Correlation between pentosidine and endothelin-1 in subjects undergoing chronic hemodialysis.

Advanced glycation end-products (AGEs), which accumulate in the blood and tissues of patients with chronic renal failure (CRF) undergoing chronic hemodialysis, play an important role in the pathogenesis of uremic complications. Endothelin 1 (ET1), a 21-amino acid peptide with vasoconstricting and mitogenic properties, is an important factor in the endothelial dysfunction occurring in uremia. The circulating levels of both AGEs and ET1 have been reported to be increased in chronic renal failure. In the present study we evaluated the possible relationship between pentosidine and ET1 plasma levels in CRF patients undergoing chronic hemodialysis treatment. The plasma concentrations of "free" and bound pentosidine (HPLC methods) and endothelin-1 (RIA method) were measured before the hemodialysis session in 40 nondiabetic CRF patients (22 males and 18 females; 54+/-3 years) on chronic hemodialysis for at least 1 year. Forty age- and sex-matched normal subjects served as a control group. In hemodialyzed patients, the overall pentosidine residues and pentosidine-free adduct plus pentosidine-free adduct bound reversibly to protein levels (24.9+/-2.04 pmol/mg protein and 110.5+/-5.9 pmol/ml, respectively) were significantly higher than those recorded in normal subjects (2.0+/-0.2 pmol/mg protein and 0.7+/-0.2 pmol/ml, respectively ). Endothelin-1 was also significantly (p<0.01) increased in CRF patients (10.6+/-0.4 pmol/ml in CRF patients and 2.7+/-0.3 pmol/ml in normal subjects). A significant positive correlation (p<0.01) was seen between "total" pentosidine (pentosidine residues and pentosidine-free adduct plus pentosidine-free adduct bound reversibly to protein) levels and endothelin-1 plasma values. The correlation between pentosidine and endothelin-1 provides further evidence that some AGEs exert a detrimental effect on the vascular endothelium, thereby contributing to the hypertension and other cardiovascular damage seen in CRF patients.

Online convective therapies: results from a hemofiltration trial.

With the introduction of the on-line preparation of dialysis fluids, the hemofiltration technique, which has never had a widespread diffusion in its old version with the infusion bags, has gained a new interest. We planned a prospective, randomized, 3-year-long study comparing survival and morbidity in ultrapure bicarbonate dialysis (BD) with on-line predilution hemofiltration (HF). Since comorbidity is one of the main factors limiting survival, the study was addressed to patients with a severe degree of comorbidity. The paper presents the preliminary results of the trial. Sixty-four patients were enrolled and randomized to either BD (N = 32) or HF (N = 32). Mean age and dialysis vintage were comparable. Twenty patients died during the study, 12 in BD and 8 in HF. The relative risk of death was 11% higher in patients treated with BD compared to those in the HF group (p < 0.005). The number of hospitalisation events per single patient was lower, even though not significantly, in HF compared to BD (1.94 + 1.26 in HF vs 2.48 + 1.98 in BD, p = NS). As concerns biochemistry, apart from beta-2-microglobulin, any other substantial difference was not found during the study, though the small solute concentration was generally a little more elevated in HF than in BD. Dialysis hypotension showed a trend to decrease in both the dialysis modalities up to near half of the trial, then, during the last year, it remained quite stable in HF, while, on the contrary, it increased in the BD group. By the end of the protocol, patients in HF showed a 2.5% incidence of acute dialysis hypotension, while patients in BD had 23%.

GIT (Glucose Infusion Test): polycentric evaluation of a new test for vascular access recirculation.

