The "fixed" charge of glomerular capillary wall as determinant of permselectivity.

The determinants of glomerular capillary wall (GCW) permeability to proteins have been subject of controversial discussion. To study this question we have developed a modified isolated perfused rat kidney model in which tubular transport processes are completely blocked by perfusion fixation with glutaraldehyde. This model allows to directly titrate the charge density of the GCW using albumin solutions buffered over a wide pH-range, a manipulation that cannot be performed in the intact kidney. Analyzing the results of these experiments helped to determine a fixed charge density of the GCW of 43 mEq/L. In the present work, we used the isolated perfused fixed rat kidney model to study the influence of this fixed charge on the transglomerular passage of proteins. To do this, the fixed kidney was perfused with albumin solutions containing different isoforms of horseradish peroxidase. The lowest sieving coefficient was obtained with the acidic isoform (0.035+/-0.008, n = 7), while the isoforms at pI 6.85 and 8.45 showed higher sieving coefficients (0.059+/-0.008, n = 7 and 0.090+/-0.008, n = 4, respectively). The highest sieving coefficient (0.59+/-0.031, n = 6) was observed in perfusion experiments of the fixed kidney with cationic HRP (pI > or = 9.30). However, when comparing the sieving coefficients, the highly cationic isoform was excluded because it has a lower molecular weight than the other isoforms. The sieving coefficients of the other isoforms were significantly different (p < 0.05. ANOVA, Scheffé test). In conclusion, the presence of a discrete (even if lower than previously thought) "fixed" charge on the GCW of 43 mEq/L restricts the transglomerular passage of isoforms of horseradish peroxidase by a factor 2-3. These results imply that the influence of charge selectivity has been overstated in the literature.

Role of albumin and glomerular capillary wall charge distribution on glomerular permselectivity: studies on the perfused-fixed rat kidney model.

The charge-related determinants of albumin permeability are the subject of controversial discussion. To study this question we have developed an isolated perfused rat kidney model in which metabolic processes are eliminated by perfusion fixation with glutaraldehyde. The fixed kidneys were perfused with albumin solutions using the following approaches: 1. Modification of the charge of both the glomerular capillary wall (GCW) and albumin using different buffer systems in a pH range spanning the isoelectric points of albumin and the glomerular basement membrane (GBM), the extracellular matrix of the GCW. 2. Modification of the charge of the GCW by perfusing the isolated kidney with cations either before or after fixation. 3. Modification of the charge of albumin by cationization. In the model, the inulin "urine" to perfusate ratio was one. This shows that the tubules have no metabolic activity, that the glomerular filtration rate (GFR) is equal to "urine" flow rate and that the "urine" collected is identical to the ultrafiltrate. Therefore, sieving coefficients in this model can simply be calculated as the ratio between "urine" and perfusate protein concentrations. We could show that: 1. pH has a significant effect on the albumin sieving coefficient: it was maximally increased at pH 4.0 [(70.3 +/- 15.9) x 10(-3), n = 10 versus (8.7 +/- 3.7) x 10(-3), n = 11, at pH 7.4]. Only a pH as low as 4.0 should lead to a pronounced neutralization of the anionic charges of albumin and the GBM; the charge density of the GCW calculated with these data is 43 mEq/l at pH 7.4. 2. Modifying the ionic composition of the GCW with protamine before fixation with glutaraldehyde causes a bigger increase in the glomerular permeability for albumin [(51.2 +/- 22.5) x 10(-3), n = 10, glomerular charge density 21 mEq/l] than modifying the albumin charge by cationization. 3. Modifying the albumin charge by cationization increases the glomerular permeability for albumin [(20.0 +/- 6.7) x 10(-3), n = 8]. These findings support the hypothesis that at the onset of proteinuria changes in the charge and configuration of the GCW could be more important pathogenetic factors than changes in the charge of serum-derived proteins.

Intravenous pulse administration of cyclophosphamide versus daily oral treatment in patients with antineutrophil cytoplasmic antibody-associated vasculitis and renal involvement: a prospective, randomized study.

