Renal response of the new-born dog to a saline load: the role of intrarenal blood flow distribution

1. The renal response to an intravenous saline load was studied in thirty new-born mongrel dogs aged 1-30 days and in seven adult dogs.2. After the infusion of isotonic saline at a rate of 2.0 ml. min(-1) kg(-1) for 15 min and then at a rate of 0.5 ml. min(-1) kg(-1) for an additional 105 min, the puppies excreted a significantly smaller fraction of the infused sodium than did the adults (P < 0.01).3. Both puppies and adults increased their glomerular filtration rates after the saline load. However, adults excreted a larger fraction of their filtered sodium than did the puppies (P < 0.01).4. There was no correlation between age and the ability to respond to a saline load during the first month of life.5. Intrarenal blood flow distribution was measured by the radioactive microsphere technique. After saline infusion in the puppy there was an increase in outer cortical blood flow but inner cortical blood flow remained relatively constant. The result was a decrease in the ratio of inner to outer cortical blood flow (IC/OC ratio). In contrast the IC/OC ratio tended to increase in the adult dog after saline expansion.6. There was no correlation between the magnitude of change of sodium excretion and the change of intrarenal blood flow distribution in the puppy.7. These results confirm that the natriuretic response of the new-born dog kidney is less efficient than that of the adult dog. This is due primarily to the failure of the puppy kidney to decrease fractional sodium reabsorption. Although the new-born dog alters intrarenal blood flow distribution in response to saline loading this alteration does not appear to play a significant role in sodium excretion.     

The Nature of Experimental Second-set Kidney Transplant Rejection: 4. The Disturbed Haemodynamics and the General Significance of Failure to Perfuse the Outer Cortical Glomeruli in Acute Renal Failure

The second-set reaction can be mimiced from a haemodynamic point of view by pharmacological vasopressors, warm and cold ischaemic factors producing vasocontriction and by the Shwartzman reaction. The second-set kidney transplant reaction is assumed to be due to antibodies which, if so, are not dependent for their cytotoxicity on complement fixation and are uninfluenced by antihistamine drugs, steroids, immunosuppression, incoagulable blood, adequate hydration and rheomacrodex. Once started, the reaction continues until the vasoconstriction is so severe that no blood enters the kidney and complete disorganization of kidney function and structure ensues. The deposition of fibrin in the vessels and glomeruli follows the severe vasomotor upset which evokes afferent vasoconstriction. Fibrin is not prevented from being deposited when the recipient of a second-set kidney is fully Arvinized so that the blood is rendered incoagulable.The second-set kidney reaction is first heralded by vasoconstriction in the outer cortex associated with acute renal failure and, as such, fits into the general phenomenon of acute renal failure associated with underperfusion of the outer cortex. There is no evidence that underperfusion of the outer cortex is due to a hyperreactivity of special vessels with a different structure from the other vessels supplying this area. There is the fact, however, that the outer cortical vessels are highly reactive to stimuli of many kinds besides angiotensin.Certain unexplained features of acute renal failure in general may be reasonably explained by reference to the effects of underperfusion of the outer cortex. Acute renal failure associated with mild signs of tubule necrosis, for example, may be explained by the fact that although there is afferent underperfusion of the outer cortex there is generally maintained a good venular collateral nutrient supply (maintained capacitance) sufficient for the oxygen requirements of tubules which are not pumping sodium because there is no outer glomerular perfusion or filtration.The significance of the nephrogram in acute renal failure is discussed and explained on the basis of lack of outer cortical glomerular perfusion with adequate perfusion of inner cortical glomeruli. Although, normally, the kidney is perfused by an unusually large volume of blood the proportion of outer cortical perfusion determines the function of the kidney rather than total renal blood flow, oxygen consumption, A-V O₂ differences and rate of transit time.     

