Effects of cyclosporin A on glomerular barrier function in the nephrotic syndrome

1992 ◽  
Vol 82 (6) ◽  
pp. 641-650 ◽  
Author(s):  
Robert Zietse ◽  
Gerrit J. Wenting ◽  
Pieter Kramer ◽  
Maarten A. Schalekamp ◽  
Willem Weimar
Keyword(s):  
Glomerular Filtration Rate ◽  
Cyclosporin A ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Minimal Change Disease ◽  
Renal Plasma Flow ◽  
Minimal Change ◽  
Effective Renal Plasma Flow ◽  
Membranous Glomerulopathy ◽  
Glomerular Barrier

1. To elucidate the mechanisms by which cyclosporin A diminishes proteinuria, we studied 20 patients with severe nephrotic syndrome. Biopsy-established pathologies included minimal change disease (n = 5), membranous glomerulopathy (n = 6), membranoproliferative glomerulonephritis (n = 5) and focal segmental glomerulosclerosis (n = 4). Before, at the end of a 90 day course of cyclosporin A, and finally 1 month after stopping cyclosporin A we determined 24 h protein excretion. Measurements of glomerular filtration rate, effective renal plasma flow, fractional clearance rates of albumin and immunoglobulins with different charges and the transglomerular sieving of uncharged dextrans of broad size distribution were used to study the effects of cyclosporin A on renal perfusion and the glomerular filtration barrier. The findings were analysed with a theoretical model of solute transport. 2. Among the different forms of glomerulopathy the response to low-dose cyclosporin A (trough levels 32.0–36.9 ng/ml) varied markedly. In minimal change disease, proteinuria decreased from 9.5 ± 3.1 to 1.3 ± 0.2 g/24 h (mean ± sem, P < 0.01). This response was due to restoration of the charge selectivity of the glomerular barrier. The depressed value of the glomerular permeability coefficient also returned to normal. Glomerular filtration rate, effective renal plasma flow and renal vascular resistance did not change. Proteinuria returned after stopping cyclosporin A, although it did not reach pretreatment levels. In membranous glomerulopathy, proteinuria fell from 9.9 ± 1.5 to 1.8 ± 0.3 g/24 h (P < 0.01). Changes in protein excretion and dextran sieving were compatible with an increase in glomerular permselectivity and a decrease in filtrate flow through the ‘shunt’ pathway. Glomerular filtration rate was maintained, although effective renal plasma flow fell significantly. Proteinuria relapsed after stopping cyclosporin A. In membranoproliferative glomerulonephritis and focal segmental glomerulosclerosis proteinuria did not respond to cyclosporin A, although cyclosporin A exerted important haemodynamic effects. 3. In minimal change disease and membranous glomerulopathy cyclosporin A exerts its beneficial effects on proteinuria through changes in the properties of the glomerular barrier, resulting in increased charge and size selectivity, respectively.

Clinical Renal Function Testing by External Double Isotope Monitoring Technique

1971 ◽  
Vol 10 (01) ◽  
pp. 16-24
Author(s):  
J. Fog Pedersen ◽  
M. Fog Pedersen ◽  
Paul Madsen
Keyword(s):  
Renal Function ◽  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Plasma Flow ◽  
Filtration Rate ◽  
Renal Plasma Flow ◽  
Correlation Coefficients ◽  
Feedback System ◽  
Effective Renal Plasma Flow ◽  
Advantages And Disadvantages

SummaryAn accurate catheter-free technique for clinical determination simultaneouslyof glomerular filtration rate and effective renal plasma flow by means of radioisotopes has been developed. The renal function is estimated by the amount of radioisotopes necessary to maintain a constant concentration in the patient’s blood. The infusion pumps are steered by a feedback system, the pumps being automatically turned on when the radiation measured over the patient’s head falls below a certain preset level and turned off when this level is again readied. 131I-iodopyracet was used for the estimation of effective renal plasma flow and125I-iothalamate estimation of the glomerular filtration rate. These clearances were compared to the conventional bladder clearances and good correlation was found between these two clearance methods (correlation coefficients 0.97 and.90 respectively). The advantages and disadvantages of this new clearance technique are discussed.

Influence of nifedipine on cyclosporin A nephrotoxicity after unilateral nephrectomy in the spontaneously hypertensive rat

1991 ◽  
Vol 81 (2) ◽  
pp. 271-279 ◽  
Author(s):  
P. G. McNally ◽  
F. Baker ◽  
N. Mistry ◽  
J. Walls ◽  
J. Feehally
Keyword(s):  
Body Weight ◽  
Glomerular Filtration Rate ◽  
Renal Impairment ◽  
Cyclosporin A ◽  
Glomerular Filtration ◽  
Plasma Flow ◽  
Filtration Rate ◽  
Renal Denervation ◽  
Renal Plasma Flow ◽  
Spontaneously Hypertensive