Introduction. Vascular access recirculation (AR), which is often unacknowledged, remains an important cause of inadequate dialytic dose. The glucose infusion test (GIT) is a new method for detecting and quantifying AR. This paper reports on a polycentric evaluation of the new test and a comparison with the classical Urea-test (UT). Methods. GIT protocol comprises withdrawal from the arterial port (sample A), injection into the venous drip chamber of 1 g glucose in 4 seconds, withdrawal from the arterial port (sample B) continuously from 13 to 17 seconds. Glucose is determined on A and B by a reflectance photometer. If B = A then there is no recirculation. If B exceeds A by at least 20 mg/dl there is recirculation. AR quantification: AR% = (B-A) / 20. GIT was performed on 623 patients from eleven dialysis centers to screen the patients for AR. Subsequently, GIT and Urea-test (UT) were compared in 189 paired tests. The reproducibility of GIT and UT was studied in 28 paired tests performed in sequence. Results. The screening test by GIT was positive in 68 cases (11 %). The majority of positivities was found in central venous catheters (CVC, 27/50 cases, 54 %), whereas only 7 % of artero-venous fistulas (AVF) were positive. In the CVC group, Tesio catheters were more frequently positive compared to Dual Lumen Catheters (64 % vs. 29 %). The comparison GIT - UT showed that results matched in 162 tests (79 negative and 83 positive both by GIT and UT), showing that on the grounds of UT, GIT has high sensitivity and specificity. In 27 tests GIT was positive, but UT negative. This disagreement is due to the different minimal limit of detection, 1 % for GIT and 5% for UT. The reproducibility was greater with GIT than with UT with a lower D% (respectively -0.6 +/- 2.5 and -0.4 +/- 6.1 %, p<0.001) and a lower coefficient of variation (17 vs 33 %). Conclusions. The screening of 623 patients by GIT confirmed that AR in AVF is normally absent, whereas an un-expectedly high frequency of moderate AR in CVC was found. The GIT-UT comparison showed that the new test is simple and immediate, and gives results with higher accuracy, sensitivity and reproducibility than UT.

Phenylalanine hydroxylation across the kidney in humans rapid communication.

UNLABELLED: Phenylalanine hydroxylation across the kidney in humans. BACKGROUND: Although phenylalanine hydroxylase activity is detectable in in vitro renal tissue preparations, no data on in vivo phenylalanine hydroxylation across the human kidney, as well as on its possible contribution to whole-body hydroxylation, currently exist. METHODS: To this aim, we have measured whole-body, renal, and splanchnic phenylalanine hydroxylation to tyrosine, as well as phenylalanine and tyrosine rates of appearance (Ra) and disposal (Rd), in postabsorptive subjects by means of renal and splanchnic arteriovenous catheterization combined with phenylalanine and tyrosine isotope infusions. RESULTS: In the kidney, a relevant phenylalanine hydroxylation activity was detected (3.51 +/- 0.97 micromol/min x 1.73 m2 of body surface), whereas it was 2.48 +/- 1. 35 micromol/min x 1.73 m2 across the splanchnic area. These two sites together accounted for virtually the entire whole-body phenylalanine hydroxylation. Renal production of tyrosine from phenylalanine hydroxylation accounted for approximately 13% of whole-body tyrosine Ra, whereas renal total tyrosine Ra accounted for approximately 34% of whole-body tyrosine Ra. In the splanchnic area, these figures were approximately 9 and 40%, respectively. Hydroxylation accounted for approximately 70% of phenylalanine Rd in the kidney, as opposed to approximately 8% in the splanchnic area. CONCLUSIONS: These data indicate that hydroxylation represents the major route of phenylalanine disposal within the kidney. The kidney and the splanchnic bed together account for all of the whole-body phenylalanine hydroxylation. These data also provide a further explanation for the reduced tyrosine pools occurring in uremia.

Diabetic nephropathy: from micro- to macroalbuminuria.

This brief review will focus on the major factors leading to incipient diabetic nephropathy (i.e. microalbuminuria) progressing to overt nephropathy (i.e. macroalbuminuria) and particularly on the role of glycaemic control and hypertension. Both experimental and cohort studies support the role of hyperglycaemia in the development of diabetic nephropathy. Some recent long-term interventional studies in microalbuminuric patients show conflicting results regarding the role played by good metabolic control in reducing the incidence of overt nephropathy. However, strict metabolic control, which is fundamental in normoalbuminuric patients, is of little use even in microalbuminuric patients. In general, levels of glycosylated haemoglobin less than two standard deviations above the upper normal range, commonly <7.5-8%, seem to protect patients from developing nephropathy. The results of many cross-sectional studies have shown that the progression of renal damage regularly is accompanied by arterial hypertension both in insulin-dependent diabetes mellitus (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM). Many long-term interventional studies have been performed in order to understand the effect of antihypertensive treatment on the incidence of proteinuria in both normotensive and hypertensive patients with IDDM or NIDDM. These data show a marked effect of antihypertensive therapy in preventing the onset of overt nephropathy, and suggest the superiority of angiotensin-converting enzyme (ACE) inhibitors. We believe that optimal blood pressure values are approximately 120/70-75 mmHg in younger patients and 125-130/80-85 mmHg in older patients. In conclusion, antihypertensive treatment, ACE inhibitors per se and possibly strict metabolic control reduce the development of nephropathy, thus playing a striking role in the secondary prevention of renal failure.