Maturation of the glomerular visceral epithelium and capillary endothelium in the puppy kidney

The present study describes the development and maturation of the glomerular visceral epithelium and capillary endothelium in an attempt to clarify kidney function in the neonate. The puppy kidney undergoes nephrogenesis for at least two weeks after birth, and thus possesses nephrons of different ages and levels of maturation. Since nephron development varies considerably from inner to outer cortex, renal corpuscles were examined within three arbitrary zones (outer, middle and inner cortex). The visceral epithelium of the smallest glomeruli, i.e., those of the outer cortex, is composed of cuboidal cells which are densely clustered and rests directly upon the limited number of small capillaries. More deeply within the outer cortex, broad, flat epithelial processes extend around the capillary, but lack any visible pedicels. Mid cortical glomerular capillaries undergo an increase in diameter and length, and at the same time the podocytes flatten and separate from one another. Pedicels begin to appear in this zone as thickened, disorganized processes. Juxtamedullary glomeruli are the largest, due primarily to their extensive capillary branching (looping). Podocytes are nearly adult-like in appearance, with many long primary processes and pedicels. The endothelial morphology of glomerular capillaries varies from one loop to another, as well as within a single loop. The immature endothelium of outer glomeruli is initially characterized by extensive expanses lacking pores, multiple cellular layers and small, scattered pinholes. Greater capillary maturity is apparent in the mid cortex, due to an increase in pore number and diameter as well as greater attenuation of endothelial cells. However, evidence of remodeling and a lack of pores still exists in some capillaries. The glomerular capillaries of the inner cortex appear the most mature, but possess regions that are still immature when compared to the adult.     

Comparison of size of juxtamedullary and outer cortical glomeruli in normal adult kidney

Summary Abnormally large glomeruli are susceptible to hyperfiltration-associated sclerosis. We used an established morphometric method to test the general belief that juxtamedullary glomeruli are larger than those in the outer cortex, in a population with no clinical or pathological evidence of renal disease. Overall, juxtamedullary glomeruli were significantly larger, but this varied according to the amount of global glomerulosclerosis present. Global sclerosis increased with age, particularly in the outer cortex, and the ratio of juxtamedullary to outer cortical glomerular size showed a positive correlation with overall, and outer cortical, global sclerosis. Thus in the truly normal adult kidney, juxtamedullary glomeruli are not significantly larger than outer cortical glomeruli. However, global sclerosis increases with age and is most marked in the outer cortex, and this leads to compensatory enlargement of predominantly the juxtamedullary glomeruli. These findings suggest that in single kidneys, or in conditions characterised by ischaemic glomerulosclerosis such as hypertension, morphological changes related to hyperfiltration may appear first, and therefore become most severe, in juxtamedullary glomeruli.     

Effect of furosemide on local and zonal glomerular filtration rate in the rat kidney

Furosemide has been reported to produce disproportional changes in blood flow in cortical zones and to inhibit tubuloglomerular feedback (TGF), suggesting that furosemide might alter the intracortical distribution of glomerular filtrate. We have tested this hypothesis by a new method for measuring local and total glomerular filtration rate (GFR) based on proximal tubular accumulation of the basic polypeptide aprotinin (mol wt 6513). Local GFR was calculated in tissue samples dissected from outer cortex (OC), inner cortex (IC) and the corticomedullary border zone (CM) from the plasma clearances of two aprotinin tracers injected i. v. before and after a 3 min i. v. infusion of 25 mg kg^-1 furosemide. The mean of five samples from each region was used to determine zonal GFR. Isotonic saline was infused at a rate corresponding to urine flow. Furosemide reduced whole kidney GFR from 1.17 to 1.00 mL min^-1 and gave a similar reduction of renal artery blood flow. Urine flow increased from 0.6 to 17% of GFR. Haematocrit (? 0.48) and plasma protein concentration (? 55 mg mL^-1) were maintained while the arterial blood pressure tended to decline (118pL5 mmHg to 108pL6 mmHg, P < 0.05). GFR in OC, IC and CM (1.58, 1.18, 0.42 mL min^-1 g^-1) fell to 87, 88 and 88% of control after furosemide infusion respectively. The furosemide/control ratio for each sample showed a coefficient of variation of about 3%. We conclude that furosemide produced a modest GFR reduction that was uniform throughout the renal cortex. The homogenous GFR response suggests a similar TGF constriction tone in preglomerular vessels of deep and superficial nephrons.     

