Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Nephrons”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 37 records · Page 2Linked to original sources
PubMed1998

In vitro branching tubulogenesis: implications for developmental and cystic disorders, nephron number, renal repair, and nephron engineering.

Branching tubulogenesis of the ureteric bud is critically important for kidney development. Recent findings using three-dimensional cell culture systems for in vitro branching tubulogenesis are likely to shed light on the mechanisms of ureteric bud morphogenesis. Here, we try to unify these findings with those obtained using genetic approaches and organ culture of the embryonic kidney into a working model of ureteric bud branching tubulogenesis. It appears that the balance between branching tubulogenesis facilitating growth factors such as epidermal growth factor receptor ligands, hepatocyte growth factor, insulin-like growth factors, and inhibitory growth factors such as transforming growth factor beta family members may regulate branching morphogenesis. Growth factors induce epithelial cell proliferation, migration, and modulate the expression of a variety of proteins. Downstream in the growth factor-mediated tubulogenesis pathway, extracellular proteases, protease inhibitors, extracellular matrix proteins, and integrins are likely to act as effectors and regulators of branching tubulogenesis. Discussed in some detail are the relevance of insights gleaned from in vitro models of branching tubulogenesis to congenital urogenital abnormalities, cystic kidney diseases, oligonephropathies and hypertension, tubular cell regeneration after injury, and tubular engineering.

Animals↗
PubMed2000

Immunomorphometric studies of proteinuria in individual deep and superficial nephrons of rats.

Heterogeneity of structure and function among nephrons is a well-recognized feature of chronic renal diseases. However, only a small number of superficial nephrons per kidney are accessible for micropuncture analysis and relationships of proteinuria to structural change in individual nephrons of experimental models are not clearly established. To directly evaluate proteinuria in many individual nephrons, we developed an immunomorphometric method of analysis. This method is based on the uniformly abundant renal synthesis of Tamm-Horsfall protein (THP) in the thick ascending limb of Henle's loop (TAL). Luminal rabbit immunoglobulin G (IgG) deposits are formed in TALs of proteinuric nephrons in rats injected with heterologous IgG anti-THP antibodies. This immunomorphometric luminal deposit method of assessing proteinuria was previously validated through analysis of heterologous immune complex nephropathy. Glomerular dysfunction in several models-spontaneously hypertensive rats (SHR), aging Sprague-Dawley (SD) rats, rats with adriamycin nephropathy (ADR), and rats subjected to subtotal nephrectomy (NX)-was characterized by immunomorphometric analysis after injection of anti-THP antibodies. Luminal IgG deposits were used to identify nephrons with increased proteinuria. Nephrons were identified histologically as either long looped (LL) or short looped (SL), and frequency of luminal deposits in these nephrons was determined. Glomerular size and sclerosis in deep and superficial zones of renal cortex were determined. Luminal deposits in LL nephrons were more frequent than luminal deposits in SL nephrons in SHRs (p < .001) and aging rats (p < .001) and SL nephrons in ADR rats (p < .02). Whole kidney levels of albuminuria correlated closely with the frequency of luminal deposits in both LL and SL nephrons of SHRs and ADR rats and in LL nephrons of aging rats (p < .005). In contrast, LL and SL deposits were equal in NX rats and did not correlate with albuminuria. A majority of luminal deposits extended beyond the first medullary TAL zone of NX rats, but was confined to this zone in the other 3 models. Deep cortical glomeruli were larger with more glomerulosclerosis than superficial cortical glomeruli. Albuminuria correlated with sclerosis of both deep (p < .002) and superficial (p < .01) glomeruli in NX rats, but not in the other three models. These studies provide a detailed characterization of a new method that allows comparison of proteinuria derived from deep and superficial nephrons. They also provide evidence that pathogenesis of the glomerulosclerosis in NX rats differs from that of the other three models. Glomerulosclerosis was closely linked to the overall level of albuminuria in NX rats, but not to luminal deposits. In the other three models, albuminuria and luminal deposits were closely linked but did not correlate with glomerulosclerosis. Furthermore, LL and SL nephron proteinuria of NX rats was comparable while LL proteinuria was markedly greater than SL proteinuria in the other three models. The luminal deposit method provides a new way to analyze heterogeneity of proteinuria among nephrons and the mechanisms underlying structural change in experimental glomerular diseases.