Somatostatin release in response to glucose is impaired in chronic renal failure.

In order to evaluate somatostatin (SRIH) secretion in uremia, plasma SRIH concentrations were determined in basal conditions and after an oral glucose tolerance test (OGTT) in 14 non-dialysed patients with chronic renal failure (CRF), seven of whom had normal glucose tolerance (NGT) and seven impaired glucose tolerance (IGT). Plasma insulin, C-peptide and glucagon and blood glucose concentrations were also evaluated. The results were compared with those obtained in a group of age- and sex-matched normal subjects. In CRF patients, plasma SRIH fasting values (8.6 +/- 0.6 and 7.8 +/- 0.6 pmol/L in NGT and IGT patients, respectively) were comparable to those recorded in controls (7.7 +/- 0.5 pmol/L). SRIH response to OGTT, evaluated as area under curves (AUC) above basal, was similar in both groups of CRF patients (412.9 +/- 84.5 and 415.6 +/- 51.9 pmol/L per min), and significantly lower than in controls (660.1 +/- 58.5 pmol/L per min). Data indicate that chronic uremia induces a loss of SRIH secretory cell responsiveness to glucose. A possible effect of impaired SRIH secretion on glucose metabolism in CRF is discussed.

Inter-organ leptin exchange in humans.

To assess the individual role of splanchnic organs, kidney, and peripheral tissues on leptin metabolism, leptin exchange across the splanchnic bed, kidney, and leg has been evaluated by the arterio-venous technique in post-absorptive non-obese subjects. Leptin levels in the hepatic and renal veins were significantly lower (p < 0.001), while femoral vein levels were consistently greater (p < 0.05) than in the artery. The fractional extraction of leptin, namely the percentage of arterial leptin extracted, was greater in splanchnic organs (16%) than in the kidney (9.5%). Urinary excretion of leptin was undetectable in most subjects, indicating that leptin is degraded within the kidney. There was no correlation between fractional extraction of leptin and glomerular filtration rate, whereas leptin fractional extraction was directly related to renal plasma flow (p = 0.017). Renal leptin clearance was about 50% of the glomerular filtration rate. Our data demonstrate that both splanchnic organs and the kidney cooperate in the disposal of leptin, while peripheral tissues add significant amounts of leptin to the circulation. In non-obese subjects the contribution of the kidney to whole body clearance is no more than 50%. The removal of leptin by the kidney depends on renal plasma flow but not on glomerular filtration rate or filtered leptin.

Intrarenal arteriosclerosis and impairment of kidney function in NIDDM subjects.

It is currently under debate whether the pathogenesis of end-stage renal failure in non-insulin-dependent diabetes mellitus (NIDDM) is a consequence of microangiopathy alone. The aim of this study was to investigate intrarenal arteriosclerosis and its correlation with kidney function in NIDDM. In 36 diabetic subjects, and in 10 age- and sex-matched healthy control subjects we measured kidney volume and resistive index of the interlobar arteries by duplex Doppler ultrasonography. Clinical and metabolic parameters, renal function and vascular sequelae of the disease were also evaluated. In diabetic subjects resistive index (median 0.72, range 0.54-0.79) was higher than in control subjects (median 0.62, range 0.57-0.66) (2p < 0.002). Kidney volume and resistive index correlated with age (p < 0.004), body mass index (p < 0.001), mean blood pressure (p < 0.001), total and LDL cholesterol (p < 0.01) and creatinine clearance (p < 0.001 and < 0.01, respectively). Kidney volume also correlated with HbA1 (p < 0.01) and resistive index with uric acid (p < 0.01). Lower body macroangiopathy was associated with increased resistive index and reduced kidney volume (2p < 0.05), while upper body macroangiopathy and microangiopathy were not. Our data suggest that macroangiopathy rather than microangiopathy is mainly responsible for impairment of kidney function in NIDDM. The resistive index of interlobar arteries seems to be a reliable marker of intrarenal arteriosclerosis and can be used as a non-invasive, easily available parameter of its evolution.