Tubular absorption of filtered cystatin-C in the rat kidney

As shown in previous studies, the two basic proteins aprotinin (Ap, 6.5 kDa) and cystatin (Cy, 13.3 kDa) can be used to estimate whole kidney glomerular filtration rate by measuring the renal cortical uptake relative to plasma concentration after i.v. injection. Local uptake of Ap can also be used to estimate local filtration rate, and the present experiments were undertaken to examine whether Cy would give a similar uptake pattern. Ap and Cy were labelled with 131I and 125I, respectively, and injected as an i.v. bolus. Frequent blood samples provided information on the filtered load. Five to 20 min after injection the kidney was clamped, frozen, and five tissue samples of 5-10 mg each were cut out from outer (OC), middle (MC) and inner cortex (IC) to be weighed and assessed for radioactivity. Five minute clearance ratios, Cy:Ap, were 1.36 +/- 0.04, 1.27 +/- 0.03 and 1.19 +/- 0.04 in OC, MC and IC, respectively. The higher Cy clearance was expected from a higher glomerular filtrate:plasma ratio of the less basic Cy (Donnan distribution). However, this does not explain the increase of Cy:Ap clearances going from IC to the OC. A surplus of extracellular uptake of Cy in superficial layers was excluded, leading to the following interpretation. In all cortical layers the proximal convoluted tubule, i.e. the protein uptake segment, is located more superficially than its parent glomerulus. A longer uptake segment for Cy than for Ap will therefore lead to a relative greater transfer of filtered Cy from IC to MC, and from MC to OC. Anatomical studies on single nephrons presented in another article lend strong support to this interpretation.     

Intrarenal Distribution of Blood Flow and Glomerular Filtration during Chronic Unilateral Ureteral Obstruction

Paired hydronephrotic (HN) and hypertrophic (HT) rat kidneys were studied after 6 days with complete unilateral ureteral obstruction without exposing the kidneys. Total HN renal blood flow (RBF), estimated by total microsphere (MS) uptake and from local ¹²⁵I-antipyrine (Ap) uptake, averaged about 3/sec (n=147) for the extensor digitorum communis muscle and 3.39±0.68 m/sec (n=142) for the femoral quadriceps muscle. 4 of control. HN kidney GFR was reduced to about 1/2 of control level as estimated from inulin clearance of HT kidney times the HN to HT ratio for mean single nephron filtration rate, determined by ¹⁴C-ferrocyanide. Whereas blood flow (Ap) was proportionately reduced in outer and inner cortex (OC and 1C), fractional flow to the outer medulla (OM) was doubled as compared to controls (p < 0.01). Filtration was well preserved in deep as compared to superficial glomeruli with a smaller deep nonfiltering fraction (p > 0.02). Thus the results oppose the current concept that HN is characterized by disproportionate circulatory damage to IC and OM with little or no filtration in deep nephrons. In HT kidneys average RBF (MS) and GFR rose by about 1/2. Whereas total blood flow (Ap) rose proportionately in OC and IC, it remained at control level in OM, indicating dissociation between the total RBF and GFR and the effective blood flow to the OM zone.     

Renal anatomy of the manatee,Trichechus manatus,linnaeus

The manatee kidney is com posed of several closely apposed lobes. These are formed by cortical folds (plicae corticales) that completely isolate the medullae, except where the medullae of adjacent lobes are partially fused. The cortex is continuous; its folds usually are separated, but only partially, by interlobar septa ex tending from the renal capsule. The cortex makes up ～57% of renal mass in adults and 68% in the calf. There are about 3 million glomeruli per kidney. The average is somewhat less than that expected of an adult eutherian of equal mass. The glomeruli, however, are large; they form 7.38%±1.33 of cortical mass, which is above that for at least ten unrelated adult eutherians. The number of glomeruli per gram of cortex is considerably greater in the calf than in the adult. The medullae are about 43% of renal mass. The cortico-medullary thickness ratio is 0.08 to 0.24. All terminal collecting ducts open at a crater (cra-tera cribrosa) of varying depth. Hair-pin loops occur at all levels of medulla, and apparently all loops bend at their thick segment. Cortical loops occur in the medullary rays. Vascular bundles were evident at the cortico-medullary border and thin tubules extended into the medulla from the central ends of the medullary rays (cortical) in seven out of the nine kidneys. The renal pelvis is separated from the central ends of the cortical folds by delicate fascia through which pass the interlobar vessels. There are no fornices and no infundibula. The collagenous tissue of the pelvic wall extends across most of the pelvic surface of the outer medulla.     

The pressure-flow relationship of different nephron populations in the rat.