Animals↗
PubMed1988

On the renal basis for essential hypertension: nephron heterogeneity with discordant renin secretion and sodium excretion causing a hypertensive vasoconstriction-volume relationship.

We propose herein that there are two functionally abnormal nephron populations in essential hypertension: (1) a group of ischemic nephrons with impaired sodium excretion which chronically hypersecrete renin. Numerically, these ischemic nephrons comprise a minor subgroup since most patients with essential hypertension exhibit no overt evidence of renal insufficiency. (2) In reaction to this, a more numerous group of normal nephrons appears in adaptive hypernatriuresis. They have an increased distal sodium supply and consequently, a chronically suppressed renin secretion. One difference between patients with renovascular hypertension and those with essential hypertension is the intermingling of these two populations of nephrons. In our hypothesis, the adapting hyperfiltering normal nephrons accomplish the hypernatriuresis in response to saline infusion, that is characteristic of all essential hypertension. However, the unsuppressed secretion of renin, that arises from the ischemic nephron population attenuates this compensatory natriuresis in the following ways: (1) by inappropriately acting on the hyperfiltering nephrons to enhance proximal tubular sodium reabsorption; (2) by activating TGF-mediated afferent constriction in these nephrons, and (3) simultaneously, the reactive secretion of renin from ischemic nephrons is diluted by non-participation of the adapting hypernatriuretic nephrons so that plasma renin settles at a level which is insufficient to fully compensate GFR in the ischemic nephrons. These adaptive responses provide a basis for the observation that the inhibition of renin activity with converting enzyme inhibitors in essential hypertension increases renal blood flow and sodium excretion. They also explain why converting enzyme inhibitors can effectively reduce blood pressure, even when renin levels are not absolutely elevated, since any circulating renin imposed upon the adapting hypernatriuretic nephrons inappropriately impairs their sodium excretion. In addition, the theory explains why basal renin secretion is either not suppressed or inadequately suppressed in patients with essential hypertension. As a result, whole kidney homeostatic function is compromised because individual nephrons are responding to their individual stimuli to fulfil their individual need, rather than acting in concert with other nephrons. The net effect of this uncoordinated response is to shift total renal function so that systemic arterial hypertension is sustained by abnormal sodium retention for the inappropriately high plasma renin level, or vice versa.(ABSTRACT TRUNCATED AT 400 WORDS)

Homeostasis↗
PubMed1991

[Development of various nephron populations in birds during ontogenesis].

Microanatomy of nephrons during ontogenesis has been studied in domestic hens. In the bird kidneys, as well as in mammalian kidneys, three populations of nephrons can be detected: juxtamedullary, or deep nephrons, superficial and situating between them intracortical nephrons. In formation of the bird renal medulla only loops of the juxtamedullary nephrons participate. During ontogenesis in the kidneys of birds, like in mammalians, juxtamedullary nephrons are the first to be formed; they can be obtained from kidneys of 14-day-old chicken embryos, however, a complete formation of the nephron structure is terminated after hatching. During development the length of the juxtamedullary nephrons increases nearly by one order, while the length of the superficial and intracortical nephrons increases no more than twice. The diameter of the glomeruli in the juxtamedullary nephrons during development increases nearly twice, in the superficial and intracortical nephrons only a slight increase is noted. A relative length of the proximal canaliculus of the intracortical and superficial nephrons gradually increases during ontogenesis and practically does not change in the juxtamedullary nephrons, in them the nephron loop becomes longer. The developmental pattern in various parts of the superficial, intracortical and juxtamedullary nephrons in general features is similar in mammalians and birds.

Age Factors↗
PubMed1987

Synchronization of proximal intratubular pressure oscillations: evidence for interaction between nephrons.

