Deep Nephrons Research Articles

Thin Limbs of Henle and Inner Medullary Collecting Ducts are the Major Points of Flow Resistance Along the Renal Tubule

The driving force for flow along the nephron and collecting ducts is generally thought to derive from the pressure in the glomerular capsule (Bowman's space). In superficial nephrons of rats, the glomerular capsular pressure has been reported to be 12–13 mmHg under euvolemic conditions. To test the adequacy of this driving force, we calculated the theoretical pressure drop along each segment of the rat superficial renal tubule using the Hagen‐Poiseuille laminar flow equation with measured flow rates, tubule diameters, and tubule lengths. We used both a rigid tube model and an elastic tube model based on compliances from the literature. The rigid tube model predicted a net pressure drop from glomerular capsule to renal pelvis of 8.8 mmHg during antidiuresis and 15.5 mmHg during water diuresis. The latter value exceeds the measured value in the glomerular capsule. In contrast, the elastic tube model predicted a 9.5 mmHg pressure drop along the length of the renal tubule during water diuresis. In both models, the greatest flow resistance (pressure drop per unit length) was in the thin descending limb of Henle's loop and the final millimeter of the inner medullary collecting duct. We extended the elastic tube model during water diuresis to long‐looped nephrons (those with loops of Henle extending into the inner medulla). The predicted net tubular pressure drop for these nephrons was 18.3–20.3 mmHg depending on the location of the loop bend. The calculated overall flow resistance was higher in deep nephrons chiefly due to the thin descending and thin ascending limbs of Henle's loop. We do not have reliable glomerular capsular pressure values for deep nephrons. However, the glomerular capsular pressures in deep nephrons are unlikely to be substantially higher than in superficial nephrons because the single‐nephron glomerular filtration rate in deep nephrons is equal to or greater than in superficial nephrons. Thus, the calculated glomerular capsular pressure is 6–8 mmHg higher than the likely actual value with the elastic tube model. This leaves an apparent discrepancy that could be explained either by 1) an underestimate of the compliance of the thin limb segments of the long‐looped nephrons; or 2) an additional driving force for flow such as the peristaltic action of the renal pelvic contractions, which could boost the flow across the restriction points in the thin descending limbs and inner medullary collecting duct.Support or Funding InformationG.G. was a member of the 2017 NIH Summer Internship Program. V.D. was a member of the 2017 Biomedical Engineering Student Internship Program at the NIH.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

A model of calcium transport along the rat nephron

We developed a mathematical model of calcium (Ca(2+)) transport along the rat nephron to investigate the factors that promote hypercalciuria. The model is an extension of the flat medullary model of Hervy and Thomas (Am J Physiol Renal Physiol 284: F65-F81, 2003). It explicitly represents all the nephron segments beyond the proximal tubules and distinguishes between superficial and deep nephrons. It solves dynamic conservation equations to determine NaCl, urea, and Ca(2+) concentration profiles in tubules, vasa recta, and the interstitium. Calcium is known to be reabsorbed passively in the thick ascending limbs and actively in the distal convoluted (DCT) and connecting (CNT) tubules. Our model predicts that the passive diffusion of Ca(2+) from the vasa recta and loops of Henle generates a significant axial Ca(2+) concentration gradient in the medullary interstitium. In the base case, the urinary Ca(2+) concentration and fractional excretion are predicted as 2.7 mM and 0.32%, respectively. Urinary Ca(2+) excretion is found to be strongly modulated by water and NaCl reabsorption along the nephron. Our simulations also suggest that Ca(2+) molar flow and concentration profiles differ significantly between superficial and deep nephrons, such that the latter deliver less Ca(2+) to the collecting duct. Finally, our results suggest that the DCT and CNT can act to counteract upstream variations in Ca(2+) transport but not always sufficiently to prevent hypercalciuria.

Functionally induced changes in water transport in the proximal tubule segment of rat kidneys.

