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• W1983132018 abstract "A 40-year-old man was admitted to the hospital for a renal biopsy; three years earlier his first renal biopsy had revealed focal segmental glomerulosclerosis. Proteinuria first had been noted on a routine physical examination at approximately age 20. The proteinuria, initially in the subnephrotic range, was not accompanied by notable activity of the urinary sediment. Around the age of 30, the patient developed hypertension and hypercholesterolemia, which were treated with an angiotensin-converting-enzyme (ACE) inhibitor and a statin, respectively. Serial urinalyses by his personal physician revealed persistent subnephrotic proteinuria. By age 37, however, the urinary protein excretion had increased to 4 g/day and the serum albumin had fallen to 3.4 g/dL. The serum creatinine level remained normal at 1.0 mg/dL. Further workup to determine the cause of proteinuric renal disease was initiated. The patient had no history of childhood renal disease or other urinary tract disease. He had no history of drug use, and serologic studies for autoimmune and infectious diseases associated with nephrotic-range proteinuria were negative. The initial renal biopsy disclosed 16 glomeruli on light microscopy, five of which had global sclerosis and one segmental sclerosis. Another glomerulus showed periglomerular fibrosis and wrinkling, consistent with ischemia. Several glomeruli demonstrated synechiae and one a “tip” lesion. The interstitium showed only minimal fibrosis with scattered small numbers of chronic inflammatory cells. Ultrastructural studies sampled 7 intact glomeruli, 3 of which showed segmental sclerosis. No electron-dense deposits were seen, and immunofluorescence demonstrated only trace epithelial staining for albumin. The patient was initially treated with prednisone, 60 mg/day, for 12 weeks. Proteinuria increased from approximately 5 g/day to 12 g/day. The patient subsequently received cyclosporine. The proteinuria declined to 1.5 g/day during the first 6-month course of cyclosporine but rose to approximately 3 g/day after cyclosporine was discontinued. Proteinuria declined to 1 g/day during a second 6-month course of cyclosporine but rose to 5 g/day after the drug was discontinued. The proteinuria declined to 2 g/day during a subsequent one-year course of cyclosporine but then rose to 4 g/day while the patient was still taking the drug. During that time, his serum creatinine rose from 1.2 mg/dL to 1.6 mg/dL. The patient continued taking an ACE inhibitor, but his blood pressure became harder to control. A second renal biopsy, the focus of our discussion today, was performed. Light microscopy disclosed 13 glomeruli, of which 2 showed global sclerosis and 2 showed segmental sclerosis. The interstitium demonstrated focal interstitial fibrosis associated with a mild chronic inflammatory infiltrate. Tubular atrophy was noted. Ultrastructural studies revealed extensive foot process effacement in one glomerulus and normal epithelial structure in another. Again, no electron-dense deposits were noted and immunofluorescence demonstrated only weak staining for C3 and IgM in the mesangium of sclerosed glomeruli. Dr. Timothy W. Meyer (Chief, Section of Nephrology, VA Palo Alto Health Care System, and Professor of Medicine, Stanford University, Palo Alto, California, USA): This patient's second renal biopsy showed changes typical of proteinuric glomerular disease advancing to renal insufficiency. The diagnosis of focal segmental glomerulosclerosis was based on the finding of segmental sclerotic lesions in 2 of 13 glomerular profiles. In addition, 2 glomeruli were globally sclerosed, and 2 appeared shrunken and collapsed with wrinkling of the basement membranes. Glomerular injury was accompanied by tubulointerstitial injury. Some tubular segments were hypertrophic, but many were atrophic. Some were filled with protein casts. The interstitium was expanded, especially around the most damaged tubules, and contained a patchy mononuclear cell infiltrate. How are these changes in glomerular, tubular, and interstitial structure related? The organization of glomeruli and tubules into individual nephrons cannot be appreciated on examination of routinely