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PubMed2006

Thiazolidinediones ameliorate diabetic nephropathy via cell cycle-dependent mechanisms.

Thiazolidinediones are ligands for peroxisome proliferator-activated receptor (PPAR)-gamma, widely used as insulin sensitizer in type 2 diabetic patients and implicated in apoptosis, cell proliferation, and cell cycle regulation. Here, the effect of thiazolidinediones on G1-phase cell cycle arrest, the hallmark in diabetic nephropathy, was investigated. Eight-week-old male Otsuka Long-Evans Tokushima fatty rats were treated with pioglitazone (1 mg x kg body wt(-1) x day(-1)) until 50 weeks of age and compared with insulin treatment. Although similar HbA(1c) levels were observed in both groups, pioglitazone significantly inhibited glomerular hypertrophy and mesangial matrix expansion and reduced urinary albumin excretion compared with the insulin-treated group. In addition, pioglitazone significantly reduced the number of glomerular p27(Kip1)-positive cells. Because prominent expression of PPAR-gamma was observed in podocytes in glomeruli and cultured cells, conditionally immortalized mouse podocyte cells were cultured under 5.5 and 25 mmol/l D-glucose supplemented with pioglitazone. Pioglitazone inhibited cell hypertrophy revealed by [(3)H]thymidine and [(3)H]proline incorporation, and pioglitazone reversed high glucose-induced G1-phase cell cycle arrest, i.e., an increase in G0/G1 phase and decrease in S and G2 phases. Pioglitazone suppressed high glucose-induced phosphorylation of p44/42 mitogen-activated protein kinase and reduced Bcl-2 and p27(Kip1) protein levels. Besides glucose-lowering action, pioglitazone ameliorates diabetic nephropathy via cell cycle-dependent mechanisms.

Albuminuria↗
PubMed2006

ZO-1 expression and phosphorylation in diabetic nephropathy.

Cellular mechanisms responsible for the loss of capillary wall permselectivity in diabetic nephropathy are not well characterized. ZO-1 is a junctional protein involved in the assembly and proper function of a number of tight junctions and is also expressed at the junction of podocytes with the slit diaphragm. We investigated the effect of diabetes and high glucose concentration on the expression of ZO-1 in animal models of both type 1 and 2 diabetes and in rat glomerular epithelial cells. In diabetic animals, immunohistochemistry and Western blotting showed decreased expression of ZO-1 in glomeruli. Immunogold electron microscopy revealed redistribution of ZO-1 from the podocyte membrane to the cytoplasm in the diabetic animals. Exposure of rat glomerular epithelial cells to high glucose resulted in a decrease in the intensity of ZO-1 staining and redistribution of ZO-1 from the membrane to the cytoplasm, changes that are attenuated by blockade of the angiotensin II type 1 receptor. ZO-1 protein expression and serine and tyrosine phosphorylation of ZO-1 were also decreased in cells exposed to high glucose. These findings suggest that alterations in the content and localization of ZO-1 may be relevant to the pathogenesis of proteinuria in diabetes.

Animals↗
PubMed1996

Atubular glomeruli and glomerular cysts--a possible pathway for nephron loss in the human kidney?

Glomerular tufts were removed and scanning electron microscopy was used to study the interior of Bowman's capsule, in order to identify atubular glomeruli. Normal renal cortex was studied from six kidneys removed for tumour and six renal transplants removed for end-stage rejection. Atubular glomeruli occurred in normal renal cortex in less than 1 percent of glomeruli, but were more common in transplant nephropathy, representing up to 61 percent of glomeruli. Glomerular cysts were identified which also lacked a tubular connection. Both atubular glomeruli and glomerular cysts contained a contracted glomerular capillary tuft and in both, Bowman's capsule was lined mostly by parietal podocytes. It is suggested that atubular glomeruli may be precursors of the glomerular cysts. The glomerular tuft may produce filtrate which exits the glomerulus via the parietal podocytes on Bowman's capsule. In normal human kidney, the formation of atubular glomeruli by disconnection from the tubule may represent an alternative pathway for the gradual nephron loss that is associated with ageing. This process may be amplified in disease: disconnection from the tubule may be an important part of irreversible nephron damage in chronic allograft nephropathy.

Adult↗
PubMed1998

Antisense WT1 transcription parallels sense mRNA and protein expression in fetal kidney and can elevate protein levels in vitro.

