Correlation between glomerular morphology and renal haemodynamic response to amino-acid administration in patients with IgA nephropathy.
(57/67)
RATIONALE: To establish relationship, if any, between renal morphology and renal haemodynamic response to amino acids. DESIGN AND METHODS: We investigated the correlation between renal haemodynamic regulation and morphology in a group of 15 patients with primary IgA nephropathy (IgAN) (age 26 +/- 2 years, BMI 24.4 +/- 1, GFR 64 +/- 5 ml/min, RPF 377 +/- 34 ml/min, FF 0.17 +/- 0.02). Twelve normal subjects (age 30 +/- 3 years, BMI 24 +/- 1, GFR 82 +/- 6 ml/min, RPF 421 +/- 42 ml/min, FF 0.19 +/- 0.02) were studied as controls. IgA patients were divided into two groups according to the histological staging of glomerular lesions: group I (n = 7) stage II, and group II (n = 8) stage III-IV. RESULTS: In the basal state GFR was similar in the two groups and averaged 64 +/- 9 and 64 +/- 6 ml/min respectively. In contrast, FF was significantly lower in group II (0.14 +/- 0.01) (P < 0.05) in comparison to group I (0.21 +/- 0.03) and controls (0.19 +/- 0.02). In order to evaluate the renal functional reserve, all study groups underwent to an intravenous amino-acid infusion designed to increase plasma amino acid levels twofold (total from 2096 +/- 145 to 4301 +/- 221 mumol/l in IgA nephropathy patients and from 2272 +/- 83 to 3844 +/- 238 mumol/l in controls). In response to amino-acid infusion, GFR rose significantly in group I (GFR 20 +/- 2% and RPF 37 +/- 4% versus basal) and controls (GFR 20 +/- 2% and RPF 20 +/- 3% versus basal) (both P < 0.01 vs basal). In contrast, in patients with more severe glomerular lesions (group II) neither GFR nor RPF rose significantly (GFR -1 +/- 4% and RPF -8 +/- 6% versus basal) (P NS versus basal, P < 0.01 versus group I and controls). CONCLUSIONS: The data show that in IgA nephropathy: severe forms of glomerular lesions are associated with a complex alteration of glomerular haemodynamic regulation, characterized by lower basal FF and loss of haemodynamic response to hyperaminoacidaemia. (+info)
Differential human renal tubular responses to dopamine type 1 receptor stimulation are determined by blood pressure status.
(58/67)
We performed the present studies to determine whether a proximal renal tubular dopamine D1-like receptor defect exists in human essential hypertension. Twenty-four subjects were studied (13 normotensive and 11 hypertensive) in a randomized, double-blind, vehicle-controlled study using fenoldopam, a selective D1-like receptor agonist. Subjects were studied in sodium metabolic balance at 300 mEq/d, after which the salt sensitivity of their blood pressure was determined. Fenoldopam at peak doses of 0.1 to 0.2 microgram/kg per minute decreased mean arterial pressure in hypertensive subjects but did not change mean pressure in normotensive subjects. Fenoldopam increased renal plasma flow to a greater extent in hypertensive than normotensive subjects. Fenoldopam increased both urinary and fractional sodium excretions in the hypertensive and normotensive groups. In normotensive but not hypertensive subjects, fenoldopam increased the fractional excretion of lithium and distal sodium delivery. In contrast, both distal fractional sodium reabsorption and sodium-potassium exchange fell significantly in hypertensive subjects. We conclude that human essential hypertension is associated with a reduction in the proximal tubular response to D1-like receptor stimulation compared with normotensive subjects. Hypertensive subjects appear to have a compensatory upregulation of renal vascular and distal tubular D1-like receptor function that offsets the proximal tubular defect, resulting in an enhanced natriuretic response to D1-like receptor stimulation. (+info)
Is endogenous erythropoietin a pathogenetic factor in the development of essential hypertension?