1. Nifedipine ameliorates cyclosporin A-induced renal impairment in surgically intact (two-kidney) rats. This study investigates the effect of nifedipine on cyclosporin A nephrotoxicity in spontaneously hypertensive rats after either uninephrectomy or uninephrectomy with contralateral renal denervation. 2. Fourteen days after uninephrectomy pair-fed rats were injected for 14 days with cyclosporin A (25 mg/kg body weight) via the subcutaneous route and with nifedipine (0.1 mg/kg body weight) via the intraperitoneal route. Renal and systemic haemodynamics were measured in conscious unrestrained rats. 3. Whole-blood levels of cyclosporin A did not differ between groups (overall 352 ± 22 ng/ml, means ± sem). After uninephrectomy, cyclosporin A decreased the glomerular filtration rate (olive oil versus cyclosporin A: 0.96 ± 0.04 versus 0.70 ± 0.06 ml min−1 100 g body weight, P < 0.02) and effective renal plasma flow (1.94 ± 0.10 versus 1.38 ± 0.13, P < 0.01), and increased renal vascular resistance {(20.2 ± 1.8) × 104 versus (31.6 ± 3.3) × 104 kPa l−1 s [(20.2 ± 1.8) × 103 versus (31.6 ± 3.3) × 103 dyn s cm−5], P < 0.02} and mean arterial pressure (146.7 ± 6.7 versus 167.3 ± 2.9 mmHg, P < 0.05). Neither renal denervation nor nifedipine prevented the reduction in glomerular filtration rate or effective renal plasma flow induced by cyclosporin A. 4. This study infers that the sympathetic nervous system does not play an active role in cyclosporin A nephrotoxicity and demonstrates that the concomitant administration of nifedipine to rats with reduced renal mass does not ameliorate cyclosporin A-induced renal impairment.

scholarly journals Simultaneous Measurement of Glomerular Filtration Rate, Effective Renal Plasma Flow and Tubular Secretion in Different Poultry Species by Single Intravenous Bolus of Iohexol and Para-Aminohippuric Acid

Animals ◽  
2020 ◽  
Vol 10 (6) ◽  
pp. 1027
Author(s):  
Lenka Stroobant ◽  
Siska Croubels ◽  
Laura Dhondt ◽  
Joske Millecam ◽  
Siegrid De Baere ◽  
...  
Keyword(s):  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Plasma Flow ◽  
Simultaneous Measurement ◽  
Filtration Rate ◽  
Renal Plasma Flow ◽  
Tubular Secretion ◽  
Effective Renal Plasma Flow ◽  
High Dose ◽  
Potential Marker

The aim of the current study was to investigate the simultaneous measurement of plasma p-aminohippuric acid (PAH) clearance as a potential marker to assess effective renal plasma flow (eRPF) and tubular secretion (TS), and the plasma clearance of iohexol (IOH) as a marker of the glomerular filtration rate in poultry species. The PAH was administered intravenously (IV) to broiler chickens, layers, turkeys, Muscovy ducks, and pigeons. Each animal received successively a single bolus dose of 10 mg PAH/kg bodyweight (BW) and 100 mg PAH/kg BW to assess the eRPF and TS, respectively. Simultaneously with both PAH administrations, a single IV bolus of 64.7 mg/kg BW of IOH was administered. A high linear correlation (R2 = 0.79) between eRPF, based on the clearance of the low dose of PAH, and BW was observed for the poultry species. The correlation between TS, based on the clearance of the high dose of PAH, and BW was moderate (R2 = 0.50). Finally, a moderate correlation (R2 = 0.68) was demonstrated between GFR and eRPF and between GFR and TS (R2 = 0.56). This presented pharmacokinetic approach of the simultaneous administration of IOH and PAH enabled a simultaneous evaluation of eRPF/TS and GFR, respectively, in different poultry species.

Lithium clearance method and the renal response to low-dose dopamine in man: a randomized, controlled study

1993 ◽  
Vol 84 (2) ◽  
pp. 237-242 ◽  
Author(s):  
Niels Vidiendal Olsen ◽  
Michael Hecht Olsen ◽  
Niels Fogh-Andersen ◽  
Bo Feldt-Rasmussen ◽  
Annelise Kamper ◽  
...  
Keyword(s):  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Plasma Flow ◽  
Filtration Rate ◽  
Low Dose ◽  
Renal Plasma Flow ◽  
Effective Renal Plasma Flow ◽  
Lithium Clearance ◽  
Clearance Studies ◽  
Sodium Clearance

1. The effect of a single dose of lithium on renal function before and during intravenous infusion of dopamine (3 μg min−1 kg−1) was investigated in 12 healthy males. In a double-blind and randomized design, 450 mg or 600 mg of lithium carbonate or placebo was administered orally at 22.00 hours on three different occasions. After an overnight fast, the subjects were water-loaded and clearance studies were started at 09.00 hours with a 1 h baseline period and three 1 h periods during dopamine infusion. 2. Baseline sodium clearance with placebo was 0.65 ± 0.35 ml/min, but with lithium it increased to 1.25 ± 0.44 (P < 0.001) and 1.17 ± 0.46 ml/min (P < 0.01) after 450 and 600 mg, respectively. Urine flow rates were unchanged compared with placebo. Lithium did not significantly affect glomerular filtration rate, but both doses slightly increased effective renal plasma flow by 7% (P < 0.05) and 10% (P < 0.01), respectively. 3. The maximal natriuretic and diuretic effects of dopamine were not reduced by lithium, but the percentage increases in sodium clearance were significantly diminished after 450 mg (P < 0.01) and 600 mg (P < 0.001) of lithium. Lithium had no effect on dopamine-induced changes in effective renal plasma flow, glomerular filtration rate or osmolal clearance. Neither lithium nor dopamine influenced plasma concentrations of renin, aldosterone or atrial natriuretic peptide. 4. In conclusion, single test doses of lithium, as normally used in lithium clearance studies, increase baseline values of sodium clearance and effective renal plasma flow. Although these effects of lithium do not reduce the maximal renal responses to low-dose dopamine, they result in an underestimation of the percentage increase in sodium excretion.

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