Protein turnover in the kidney and the whole body in humans.

For a better understanding of protein synthesis and degradation in the human kidney, the arteriovenous difference technique across the kidney, splanchnic organs, and leg muscle was combined with labeled leucine and phenylalanine isotope dilution models. Results indicate that in the postabsorptive state, the protein balance across the human kidney is negative because the rate of leucine release from protein degradation is greater than the amount used for protein synthesis. In the splanchnic bed, net protein balance is neutral since the amount of leucine deriving from protein degradation is similar to the amount utilized for protein synthesis. In the leg muscle, protein degradation exceeds protein synthesis. The kidney exhibits the highest leucine metabolic activity when expressed in terms of total organ leucine content. The estimated fractional protein synthesis rate in the human kidney is about 40% per day (vs. about 2% in muscle and 12% in the splanchnic bed). The human kidney presents high rates of protein turnover and accounts for a significant fraction of whole-body protein degradation, protein synthesis, and leucine oxidation.

Protein and amino acid metabolism in splanchnic organs in metabolic acidosis.

Metabolic acidosis causes a cooperative participation of different organs such as the liver, kidney, and muscle in restoring acid-base balance. In splanchnic organs, metabolic acidosis has repercussions on several nitrogen metabolism pathways. The decrease in urea synthesis due to reduced activity of urea cycle enzymes, ammonia uptake and amino acid transport, and changes in glutamine metabolism support renal ammoniagenesis thus offering a response to rid the body of excess protons. While some of the mechanisms are adaptive others may be harmful for the body. Metabolic acidosis may have effects on splanchnic protein turnover. In severe acidosis, synthesis of secreted liver proteins may be reduced. Acidosis may also modulate the response of the liver to growth hormone (GH) for insulin-like growth factor-I synthesis, thus inducing a state of GH resistance. Splanchnic abnormalities in acidosis might contribute to the malnutrition observed in uremia.

Kidney, splanchnic, and leg protein turnover in humans. Insight from leucine and phenylalanine kinetics.

The rate of kidney protein turnover in humans is not known. To this aim, we have measured kidney protein synthesis and degradation in postabsorptive humans using the arterio-venous catheterization technique combined with 14C-leucine, 15N-leucine, and 3H-phenylalanine tracer infusions. These measurements were compared with those obtained across the splanchnic bed, the legs (approximately muscle) and in the whole body. In the kidneys, protein balance was negative, as the rate of leucine release from protein degradation (16.8 +/- 5.1 mumol/min.1.73 m2) was greater (P < 0.02) than its uptake into protein synthesis (11.6 +/- 5.1 mumol/min. 1.73 m2). Splanchnic net protein balance was approximately 0 since leucine from protein degradation (32.1 +/- 9.9 mumol/min. 1.73 m2) and leucine into protein synthesis (30.8 +/- 11.5 mumol/min. 1.73 m2) were not different. In the legs, degradation exceeded synthesis (27.4 +/- 6.6 vs. 20.3 +/- 6.5 mumol/min. 1.73 m2, P < 0.02). The kidneys extracted alpha-ketoisocaproic acid, accounting for approximately 70% of net splanchnic alpha-ketoisocaproic acid release. The contributions by the kidneys to whole-body leucine rate of appearance, utilization for protein synthesis, and oxidation were approximately 11%, approximately 10%, and approximately 26%, respectively; those by the splanchnic area approximately 22%, approximately 27%, and approximately 18%; those from estimated total skeletal muscle approximately 37%, approximately 34%, and approximately 48%. Estimated fractional protein synthetic rates were approximately 42%/d in the kidneys, approximately 12% in the splanchnic area, and approximately 1.5% in muscle. This study reports the first estimates of kidney protein synthesis and degradation in humans, also in comparison with those measured in the splanchnic area, the legs, and the whole-body.

Plasma clearance rate of 51Cr-EDTA provides a precise and convenient technique for measurement of glomerular filtration rate in diabetic humans.