To eliminate freezing artifacts in the proximal tubule cells, two cryotechniques were applied to normal rat kidneys, ie, freeze substitution and special freeze drying. In addition, salt depletion and salt loading were applied to groups of rats to evaluate whether the segmental structure of the proximal tubule could be altered. In the superficial part of the renal cortex of normal kidneys, the typical first segment structure in the proximal tubule was generally present in the early postglomerular fraction of the tubule. However, in the second segment, a special cellular phenomenon was constantly present, comprising a significant intercellular space that was easily identified using a light microscope. In the third segment, in which the presence of basolateral interdigitations is minimal, the small lateral space, which was found to be present in cryopreparations between neighboring cells from the normal kidney, was found to be enlarged by heavy salt loading of short duration. It is concluded that these cryotechniques demonstrate quantitative structural variations between superficial and deep nephrons, as well as the presence of extracellular areas between the cells of the second and the third segment, representing a structural background for the essential transport of water from the proximal tubules to the peritubular capillaries.

A 42-Year-Old Woman With Flaccid Paralysis

A 42-Year-Old Woman With Flaccid Paralysis

Immunohistochemical Localization of Distinct Angiotensin II AT1 Receptor Isoforms in the Kidneys of the Sprague‐Dawley Rat and the Desert Rodent Meriones Crassus

Employing a purified lgG fraction of a polyclonal anti-AT1 receptor anti-body, raised against a synthetic octapeptide encompassing residues 14-21 of the first extracellular domain of the AT1 polypeptide, selective AT1 receptor expression was immunohistochemically demonstrable within renal structures in Sprague-Dawley (SD) rats and the desert rodent Meriones crassus. In both animal models, prominent AT1 receptor labelling was evident in renal vascular elements, particularly cortical inter-lobular arteries (IA) as well as vasa recta bundles in the inner stripe of the outer medulla. Less intense labelling was observed among peritubular capillary endothelia within the deep cortex, and at both the outer stripe and the inter-bundle regions of the inner stripe of the outer medulla. The binding of the anti-peptide anti-body was, however, lacking among glomeruli and, except for the intense labelling confined to basement membranes of Bowman's capsule of deep nephrons, was virtually absent in all renal tubular structures of both animal models. Structural assessment of the expressed AT1 receptors by two-dimensional Western blotting revealed that a spectrum of structurally distinct AT1 receptor isoforms is expressed in the renal tissues of both animal models. This spectrum was constituted by isoforms of equal size (70 kDa) but distinct pls in SD rats, and of both different sizes (67-73 kDa) and isoelectric points in M. crassus. In either species, the charge and/or size heterogeneity of AT1 receptor isoforms may be attributed in part to differential post-translational glycosylation mechanisms of the AT1 receptor polypeptide backbone. The potential for the differential glycosylation state of AT1 receptors to alter recognition properties may add another level of complexity to tissue-specific and/or species-specific mechanisms underlying angiotensin II interactions in the kidney.

Expression of Visinin-Like Protein-3 in Mouse Kidney

In renal proximal brush borders the Na/Pi cotransporter NaPi-IIa is part of a heteromultimeric complex including the PDZ proteins PDZK1 and NHERF1, which interact with the C terminus of NaPi-IIa. In this study, a yeast two-hybrid screen against the N terminus of the Na/Pi cotransporter NaPi-IIa was performed. Thereby we identified visinin-like protein-3 (VILIP-3), a member of neuronal calcium sensors. In this study, expression and protein localization of VILIP-3 in the mouse kidney was performed by immunofluorescence and RT-PCR using laser-assisted microdissected nephron segments. VILIP-3 was found to be abundant in distal and collecting ducts where it partly colocalized with calbindin D28K. In addition VILIP-3 was observed in the brush borders of proximal tubular S1 and S3 segments of both superficial and deep nephrons.

Effect of exogenous and endogenous angiotensin II on intrarenal distribution of glomerular filtration rate in rats.