Recent studies have identified antisense WT1 mRNAs whose expression is regulated by a promoter located in the first intron of the WT1 gene. Transcription directed by the antisense promoter is positively autoregulated by the WT1 protein implicating the antisense RNA in the control of WT1 gene expression. To elucidate further the biological role of the antisense RNA in the developing kidney, its distribution of expression has been examined relative to WT1 sense mRNA and WT1 protein. Using strand-specific WT1 riboprobes, the expression of WT1 and the antisense message were examined by in situ hybridization in the developing human fetal kidney at different gestational ages. The expression of the antisense strand was strongest in the podocytes and glomeruli and also in the S-form nephrons and the condensing blastema in the developing kidney. Expression was also seen in the podocytes of the mature kidney. The WT1 protein and sense mRNA for WT1 also showed a similar pattern, suggesting that the antisense transcript does not function simply as a downregulator of protein production. Expression of antisense WT1 exon 1 in cells constitutively producing high levels of WT1 also demonstrated no downregulation of protein and in most cases actually showed upregulated WT1 protein expression. These results strongly suggest that WT1 antisense transcripts positively modulate WT1 protein levels in vivo.

Blotting, Northern↗
PubMed1979

Development of the renal corpuscle during metamorphosis in the lamprey.

The renal corpuscle of the adult lamprey, Petromyzon marinus L., is formed during the programmed period of metamorphosis. Development is initiated early in this metamorphic period and is marked by the synchronous formation and growth of rudimentary nephron units (RNU) from longitudinal cord of nephrogenictissue extending from the posterior tip of the degenerating larval kidney to the cloaca and connected to the peritoneal epithelium. Detachment of the RNU from the peritoneum involves autolysis and cell death and is accompanied by their branching into five or six hexagonally-arranged nephrons which radiate from the original point of attachment. Differentiation of the epithelial cells at the proximal ends of the nephrons is preceded by the widening of lateral intercellular spaces, the formation of tubular lumina (primitive urinary spaces), the loss of apical cell junctions, and the development of a capillary network with its associated mesangium. With the extension of the capillaries and mesangium between the proximal ends of adjacent undifferentiated nephrons, visceral epithelial cells (podocytes), with long cell processes (trabeculae) and slit membranes, make their appearance. The urinary spaces resulting from this form of development are lined by the epithelium of the dilated ends of the nephrons (nephric capsules). The cells of these capsules differentiate mainly into podocytes, but a few parietal cells connect to the draining tubule. This method of development explains the unique form of the renal corpuscle in the adult lamprey. Despite the type of morphogenesis, this renal corpuscle possesses the fine-structural features seen in the renal corpuscles of other vertebrates.

Animals↗
PubMed2003

Microvascular basement membranes in diabetes mellitus.

The alterations in the microvascular system of diabetes mellitus patients are responsible for the most devastating complications of this widespread disease. In the kidney, the microangiopathy leads to thickening of the glomerular capillary basement membrane but also to the expansion of the mesangial matrix and thickening of the tubular basement membrane. Several mechanisms are implicated in the pathogenesis of diabetic renal microangiopathy. These include increased synthesis of type IV collagen following hyperglycaemia-induced alteration of the pattern of podocyte-integrin expression, decreased expression of matrix metalloproteinases (MMP-2 and 3), and increased expression of tissue inhibitor of metalloproteinase (TIMP). An altered morphology of podocytes accompanies these basement membrane alterations. Other factors which may contribute to renal matrix accumulation include vascular endothelial growth factor (VEGF), since treatment with anti-VEGF antibodies attenuates glomerular basement membrane thickening, platelet-derived growth factor (PDGF) (B chain) and its receptor, which appear to be highly expressed in mesangial and visceral epithelial cells and might play a role in the development of diabetic nephropathy. Also oxygen radicals/oxidative stress may play a role in matrix accumulation in diabetic nephropathy as aminoguanidine, an inhibitor of the formation of advanced glycation end-products but with antioxidant properties, attenuates diabetic nephropathy. Retinal diabetic microangiopathy follows much the same principles, be it that microvascular proliferation is a distinctive element in the retina. Nephropathy and retinopathy occur frequently but not always together, indicating that in their multifactorial pathogenesis much remains to be clarified.

Basement Membrane↗
PubMed1993

Experimental adriamycin nephropathy. Fine structure, morphometry, glomerular polyanion, and cell membrane antigens.