OBJECTIVE: There is growing concern about the toxic side effects of daily oral cyclophosphamide (CYC) treatment. Intravenous (i.v.) pulse administration of CYC has been shown to be effective in patients with systemic lupus erythematosus, but contradictory results have been reported in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. METHODS: The efficacy and toxicity of i.v. pulse administration of CYC (0.75 gm/m2) versus daily oral CYC treatment (2 mg/kg body weight) were investigated in a prospective, randomized, multicenter study in patients with ANCA-associated vasculitis and renal involvement. RESULTS: The cumulative CYC dose was reduced by 57% in patients with i.v. pulse treatment (n = 22) compared with patients treated with daily oral therapy (n = 25). Patient survival, remission rate, time of remission, relapse rate, and outcome of renal function were not different between the 2 treatment groups. However, the rate of leukopenia (P < 0.01) and severe infections (P < 0.05 by 1-tailed test) was significantly reduced in the i.v. pulse group compared with the group receiving daily oral treatment. Moreover, gonadal toxicity was reduced in the i.v. pulse group, as indicated by significantly lower levels of follicle-stimulating hormone. CONCLUSION: This randomized study shows that i.v. CYC administration is an effective therapeutic tool with low toxicity in patients with ANCA-associated vasculitis and renal involvement.

Is tubuloglomerular feedback a tool to prevent nephron oxygen deficiency?

The purpose of the study was to analyze whether rhythmic oscillations of proximal tubular pressure and distal fluid conductivity at the renal surface are induced by oxygen deficiency of thick ascending limb (TAL) segments. Oxygen pressure was measured in halothane anesthetized Munich-Wistar rats by a multi-wire micro-gold electrode at the kidney surface. Signals from wires placed upon glomeruli and tubuli exhibited pO2 oscillations with exactly the same frequency (in mean 30 mHz) as have been described for proximal tubular pressures or distal fluid conductivities. This supports our suggestion that a limited oxygen supply to the nephron forces TAL segments to oscillate between aerobic and anaerobic energy production. A switch to glycolysis reduces TAL's transport efficiency dramatically. At the macula densa, the terminal end of the TAL segment, the thereby elevated sodium concentration operates as a switch by means of the TGF to adapt the filtered load to the oxygen supply of the individual nephron. In this way proximal tubules may also be protected from oxygen deficiency, which is essential due to their low glycolytic capacity. An enhanced halothane concentration of 2% or the use of barbiturates, such as Inactin, blocks oscillations completely as furosemide blocks oscillations as well as the feedback response. Reduction of the hematocrit by exchange transfusion mainly reduces supratubular pO2 values, and to a lesser extent also reduces supraglomerular pressures. This demonstrates that oxygen shunt diffusion in the kidney cortex and medulla is a prerequisite for both the function of a sensor to measure pO2 and oxygen capacity to regulate erythropoietin secretion and to enable an effective adjustment of blood flow to the metabolic and functional demands of the kidney.

Mechanisms of glomerular proteinuria and hematuria.

The barrier function of glomerular capillaries in vivo, which prevents the leakage of plasma proteins and cellular elements, depends not only on the basic morphological and physico-chemical fine structure of the glomerular capillary wall, but also on a functional barrier maintained by components obtained from blood. Together, both restrict the leakage of plasma proteins and cells in vivo. Two types of morphological defects are claimed to represent the normal condition: a larger type of leak, which enables the passage of red cells through the glomerular capillary wall one after the other without interruption by a plasma pulse and which must be present more frequently in thin basement membrane disease. This type of leak is sealed by penetrating cells and uncovered for protein filtration in the isolated (cell-free) perfused rat kidney. A smaller type of leak cannot be sealed by red cells, but also contributes to the enhanced protein permeability in perfusion with a monocomponent albumin solution. This type of leak is uncovered in vivo by angiotensin or catecholamines and is the basic route responsible for the unselective "functional proteinuria" of different types. Mechanisms which induce lesions under pathological conditions may also be active under everyday conditions, although to a smaller extent.

The physiological and pathophysiological basis of glomerular permeability for plasma proteins and erythrocytes.

The barrier function of glomerular capillaries in vivo, which prevents the leakage of plasma proteins and cellular elements, depends on the basic morphological and electro-chemical fine structure of the glomerular capillary wall, and on a functional barrier maintained by components obtained from blood, which effect the definitive barrier against the leakage of plasma proteins and cellular elements. The functional component of the barrier may explain the variability and some of the phenomena known as functional proteinuria. A certain size and number of morphological "defects" are thought to represent the normal condition, but under pathological conditions they may increase in size and number, resulting in a shift to an increasing permeability for higher molecular mass proteins; also an increase of the size and number of larger defects may enable more red cells to pass the barrier compared with the normal condition. These defects are different from the minimal glomerular lesions which are due to charge defects in the glomerular capillary membrane, primarily the lamina rara interna and the lamina rara externa of the basement membrane.