The mechanisms behind the autoregulation of the total renal blood flow and the glomerular filtration rate are unclear. In this investigation a modified microsphere technique was applied to measure the blood flow at different depths in the renal cortex during normotensive and hypotensive conditions. No autoregulation was found in the outer cortex while it was well pronounced in the inner one. During similar conditions, glomerular capillary pressure, welling point pressure and intratubular pressure were recorded. By combining these results with the blood flow data, the preglomerular and postglomerular resistances were calculated. It was then found that the preglomerular resistance decreased and the postglomerular resistance increased when the blood pressure was lowered. The results indicate a redistribution of blood flow from the outer parts to the inner parts of the cortex when the blood pressure is decreased. The redistribution of the blood flow might explain the well known linear relationship between the arterial pressure and the urine flow. The single nephron filtration rate of the outermost glomeruli could be calculated and the results seem to indicate a non-equilibrium at the end of the glomerular capillaries.     

Factors affecting the maturation of glomerular filtration rate and renal plasma flow in the new-born dog

1. The maturation of glomerular filtration rate was studied by comparison of thirty-six new-born mongrel dogs aged 1-35 days with six adult dogs.2. Under mannitol diuresis, glomerular filtration rate (GFR) rose from 0.16 ml. min(-1).g kidney(-1) at 1 day of age to 0.34 ml. min(-1).g kidney(-1) at 1 month of age. Adult GFR averaged 0.68 ml. min(-1).g(-1). There was good correlation of GFR with arterial blood pressure (r = 0.76, P < 0.001). Part of the statistical correlation of GFR with blood pressure was found to be independent of the relationship between blood pressure and age.3. Acute increases or decreases in blood pressure resulted in parallel changes in GFR in the puppies. There was no change of GFR with change of blood pressure in adult dogs. Carotid artery clamping, independent of blood pressure changes, produced increased renal vascular resistance and decreased GFR in the pups.4. Renal plasma flow (RPF) increased from 0.70 ml. min(-1).g(-1) at 1 day of age to 1.80 ml. min(-1).g(-1) at 1 month and showed good correlation with blood pressure (r = 0.67, P < 0.001). Filtration fraction (GFR/RPF) and renal vascular resistance did not vary with age in the pup and were the same as those for the adult.5. These results support the hypothesis that maturation of GFR and RPF are closely related to maturation of arterial blood pressure in the mongrel dog. The factors other than blood pressure which also affect renal maturation in the dog still need to be more clearly defined.     

Renal Cortical Blood Redistribution after Bumetanide Related to Heterogenicity of Cortical Prostaglandin Metabolism in Dogs

Bumetanide is shown to increase renal blood flow and to augment the proportion of the cortical blood flow to middle cortex. This redistribution still takes place even when renal blood flow is maintained constant by renal artery clamping. Indomethacin pretreatment inhibits the increase of renal blood flow as well as the cortical blood redistribution. In vitro examinations of canine kidney tissue slices suggest that outer cortex and papilla are sites of prostaglandin synthesis. No differences in prostaglandin E degradation are observed within the cortex. This suggests a relative autonomy for prostaglandins in the outer cortex, whilst inner cortical areas are dependent on medullary/papillary prostaglandin E supply. The renal hemodynamic effect of bumetanide is therefore thought to be a result of a stimulation of mainly medullary/papillary prostaglandin synthesis.     

The effect of a converting enzyme inhibitor on autoregulation and intrarenal distribution of glomerular filtration in the rat

The role of the renin-angiotensin system in the autoregulation and distribution of the single nephron glomerular filtration rate (SNGFR) in anaesthetized, normotensive rats was investigated. SNGFR in outer cortical (OC) and inner cortical (IC) nephrons of the left kidney were measured with a modified Hanssen technique at three levels of renal arterial pressure (RAP): at a spontaneous arterial pressure; at a value within the autoregulatory limit, 100 mmHg; and at the lower limit of the autoregulatory range, 70 mmHg. This was done in control rats and in rats given a continuous i.v. infusion of the converting enzyme inhibitor (CEI) captopril (3 mg . h-1 X kg-1 BW). In control rats there was complete autoregulation of SNGFR in both OC and IC nephrons when RAP was reduced to 100 mmHg. Further reduction to 70 mmHg elicited different responses among the cortical layers, associated with a decrease in SNGFR. A fractional redistribution of glomerular filtration rate towards IC nephrons was evident. Administration of CEI at spontaneous RAP increased SNGFR in IC nephrons compared with values in control rats, but did not notably alter SNGFR in OC nephrons. Reduction of RAP to 100 mmHg during CEI infusion caused SNGFR to decrease below control values in both OC and IC nephrons, and the autoregulation as found in control rats was impaired. When RAP was lowered to 70 mmHg during CEI administration there was a progressive decrease in SNGFR in all cortical layers, although absolute changes were much greater in IC nephrons than in OC nephrons.(ABSTRACT TRUNCATED AT 250 WORDS)     