Different changes in glomerular filtration rates (GFR) in deep and superficial glomeruli have been suggested to influence renal NaCl excretion and concentrating ability. Angiotensin II (AngII) has been implicated in such changes, but the experimental evidence has been conflicting, probably because of the methodological limitation of just one 'snapshot' measurement of local GFR per kidney. We have therefore studied the effect of AngII and AT(1)-receptor blockade on glomerular filtration in outer, middle and inner cortex (OC, MC and IC, respectively) in pentobarbitone-anaesthetised rats using the aprotinin (Ap) method, providing control and experimental measurements in the same kidney. Glomerular filtration rate per gram cortical tissue was measured based on 'free' glomerular filtration of Ap followed by complete tubular uptake and a 20 min sojourn in the proximal tubular cells before breakdown and incipient return to the plasma.(125)I-labelled Ap was injected I.V. to determine control Ap clearance, followed after 13 min by injection of AngII or the A1 type AngII receptor blocker losartan and 2 min thereafter by (131)I-labelled Ap to determine clearance in the experimental period. Tracer activity in frequent blood samples and in tissue samples allowed calculation of GFR in the two periods. Mean GFR control values were: 1.13 ml min(-1) in whole kidney and 1.44, 1.27 and 0.76 ml min(-1) per gram cortical tissue in OC, MC and IC, respectively. The most sensitive and comprehensive measure of altered GFR distribution is the ratio between the relative filtration change in inner versus that in outer cortex, F = (IC(E)/IC(C))/(OC(E)/OC(C)), where subscripts E and C stand for experimental and control, respectively. F values greater than 1.00 directly indicate and quantify a relatively greater increase of filtration rate in inner than in outer cortex. We found in salt-replete rats that at practically unchanged total GFR, intravenous and intra-arterial infusion of AngII increased F to 1.07 and 1.04 (P < 0.05) whereas losartan reduced F to 0.99. After pretreatment with the inhibitor of nitric oxide production L-NAME, losartan increased total GFR by 8 % and F fell to 0.95 (P < 0.05). In salt-depleted rats losartan reduced F to 0.95 (P < 0.05) at unchanged total GFR. All IC/OC changes induced by losartan were significantly different from that obtained by AngII infusions. We conclude that deep nephrons have higher postglomerular AngII tone and also higher AngII sensitivity than superficial nephrons. The better preserved GFR in deep cortex during AngII action may contribute towards maintaining the renal concentrating ability by providing NaCl for reabsorption by the ascending limb of the loop of Henle.

Evolution of experimentally induced papillary necrosis to focal segmental glomerulosclerosis and nephrotic proteinuria.

Bromoethylamine (BEA)-induced papillary necrosis is a reproducible model for analgesic nephropathy. We induced this lesion in groups of male Sprague-Dawley rats and followed the functional and histological changes for 1 year. We found that by 1 month, necrosis of the papilla was complete, glomerular filtration rate was depressed, and urine albumin excretion was increased. There was an extensive interstitial fibrosis characterized by a mononuclear cell infiltrate and patchy tubular atrophy. By 6 months, there was re-epithelialization of the papillary stump accompanied by a marked increase in albuminuria and an improvement in concentrating ability. Changes seen at 9 months were more advanced. There was extensive cortical fibrosis manifested by pitting of the surface of the kidney. At 1 year, renal function remained impaired (creatinine clearance reduced by 65% to 0.26 mL/min/100 g), and the animals were now markedly nephrotic, with albuminuria of 254 mg of albumin/24 h. In the BEA rats, there was selective destruction of the deep nephrons leading to an increase in the volume-ratio of superficial to deep nephrons. Glomerular changes, affecting approximately 60% of the glomeruli, were characteristic of focal segmental glomerular sclerosis. This model of papillary necrosis/interstitial fibrosis is associated with chronic renal insufficiency and leads to the development of focal glomerular sclerosis and nephrotic proteinuria by 6 to 12 months after its induction.

Renal tubular lithium reabsorption in potassium-depleted rats.

1. In order to identify the tubular sites responsible for the reduced fractional excretion of lithium (FELi) during potassium depletion, free-flow micropuncture was performed in anaesthetized rats that had been fed a low potassium (low-K+) diet or a control diet for 5-6 days. FELi in low-K+ rats was 0.09 +/- 0.02, compared with 0.25 +/- 0.01 in control animals. 2. Fractional water reabsorption in proximal convoluted tubules was enhanced in potassium-depleted rats. However, fractional lithium reabsorption was not. Consequently, the tubular fluid-to-plasma lithium concentration ratio at the late proximal convoluted tubule was raised in the low-K+ animals (1.50 +/- 0.03 vs. 1.18 +/- 0.02; P < 0.001). 3. Fractional lithium delivery to the early distal tubule in low-K+ rats (0.31 +/- 0.01) was similar to that in control animals (0.30 +/- 0.02). However, whereas in control rats there was no significant difference between early and late distal tubular deliveries of lithium, late distal fractional lithium delivery in the low-K+ group was reduced markedly (to 0.10 +/- 0.01). 4. Treatment of potassium-depleted rats with amiloride had no effect on lithium reabsorption in the proximal convoluted tubule or loop of Henle. However, fractional lithium delivery to the end of the distal tubule was increased slightly (to 0.15 +/- 0.02; P < 0.05) and FELi was increased substantially (to 0.22 +/- 0.01; P < 0.001). 5. It is concluded that two factors contribute to the reduced FELi seen in potassium-depleted rats: lithium reabsorption in the superficial distal tubules and amiloride-sensitive lithium reabsorption in the collecting ducts. The data also suggest heterogeneity with respect to lithium handling between superficial and deep nephrons during potassium depletion.