It has not yet been fully clarified whether the plasma or renal clearance approach is the most reliable to investigate GFR in humans. The study presented here aimed to compare plasma decay with renal clearance of 51Cr-EDTA in 27 diabetic patients with patterns of renal function broadly dispersed in a wide range of values. Moreover, the comparison was also performed with renal clearance of nonlabeled iothalamate in a subgroup of 17 patients. A biexponential function was found to fulfill statistical and heuristic criteria for the modeling analysis of plasma 51Cr-EDTA decay with 19 samples after bolus intravenous 51Cr-EDTA injection. Individual GFR values from 51Cr-EDTA plasma clearance highly correlated with those from renal clearance (r2 = 0.977, P < 0.0001), but resulted on average about 2.5 mL.min-1.1.73 m-2 higher (66.8 +/- 6.5 mL.min-1.1.73 m-2 (mean +/- SE) versus 64.3 +/- 6.4, P < 0.02). This difference remained relatively constant from patients with normal renal function to those with impaired renal function, suggesting that the plasma clearance is slightly less accurate than renal clearance approach because of a constant extrarenal clearance rate. In the subgroup studied, a similar difference was found between GFR values from 51Cr-EDTA plasma clearance (84.7 +/- 7.3) and renal clearance of iothalamate (82.8 +/- 7.3), although not statistically significant (P = 0.4). Individual GFR values well correlated (r2 = 0.913, P < 0.0001). The precision and reproducibility of the experimental approaches were assessed by comparing three coefficients of variation: (1) CVb of the bolus injection, because of measurement errors; (2) CVc of the continuous infusion, which additionally includes errors of urine volume measurement and physiological variability in the same day; and (3) CVr of repeated measurements by using bolus injection, which also accounts for physiological variability in different days. CVc of iothalamate and 51Cr-EDTA infusions were 7.5 +/- 1.9% and 7.4 +/- 1.2% respectively. CVb and CVr of bolus injection of 51Cr-EDTA were 2.6 +/- 0.3% and 3.5 +/- 0.8% respectively. CVb and CVr of bolus injection of 51Cr-EDTA, but not CVc of iothalamate and 51Cr-EDTA infusions were twofold to tenfold lower than the percent yearly change reported in IDDM and NIDDM patients. More particularly, CVr was significantly less than CVc. In order to make the test less cumbersome, a reduced sampling schedule with seven samples was designed and validated. GFR measured with seven samples was 66.1 +/- 6.4 (P = 0.1 when compared with the full 19-sample schedule) with a CVb of 3.5 +/- 0.5%. This seven-sample protocol was not different from that obtained with the previously described simplified method of Brøchner-Mortensen (63.9 +/- 6.8, P = 0.16), yet yielding a statistically more accurate estimate (coefficient of variation for Brøchner-Mortensen method = 12.1 +/- 2.9, P = 0.004). Moreover, only bolus injection, along with modeling analysis of plasma clearance rate, allows the accurate measurement of the extracellular fluid volume, an important parameter in diabetic patients. It was concluded that the reduced seven-plasma sample protocol is able to detect as small as 4 to 5% changes per year in a single patient. Moreover, it provides precise and accurate estimate of GFR in diabetic patients with hyperfiltration, who are postulated to be at higher risk to develop renal damage.

Renal metabolism of C-peptide in patients with early insulin-dependent diabetes mellitus.

Renal metabolism of C-peptide was studied in 6 patients with early insulin-dependent diabetes mellitus (IDDM) with residual beta cell activity and in 11 nondiabetic subjects by the arterial-venous difference technique both in the postabsorptive state and for 80 min after ingestion of an amino acid mixture (0.8 g/kg). Urinary C-peptide (Cp) excretion, glomerular filtration rate and renal plasma flow were also measured. In the postabsorptive state in IDDM, renal uptake of Cp is reduced, while its urinary excretion and clearance are significantly increased. As a result, net renal extraction is markedly reduced. In contrast to controls, renal uptake and net extraction of C-peptide after amino acid ingestion do not increase in patients; the peritubular uptake evident in normal subjects is not detectable. Urinary excretion and clearance of Cp remain significantly higher in IDDM patients. In both groups, renal uptake of C-peptide is directly related to its renal load: however, in IDDM, the increase in Cp uptake for each increment in renal load is 35% lower than in controls (p < 0.001). Furthermore, as opposed to controls, urinary Cp excretion is not correlated with its arterial levels. Therefore IDDM patients have marked defects in renal handling of endogenous Cp, regarding both the amount metabolized by renal tissue and that reabsorbed by tubular cells. These data indicate an early alteration in the diabetic kidney that also impairs the reliability of urinary Cp evaluation as an index of residual beta cell activity in IDDM patients.