prepared tissue sections. But physiologic studies have suggested that even when disease causes structural changes like those seen in this biopsy specimen, glomerular and tubular function remain closely integrated. Evidence that glomerular and tubular function remain linked in diseased kidneys can be usefully summarized by the term “intact nephron hypothesis,” as originally proposed by Neal Bricker in 19601.Bricker N.S. Morrin P.A. Kime Jr, S.W. The pathologic physiology of chronic Bright's disease. An exposition of the “intact nephron hypothesis.Am J Med. 1960; 28: 77-97Abstract Full Text PDF PubMed Scopus (134) Google Scholar. This hypothesis does not imply that each nephron is either untouched by disease or obliterated. Rather, the initial population of homogeneous nephrons is replaced by a lesser population in which neighboring structures exhibit heterogeneous patterns of form and function. Important support for the intact nephron hypothesis was provided by micropuncture studies by Carl Gottschalk and colleagues in the 1970s2.Gottschalk C.W. Function of the chronically diseased kidney. The adaptive nephron.Circ Res. 1971; 28: S1-S13Google Scholar, 3.Kramp R.A. MacDowell M. Gottschalk C.W. Oliver J.R. A study by microdissection and micropuncture of the structure and the function of the kidneys and the nephrons of rats with chronic renal damage.Kidney Int. 1974; 5: 147-176Abstract Full Text PDF PubMed Scopus (26) Google Scholar, 4.Allison M.E. Wilson C.B. Gottschalk C.W. Pathophysiology of experimental glomerulonephritis in rats.J Clin Invest. 1974; 53: 1402-1423Crossref PubMed Scopus (98) Google Scholar. These studies showed that in rats with chronic glomerulonephritis, glomerular filtration rate (GFR) for single nephrons varied from one-third to three times normal. Yet the fraction of sodium and water reabsorbed was the same in proximal tubules connected to hypofiltering and hyperfiltering glomeruli. Similar results were obtained in rats with tubular disease caused by heavy metals. Filtration was markedly reduced in glomeruli attached to the most severely damaged tubules, but the balance between glomerular filtration and proximal fluid reabsorption was maintained. The mechanisms that keep glomerular and tubular function linked as renal disease progresses are not fully understood. Tubuloglomerular feedback might reduce single-nephron GFR when damaged tubules fail to reabsorb a normal amount of filtrate, and changes in peritubular Starling forces might limit proximal reabsorption when filtration is reduced in damaged glomeruli. Ultimately, these functional changes are associated with structural changes. If the flow of filtrate is stopped, tubules atrophy5.Tanner G.A. Evan A.P. Glomerular and proximal tubular morphology after single nephron obstruction.Am J Physiol. 1989; 36: 1050-1060Google Scholar. If tubules are injured, upstream glomeruli shrink and can become sclerotic3.Kramp R.A. MacDowell M. Gottschalk C.W. Oliver J.R. A study by microdissection and micropuncture of the structure and the function of the kidneys and the nephrons of rats with chronic renal damage.Kidney Int. 1974; 5: 147-176Abstract Full Text PDF PubMed Scopus (26) Google Scholar, 6.Marcussen N. Atubular glomeruli and the structural basis for chronic renal failure.Lab Invest. 1992; 66: 265-284PubMed Google Scholar, 7.Marcussen N. Ottosen P. Christensen S. Olsen T. Atubular glomeruli in lithium-induced chronic nephropathy in rats.Lab Invest. 1989; 61: 295-302PubMed Google Scholar, 8.Marcussen N. Atubular glomeruli in cisplatin-induced chronic interstitial nephropathy.APMIS. 1990; 98: 1087-1097Crossref PubMed Scopus (36) Google Scholar. More than 60 years ago, Jean Oliver used serial histologic sections to reconstruct individual nephrons from patients dying with renal failure. He demonstrated that the kidneys of these patients contained large glomeruli connected to hypertrophic tubules and shrunken glomeruli connected to atrophic tubules Figure 19.Oliver J. Architecture of the Kidney in Chronic Bright's Disease. Paul B. Hoeber, New York1939Google Scholar. Oliver also microdissected individual nephrons from diseased kidneys. Of note, he was not convinced that tubular atrophy and glomerular atrophy were invariably associated. He identified