Differential expression of angiotensin II receptors during early renal morphogenesis.

Angiotensin II (ANG II) and its receptors, AT1 and AT2, may modulate kidney development. To define the temporal and spatial distribution of AT1 and AT2 receptors and their mRNAs during nephrogenesis, fetal, newborn, and adult rat kidneys were studied using reverse transcription-polymerase chain reaction and radioligand binding autoradiography. AT1 expression was minimal at embryonic day 14 (E14), highly expressed at E20, and persisted into adulthood. Conversely, AT2 expression was easily detected from E14 through postnatal day 7 but was undetectable by postnatal day 28. At E14, 76% of the receptors were AT2, 24% were AT1, and both were found in the undifferentiated mesenchyme. By E17, AT1 comprised 40% of the receptors and localized to mature nephron segments, whereas AT2 remained within both condensed mesenchyme and differentiating epithelia. The dissociation constants for AT1 and AT2 were 0.45 +/- 0.09 nM and 0.73 +/- 0.15 nM, respectively, at E17, similar to adult values. By E20, AT1 and AT2 colocalized to the outer medullary stripe, deep nephrons, medullary rays, and blood vessels, while AT2 continued to predominate in the actively differentiating cortex. The presence of both subtypes of receptors capable of binding ANG II during early nephrogenesis and the time-dependent and structure-specific regulation of receptor localization confirm a regulated developmental program for receptor expression and suggest important roles for AT1 and AT2 in renal morphogenesis.

Pathophysiology of the renal acidification defect present in the syndrome of familial hypomagnesaemia-hypercalciuria.

A distal acidification defect is frequently observed in the syndrome of familial hypomagnesaemia-hypercalciuria and hence this condition can be confused with primary distal renal tubular acidosis (RTA). This study demonstrates that in four unrelated patients with familial hypomagnesaemia-hypercalciuria the acidification defect is functionally different from that present in primary distal RTA. All patients exhibited hypomagnesaemia, hypermagnesuria, hypercalciuria, hyposthenuria, nephrocalcinosis and slight reduction of glomerular filtration rate (GFR). A moderate degree of metabolic acidosis was also present and basal data showed an inappropriately high urine pH (5.7-5.9) and a positive urine anion gap (Na + K-Cl = 11-28 mmol/l). Stimulation of distal acidification induced a fall in urine pH (4.7-5.6), but ammonium excretion remained low despite factoring by GFR (26-46 mumol/min per 1.73 m2, 35-54 mumol/100 ml GF). The urine to blood PCO2 gradient also remained low after sodium bicarbonate loading (1.3-17.7 mmHg). These results are best explained by both defective ammonia transfer to the deep nephron and impaired hydrogen ion secretion at the level of the medullary collecting duct, and probably are secondary effects of the medullary interstitial nephropathy.

Expression of Na-P(i) cotransport in rat kidney: localization by RT-PCR and immunohistochemistry.

We have recently identified a rat kidney cortex Na-dependent transport system for phosphate (P(i)) by expression cloning (NaP(i)-2) (S. Magagnin, A. Werner, D. Markovich, V. Sorribas, G. Stange, J. Biber, and H. Murer. Proc. Natl. Acad. Sci. USA 90: 5979, 1993). In this study we have used reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry to establish the sites of expression of the NaP(i)-2-related mRNA and protein. RT-PCR was performed with single microdissected nephron segments. From these experiments we conclude that NaP(i)-2 mRNA is predominantly expressed in the proximal tubules of superficial and deep nephrons. No NaP(i)-2 mRNA was detected in the thick ascending limb of Henle's loop; however, faint NaP(i)-2 related PCR products were also observed in collecting ducts. Expression of the NaP(i)-2 protein was examined with the use of polyclonal antibodies raised against synthetic NaP(i)-2-derived peptides. Strong specific anti-NaP(i)-2 antiserum-mediated immunofluorescence was found in the convoluted part of proximal tubules and gradually decreased along the straight part. Immunofluorescence indicated that the NaP(i)-2 protein is present in the brush border of proximal tubular cells. In addition, NaP(i)-2-specific immunofluorescence was also observed in subapical vesicles. The described distribution of the NaP(i)-2 protein is in agreement with previously described nephron sites of P(i) reabsorption in the rat kidney and therefore suggests that the NaP(i)-2 transport system represents an Na-P(i) cotransporter involved in proximal tubular apical transport of phosphate.