Two doses of adriamycin (2 mg/kg i.v.) were administered to young adult rats with a 22-day interval and the kidneys were examined 51, 79, and 107 days after the first injection. Light microscopy showed early prominent intraglomerular microcystic spaces and progressive, though not severe, segmental glomerulosclerosis with focal interstitial scarring and round-cell infiltration. The main features of the ultrastructure were widespread fusion of foot processes, focal cytoplasmic rarefaction of podocytes, and non-specific sclerosis of the mesangium without signs of severe degenerative changes or mesangiolysis. The segmental microcystic structures corresponded to agglomerated intrapodocytic vacuoles. The scatter of glomerular polyanion sites visualized by polyethylenimine-phosphotungstic acid resembled that of control animals but the quantitative assessment revealed a significant reduction. CD4-positive cells were the predominant element of the interstitial infiltrates. Most of the infiltrating cells expressed Ia antigens, whereas Ia-positive intraglomerular resident mononuclear cells were depleted. The adriamycin lesion resembles the post-five-sixths nephrectomy ablation nephropathy in the subpopulations of the interstitial infiltrate but differs from it in the reduction of intraglomerular resident macrophages, the absence of destructive mesangial damage, and reduced segmental glomerulosclerosis. The main feature is the prolonged damage of podocytes, especially of their cytoskeletal system.

Animals↗
PubMed1994

Cell-type-specific nuclear translocation of fibroblast growth factor-2 isoforms during chicken kidney and limb morphogenesis.

Analysis of the fibroblast growth factor-2 (FGF-2 or bFGF) proteins during chicken embryonic pattern formation and organogenesis revealed that three isoforms (18.5, 20.0, and 21.5 kDa) were synthesized by alternative translation initiation from one coding region. A highly specific antiserum was raised and used for studying the temporal and spatial distribution of the FGF-2 isoforms during chicken embryogenesis. The distribution of FGF-2 proteins during limb pattern formation has been unraveled. Their presence in both ectodermal and mesenchymal cells is consistent with an involvement in regulating the balance of growth and differentiation. High levels of FGF-2 proteins were furthermore detected in all epithelial cells of the developing kidney from the pronephric stage onward. The proteins were in general predominantly cytoplasmic, but a specific subpopulation of limb mesenchymal cells and kidney epithelial cells (podocytes) showed a striking nuclear localization. Nuclear translocation of the FGF-2 proteins occurred in differentiating podocytes of meso- and metanephric glomeruli and was maintained in adult kidneys. These results, in contrast to previous in vitro studies, revealed that nuclear accumulation of FGF-2 proteins is restricted to few specific cells during embryogenesis.

Amino Acid Sequence↗
PubMed1998

The vascular pole of the renal glomerulus of rat.

In the present study we provide a detailed structural analysis of the vascular pole of superficial and midcortical glomeruli of the rat kidney. A description of the juxtaglomerular portions of the afferent and efferent arterioles, the extraglomerular mesangium and the glomerular stalk is included. The specific structural elaboration of the epithelial transition from the podocytes to the parietal epithelium is emphasized, with particular attention to the arrangement of the cytoskeleton and its connections to extracellular matrix elements. The branching patterns of the afferent and efferent arterioles are quite different. Immediately at the glomerular entrance, the afferent arteriole divides into its primary branches. In contrast, the efferent arteriole has a specific outflow segment (consisting of an intraglomerular portion and a portion associated with the extraglomerular mesangium) established by the confluence of capillary tributaries deep inside the glomerular tuft. Just at the transition from inside to outside, this segment includes a prominent narrow portion with conspicuous endothelial cells bulging into the vessel lumen. The extraglomerular mesangium has been found to represent a solid block of cells and matrix filling the space between the macula densa and both arterioles and extending into the entrance funnel. Peripherally located extraglomerular mesangial cells attach to the outer aspect of the parietal basement membrane. As a whole, the extraglomerular mesangium occludes the glomerular tuft. The results appear relevant with respect to four major aspects: (1) a support function counteracting the expansile forces resulting from the high intraglomerular pressures, (2) a direct functional influence of the afferent on the efferent arteriole, resulting from their narrow assemblage at the glomerular entrance, (3) a specific shear stress receptor function of the intraglomerular segment of the efferent arteriole, and (4) fluid leakage from the glomerular tuft through the stalk and the extraglomerular mesangium into the cortical interstitium. 1. The glomerulus is a high-pressure compartment; expansile forces continuously tend to expand glomerular capillaries, the glomerular stalk, and the glomerular entrance. Counteracting centripetal forces at the vascular pole appear to be developed as circular forces by the cytoskeleton of podocytes and parietal cells surrounding the glomerular entrance and as interconnecting forces between both arterioles and between opposing walls of the glomerular entrance, as well as of the glomerular stalk. These interconnecting forces are developed by the extraglomerular mesangium which--as a whole--forms a spiderlike closure device holding the glomerular entrance together. In addition, the extraglomerular mesangium develops occluding forces, allowing a gradual pressure drop between the glomerular stalk and the macula densa. 2. At the glomerular entrance, the outflow segment of the efferent arteriole is narrowly associated with the bifurcation of the afferent arteriole. Both are enclosed together in a common compartment surrounded by the glomerular basement membrane; there is no pressure barrier individually encompassing each vessel. Therefore, it may readily be suggested that the hydrostatic pressure of the afferent arteriole acts on the efferent arteriole. As a consequence, the luminal width of the efferent arteriole at this site, i.e., its resistance, may be directly modified by the pressure in the afferent arteriole. 3. The efferent arteriole at the transition of the intraglomerular segment to the segment that passes through the extraglomerular mesangium has a conspicuously narrow portion with endothelial cells protruding into the vessel lumen. In addition, this segment is prominent by the expression of the neuronal type of nitric oxide synthase. We therefore propose that this segment acts as a specific shear stress receptor. The possible relevance of a shear stress receptor at this site would be