some aglomerular tubules in his microdissection studies, and he thought they might continue to function like the tubules in the then-recently-described aglomerular fishes. But subsequent functional studies have shown that significant tubular function does not persist without glomerular function in patients with renal disease1.Bricker N.S. Morrin P.A. Kime Jr, S.W. The pathologic physiology of chronic Bright's disease. An exposition of the “intact nephron hypothesis.Am J Med. 1960; 28: 77-97Abstract Full Text PDF PubMed Scopus (134) Google Scholar. When we see a damaged glomerulus attached to an atrophic tubule, has glomerular injury caused tubular injury, has tubular injury caused glomerular injury, or both? The answer might be different for individual nephrons as well as for individual patients. In today's patient, a biopsy was first performed more than 10 years after renal disease was detected. We cannot exclude the possibility that focal glomerulosclerosis developed in response to an antecedent tubular or interstitial injury, but we do have strong evidence that once established, proteinuric glomerular injury can cause tubular injury10.Addis T. Oliver J. The Renal Lesion in Bright's Disease. Paul B. Hoeber, New York1931Google Scholar, 11.Williams P.S. Fass G. Bone J.M. Renal pathology and proteinuria determine progression in untreated mild/moderate chronic renal failure.Q J Med. 1988; 67: 343-354PubMed Google Scholar, 12.Remuzzi G. Bertani T. Is glomerulosclerosis a consequence of altered glomerular permeability to macromolecules?.Kidney Int. 1990; 38: 384-394Abstract Full Text PDF PubMed Scopus (370) Google Scholar, 13.Kees-Folts D. Sadow J.L. Schreiner G.F. Tubular catabolism of albumin is associated with the release of an inflammatory lipid.Kidney Int. 1994; 45: 1697-1709Abstract Full Text PDF PubMed Scopus (138) Google Scholar, 14.Eddy A.A. Experimental insights into the tubulointerstitial disease accompanying primary glomerular lesions.J Am Soc Nephrol. 1994; 5: 1273-1287Crossref PubMed Google Scholar, 15.Remuzzi G. Nephropathic nature of proteinuria.Curr Opin Nephrol Hypertens. 1999; 8: 655-663Crossref PubMed Scopus (61) Google Scholar, 16.Becker G.J. Hewitson T.D. The role of tubulointerstitial injury in chronic renal failure.Curr Opin Nephrol Hypertens. 2000; 9: 133-138Crossref PubMed Scopus (134) Google Scholar. The question then becomes, to what extent does tubular injury contribute to loss of nephron function? In some nephrons, the tubule might atrophy only when glomerular injury lowers the single-nephron GFR. In others, proteinuric glomerular injury could cause tubular injury by means other than reduction in filtration, and this secondary tubular injury then might cause loss of function while the glomerulus is still perfused and part of its surface remains available for filtration. To the extent that this is the case, treatment to limit tubular injury could slow the loss of renal function even when glomerular injury cannot be prevented. Early studies that analyzed renal biopsy specimens are often said to have established that tubular and interstitial injury are the major contributors to loss of renal function, even in primary glomerular diseases17.Risdon R.A. Sloper J.A.C. de Wardener H. Relations between renal function and histological changes found in renal biopsy specimens from patients with persistent glomerular nephritis.Lancet. 1968; II: 363-366Abstract Google Scholar, 18.Schainuck L.I. Striker G.E. Cutler R.E. Benditt E.P. Structural-functional correlations in renal disease.Hum Pathol. 1970; 1: 631-641Abstract Full Text PDF PubMed Scopus (424) Google Scholar, 19.Bohle A. Kressel G. Muller C.A. Muller G.A. The pathogenesis of chronic renal failure.Pathol Res Pract. 