Microsphere size and determination of intrarenal blood flow distribution in the rat

The influence of microsphere size upon the estimation of cardiac output (CO), renal blood flow (RBF) and its cortical distribution (ICBFD) was evaluated by simultaneous injection of 8.5±0.8 m (SD) and 12.7±1.2 m (SD) spheres in control conditions and after hemorrhagic hypotension (HH rats). The values of CO and RBF were unaffected whilst the ratio of flow to outer and inner halves of cortex (OCF/ICF) was 32% higher with 12.7 m than with 8.5 m spheres in both groups.Microscopic analysis of cleared kidney slices confirmed that large spheres were more concentrated in outermost and less concentrated in innermost glomeruli than small spheres. In addition, the ratio of sphere number per outermost to that per innermost glomerulus (f _s /f _jm ), an approximation of glomerular blood flow distribution was 1.74 and 1.76 with large spheres and 0.98 and 1.06 with small spheres in control and HH rats respectively.It is concluded that the artifact due to sphere size was not minimized in low flow conditions (HH rats) and that 8.5 m spheres may be a more realistic marker of glomerular blood flow distribution in the rat than 12.7 m spheres.Attaché de Recherches I.N.S.E.R.M.     

Renal blood flow distribution at varying perfusion pressure in the alloperfused dog kidney

Tissue blood flow (TBF), its percent distribution and glomerular blood flow (GBF) were measured using labelled microspheres 15 m in diameter (M) and chicken red blood cells (CRBC) at perfusion pressures (PP) of 17.3, 12.8 and 8.0 kPa (130, 95 and 60 mm Hg) in isolated alloperfused dog kidneys. Renal blood flow (RBF) was never interrupted during the isolation. Experiments with M showed a marked inequality of the tissue blood flow in different parts of the renal cortex at a constant PP of 17.3 kPa. TBF was highest in the outermost quarter and lowest in the juxtamedullary one. Using CRBC, a homogeneous TBF was observed in the outer 3/4 of the renal cortex with a lower flow in the innermost quarter. With M, a typical percent redistribution of TBF and GBF into the inner cortical regions was indicated during PP reduction. With CRBC, this phenomenon was observed only at PP below the range of RBF autoregulation (8.0 kPa) and was much less conspicuous than with M. The smaller size and higher elasticity of CRBC as compared with M, may result in a more realistic reflection of cortical blood flow distribution. The GBF of outermost superficial glomeruli decreases, even with CRBC, with each PP reduction, the difference exhibiting only a 5% significance level. The lower limit of BF autoregulation in these glomeruli seems to be some-what higher than that of total RBF autoregulation.     

Mechanism of intrarenal blood flow redistribution after carotid artery occlusion.

Bilateral carotid artery occlusion results in an increase in mean arterial pressure, an increase in renal sympathetic nerve activity, and a redistribution of renal blood flow from inner to outer cortex. To elucidate the mechanism of the renal blood flow redistribution, carotid artery occlusion was performed in anesthetized dogs with the left kidney either having renal perfusion pressure maintained constant (aortic constriction) or having alpha-adrenergic receptor blockade (phenoxybenzamine); the right kidney of the same dog served to document the normal response. When renal perfusion pressure was maintained constant, renal blood flow distribution (microspheres) was unchanged by carotid artery occlusion. In the presence of renal alpha-adrenergic receptor blockade, carotid artery occlusion elicited the usual redistribution of renal blood flow from inner to outer cortex. The redistribution of renal blood flow observed after carotid artery occlusion is mediated by the increase in renal perfusion pressure rather than the increase in renal sympathetic nerve activity.     