(59/67)
BACKGROUND: Recent experimental studies have found that erythropoietin elicits vasoconstriction and proliferation of endothelial cells. We conducted the following study to assess the possible interactions between endogenous erythropoietin, systemic and renal haemodynamics at different stages of essential hypertension. METHODS: We examined 47 patients with borderline essential hypertension (age 26 +/- 3 years) and 49 patients with established essential hypertension WHO stage I-II (age 52 +/- 10 years), and compared them to 42 normotensive individuals (age 26 +/- 3 years). The concentration of erythropoietin (radioimmunoassay), 24-h ambulatory blood pressure (Spacelab 90207), systemic haemodynamics (Doppler sonography) and renal haemodynamics (para-aminohippuric acid and inulin clearance) were determined. RESULTS: Erythropoietin was within normal range and similar among the three groups. In patients with established essential hypertension, a close correlation was found between erythropoietin and systolic (r = 0.45, P < 0.002) and diastolic (r = 0.51, P < 0.001) ambulatory blood pressure. In contrast, ambulatory blood pressure was not correlated with erythropoietin in subjects with borderline hypertension. Total peripheral resistance (r = 0.41, P < 0.02) was linked to erythropoietin in established but not in borderline hypertension. However, erythropoietin was inversely correlated with renal plasma flow in both established and borderline hypertension (r = -0.33, P < 0.05, and r = -0.34, P < 0.05 respectively). In normotensive subjects, in contrast, erythropoietin was not correlated with any of the determined variables. In neither group erythropoietin was linked to the haematocrit or hemoglobin concentration. CONCLUSION: The correlation between erythropoietin and renal vascular changes which is already present in borderline hypertension and is confirmed in established hypertension indicates an involvement of erythropoietin in the development of essential hypertension. The presence of normal concentrations of endogenous erythropoietin in all groups suggests a dysregulation of erythropoietin in patients with essential hypertension as the pathophysiological link between erythropoietin and vascular changes. (+info)
Systemic and renal effects of an ET(A) receptor subtype-specific antagonist in healthy subjects.
(60/67)
1. Endothelins (ETs) might play a pathophysiological role in a variety of vascular diseases. The aim of the present study was to characterize the effects of BQ-123, a specific ET(A) receptor antagonist on systemic and renal haemodynamics in healthy subjects. This was done at baseline and during infusion of exogenous ET-1. 2. The study was performed in a balanced, randomized, placebo-controlled, double blind 4 way cross-over design in 10 healthy male subjects. Subjects received co-infusions of ET-1 (2.5 ng kg(-1) min(-1) for 120 min) or placebo and BQ-123 (15 microg min(-1) for 60 min and subsequently 60 microg min(-1) for 60 min) or placebo. Renal plasma flow (RPF) and glomerular filtration rate (GFR) were assessed by the para-aminohippurate (PAH) and the inulin plasma clearance method, respectively. 3. BQ-123 alone had no renal or systemic haemodynamic effect. ET-1 significantly reduced RPF (-24%, P<0.001) and GFR (-12%, P=0.034). These effects were abolished by co-infusion of either dose of BQ-123 (RPF: P=0.0012; GFR: P=0.020). 4. BQ-123 reversed the renal haemodynamic effects induced by exogenous ET-1 in vivo. This indicates that vasoconstriction in the kidney provoked by ET-1 is predominantly mediated by the ET(A) receptor subtype. (+info)
Progressive glomerular injury in the MWF rat is predicted by inborn nephron deficit.
(61/67)
It has been suggested that a reduced number of nephrons may predispose to systemic hypertension and glomerular injury. Compensatory hemodynamic changes, due to a low number of glomeruli, might be responsible for glomerular functional and structural changes. It is difficult to evaluate this hypothesis in humans because of limitations in estimating the number of nephrons in the living kidney. The aim of the present study was to estimate nephron number, single glomerular hemodynamics, and glomerular volume in male and female MWF rats, a strain that spontaneously develops systemic hypertension, proteinuria, and glomerulosclerosis. Male and female Wistar rats were used as controls. At 12 to 14 wk of age, male MWF rats developed proteinuria, whereas female MWF and Wistar rats showed normal urinary protein excretion rate. Glomerular number was significantly reduced in male and female MWF rats (13,690+/-1,489 and 12,855+/-1,781 gl/ kidney, respectively) compared with Wistar rats (26,955+/-2,171 and 27,166+/-1,754 gl/kidney, respectively). The mean number of nephrons per unit of body weight was also lower in MWF males (88+/-10) compared with MWF females (139+/-20) and compared with male and female Wistar animals (142+/-14 and 221+/-22 gl/g body wt). Whole-kidney hemodynamic parameters and the number of nephrons were used to calculate single-nephron filtration rate and plasma flow. Both measures were markedly elevated in male MWF rats relative to values obtained in the other three groups. Similarly, glomerular volume was significantly greater in MWF males than in other animals. These results suggest that an inborn deficit of nephrons may be responsible for spontaneous development of later-in-life hypertension and renal dysfunction. The data also indicate the need to investigate the role of this potential pathogenetic factor for human hypertension and kidney disease in humans. (+info)
Renal arginine metabolism in fasted rats with subacute short bowel syndrome.