1989; 185: 421-440Crossref PubMed Scopus (50) Google Scholar. These studies found that renal function is better correlated with scores for tubular atrophy and interstitial expansion than with scores for glomerular injury. Their results have stimulated a great deal of valuable work. But the correlations of function and structure originally reported did not in fact provide conclusive evidence that tubular injury is more often the proximate cause of nephron loss than is glomerular injury. One problem has been unequal sampling of glomeruli and tubules. Glomerular injury has been scored by examination of as few as 10 profiles, while tubular injury has usually been assessed by examination of a larger sample. A potentially greater problem has been posed by the semiquantitative methods used to assess glomerular injury. The structural features on which injury scores have been based might not accurately reflect filtration capacity. A particular problem is that glomerular size and capillary surface area usually have not been measured. When more detailed morphometric measurements have been made, GFR has been correlated with changes in glomerular structure20.Ting R.H. Kristal B. Myers B.D. The biophysical basis of hypofiltration in nephrotic humans with membranous nephropathy.Kidney Int. 1994; 45: 390-397Abstract Full Text PDF PubMed Scopus (19) Google Scholar,21.Pagtalunan M.E. Miller P.L. Jumping-Eagle S. et al.Podocyte loss and progressive glomerular injury in type II diabetes.J Clin Invest. 1997; 99: 342-348Crossref PubMed Scopus (808) Google Scholar. Overall, it seems likely that tubular and glomerular structure change together, as originally suggested by Bricker1.Bricker N.S. Morrin P.A. Kime Jr, S.W. The pathologic physiology of chronic Bright's disease. An exposition of the “intact nephron hypothesis.Am J Med. 1960; 28: 77-97Abstract Full Text PDF PubMed Scopus (134) Google Scholar and Gottschalk2.Gottschalk C.W. Function of the chronically diseased kidney. The adaptive nephron.Circ Res. 1971; 28: S1-S13Google Scholar. Analysis of biopsies has emphasized that tubules can be injured and renal function lost when glomeruli are not globally sclerosed. But further study is required to determine the extent to which tubular injury per se contributes to loss of function. We could better estimate the extent to which tubular injury causes loss of function if we could identify glomerular structural changes that are caused by tubular injury. The use of serial sectioning to examine glomeruli and tubules of individual nephrons provides one means of doing this. The serial sectioning technique was first applied by Marcussen to analyze structural changes responsible for loss of renal function in rats with nephrotoxic injury6.Marcussen N. Atubular glomeruli and the structural basis for chronic renal failure.Lab Invest. 1992; 66: 265-284PubMed Google Scholar. Remarkably, Marcussen and colleagues found large numbers of shrunken “atubular” glomeruli with open capillary loops but no attached tubules in rats with renal insufficiency caused by cis platinum and by lithium6.Marcussen N. Atubular glomeruli and the structural basis for chronic renal failure.Lab Invest. 1992; 66: 265-284PubMed Google Scholar, 7.Marcussen N. Ottosen P. Christensen S. Olsen T. Atubular glomeruli in lithium-induced chronic nephropathy in rats.Lab Invest. 1989; 61: 295-302PubMed Google Scholar, 8.Marcussen N. Atubular glomeruli in cisplatin-induced chronic interstitial nephropathy.APMIS. 1990; 98: 1087-1097Crossref PubMed Scopus (36) Google Scholar. Other glomeruli with similar appearance were attached only to atrophic structures representing the vestiges of normal tubular segments. The reduction in GFR closely correlated with the fraction of glomeruli that were either atubular or attached to vestigial tubules. We applied the serial section technique to examine disease progression in experimental glomerular disease. An initial study examined renal structure at 10 and 25 weeks after five-sixths renal ablation22.Gandhi M. Olson J.L. Meyer T.W. The contribution of tubular injury to loss of remnant kidney function.Kidney Int. 1998; 54: 1157-1165Abstract Full Text Full Text PDF PubMed Scopus (70) Google Scholar. As expected, renal ablation induced hypertension and progressive glomerular injury manifested by heavy proteinuria. By 25 weeks, remnant kidney GFR had decreased to approximately 25% of the value seen at 10 weeks. Examination of serial sections revealed that this decrease in renal function was associated with an increase in the percentage of glomeruli no longer connected to normal tubules. At 10 weeks, an average of 20% of glomeruli were atubular or connected only to vestigial tubules, while at 25 weeks this portion had increased to approximately 75%. Of note, the prevalence of glomeruli no longer connected to normal tubules greatly exceeded the prevalence of glomeruli that were globally sclerosed. In a subsequent study that examined glomerular and tubular injury in rats with adriamycin nephrosis, we found that GFR fell to approximately 20% of normal after 16 weeks of nephrosis23.Javaid B. Olson J.L. Meyer T.W. Glomerular injury and tubular loss in adriamycin nephrosis.J Am Soc Nephrol. 