Previous studies in rat kidneys have demonstrated that oscillations in the proximal intratubular pressure are a prominent feature of the tubulo-glomerular feedback mechanism (TGF) operating during free flow conditions. The purpose of the present study was to investigate whether a subpopulation of synchronized, interacting nephrons could be detected. In group A nephrons, i.e., nephrons with a high probability of having their afferent arterioles arising from the same interlobular artery, 29 out of 33 pairs of nephrons were found to show synchronized pressure oscillations. In group B nephrons, not expected to have this common origin of their afferent arterioles, only 1 out of 23 pairs was found to be synchronized. The standard deviation of the frequency differences was 0.063 cycles per minute in group A nephron pairs and 0.202 cycles per minute in group B pairs (p less than 0.05), showing the greater homogeneity in frequency in group A. Furthermore, nephrons having synchronized pressure oscillations were found to interact with each other. Thus, perturbation of the proximal tubular pressure oscillations in one nephron by loop microperfusion affected the amplitude of the pressure oscillations in the non-perfused nephron; and reactivation of pressure oscillations in one nephron was followed by reactivation of oscillations in the non-perfused nephron. Thus, the present results show that there exists a well defined subpopulation of nephrons, in which the TGF-mediated proximal pressure oscillations are synchronized. This synchronization is a result of interaction between the different nephrons.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2006

The role of nephron sparing surgery for metastatic (pM1) renal cell carcinoma.

PURPOSE: Studies have demonstrated increased time to progression when cytoreductive nephrectomy is performed for metastatic renal cell carcinoma. We evaluated the role of nephron sparing surgery in these patients. MATERIALS AND METHODS: We selected all patients with pM1 renal cell carcinoma treated with nephron sparing surgery or radical nephrectomy, and all patients with pM0 renal cell carcinoma undergoing nephron sparing surgery for solitary kidney from 1970 to 2002 from the Mayo Clinic Nephrectomy Registry. RESULTS: We identified 16 patients who underwent nephron sparing surgery for pM1 renal cell carcinoma. Solitary kidney was present in 12, 3 had bilateral synchronous disease and 1 had elective nephron sparing surgery. Cancer specific survival rates at 1, 3 and 5 years were 81%, 49% and 49%, respectively. We identified 404 patients who underwent radical nephrectomy for pM1 renal cell carcinoma. Cancer specific survival rates at 1, 3 and 5 years were 51%, 21% and 13%, respectively. The pM1 nephron sparing surgery for solitary kidney cases were more likely to have early (33% vs 10%, p = 0.009) or late (50% vs 19%, p = 0.018) complications compared with pM1 radical nephrectomy cases. There were no significant differences in early (p = 0.475) or late (p = 0.350) complications between pM1 nephron sparing surgery cases and 139 pM0 nephron sparing surgery cases. CONCLUSIONS: Cancer specific survival rates in pM1 nephron sparing surgery cases were comparable to pM1 radical nephrectomy cases. Although there were differences in early and late complications between the pM1 nephron sparing surgery and pM1 radical nephrectomy groups, there were no differences when compared with imperative pM0 nephron sparing surgery cases. This study demonstrates that nephron sparing surgery can achieve adequate cytoreductive therapy while preserving renal function, with postoperative complication rates similar to those of pM0 nephron sparing surgery cases.

Aged↗
PubMed1978

Deep nephron function after release of acute unilateral ureteral obstruction in the young rat.