Localization of NaPi-1, a Na/Pi cotransporter, in rabbit kidney proximal tubules. II. Localization by immunohistochemistry.

Polyclonal antibodies have been raised against a C-terminal peptide of NaPi-1, a recently cloned Na-Pi cotransport system of rabbit kidney cortex with a predicted (unglycosylated) molecular mass of 52 kDa. By Western blot analysis using brush-border membranes isolated from rabbit kidney cortex, two proteins with apparent molecular masses of 64 kDa and 35 kDa were specifically recognized (peptide protectable) by the antiserum obtained. The 64-kDa protein was found to migrate in parallel with the luminal membrane during separation by free-flow electrophoresis of brush-border and basolateral membranes. In immunofluorescence studies using cryostat sections of rabbit kidney, specific binding of antibodies was observed in proximal tubules (including S1, S2 and S3 segments) of superficial and deep nephrons. Anti-(NaPi-1)-antibody-mediated fluorescence was restricted to the brush border of proximal tubular cells. No specific immunoreaction was observed in other tubular segments. The results suggest that the native NaPi-1-related protein (Na-Pi cotransport system) has an apparent molecular mass of 64 kDa and is uniformly expressed in the apical membrane of proximal tubules of all nephron generations in the rabbit kidney. Immunohistochemical localization of the Na-Pi cotransport system NaPi-1 confirms the segmental localization within the nephron of NaPi-1-related mRNA as revealed by the reverse transcriptase/polymerase chain reaction (see preceding paper).

Simulation of lithium transport along the thin segments of Henle's loop

Although the renal clearance of lithium is widely used as an index of sodium and water delivery to the end of the proximal tubule, micropuncture studies of superficial nephrons suggest that lithium may be reabsorbed additionally in the loop of Henle. In order to examine the possibility of lithium transport in the thin loop segments of deep nephrons, we conducted a computer simulation study using a modification of the mathematical model reported previously. The data for the model were obtained from measurements of osmolality and electrolyte concentrations in systemic plasma and renal papillary interstitial fluid of control and furosemide-treated rats. Papillary interstitium/plasma Li+ concentration ratios were 3.23 and 1.48 in the control and the furosemide group, respectively. Assuming that solute concentration in the renal medulla increases as an exponential function, and applying phenomenological coefficients obtained from hamsters, the transport profiles of Li+ along the thin loop segments were calculated to be very similar to those of Na+. In the control group, about 82% of delivered Li+ was reabsorbed along the entire thin loop segments, with all segments contributing equally. This value may represent the highest possible capacity of the thin loop segments. In the furosemide group, Li+ reabsorption in the thin loop was reduced to 31% of delivered Li+. From these analyses, we conclude that an appreciable amount of lithium may be reabsorbed in the thin loop segments of long-looped nephrons by passive mechanisms. Furosemide inhibits Li+ reabsorption by dissipating the osmotic concentration gradient in the renal medulla.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of renal medullary circulation on arterial pressure