Importance of NO/EDRF for glomerular and tubular function: studies in the isolated perfused rat kidney.

The effect of the addition of N omega-nitro-L-arginine (L-NNA, 10 and 100 microM) to isolated rat kidneys perfused with a complex medium containing 21 amino acids has been studied. A cyclooxygenase inhibitor was added throughout to block prostaglandin synthesis. L-NNA caused significant reductions in renal perfusion flow rate (PFR, 9.8 +/- 1.4 vs. 15.9 +/- 1.1 ml.min-1.g kidney wt-1, P less than 0.0001), glomerular filtration rate (GFR, 566 +/- 57 vs. 705 +/- 47 microliters.min-1.g kidney wt-1, P less than 0.05) and an increase in the relative filtration fraction (%FF, 7.0 +/- 0.6 vs. 5.2 +/- 0.4%, P less than 0.05) compared to control kidneys. L-NNA perfused kidneys had a lower absolute sodium (72 +/- 9 vs. 88 +/- 4 mumol.min-1.g kidney wt-1, P less than 0.05) and glucose reabsorption (3.5 +/- 0.5 vs. 5.4 +/- 0.4 mumol.min-1.g kidney wt-1, P less than 0.05), corresponding mainly to a lower sodium and glucose filtration. However, the relative reabsorption of sodium and glucose in the presence of L-NNA was attenuated, too (82.8 +/- 2.0 vs. 87.0 +/- 3.3% P less than 0.05 and 91.3 +/- 1.1 vs. 94.1 +/- 0.5%, P less than 0.05). Potassium handling and protein excretion were not changed significantly; fractional protein excretion increased slightly with the addition of L-arginine (47 +/- 5 vs. 55 +/- 7 ng.microliters-1, P less than 0.05). The differences between control and L-NNA treated kidneys (with the exception of differences in FRGluc) could be fully (L-NNA, 10 microM) or partially (L-NNA 100 microns) reversed by adding L-arginine (1 mM) to the perfusion medium. The observed results could be obtained in two different rat strains (Sprague-Dawley and Wistar). Only L-NNA and L-arginine caused the observed changes, while D-NNA and D-arginine were without effect. It is concluded that NO/EDRF is basally released from the isolated perfused rat kidney, and is of importance not only in the regulation of renal hemodynamics but also in the regulation of renal tubular function.

Effect of arginine depletion on glomerular and tubular kidney function: studies in isolated perfused rat kidneys.

The effect of L-Arg depletion on glomerular hemodynamics and tubular function of isolated rat kidneys perfused with a medium containing 21 amino acids has been studied. A cyclooxygenase inhibitor was added throughout for blockade of prostaglandin synthesis. Arg depletion caused significant (approximately 30%) reductions in renal perfusion flow rate (PFR, 13.9 +/- 1.2 vs. 19.8 +/- 0.6 ml.min-1.g (kidney wt-1), glomerular filtration rate (GFR, 598 +/- 79 vs. 924 +/- 42 microliters.min-1.g kidney wt-1), and urine flow rate (139 +/- 38 vs. 192 +/- 13 microliters.min-1.g kidney wt-1) compared with control kidneys, which were perfused with a physiological concentration of Arg (200 microM). Filtration fraction (FF) increased with Arg depletion (5.1 +/- 0.4 vs. 4.4 +/- 0.4%). Arg-depleted kidneys had a lower absolute sodium (TNa, 75.7 +/- 8.8 vs. 107.9 +/- 6.0 mumol.min-1.g kidney wt-1) and glucose reabsorption (T glucose, 3.7 +/- 0.6 vs. 5.6 +/- 0.5 mumol.min-1.g kidney wt-1), corresponding to a lower sodium and glucose filtration. Potassium handling and reabsorption of free water were not changed. Oxygen consumption (QO2) was lower in Arg-depleted kidneys (4.6 +/- 0.3 vs. 5.5 +/- 0.5 mumol.min-1.g kidney wt-1). The effects of Arg depletion were completely reversed by the addition of Arg (1 mM) at 120 min and partly reversed by the addition of citrulline (1 mM). Ornithine depletion or addition had no effect on PFR, GFR, FF, TNa, T glucose, and QO2. N omega-methyl-L-arginine, a specific inhibitor of nitric oxide endothelium-derived relaxing factor, produced the same effect as Arg depletion.(ABSTRACT TRUNCATED AT 250 WORDS)

Metabolism of cysteinyl leukotrienes by the isolated perfused rat kidney.