Relationship between glucose and sodium excretion in the new-born dog

1. The relationship between renal glucose and sodium excretion was studied in thirty-three new-born dogs aged 1-14 days and in ten adult dogs.2. Glucose was infused into the animals at rates sufficient to produce an amount of filtered glucose at least 1.5 times the tubular transport of glucose (saturating glucose load). In both puppies and adults tubular glucose reabsorption at saturating glucose loads varied directly with the glomerular filtration rate (r = 0.54 and 0.73 respectively, P < 0.01 for both).3. In the puppy, as the fraction of filtered sodium excreted (C(Na)/C(In)) increased from 0.05 to 0.45, the ratio, renal tubular glucose transport divided by glomerular filtration rate at saturating glucose loads, (T(G)/GFR)(m), decreased from 3.7 to 1.7 mg/ml. (r = -0.75, P < 0.01). In the adult C(Na)/C(In) was below 0.08 in all experiments and (T(G)/GFR)(m) was within the 95% confidence limits predicted by regression analysis of the data from puppies. Although mean (T(G)/GFR)(m) was greater in the adult than in the puppy (P < 0.01), when puppies had C(Na)/C(In) similar to that for adults, they had (T(G)/GFR)(m) values equivalent to that for the adult.4. There was excellent correlation between glucose excretion and water excretion for both adult and new-born dogs (r = 0.93 and 0.87, respectively). However, for any glucose loss, water loss was greater in the puppy than in the adult (P < 0.01).5. During the control period total sodium excretion (per gram kidney) and C(Na)/C(In) were similar in the new-born and adult dog. However, during glucose loading, the puppies excreted more sodium and had a higher C(Na)/C(In) than did the adult, although glucose excretion was greater in the adult than in the puppy (P < 0.01 for all comparisons).6. Glomerular blood flow, as measured by radioactive microspheres, was redistributed towards inner cortical nephrons during glucose loading in the puppy. There was no such redistribution of glomerular blood flow in the adult.7. Sodium reabsorption beyond the proximal tubule was blocked with ethacrynic acid and chlorothiazide. In the puppy, the increase of C(Na)/C(In) following a glucose load was the same whether the glucose load followed control or distal blockade collections, suggesting that reductions of sodium reabsorption following a glucose load probably came from the proximal tubule. C(Na)/C(In) during glucose loading plus distal blockade was significantly (P < 0.01) higher in the puppy (0.598) than in the adult (0.280), indicating that glucose diuresis produced a greater inhibition of proximal tubular sodium reabsorption in the new-born than in the adult dog.These results support the hypothesis that the high sodium excretion rate during glucose diuresis in the new-born dogs appears to be due to the greater sensitivity of the neonatal proximal tubule to the osmotic effect of glucose. When presented with a glucose osmotic load the new-born dog diminishes net proximal sodium reabsorption more than does the adult and thus depresses tubular glucose reabsorption to a greater extent. The lower values of maximal glucose transport rates found in new-born animals may be related, therefore, to the higher fractional sodium excretion rates during glucose diuresis rather than to a diminished intrinsic glucose transport capacity in the new-born kidney.     

Glomerular calcification in hypercalcemic nephropathy

Hypercalcemic nephropathy has been classified as a tubulointerstitial renal disease. The presence of glomerular pathologic findings attributable to hypercalcemia has been observed in only a few patients and therefore has been considered an unusual finding. In the current study, calcium deposition within glomeruli was investigated in 2 patients with extreme elevations in serum calcium levels and hypercalcemic nephropathy. The study material consisted of a renal biopsy specimen from a 31-year-old woman (patient 1) who had T-cell lymphoma/leukemia and a serum calcium level of 20.2 mg/dL (5.0 mmol/L) and autopsy kidney specimens from a 19-year-old woman (patient 2) who was being evaluated for primary hyperparathyroidism and a calcium level of 18.4 mg/dL (4.6 mmol/L). The renal biopsy specimen for patient 1 exhibited calcium deposits present in the glomerular capillary basement membranes, where they were associated with segmental sclerosing lesions (21% of glomeruli). Nine percent of the cortical tubules contained calcifications. In patient 2, calcium was found in the mesangial areas in 95% of glomeruli, filling the Bowman space in 7% of glomeruli, or associated with capillary basement membranes and segmental sclerosing lesions (12% of glomeruli). Fifteen percent of cortical tubules, 4% of outer medullary tubules, and 40% of inner medullary tubules were calcified. In neither case was there immunofluorescence or electron microscopic evidence of primary glomerular disease. Thus, glomerular calcification may exceed that occurring in the cortical and outer medullary tubules and may play a significant role in the loss of renal function in hypercalcemic nephropathy. Glomerular calcinosis may also be recognized as an additional cause of segmental glomerulosclerosis and nephrotic range proteinuria in patients with extremely high levels of serum calcium.     