PRESSURE-NATRIURESIS EFFECTS IN HYPERTENSION: Considerable advances have been made in our understanding of pressure-natriuresis and the effects of this mechanism in hypertension. We have shown that in the absence of changes in neural and endocrine factors, sodium and water excretion doubled when arterial pressure was increased by only 10 mmHg. These responses were greatly blunted or obscured by elevations in renal sympathetic tone, infusion of the vasoconstrictors angiotensin and vasopressin or by inhibition of paracrine factors such as eicosanoids and nitric oxide. The pressure-natriuresis response is closely associated with changes in papillary blood flow as determined by laser-Doppler flowmetry. In volume-expanded rats, papillary blood flow is not well autoregulated, which results in elevations of vasa recta capillary pressure and renal interstitial fluid pressure. The increased interstitial fluid pressure is transmitted from the medulla to the cortex in the encapsulated organ and is associated with inhibition of sodium transport in the proximal tubule and/or the thin descending loop of Henle of deep nephrons. Selective reductions in medullary blood flow by infusion of the nitric oxide inhibitor N6-nitro-L-arginine methylester (L-NAME) into the renal medullary interstitial space resulted in decreased interstitial fluid pressure and reduced sodium excretion. The mechanisms by which small elevations in renal interstitial fluid pressure alter tubular sodium reabsorption remain to be determined. PRESSURE-NATRIURESIS EFFECTS IN HYPERTENSIVE RATS: Our studies have also shown that the pressure-natriuresis response is blunted in spontaneously hypertensive rats (SHR) compared to normotensive Wistar-Kyoto (WKY) rats. This abnormality is associated with shifts in the relationships among papillary flow, renal interstitial pressure and renal perfusion pressure towards higher pressures. The calcium antagonist nisoldipine corrected the defect in vasa recta hemodynamics in SHR and normalized relationships among sodium excretion, renal interstitial pressure and renal perfusion pressure. These studies indicate that sodium and water excretion is very sensitive to small changes in renal perfusion pressure due to associated changes in papillary blood flow, and that alterations in medullary hemodynamics can have an important effect on the relationship between arterial pressure and sodium and water excretion.

Nitric oxide modulates vascular tone in preglomerular arterioles.

Blockade of nitric oxide reduces renal blood flow, but the site or sites at which nitric oxide alters renal vascular resistance are unknown. The effects of N omega-nitro-L-arginine (100 microM), an inhibitor of nitric oxide synthesis, on the pressure-diameter relation of renal arterioles was studied using a rat juxtamedullary microvascular preparation perfused in vitro with a physiological salt solution containing 5% albumin. The basal diameters of the main arcuate and interlobular arteries and the proximal and distal afferent arterioles averaged 438 +/- 26, 64 +/- 4, 30 +/- 1, and 20 +/- 1 microns, respectively, at a perfusion pressure of 80 mm Hg. The diameters of the arcuate and interlobular arteries increased by 14 +/- 2% and 7 +/- 2%, whereas the proximal and distal afferent arterioles decreased by 3 +/- 1% and 7 +/- 2% when perfusion pressure was elevated to 160 mm Hg. Nitro-arginine had no effect on the basal diameters of arcuate and interlobular arteries. Nitro-arginine reduced the diameters of afferent arterioles by 7 +/- 2% at all perfusion pressures studied. Nitro-arginine increased active vascular tone in the interlobular artery and afferent arterioles and enhanced autoregulation of glomerular capillary pressure. L-Arginine (1 mM), the precursor to nitric oxide production, reversed the effects of nitro-arginine. These findings suggest that nitric oxide modulates vascular tone of the interlobular artery and afferent arterioles of deep nephrons and influences the ability of the preglomerular vasculature to autoregulate glomerular capillary pressure.

Acute and chronic changes in renal function following unilateral nephrectomy

Free-flow micropuncture was used to assess proximal and distal tubular function in rats immediately (2 to 5 hours), five days and 30 days after uninephrectomy (UN); results were compared with those in sham-operated littermates. Excretion rates of water, sodium and potassium were approximately doubled in the remaining kidney of UN rats. Two to five hours after UN there were small increases in glomerular filtration rate (GFR) and single nephron GFR which at this stage were not accompanied by an increase in absolute proximal reabsorption; that is, fractional proximal reabsorption fell. After five days, GFR and single nephron GFR had increased further; at this stage absolute proximal reabsorption was also significantly elevated. After 30 days, kidney weight, GFR, single nephron GFR and absolute proximal reabsorption had all increased by approximately 40%, and glomerulotubular balance in the proximal tubule had been fully restored. Data derived from distal tubular collections indicated that at every stage after UN: (a) fluid delivery to both early and late distal puncture sites was increased; (b) in contrast, there was no increase in sodium delivery to the late distal tubule, suggesting that the natriuresis resulted from reduced sodium reabsorption beyond the distal tubule and/or increased delivery of sodium from deep nephrons; and (c) there was a marked increase in potassium secretion into the accessible portion of the distal tubule which was more than adequate to explain the observed kaliuresis.