The metabolism of cysteinyl leukotrienes by the isolated perfused rat kidney was investigated. For this purpose LTC4, LTD4 or LTE4 were studied in separate experiments. The isolated perfused rat kidney metabolized all cysteinyl leukotrienes to the final metabolite N-acetyl-LTE4. In the presence of 5% albumin 50% of LTC4 was metabolized to LTD4 (22%), LTE4 (15%) and N-acetyl-LTE4 (13%) within 60 min. Excretion of radioactivity into urine was less than 1%. In contrast, in the absence of albumin, LTC4 was completely metabolized within 45 min to N-acetyl-LTE4, the sole and final metabolite of LTC4 found in the perfusion medium as well as in urine. After 60 min 19% and 42% of total radioactivity were found in the perfusion medium and in urine, respectively. Isolated glomeruli metabolized LTC4 to LTD4 and to LTE4 but not to N-acetyl-LTE4 at a rate comparable to the rate observed by the isolated perfused kidney in the absence of albumin. In contrast to isolated glomeruli isolated tubuli metabolized LTE4 to N-acetyl-LTE4 at a rate comparable to that observed by the isolated perfused kidney in the absence of albumin. The present study shows that the isolated perfused rat kidney metabolizes cysteinyl leukotrienes to the sole and final metabolite N-acetyl-LTE4. In the presence of albumin metabolism is slowed down and excretion of N-acetyl-LTE4 into urine is prevented.

Oxygen-dependent erythropoietin production by the isolated perfused rat kidney.

In this study we have investigated the role of oxygen delivery and of classic second messengers on erythropoietin production by the isolated perfused rat kidney. We found that the rat kidney was capable of de novo synthesis of erythropoietin. The erythropoietin production rate was inversely related to the oxygen pressure in the perfusate and increased from 0.17 to 1.85 U erythropoietin h-1 g kidney-1 when arterial PO2 was lowered from 500 mmHg to 30 mmHg. Addition of forskolin (10 microM) and 8-bromo-cGMP (100 microM) to the perfusate elicited significant effects on the renal vascular resistance, but had no significant effect on erythropoietin production. Hypoxia-induced erythropoietin formation, however, was blocked by calmidazolium (1 microM) and W-7 (10 microM), two structurally different putative calmodulin antagonists. Calmidazolium and W-7 had no effect on other functional parameters of the isolated perfused rat kidney such as flow rate, glomerular filtration rate or sodium reabsorption. Our findings suggest that the oxygen-sensing mechanism that controls renal erythropoietin production is primarily located in the kidney itself. A calcium/calmodulin-dependent cellular reaction could be involved in the signal transduction process.

Role of erythropoietin in adaptation to hypoxia.

The glycoprotein hormone erythropoietin (EPO) counteracts tissue hypoxia by increasing the systemic oxygen-carrying capacity. It induces augmentation of red blood cell mass by stimulating the formation and differentiation of erythroid precursor cells in the bone marrow. EPO production is increased under various forms of diminished oxygen supply such as anemic or hypoxic hypoxia. In the adult organism, the kidneys are the major source of EPO. The precise nature of the cells responsible for renal EPO production, however, has not yet been elucidated. Most likely, peritubular cortical cells, e.g. interstitial or endothelial cells, are involved in the elaboration of the hormone. From the observation that isolated perfused rat kidneys produce EPO in an oxygen-dependent fashion we conclude that the 'oxygen sensor' that controls hypoxia-induced EPO synthesis is located in the kidney itself. Within the kidneys, the local venous oxygen tension which reflects the ratio of oxygen supply to oxygen consumption is measured and transformed into a signal that regulates the formation of EPO. However, the mechanism by which a decrease of oxygen delivery to the kidneys is linked to an enhanced EPO gene expression is not yet known. Two possible mechanisms of regulation are discussed: First, renal hypoxia could lead to enhanced formation of metabolic mediators, for example prostaglandins or adenosine, which might stimulate EPO gene transcription by increasing cellular levels of second messenger molecules. Second, some kind of molecular 'oxygen receptor' such as a heme protein, that controls EPO formation by an oxygen-dependent conformational change, could mediate signal transduction.