The effects of acute unilateral ureteral obstruction (UUO) of 18 h duration on deep nephron function was evaluated in 14 weanling rats with the technique of micropuncture. After release of UUO, 3.4 +/- 0.66% (SE) of the filtered water remained at the tip of the collecting duct nearly fivefold greater than in controls (0.75 +/- 0.10%). Similar differences were seen in fractional sodium that remained at this site. The ratio of tubular fluid osmolality to that of plasma was also reduced in the UUO group (1.53 +/- 0.06 vs. 4.60 +/- 0.26 in controls, P less than 0.001). Single nephron glomerular filtration rate of cortical and deep nephrons was significantly less (P less than 0.001) after release of UUO. Although the percentage of filtering nephrons was significantly reduced in both nephron populations, the decline in glomerular filtration rate was greater in cortical than in juxtamedullary nephrons (cortical:juxtamedullary nephrons = 27.6 +/- 4.5% vs. 53.3 +/- 5.2% in controls, P less than 0.005) which suggests that single nephron glomerular filtration rate is redistributed to deep nephrons after release of UUO. In contrast to cortical nephrons, the amount of tubular fluid which remains near the bend of the loop of Henle of deep nephrons was greater after release of UUO. This appeared to be the result of a decrease in the reabsorption of both water (tubular fluid:plasma inulin = 2.41 +/- 0.16 vs. 7.94 +/- 0.69 in controls, P less than 0.001) and sodium (52.3 +/- 4% vs. 40.7 +/- 2.9% of the filtered sodium in controls, P less than 0.02). It is suggested that this altered reabsorption occurs along both the proximal tubule and descending limb of the loop of Henle of juxtamedullary nephrons. Inner medullary plasma flow (IMPF), as measured with the [125I]albumin-accumulation technique, was significantly depressed before release of UUO, but exceeded control values 90 min postrelease. Such changes imply that the filtration fraction of deep nephrons is decreased and that physical factors in the proximal tubular reabsorption of sodium have been altered. When papillary solute content was measured before release of UUO it was low (428 +/- 23 vs. 1,205 +/- 106 mosmol/kg in controls, P less than 0.001) which indicates that the decline in papillary osmolality is not a consequence of the increased IMPF seen after ureteral release, but rather precedes it. In fact, the decline in papillary osmolality may contribute to the increase in IMPF after release of UUO and to the decreased reabsorption of fluid along the descending limb of the loop of Henle.

Animals↗
PubMed1997

The pathologic physiology of chronic Bright's disease. An exposition of the "intact nephron hypothesis".

Clinical and experimental data relating to the functional capacity of the surviving nephrons of the chronically diseased kidney for the most part support the thesis that these nephrons retain their essential functional integrity regardless of the nature of the underlying form of chronic Bright's disease. There are instances in which specific alterations of function correlate with pathologic involvement of a particular site of the nephron but these appear to represent the exceptions, and in general the more advanced the disease becomes, the less evident are the differentiating features. Studies on dogs with unilateral renal disease indicate that the functional capacity of the nephrons of the diseased kidney parallels that of the nephrons of the contralateral normal kidney. These data tend to exclude widespread intrinsic damage to the functioning nephrons by the underlying pathologic processes. From these observations, as well as from certain supporting clinical and experimental observations, it is suggested that the majority of surviving nephrons in the patient with bilateral renal disease similarly are functionally intact. Concepts of the pathologic physiology of the kidney, based on the "intact nephron hypothesis", are presented. Within the framework of this hypothesis it is concluded that (1) the diseased kidney consists of a diminished number of nephrons, most of which retain essentially normal functional abilities; (2) certain of the apparent abnormalities in function in bilateral renal disease may relate to adaptive changes imposed by the decreased nephron population and the attendant derangements in body fluids rather than to structural distortion of nephrons; (3) the over-all flexibility of the diseased kidney decreases as the number of constituent nephrons decreases; but (4) there is an orderly and predictable pattern of excretion for all substances.

Animals↗
PubMed1992

Tubule-tubule and tubule-arteriole contacts in rat kidney distal nephrons. A morphologic study based on computer-assisted three-dimensional reconstructions.