Animals↗
PubMed1981

Testosterone-dependent changes in vivo and in vitro in the structure of the renal glomeruli of the teleost Gasterosteus aculeatus L.

During the reproductive period of the male stickleback, structural and functional changes of the kidney take place, both in the glomeruli and in the renal tubule cells. The structural changes in the glomeruli involve almost all glomerular components and point to a reduction of the glomerular filtration rate. The purpose of this study was to investigate whether these changes are controlled by testosterone, indirectly or directly. In vivo experiments demonstrated that exposures of immature castrates for 8 days to methyltestosterone leads to activation of mesangial cells and podocytes, to slight expansion of mesangial matrix and slight thickening of basal lamina. Observations on cultured renal tissue showed that two androgens, 11-ketotestosterone and methyltestosterone, are also able to stimulate the secretory activity of podocytes and mesangial cells in vitro. The results therefore indicate, that most glomerular changes in male sticklebacks during the reproductive season are directly effected by testosterone.

Animals↗
PubMed1983

Glomerular ultrastructure of the trout, Salmo gairdneri. Glomerular capillary epithelium and the effects of environmental salinity.

The epithelial ultrastructure of the glomerulus of fresh- and sea-water adapted rainbow trout, Salmo gairdneri was examined by scanning and transmission electron microscopy after in vivo-perfusion fixation. Adaptation to seawater for a period of up to 9 weeks was not associated with a change in glomerular size, although after one year in seawater both glomeruli and their capsules were significantly smaller than the glomeruli of freshwater adapted fish. In freshwater adapted trout the epithelial ultrastructure conformed to the general vertebrate pattern, with rounded podocytes, well-defined primary processes and interdigitating pedicels. Adaptation to seawater was associated with a marked increase in the frequency of cytoplasmic microprojections. In many glomeruli there was a flattening of the podocytes, broadening of the primary processes, and areas of closely-packed pedicels were common. These observations are discussed in the light of previous studies on the mammalian kidney and the changes of single nephron function known to be associated with adaptation of trout to increased environmental salinities.

Adaptation, Physiological↗
PubMed1988

Ultrastructure of the kidney of a South American caecilian, Typhlonectes compressicaudus (Amphibia, Gymnophiona). I. Renal corpuscle, neck segment, proximal tubule and intermediate segment.