Radioactive microsphere distribution and single glomerular blood flow in the normal rabbit kidney

Summary Intracortical distribution of blood flow was studied in the rabbit kidney with 15 m labelled microspheres (M) injected into the left ventricule. M injection did not alter renal function. Thanks to arterial filling of left kidney with silicone rubber, efferent vascular patterns of the glomeruli could be precisely identified. Glomeruli of different populations were sampled by microdissection and their radioactivity measured. Assuming that intracortical distribution of M reflected distribution of flow to the glomeruli, individual glomerular blood flows (GBF) were determined. In hydropenic rabbits, GBF was higher in deep glomeruli providing vasa recta (G4) (193±14 nl·min^–1) than in most other superficial (G1 and G2) and deep glomeruli (G3) (190±27, 113±10 and 127±9 nl·min^–1 respectively; . The exact significance of GBF found in superficial glomeruli with straight ascending efferent arterioles supplying aglomerular suscapsular cortex (G1) was questioned because of the possible axial streaming of spheres. Afferent medulary blood flow was calculated to represent 9.0±0.9% of total renal blood flow.Attaché de Recherches I.N.S.E.R.M.     

The effect of pressor doses of Angiotensin II on autoregulation and intrarenal distribution of glomerular filtration rate in the rat

This study was designed to investigate the effect of pressor doses of exogenous Angiotensin II (AII) on autoregulation and intrarenal distribution of single nephron glomerular filtration rate (SNGFR) in anesthetized, normotensive rats. SNGFR at all cortical levels of the left kidney was measured with a modified Hanssen technique at three renal arterial pressures (RAP): Spontaneous, 100±1 mmHg and 70±1 mmHg. In control rats, both outer cortical (OC) and inner cortical (IC) nephrons showed complete autoregulation of SNGFR when RAP was redced to 100±1 mmHg. Further reduction to 70±1 mmHg resulted in different responses among the cortical layers, accompanying a decrease in SNGFR.The SNGFR_Ic/SNGFR_oc ratio increased from 1.36±0.053 to 1.52±0.047 and a fractional redistribution of glomerular filtration rate towards IC nephrons was seen. When the kidney was submitted to a RAP of 70±1 mmHg, there was a concomitant increase in central arterial pressure (CAP) from 120±4.3 to 134±3.2 mmHg. A continuous i. v.infusion of All (0.5 μg · min^-1· kg^-1 BW) increased mean arterial pressure from 123±1.4 to 142±3.8 mmHg, an effect corresponding to that on peripheral vascular resistance during reduction of RAP to 70±1 mmHg in control rats. This dose reduced SNGFR at all cortical levels, but did not per se lead to redistribution of SNGFR.A reduction in RAP to 100±1 mmHg during All administration resulted in impaired autoregulation of SNGFR in both OC and IC nephrons. Our results show that exogenous All impairs autoregulation and cannot per se have an effect mimicking the fractional redistribution seen in control rats with a reduction of RAP below the limit for autoregulation. However, in this situation intrarenally formed All may still be of importance for autoregulation and distribution of glomerular filtration rate.     

The Nature of Experimental Second-set Kidney Transport Rejection: 5. Nephrograms in Second-set Reactions and Their General Significance in Acute Renal Failure

The detailed characteristics of a nephrogram are more meaningful if studied in relation to the corresponding arteriogram. The appearance of a nephrogram in several forms of acute renal failure, including the second-set kidney transplant reaction, can be explained by a diversity of function among the nephrons. Those nephrons derived from outer cortical glomeruli are considered to be mainly geared to excretion and reabsorption whereas those nephrons derived from inner cortical glomeruli, are mainly geared to reabsorption and concentration. A nephrogram appearing in a severely oliguric or anuric kidney can be explained on the basis that outer cortical filtration has been seriously reduced or has ceased while inner cortical filtration continues but the filtrate is concentrated and reabsorbed. A kidney involved in this haemodynamic upset would more precisely be diagnosed as being in a state of acute excretory renal failure. The severe interference with excretory function is compatible with a total renal blood flow reduced by only 20-40 per cent.After several hours involvement in the severe haemodynamic upset evoked by a second-set kidney transplant reaction, inner cortical perfusion fails and at this stage no nephrogram is observed. A similar lack of a nephrogram associated with inadequate cortical perfusion was observed at 24 hr after subjecting a kidney to 2 hr total warm ischaemia which causes cortical necrosis.These principles permit a review of intravenous pyelographic techniques to be made with the recommendation of using small physiological doses of anti-diuretic substances, about half the currently recommended dose of contrast and free but not excessive access to water because the above injected doses of anti-diuretic hormone act maximally during an established water diuresis.