Sodium handling by deep nephrons and the terminal collecting duct in glomerulonephritis

The present study was designed to characterize the effects of anti-glomerular basement membrane (anti-GBM) glomerulonephritis (GN) on sodium handling by surface nephrons, deep nephrons and the terminal collecting duct segment. Studies were performed in rats during hydropenia and volume expansion. In hydropenia, the glomerular filtration rate (GFR) and sodium excretion tended to be lower in rats with GN than in controls. However, the major differences between the control and GN animals were seen in volume expansion. In the volume expanded groups fractional excretion of sodium was greater in controls (3.20 +/- 0.51%) than in GN (1.20 +/- 0.36%, P less than 0.01). Despite this, delivery to end proximal sites was similar in the two groups in absolute terms and higher in the expanded GN group compared to the expanded controls. Absolute sodium delivery to the bend of the loop of Henle in the expanded GN rats was decreased in absolute terms but increased in fractional terms compared to expanded controls. However, fractional delivery of sodium to the base of the terminal collecting duct was less in GN (3.71 +/- 1.39%) than in controls (7.19 +/- 0.96%, P less than 0.002). In both groups, fractional delivery between tip of the collecting duct fell compared to base (P less than 0.05) but delivery to the tip was again greater in controls (5.49 +/- 1.08%) than in GN (1.51 +/- 0.47%). In GN 62.6 +/- 5.0% of delivered sodium was reabsorbed between collecting duct sites, nearly twofold that of controls (28.8 +/- 9.4%, P less than 0.01). Thus, fractional sodium reabsorption in the collecting duct was enhanced by GN.

Alterations in Renal Medullary Hemodynamics and the Pressure-Natriuretic Response in Genetic Hypertension

The concept that the kidney plays a major role in the long-term control of arterial pressure is based on the pressure-natriuretic response. According to this hypothesis, hypertension can only develop when the relationship between sodium excretion and arterial pressure is altered. Transplantation studies have indicated that some form of renal dysfunction underlies the development of genetic forms of hypertension in the spontaneously hypertensive rat (SHR) and in the Dahl salt-sensitive (S) rat. Nonetheless, the factors responsible for "resetting the kidney in hypertension" remain unknown. We have reported that the pressure-natriuretic relationships of SHR and Dahl S rats of the Brookhaven and Rapp strains are shifted toward higher pressures prior to the development of the disease. Papillary blood flow is also reduced in very young "prehypertensive" SHR. Recent studies on the mechanism of pressure-diuresis indicate that it is mediated by inhibition of sodium reabsorption in the proximal tubule and/or thin descending limb of Henle of deep nephrons. It is also associated with changes in renal interstitial pressure and the pressure and flow in the vasa recta circulation. These observations suggest that an elevation in renal medullary vascular resistance may be responsible for shifting the pressure-natriuresis relationship toward higher pressures in hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of Residual Glomerular Function in Experimental Papillary Necrosis and Renal Infarction

The purpose of this study was to examine the course of residual glomerular function in two models of renal ablation both with equivalent degrees of nephron reduction (1 1/3 nephrectomy). The remnant group underwent right nephrectomy and infarction of one third of the left kidney, yielding constant proportions of remnant deep and superficial nephrons, while the bromoethylamine (BEA) group underwent right nephrectomy and chemical ablation by BEA (50 mg intravenously [IV]) of the deep nephrons of the left kidney, leaving superficial nephrons. Ten weeks following ablation, greater whole kidney permselective defects indicative of worse injury occurred in the remnant group compared with the BEA group, as manifested by increased excretion of total protein (.65 +/- .14 v .23 +/- .04 g/d [65 +/- 14 v 23 +/- 4 mg/24 h]; P less than 0.05) and greater fractional clearance of albumin (71.8 +/- 42.1 v 9.0 +/- 3.4 X 10(-4); P less than 0.05) and IgG (17.9 +/- 10.2 v 3.6 +/- 1.2 x 10(-4); P less than 0.05). Glomerular filtration rate (GFR) and renal plasma flow (RPF) were similar in the ablated groups, but lower than a sham-operated control group. Superficial single nephron GFR (SNGFR) and mean glomerular capillary pressure (PGC) were elevated similarly in the ablated groups compared with the control group. Based on the differences in the two models, the site of the increased proteinuria in the remnant group could be the deep nephrons and/or the nephrons adjacent to the scar.