The ultrastructure of the renal corpuscle, the neck segment, the proximal tubule and the intermediate segment of the kidney of a South American caecilian, Typhlonectes compressicaudus (Amphibia, Gymnophiona) was examined by means of transmission electron microscopy (TEM), scanning electron microscopy (SEM) and freeze-fracture technique. The glomerular filter apparatus consists of the podocyte epithelium, a distinct basement membrane, a subendothelial space and the capillary endothelium. Emanating from the podocyte cell body, several long primary processes encircle neighboring capillaries. The short slender foot processes originating from the primary processes interdigitate with those from other primary processes, thereby forming the meandering filtration slit. Thick bundles of microfilaments are found in the primary processes, but absent in the foot processes. The basement membrane consists of a lamina rara externa and a rather thin lamina densa (50 nm thickness). The wide subendothelial space contains abundant microfibrils, a few collagen fibrils and many thin processes of mesangial cells. The endothelium is flat and fenestrated (compared to mammals displaying relatively few fenestrations); some of the fenestrations are bridged by a diaphragm. The glomerular mesangium is made up of the mesangial cells and a prominent mesangial matrix containing microfibrils and collagen fibrils. The cells of the neck and intermediate segments display numerous cilia with their microtubules arranged in the typical 9 + 2 pattern. The basal bodies of the cilia are attached to thick filaments with a clear crossbanding pattern of 65 nm periodicity. The proximal tubule is composed of cells typical for this segment (PT cells) and light cells lacking a brush border (bald-headed cells). The PT cells measure 10-25 micron in height and 15-30 micron in width and do not interdigitate at their lateral borders with each other. Their basolateral cell membrane is amplified by many folds projecting into lateral intercellular spaces and into basal recesses. The brush border is scarce and composed of loosely arranged short microvilli.

Amphibians↗
PubMed1987

Ultrastructure of the nephron of freshwater turtles, Pseudemys scripta elegans and Mauremys caspica.

The nephrons of the freshwater turtles Pseudemys scripta elegans and Mauremys caspica consist of renal corpuscle, neck segment, proximal tubule, intermediate segment, distal tubule and collecting duct. The renal corpuscle has large and scarce capillaries with clear and dark fenestrated endothelial cells containing some rod-shaped bodies, a thin filtration barrier and a well-developed mesangium, the cells of which show secretory, phagocytic and contractile features, and in M. caspica a cilium. The podocytes with a well-developed Golgi apparatus seem to be active secretory cells. Numerous dense bodies similar to lysosomes, but not previously reported in vertebrates, are conspicuous in podocytes of M. caspica. The proximal tubule displays a well-developed brush border with long and densely-packed microvilli and no basal labyrinth; mitochondria are scattered throughout the cytoplasm. Several dense and clear vesicles related to the prominent endocytotic apparatus can be seen. Wavy filament bundles, not previously reported in vertebrate kidneys, can be observed in proximal tubule cells of M. caspica. Three regions can be distinguished in the well-developed intermediate segment as well as in the distal tubule; the latter has a few short microvilli or a smooth luminal surface and lateral interdigitated processes. The collecting duct, the cells of which contain numerous mucous droplets, is similar in both sexes; there is no sexual segment.

Animals↗
PubMed1975

The fine structure of the kidney of the hagfish (Myxine glutinosa L.): A thin section and freeze-fracture study.

The fine structure of the kidney (glomerulus and archinephric duct) of the hagfish. Myxine glutinosa (L.) was studied in thin sections and by freeze-fracture technique. The glomerular filtration barrier is similar to that of mammalian kidneys. However, endothelial fenestrations are relatively scanty and the basement membranes of endothelial cells and podocytes always appear separated by a layer of collagen fibrils and microfibrils often surrounding numerous and extended mesangial cells. Between podocytes and their processes maculae occludentes and peculiar junctions of another type occur. The zonulae occludentes between epithelial cells of the archinephric duct are composed of five or more strands, occasionally of only one or two.

Animals↗
PubMed1976

The effect of prolactin on kidney structure of the euryhaline teleost Gasterosteus aculeatus during adaptation to fresh water.

The effect of injections of ovine prolactin on kidney structure was examined in the first 10 days following transfer of seawater sticklebacks to fresh water. In hormone injected animals as well as in controls the glomeruli increase slightly in size after transfer. The podocytes intensify the secretion of mucopolysaccharides, which is indicative of increased turnover of the components of the glomerular basal lamina. The nuclei of the podocytes become enlarged, while those of the juxtaglomerular cells decrease in size. These changes are related to the well known rise of the glomerular filtration rate following transfer to fresh water. Structural indications that prolactin is involved in the control of glomerular filtration were not found. The epithelial cells of the three nephronic segments and of the ureter become considerably better developed after transfer to fresh water. Cell height, nuclear and mitochondrial volume, and surface of the membranes of the basal labyrinth increase in all tubular epithelia, although not to the same extent. Increases are moderate in the first proximal segment, but increasingly higher for the second proximal segment, collecting duct and the ureter. Especially the growth of membrane surface of the basal labyrinth, site of ion transport mechanisms, is impressive. In controls, values characteristic for freshwater fishes are reached in 6 to 9 days for all parameters for cellular development. Prolactin injections greatly stimulate growth rates in all tubular epithelia: freshwater values are reached within 3 days. No further increase was found, however.