Evidence for a preglomerular oxygen diffusion shunt in rat renal cortex.

Although blood flow to the renal cortex is high and oxygen extraction is low, the renal cortex is remarkably susceptible to hypoxia. Because erythropoietin production has been localized mainly to the renal cortex, the aim of this study was to find a common denominator for both the high susceptibility to hypoxia and oxygen sensing within the renal cortex. By direct measurement of oxygen pressure with microcoaxial needle sensors at superficial glomeruli of the in situ kidney of anesthetized Munich-Wistar-Frömter rats, we obtained mean partial pressure of O2 (PO2) values of 46 +/- 13 (SD) mmHg (n = 71). The simultaneously measured systemic PO2 in arterial blood was 90 +/- 8 mmHg (n = 54). Changing the respirator gas from air to pure oxygen enhanced systemic arterial PO2 to 593 +/- 27 mmHg, whereas PO2 at the superficial glomeruli increased only to a mean of 80 +/- 28 mmHg (n = 71). These data suggest significant preglomerular shunting of oxygen within the cortical vasculature, most likely between interlobular vessels, which are arranged in a countercurrent fashion and represent quantitatively the largest contact area between arteries and veins within the renal cortex.

Sodium reabsorption in the isolated perfused kidney of normotensive and spontaneously hypertensive rats.

Kidneys of 3-month-old spontaneously hypertensive rats (SHR) of the Münster strain and age- and weight-matched normotensive rats (Wistar-Kyoto; WKY) were isolated and perfused at a constant pressure of 100 mmHg with a modified, albumin-free Krebs-Henseleit solution. Fractional Na+ reabsorption, which is independent of the glomerular filtration rate under these conditions, was significantly elevated in SHR kidneys compared with WKY kidneys during 90 min of perfusion (P less than 0.01). Renal perfusion flow rates did not differ between SHR and WKY. These data support the concept of an intrinsic renal abnormality in Na+ excretion that may contribute to the maintenance of hypertension in SHR.

Study on the renal handling of sex dependent proteins in male rats studied by micropuncture techniques and by the isolated perfused rat kidney.

The separation of sex dependent urinary proteins of the rat (SDP) by micro-disc electrophoresis results in at least eight well defined protein bands with differing molecular weights. The hepatic origin of a sex dependent urinary protein, named alpha 2u-globulin, has been demonstrated before by other authors applying immunological methods. In the present study, it could been shown that SDP circulate in the plasma at a concentration of 23.8 mg/l. The origin of those protein bands which appear typically upon electrophoresis was still under dispute because they could not been demonstrated in proximal tubular fluid. The present study confirms the extrarenal source of SDP and suggests identity with alpha 2u-globulin. The attempt to track down SDP from plasma to excreted urine demonstrated that, in contrast to proximal fluid, samples from nephron parts distal to the loop of Henle contain large amounts of SDP. An isolated kidney model was used to determine the sieving coefficient and tubular reabsorption of SDP, obtained from male rat urine. We have found a correlation between the sieving coefficient and the molecular weight of SDP. The sieving coefficient ranged from 0.375 to 0.834. The tubular reabsorption which has been determined with an isolated kidney perfused with albumin and erythrocytes also showed variation with regard to molecular weight and was 61.7%, on average.

Renal mesangium is a target for calcitonin gene-related peptide.

Rat calcitonin gene-related peptide (CGRP alpha; EC50, 1 nM) was shown to stimulate cAMP formation in cultured rat renal mesangial cells. CGRP concentration dependently (EC50, 1 nM) also inhibited contraction of mesangial cells by angiotensin II (10 nM). Angiotensin II (10 nM) caused a transient increase of the intracellular calcium concentration from 140 nM to 480 nM in the mesangial cells, but these calcium transients were not altered by CGRP. CGRP (10 nM) decreased vascular resistance in the isolated rat kidney perfused at constant pressure (100 mm Hg; P less than 0.01). The decreased vascular resistance was accompanied by a rise of the glomerular filtration fraction. CGRP, moreover, attenuated the effects of angiotensin II on renal vascular resistance and glomerular filtration (P less than 0.01). In conclusion, CGRP causes relaxation of renal mesangial cells and decreases renal vascular resistance. As a result CGRP raises glomerular filtration and the filtration fraction. The effect may be linked to cyclic AMP formation. Thus, regulation of renal vascular and glomerular function may represent a novel action of CGRP apart from its cardiovascular effects.

