that the direct renal effects of these drugs are the results of direct tubular effects associated in some way with hemodynamic alterations.