2001; 12: 1392-1400Google Scholar. The reduction in GFR again closely correlated with the appearance of glomeruli that were atubular or connected only to vestigial tubules. Most recently, we have found that some glomeruli become atubular during even a brief episode of acute puromycin nephrosis24.Rasch R. Nyengaard J.R. Marcussen N. Meyer T.W. Renal structural abnormalities following recovery from acute puromycin nephrosis.Kidney Int. 2002; 62: 496-506Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar. Limitations in the interpretation of serial sections must be acknowledged. In the models of toxic injury studied by Marcussen and colleagues6.Marcussen N. Atubular glomeruli and the structural basis for chronic renal failure.Lab Invest. 1992; 66: 265-284PubMed Google Scholar, 7.Marcussen N. Ottosen P. Christensen S. Olsen T. Atubular glomeruli in lithium-induced chronic nephropathy in rats.Lab Invest. 1989; 61: 295-302PubMed Google Scholar, 8.Marcussen N. Atubular glomeruli in cisplatin-induced chronic interstitial nephropathy.APMIS. 1990; 98: 1087-1097Crossref PubMed Scopus (36) Google Scholar, atubular glomeruli were reduced in size but otherwise appeared normal. It could reasonably be presumed that loss of nephron function was due entirely to tubular injury. But this was not the case in our studies of proteinuric glomerular disease. In these studies, many atubular glomeruli also exhibited segmental sclerotic injury22.Gandhi M. Olson J.L. Meyer T.W. The contribution of tubular injury to loss of remnant kidney function.Kidney Int. 1998; 54: 1157-1165Abstract Full Text Full Text PDF PubMed Scopus (70) Google Scholar,23.Javaid B. Olson J.L. Meyer T.W. Glomerular injury and tubular loss in adriamycin nephrosis.J Am Soc Nephrol. 2001; 12: 1392-1400Google Scholar. Thus, the extent to which prevention of tubular injury would have preserved function was not clear. Moreover, the finding of atubular glomeruli does not identify the cause of tubular atrophy. Marcussen and coworkers also found atubular glomeruli in ischemic renal injury7.Marcussen N. Ottosen P. Christensen S. Olsen T. Atubular glomeruli in lithium-induced chronic nephropathy in rats.Lab Invest. 1989; 61: 295-302PubMed Google Scholar. It is possibly relevant to the current case that we have observed a subpopulation of glomeruli with reduced volume in rats with renal insufficiency caused by chronic cyclosporine administration25.Lafayette R.A. Mayer G. Meyer T.W. The effects of blood pressure reduction on cyclosporine nephrotoxicity in the rat.J Am Soc Nephrol. 1993; 3: 1892-1899PubMed Google Scholar. Serial sections were not made, but these glomeruli looked like those found to be atubular in other studies. Thus, overall, the serial section technique has confirmed that glomerular structure does not remain normal as tubules atrophy. It also has provided improved quantitation of the extent of tubular loss. But morphologic criteria for determining the cause of tubular loss have not yet been developed, and we cannot currently tell whether tubular injury is due to ischemia, obstruction, protein leakage from the glomerulus, or other causes. Finally, I should note that serial sectioning has been carried out mostly in rat models, and we do not know how the appearance of atubular glomeruli might change over the long course of human renal disease. Despite these caveats, serial sectioning might provide an index of the contribution of tubular injury to loss of renal function. In the patient described today, a separate biopsy core was embedded in Epon and serially sectioned at 3 micron intervals. A total of 16 glomeruli were examined, of which 4 were globally sclerotic, 2 were atubular, and 4 were connected to vestigial tubules Figure 2. Only 6 glomeruli remained connected to normal-appearing tubules. The volume of these 6 glomeruli averaged 8.8 ± 1.7 (SD) × 106μ3, a value much greater than the average value of 2.6 ± 0.8 × 106μ3 obtained using the same method in normal subjects21.Pagtalunan M.E. Miller P.L. Jumping-Eagle S. et al.Podocyte loss and progressive glomerular injury in type II diabetes.J Clin Invest. 