[Kidney medullary hypoxia: a key to understanding acute renal failure?]. / Die Nierenmarkhypoxie: ein Schlüssel zum Verständnis des akuten Nierenversagens?

The ability to produce a concentrated urine is imposed by a uniquely low ambient oxygen pressure in the renal medulla due to shunt diffusion within the vascular bundles. As the thick ascending limb of Henle's loop (TAL-segment) is able to glycolyse anaerobically, a phase of oxygen deficiency may be bridgespanned. It allows an exceptionally high oxygen extraction of 80% in this area. If oxygen capacity is reduced systematically, which can be effected in the isolated kidney model by using cell free perfusate, a typical pattern of lesions occur in TAL-segments. Segments near vascular bundles remain intact, as they take advantage from a radial oxygen diffusion originating from vascular bundles. The extent of lesions is increasing directed to the inner medulla due to the reduction of oxygen pressure, whereas lesions are not present in the inner medulla itself. Cells of TAL-segments are swelling during oxygen deficiency, when transport work surpasses the available energy necessary due to the luminal fluid inflow. Lesions could be prevented, when oxygen capacity was enhanced by adding erythrocytes or when transport was blocked by furosemide. Swollen cells in TAL-segments however are able to aggravate medullary hypoxia by an outflow block in vivo. Secondly, it can be demonstrated, that oxygen shunt diffusion is not only present in renal medulla but also within renal cortex especially as a preglomerular diffusion shunt for blood gases. Thus PCO2 has been measured to be 65 mmHg in the outermost cortical zone and thereby some 20 mmHg higher than renal venous blood.(ABSTRACT TRUNCATED AT 250 WORDS)

Renal handling of cadmium and cadmium-metallothionein: studies on the isolated perfused rat kidney.

The isolated kidney perfusion model was used to study the uptake of Cd and metallothionein (MT)-complexed Cd. Cd2+ at concentrations above 40 nM strongly depressed the glomerular filtration rate (GFR), whereas MT-complexed Cd (Cd-MT) at concentrations of 0.8-920 nM had no effect on the GFR. In contrast to Cd2+, Cd-MT was readily reabsorbed by the kidney and uptake saturation for Cd-MT occurred at 240 nM. The maximal transport rate for Cd-MT calculated in this study was 18 pmoles Cd-MT . g-1 . min-1. The accumulation of Cd in the kidney was more efficient in the experiment using Cd-MT, in which case the Cd kidney contents were about 2-4 times higher than compared to CdCl2.

Influence of cyclosporine A on adaptive hypertrophy after unilateral nephrectomy in the rat.

The functional challenge to a transplanted kidney is comparable to that of a single kidney after unilateral nephrectomy. The single kidney model was used in rats to study the influence of the immunosuppressant CyA. Using this model interference with immunological or preservation/transplantation problems can be excluded. Two month old rats were studied 4 weeks after unilateral nephrectomy. After unilateral nephrectomy the juvenile rats had been fed for 28 days with 10 or 15 mg/kg BW CyA daily. These rats were compared to intact control rats and to age-matched uni-nephrectomized rats. Single kidney weight was measured in one group. Single kidney function was measured in a second group, first in the metabolic cage and then in experiments with isolated kidneys perfused under standard conditions. The glomerular filtration coefficient Kf was measured by micropuncture techniques. Glomerular capillary surface area was estimated after perfusion fixation in order to calculate the effective hydraulic permeability k of the glomerular capillary wall (k = Kf/S). Standard allogeneic skin transplantation across the MHC barrier was used to establish that the CyA dosage used was immunosuppressive. The results showed that the single kidney mass (as a measure of tubular hypertrophy) and GFR were suppressed under the influence of CyA compared to controls. Analysis of glomerular filtration parameters in the isolated perfused kidneys on the single nephron level had the following results: a small increase of the glomerular capillary surface (morphometry) was suppressed under CyA, whereas the effective hydraulic permeability (k) increased by almost 40% whether CyA was given or not.