Disposal of exogenous amino acids by muscle in patients with chronic renal failure.

Muscle exchange of amino acids (AAs) was evaluated by using the arteriovenous-difference technique across the leg in seven patients with chronic renal failure (CRF) and eight control subjects before and for 75 min after the ingestion of an AA mixture simulating an animal-protein meal. Total AAs increased in arterial blood much more in patients with CRF after AA ingestion than in control subjects, as a consequence of an exaggerated increase in nonessential AAs (NEAAs) (+127%). Moreover, total AAs were taken up by the leg in larger amounts than in control subjects (+71%, P < 0.0025) because of increased uptake of NEAAs (+156%, P < 0.005). Branched-chain AA uptake by the leg was, in absolute values, similar to that of control subjects; however, because of the increased uptake of total AAs, branched-chain AA uptake was only 30% of total AA extraction, compared with 46% in control subjects. Abnormalities in AA uptake by muscle paralleled those in arterial AAs. In fact the same AAs that increased abnormally in blood were taken up by the leg at higher rates than in control subjects. Variations in arterial concentrations and muscle uptake of AAs were inversely related to arterial bicarbonate concentration, suggesting a role for acid-base status in modifying both the arterial supply and muscle metabolism of AAs. Results indicate that in CRF patients the normal pattern of postprandial AA repletion is disrupted. Muscle tissue faces the increased and unbalanced postprandial supply of AAs with an augmented and unbalanced uptake. Data are consistent with an abnormal use of exogenous AAs in CRF patients, possibly induced by metabolic acidosis.

Plasma beta-endorphin levels and glucose tolerance in patients with chronic renal failure.

In order to examine the role of endogenous opioid peptides on glucose metabolism in uraemic patients, plasma concentrations of beta-endorphin, glucose, insulin and C-peptide were determined before and during an oral glucose tolerance test (OGTT) in nine non-dialysed patients with chronic renal failure (CRF). The results are compared with those obtained in a group of age-matched normal subjects. In CRF patients, plasma beta-endorphin fasting values (16.0 +/- 1.9 pmol/l) were significantly higher than those of the controls (6.6 +/- 0.6 pmol/l) and significantly correlated with the degree of renal function impairment. After glucose load, plasma beta-endorphin in CRF patients tended to decline, whereas in normal subjects increased. The fasting and the mean OGTT plasma beta-endorphin values negatively correlated with insulin initial response to glucose, insulin and C-peptide mean OGTT values, but not with glucose OGTT mean values. Data indicate that chronic uraemia induces a significant increase in circulating plasma beta-endorphin levels, with a loss of opioid system responsiveness to glucose. The possibility that this hyper-endorphinism may have a biological importance at least as a contributory factor of impaired glucose tolerance in uraemia may be suggested.

[Dopamine-induced variations in intrarenal resistance. Evaluation with Doppler ultrasound]. / Variazioni delle resistenze intrarenali indotte dalla dopamina. Valutazione con eco Doppler.

Low-dose dopamine is commonly used for the management of acute renal failure because of its exclusively renal vasodilator effect which is mediated through two specific receptors. However, the experimental background of this role is controversial in man. Indeed, the available data come mainly from animal trials and uncontrolled studies in patients with left ventricular dysfunction who need other drugs to improve cardiac output. This work was aimed at investigating Doppler value in assessing the effects of low-dose dopamine infusion in healthy subjects. Heart rate, arterial blood pressure and RI were measured before, during (at 10, 20 and 30 minutes) and after low-dose dopamine infusion in 4 healthy volunteers. In all subjects the RI reduced significantly, returning to the initial values after drug infusion. Indeed, the average RI (0.648 +/- 0.015 before drug administration) decreased to 0.595 +/- 0.026 within 10 min of infusion and remained almost the same during the infusion (0.596 +/- 0.024 within 20 min of infusion, 0.585 +/- 0.032 within 30 min). Within 10 min of the end of infusion, the average RI returned to similar values to those measured before drug administration (0.643 +/- 0.02). Changes in heart rate and arterial blood pressure were not significant. Our results confirm the vasodilator role of low-dose dopamine to be free of systemic effects in healthy volunteers with no therapeutic support which would cause extrarenal decrease in peripheral vascular resistance.