Adaptation, Physiological↗
PubMed1975

The glomeruli of the human and the rat kidney studied by freeze-fracturing.

Glomeruli isolated from rat and human kidneys were studied using the freeze-fracture technique. Discontinuous zonulae occludentes and gap junctions were found in the replicas of the split plasma membrane of the endothelial cells. A diaphragm across the endothelial pores was not demonstrated. The central layer of the basement membrane, corresponding to the lamina densa described in thin sections, revealed a coarse substructure. A slit membrane between the pedicles of the podocytes was not detectable; however, its position was indicated by the different texture of the replica, which abruptly changed at the transition of the basement membrane to the primary urinary space. Furthermore, at the level of the slit membrane arrays of particles were present within the cleaved membrane of the pedicles, probably representing the attachment points of the slit membrane. Isolated strands of a zonula occludens as well as gap junctions were seen on the split plasma membrane of the podocytes. The mesangial cells could be identified by their contiguity to the endothelial cells and by their numerous gap junctions.

Adult↗
PubMed1980

Changes in glomerular structure after sexual maturation and seawater adaptation in males of the euryhaline teleost Gasterosteus aculeatus L.

In sexually mature male sticklebacks, the renal tubular cells are transformed from ion reabsorbing to mucus secreting cells and in these fish concomitant changes take place in the glomeruli. The present study compares glomerular structure of immature males in fresh water (controls) to those of mature males in fresh water and to immature male sticklebacks in seawater. Glomerular structure is markedly altered in the latter two groups and the changes are similar to a large extent. In these two groups the renal capsules and glomeruli are smaller and the lumina of the glomerular capillaries decrease in diameter, while the number and size of the endothelial fenestrations are reduced. Mesangial cells proliferate and the mesangial matrix greatly expands in both the centrolobular region and the subendothelial space around the capillaries. The secretory activity of the podocytes is enhanced and is responsible for the observed increase in thickness of the outer layer of the basal lamina, the lamina rara externa. The area covered by the filtration slit membranes is reduced, probably as a consequence of fusion of the pedicels of the podocytes. The permeability characteristics of the glomerular filtration barrier for macromolecules, as studied with ferritin injections, remain unaltered. However, the observed differences point to a reduction of the glomerular filtration rate (GFR) during maturation in male sticklebacks, as well as during adaptation of sticklebacks to seawater. This conclusion is in line with physiological evidence.

Adaptation, Physiological↗
PubMed1990

Changes in renal morphology and renin secretion in the golden-mantled ground squirrel (Spermophilus lateralis) during activity and hibernation.

Chronological changes in renal glomerular morphology and plasma renin activity were investigated during active and hibernating periods in the golden-mantled ground squirrel Spermophilus lateralis. The objective of this study was to determine whether the glomerular endothelium, visceral epithelium (podocytes), basement membrane, mesangial cells, proximal convoluted tubule cells and plasma renin activity exhibit measurable sequential differences between as well as within active and hibernating states at various time points. Limitations in the size of the experimental population prevented an evaluation of changes in these parameters during other important periods such as periodic arousal between hibernation bouts. In this study, glomerular endothelial pore number and epithelial filtration slit number significantly decreased by early hibernation when compared to those during summer activity, and then they increased back toward summer levels by late hibernation. In contrast, podocytic pedicel width along the glomerular basement membrane increased from summer activity to early hibernation, before significantly decreasing again by late hibernation. Mesangial cell and proximal convoluted tubule cell activity appeared increased during hibernation as compared to summer activity, whereas the width of the glomerular basement membrane showed no significant alterations throughout. Plasma renin activity significantly increased during early hibernation and mid-hibernation when compared to summer levels but had decreased by late hibernation toward summer values. The glomerular and plasma renin activity changes observed in this study clearly illustrate the drastic structural and functional adjustments which hibernating species make during torpor and also correlate well with the reported decrease in renal perfusion pressure and urine formation during hibernation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