1997; 99: 342-348Crossref PubMed Scopus (808) Google Scholar. In contrast, the volume of glomeruli that were atubular or connected only to vestigial tubules averaged only 2.0 ± 1.0 × 106μ3, similar to the value of 1.7 ± 0.5 × 106μ3 obtained in globally sclerotic glomeruli. These results are consistent with the hypothesis that tubular injury contributed significantly to nephron loss in this case while hypertrophy of remnant functioning nephrons limited the reduction in GFR. Clearly, further studies are required to assess the contribution of tubular injury to the progression of human glomerular disease. Acknowledging that the extent to which tubular injury contributes to the progression of glomerular disease has not been fully established, we pass on to the question of how tubules are injured. The processes responsible for tubular injury of course might differ in different cases. At present, we can only compile a list of potential mechanisms of injury Table 1. One simple but often-neglected mechanism is luminal obstruction. Dilated tubular segments with flattened epithelial cells and lumina filled with protein casts are commonly seen in diseases characterized by heavy proteinuria, especially in animal models. The potential contribution of cast formation to tubulointerstitial disease was pointed out by Bertani et al in their original description of chronic adriamycin nephrosis26.Bertani T. Rocchi G. Sacchi G. et al.Adriamycin induced glomerulosclerosis in the rat.Am J Kidney Dis. 1986; 7: 12-19Abstract Full Text PDF PubMed Scopus (86) Google Scholar,27.Bertani T. Cutillo F. Zoja C. et al.Tubulo-interstitial lesions mediate renal damage in adriamycin glomerulopathy.Kidney Int. 1986; 30: 488-496Abstract Full Text PDF PubMed Scopus (175) Google Scholar. That luminal obstruction causes atubular atrophy was elegantly demonstrated by Tanner and Evan5.Tanner G.A. Evan A.P. Glomerular and proximal tubular morphology after single nephron obstruction.Am J Physiol. 1989; 36: 1050-1060Google Scholar,28.Evan A.P. Tanner G.A. Proximal tubule morphology after single nephron obstruction in the rat kidney.Kidney Int. 1986; 30: 818-827Abstract Full Text PDF PubMed Scopus (18) Google Scholar, who showed that chronic obstruction of single proximal tubules led to atrophy of both upstream and downstream segments. The latter result suggests that tubules atrophy when delivery of filtrate is reduced for any reason. Glomeruli of obstructed tubules eventually shrink and appear collapsed. Indeed, as Figure 3 illustrates, such glomeruli have the same appearance as the atubular glomeruli seen by Marcussen and coworkers in models of toxic tubular injury6.Marcussen N. Atubular glomeruli and the structural basis for chronic renal failure.Lab Invest. 1992; 66: 265-284PubMed Google Scholar, 7.Marcussen N. Ottosen P. Christensen S. Olsen T. Atubular glomeruli in lithium-induced chronic nephropathy in rats.Lab Invest. 1989; 61: 295-302PubMed Google Scholar, 8.Marcussen N. Atubular glomeruli in cisplatin-induced chronic interstitial nephropathy.APMIS. 1990; 98: 1087-1097Crossref PubMed Scopus (36) Google Scholar. The extent to which cast formation causes tubular loss in glomerular disease will become clear only when cast formation can be prevented. So far, this has not been accomplished. We recently tried to limit cast formation in rats with adriamycin nephrosis by decreasing urine concentration with a vasopressin V2 receptor blocker23.Javaid B. Olson J.L. Meyer T.W. Glomerular injury and tubular loss in adriamycin nephrosis.J Am Soc Nephrol. 2001; 12: 1392-1400Google Scholar. This maneuver had no effect on cast formation or any other aspect of renal injury, however.Table 1Potential mechanisms of tubular injuryObstruction of tubular lumen by castsObliteration of tubular neck by glomerular tuft adhesionsEffects of filtered macromolecules on tubular cells Actions of proteins with specific tubular receptors (growth factors,etc.) Results of “excessive” endocytosis of filtered plasma proteins Toxic effects of molecules bound to plasma proteins (lipids, etc.) Toxic effects of heme Open table in a new tab Kriz and colleagues described another mechanism by which glomerular injury can cause tubular loss before glomeruli are completely sclerosed29.Kriz W. Hosser H. Hahnel B. et al.Development of vascular pole-associated glomerulosclerosis in the Fawn-hooded rat.J Am Soc Nephrol. 