(62/67)
1. Arginine can be produced in the kidney from citrulline. An important source of circulating citrulline is the intestinal breakdown of glutamine. Consequently, partial enterectomy leads to decreased plasma citrulline levels. The aim of the present study was to investigate the effect of diminished arterial citrulline levels on renal arginine production and total-body free arginine pools.2. Renal amino acid metabolism was studied 24 h after 75% small bowel resection in rats fasted overnight (16 h) (n=12; total fast 40 h). Sham-operated (n=9) and non-operated 16-h and 40-h fasted controls were studied in parallel (n=8/n=7). During anaesthesia, L-(2, 3-3H)-arginine and para-aminohippuric acid were infused until steady state. Subsequently, arterial and renal venous blood samples were taken. Concentrations of para-aminohippurate and amino acids and specific activity of arginine and citrulline were measured to calculate renal plasma flow, net renal uptake or release, and unidirectional influx or efflux of arginine and citrulline, as well as whole-body arginine turnover.3. Arterial citrulline was decreased in enterectomized rats compared with sham-operated rats (23+/-3 versus 44+/-6 microM). Net renal citrulline uptake and arginine release were almost stoichiometric (-36+/-7 and 38+/-6 nmol.min-1. 100 g-1 body weight respectively in sham-operated rats) and were both diminished by 50% in enterectomized versus sham-operated rats. In all groups, net renal arginine production accounted for less than 10% of whole-body rate of arginine appearance (488 nmol.min-1.100 g-1 body weight in the sham group). Despite decreased net renal citrulline consumption and renal arginine production in enterectomized rats, whole-body rate of arginine appearance and arterial arginine did not change significantly.4. In conclusion, net renal arginine production is reduced 24 h after 75% enterectomy in fasted rats. However, this does not have important effects on whole-body arginine production. (+info)
Nature of glomerular dysfunction in pre-eclampsia.
(63/67)
BACKGROUND: Pre-eclampsia is characterized by hypertension, proteinuria and edema. Simultaneous studies of kidney function and structure have not been reported. We wished to explore the degree and nature of glomerular dysfunction in pre-eclampsia. METHODS: Physiologic techniques were used to estimate glomerular filtration rate (GFR), renal plasma flow and afferent oncotic pressure immediately after delivery in consecutive patients with pre-eclampsia (PET; N = 13). Healthy mothers completing an uncomplicated pregnancy served as functional controls (N = 12). A morphometric analysis of glomeruli obtained by biopsy and mathematical modeling were used to estimate the glomerular ultrafiltration coefficient (Kf). Glomeruli from healthy female kidney transplant donors served as structural controls (N = 8). RESULTS: The GFR in PET was depressed below the control level, 91 +/- 23 versus 149 +/- 34 ml/min/1.73 m2, respectively (P < 0.0001). In contrast, renal plasma flow and oncotic pressure were similar in the two groups (P = NS). A reduction in the density and size of endothelial fenestrae and subendothelial accumulation of fibrinoid deposits lowered glomerular hydraulic permeability in PET compared to controls, 1.81 versus 2.58 x 10(-9) m/sec/PA. Mesangial cell interposition also curtailed effective filtration surface area. Together, these changes lowered the computed single nephron Kf in PET below control, 4.26 versus 6.78 nl/min x mm Hg, respectively. CONCLUSION: The proportionate (approximately 40%) depression of Kf for single nephrons and GFR suggests that hypofiltration in PET does not have a hemodynamic basis, but is a consequence of structural changes that lead to impairment of intrinsic glomerular ultrafiltration capacity. (+info)
Renal and haemodynamic effects of amlodipine and nifedipine in hypertensive renal transplant recipients.
(64/67)
BACKGROUND: Immunosuppressive treatment with cyclosporin A (CsA) improves the survival of renal allografts, but is associated with renal vasoconstriction and hypertension. Previous reports suggest that the calcium-channel blockers nifedipine and amlodipine may improve graft function in CsA-treated patients. We have compared the effects of amlodipine (5-10 mg once daily) and nifedipine retard (10-40 mg twice daily) on renal function and blood pressure in renal transplant recipients treated with CsA. METHODS: This was a multicentre, two-way, crossover study in 27 evaluable hypertensive patients with renal insufficiency following renal transplantation, who were maintained on a stable dose of CsA. Patients received either amlodipine (5-10 mg once daily) or nifedipine retard (10-40 mg twice daily) for 8 weeks, and were then crossed over to the other treatment for a further 8 weeks. RESULTS: Trends were seen during amlodipine treatment towards larger improvements, in serum creatinine (by 8% of baseline on amlodipine vs 4% on nifedipine), lithium clearance (13% vs 2%), and glomerular filtration rate 11% vs 7%). Effective renal plasma flow was increased by 11% of baseline on nifedipine vs 9% on amlodipine. There were no significant differences between treatments. Amlodipine and nifedipine lowered systolic blood pressure to a similar extent (21 mmHg vs 15 mmHg respectively, P=0.25), but amlodipine was more effective than nifedipine in lowering diastolic blood pressure (13 mmHg vs 8 mmHg, P=0.006). Both treatments were well tolerated. CONCLUSION: Once-daily amlodipine is at least as effective as twice-daily nifedipine retard in controlling blood pressure and does not adversely affect graft function in hypertensive renal allograft recipients. (+info)