BACKGROUND: Functional investigations of the tubulo-glomerular feedback mechanism have indicated the existence of a contact between the distal nephron and the macula densa region. The structural justification of such a contact is investigated. EXPERIMENTAL DESIGN: Tubule-tubule and tubule-arteriole contacts were investigated in distal nephrons from normal rat kidneys. Computer-assisted three-dimensional reconstructions of distal nephrons were made from serial sections of renal cortical tissue and selected sections were examined by electron microscopy. RESULTS: In 14 of 15 reconstructed nephrons, the distal convoluted tubule or the connecting tubule approached the macula densa region. A wall-to-wall contact between two tubules corresponding to a three-dimensional distance below 28 microns between the axes of the two tubules was found in only five of the reconstructed tubules. The distal nephron contacts to afferent and efferent arterioles of the same nephron were also examined. The efferent arteriole revealed no consistent contacts but the afferent arteriole contacted the distal convoluted tubule/connecting tubules consistently in all 10 of the superficial nephrons and in 3 of 5 midcortical nephrons. Electron microscopy confirmed a close contact between the distal tubule and the afferent arteriole in superficial nephrons and small nerves were often found at or near the site of contact, but the morphology at the site of contact was not unique. The arteriole contacts were made with late distal convoluted tubules, connecting tubules, or cortical collecting ducts. CONCLUSIONS: In conclusion, the present study shows that tubule-tubule contacts are inconsistent between the macula densa region and the distal nephron but that the tubule-afferent arteriole contact is consistent and close in superficial nephrons. This morphology is compatible with the existence of a feedback mechanism between the superficial distal nephron and the afferent arteriole, apart from the one located at the juxtaglomerular apparatus.

Animals↗
PubMed1989

Nephron heterogeneity: clue to the pathogenesis of essential hypertension and effectiveness of angiotensin-converting enzyme inhibitor treatment.

It is proposed that in essential hypertension there are two functionally abnormal populations of nephrons. One is ischemic; chronically hypersecreting renin and underexcreting sodium. The other, the larger population, is in adaptive hypernatriuresis with its renin secretion chronically suppressed. Nephrons in these two populations, each with its own detector-effector apparatus for renin secretion and sodium excretion, behave according to their individual needs, producing a physiologic discordance expressed in high blood pressure even with plasma renin levels in the so-called "normal" range. The unsuppressed and inappropriate renin secretion from the ischemic nephrons impairs renal function in ischemic and hyperfiltering nephrons alike, but in very different ways. To maintain glomerular filtration rate and an adequate excretion of sodium, the ischemic nephrons require a higher rate of renin secretion than they are actually receiving, because at low perfusion pressures maximal angiotensin II-induced efferent arteriolar constriction is needed to maintain glomerular filtration rate. On the other hand, the compensating hypernatriuretic nephrons become unable fully to excrete dietary sodium because they are exposed to an unwanted, inappropriately high angiotensin II level coming from the ischemic nephrons. This angiotensin II impairs sodium excretion (adaptive hypernatriuresis) from unaffected, adapting nephrons by promoting proximal sodium reabsorption and by inducing afferent constriction. The net result is that all nephrons are exposed to angiotensin II levels inappropriate for their needs. This leads to impaired ability to excrete sodium by both populations of nephrons, with sodium retention in the presence of abnormal renin secretion and perpetuation of the hypertension. The hypothesis is consistent with the hallmark pathology of multifocal afferent arteriolar narrowing seen in essential hypertension as well as with the characteristic renal hemodynamic pattern of vasoconstriction with reduced renal blood flow but with maintained glomerular filtration rate. The "normal" glomerular filtration rate as well as the often "normal" plasma renin activity may be seen as the sum of effects on the two abnormally acting populations of nephrons. Further, since any circulating renin is inappropriate in the presence of hypertension, the hypothesis helps explain why angiotensin-converting enzyme inhibitors reduce blood pressure even when renin levels are not elevated.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1986

Superficial and juxtamedullary nephron function during converting enzyme inhibition.