1998; 9: 381-396PubMed Google Scholar,30.Kriz W. Hosser H. Hahnel B. et al.From segmental glomerulosclerosis to total nephron degeneration and interstitial fibrosis: A histopathological study in rat models and human glomerulopathies.Nephrol Dial Transplant. 1998; 13: 2781-2798Crossref PubMed Scopus (127) Google Scholar. They examined the relation of tubular and glomerular structure in experimental models of heavy proteinuria in which podocyte injury induced adhesion of the tuft to Bowman's capsule. Adhesion formation was followed by accumulation of amorphous material in a paraglomerular space that sometimes extended along the capsule to surround the neck of the tubule. Tracer studies indicated that the amorphous material included plasma proteins delivered to the paraglomerular space by “misdirected” filtration from glomerular capillary loops adherent to the capsule31.Kriz W. Hartmann I. Hosser H. et al.Tracer studies in the rat demonstrate misdirected filtration and peritubular filtrate spreading in nephrons with segmental glomerulosclerosis.J Am Soc Nephrol. 2001; 12: 496-506PubMed Google Scholar. Tubular degeneration was observed where the material extended down the tubule, separating the tubular cells from the underlying basement membrane. Presumably, infiltration of the amorphous material disrupted cell-membrane connections essential for maintenance of normal cell structure32.Frisch S.M. Ruoslahti E. Integrins and anoikis.Curr Opin Cell Biol. 1997; 9: 701-706Crossref PubMed Scopus (953) Google Scholar. Kriz et al initially described the extension of adhesions as causing tubular loss in Fawn hooded and Milan normotensive rats, but also identified this process in other rodent models29.Kriz W. Hosser H. Hahnel B. et al.Development of vascular pole-associated glomerulosclerosis in the Fawn-hooded rat.J Am Soc Nephrol. 1998; 9: 381-396PubMed Google Scholar, 30.Kriz W. Hosser H. Hahnel B. et al.From segmental glomerulosclerosis to total nephron degeneration and interstitial fibrosis: A histopathological study in rat models and human glomerulopathies.Nephrol Dial Transplant. 1998; 13: 2781-2798Crossref PubMed Scopus (127) Google Scholar, 31.Kriz W. Hartmann I. Hosser H. et al.Tracer studies in the rat demonstrate misdirected filtration and peritubular filtrate spreading in nephrons with segmental glomerulosclerosis.J Am Soc Nephrol. 2001; 12: 496-506PubMed Google Scholar. We recently observed this form of injury in adriamycin nephrosis23.Javaid B. Olson J.L. Meyer T.W. Glomerular injury and tubular loss in adriamycin nephrosis.J Am Soc Nephrol. 2001; 12: 1392-1400Google Scholar. Small tuft-to-capsule adhesions formed early in the course of nephrosis. Subsequently, the adhesions enlarged and amorphous material spread circumferentially along the capsule beneath a layer of fibroblast-like cells. Tubular atrophy leading to obliteration of the glomerular-tubular connection was present where the amorphous material reached the tubular neck. One difference between our results and those of Kriz et al29.Kriz W. Hosser H. Hahnel B. et al.Development of vascular pole-associated glomerulosclerosis in the Fawn-hooded rat.J Am Soc Nephrol. 1998; 9: 381-396PubMed Google Scholar,30.Kriz W. Hosser H. Hahnel B. et al.From segmental glomerulosclerosis to total nephron degeneration and interstitial fibrosis: A histopathological study in rat models and human glomerulopathies.Nephrol Dial Transplant. 1998; 13: 2781-2798Crossref PubMed Scopus (127) Google Scholar was that Bowman's space was usually not enlarged around glomeruli that had their connections to tubules severed by spreading adhesions. Enlargement of Bowman's space also has not been observed in studies of tubular injury induced by nephrotoxins or luminal obstruction5.Tanner G.A. Evan A.P. Glomerular and proximal tubular morphology after single nephron obstruction.Am J P" @default.
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• W1983132018 date "2003-02-01" @default.
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• W1983132018 title "Tubular injury in glomerular disease" @default.
• W1983132018 cites W1512243736 @default.
• W1983132018 cites W1592962814 @default.
• W1983132018 cites W1968788071 @default.
• W1983132018 cites W1968898857 @default.
• W1983132018 cites W1973138150 @default.
• W1983132018 cites W1977303408 @default.
• W1983132018 cites W1978581565 @default.
• W1983132018 cites W1981393628 @default.
• W1983132018 cites W1982529831 @default.
• W1983132018 cites W1991831723 @default.
• W1983132018 cites W1993196935 @default.
• W1983132018 cites W2002975107 @default.
• W1983132018 cites W2011918700 @default.
• W1983132018 cites W2021915768 @default.
• W1983132018 cites W2021935113 @default.
• W1983132018 cites W2024272971 @default.
• W1983132018 cites W2025882145 @default.
• W1983132018 cites W2026530727 @default.
• W1983132018 cites W2026639881 @default.
• W1983132018 cites W2028317647 @default.
• W1983132018 cites W2033905400 @default.
• W1983132018 cites W2035725566 @default.
• W1983132018 cites W2038908377 @default.
• W1983132018 cites W2039872965 @default.
• W1983132018 cites W2040704220 @default.
• W1983132018 cites W2040990167 @default.
• W1983132018 cites W2042063432 @default.
• W1983132018 cites W2050780076 @default.
• W1983132018 cites W2051046569 @default.
• W1983132018 cites W2053200320 @default.
• W1983132018 cites W2053723208 @default.
• W1983132018 cites W2055574122 @default.
• W1983132018 cites W2058669050 @default.
• W1983132018 cites W2064574428 @default.
• W1983132018 cites W2066015803 @default.
• W1983132018 cites W2066297692 @default.
• W1983132018 cites W2068509905 @default.
• W1983132018 cites W2080199877 @default.
• W1983132018 cites W2083787650 @default.
• W1983132018 cites W2083921005 @default.
• W1983132018 cites W2085146138 @default.
• W1983132018 cites W2091754751 @default.
• W1983132018 cites W2092168816 @default.
• W1983132018 cites W2093448087 @default.
• W1983132018 cites W2093671836 @default.
• W1983132018 cites W2104790008 @default.
• W1983132018 cites W2111703816 @default.
• W1983132018 cites W2111946284 @default.
• W1983132018 cites W2119745892 @default.
• W1983132018 cites W2121363636 @default.
• W1983132018 cites W2123627837 @default.
• W1983132018 cites W2123769953 @default.
• W1983132018 cites W2125964049 @default.
• W1983132018 cites W2127530565 @default.
• W1983132018 cites W2136253087 @default.
• W1983132018 cites W2136291709 @default.
• W1983132018 cites W2141691432 @default.
• W1983132018 cites W2154365158 @default.
• W1983132018 cites W2156864757 @default.
• W1983132018 cites W2159887906 @default.
• W1983132018 cites W2168033876 @default.
• W1983132018 cites W2168918540 @default.
• W1983132018 cites W2286727159 @default.
• W1983132018 cites W2313030564 @default.
• W1983132018 cites W2319844561 @default.
• W1983132018 cites W2334438904 @default.
• W1983132018 cites W2626401718 @default.
• W1983132018 cites W4246557706 @default.
• W1983132018 cites W4320578728 @default.
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