The influence of the renin-angiotensin system on whole-kidney and regional single-nephron function was studied in anesthetized Munich-Wistar rats by use of a converting enzyme inhibitor (CEI), captopril (3 mg . h-1 . kg-1 body wt-1). Single-nephron glomerular filtration rate (SNGFR) was measured in superficial (S) and juxtamedullary (JM) nephrons by a micropuncture technique that blocked tubuloglomerular feedback (TGF) activity. Hydrostatic free-flow pressure (FFP) measurements were conducted in S proximal tubules, in JM loops of Henle, and in papillary vasa recta. Glomerular filtration rate (GFR) and urinary electrolyte excretion were measured in the contralateral kidney. In the control situation SNGFR of S nephrons was 35.4 +/- 2.24 nl . min-1 . g kidney wt-1 and of JM nephrons was 75.0 +/- 9.41 nl . min-1 . g-1 kidney wt-1. Thus it was more than twice as high in JM as in S nephrons when the TGF activity was blocked. In this situation administration of CEI had no additional effect on either S or JM nephrons. However, administration of CEI resulted in a significant increase in whole-kidney GFR by 25% (P less than 0.05) and in urine flow rate by 60% (P less than 0.001) under free-flow conditions. Further, intratubular FFP increased significantly in JM nephrons by an average of 2.9 +/- 0.52 mmHg (P less than 0.001), indicating an increase in tubular urine flow in JM nephrons, whereas S nephrons were unaffected. These results suggest an active preglomerular vasoconstriction in JM nephrons under normal free-flow conditions. This seems to be mediated by TGF and modulated by angiotensin II.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1986

Evidence for a new type of juxtamedullary nephron in the rabbit kidney.

The microanatomy of a unique type of juxtamedullary nephrons has been studied in the rabbit kidney by means of corrosion casts, scanning electron microscopy and the air cast method. The nephrons described in this paper are located in the outer stripe of the outer medulla and are the only nephrons that are not arranged radially within the kidney. They differ from other juxtamedullary nephrons in the morphology and course followed by the proximal tubule and by the close relationship that they establish with the arcuate vessels. The glomerulus of these nephrons is supplied by a short afferent arteriole that arises directly from the arcuate artery. Because of the special characteristics of these nephrons we have named them 'arcuate nephrons'. The morphology, spatial relationships and vascularization of the arcuate nephrons suggest that these nephrons differ functionally from the other juxtamedullary nephrons. Possible developmental factors responsible for the special microanatomy of the arcuate nephrons are analyzed.

Animals↗
PubMed2005

Quantitative analysis of the nephron during human fetal kidney development.

BACKGROUND: The development of human kidney is a complex process. The number, shape, size, and distribution of nephrons as functional units in a kidney, provide some important information about the organization of the kidney. The aim of this study was to extend the knowledge of the developing human kidney by studying nephrons in the kidney's cortex during gestation. METHODS: Kidney tissue specimens of 32 human fetuses, the gestational age from IV lunar month (LM IV) to LM X, were analysed. Specimens were divided in ten groups based on gestational age. Stereological methods were used at the light microscopic level to estimate the volume densities of the corpuscular and tubular components of the nephron in the cortex of the developing human kidney. RESULTS: Nephron polymorphism was the main characteristic of the human fetal kidney during development. In younger fetuses, just below the renal capsule, there was a wide nephrogenic zone. It contained the condensed mesenchyme and terminal ends of the ureteric bud. Nephrons, in the different stages of development, were located around the ureteric bud which branched in the cortical nephrogenic zone and induced nephrogenesis. More mature nephrons were located in the deeper part of the cortex, close to the juxta-medullary junction. During gestation, nephrogenesis continually advanced, and the number of nephrons increased. Glomeruli changed their size and shape, while the tubules changed their length and convolution. Renal cortex became wider and contained the more mature glomeruli and the more convoluted tubules. The volume density of the tubular component of the nephron increased continually from 10.53% (LM IVa) to 27.7% (LM X). Renal corpuscles changed their volume density irregularly during gestation, increasing from 13% (LM IVa) to 15.5% (LM IVb). During the increase of gestational age, the volume density of corpuscular component of the nephron decreased to 11.7% (LM VIII), then went on increasing until the end of the intrauterine development (LM X) when corpuscles occupied 16.73% of the cortical volume. The volume density of the developing nephrons (corpuscular and tubular portion) showed the significant positive correlation (r = 0.85; p<0.01) with gestational age. CONCLUSION: The present study was one of few quantitative studies of the human developing nephron. Knowledge about the normal development of the human kidney should be important for the future medical practice.

Female↗