Three-dimensional analysis of glomerular morphology in patients with subtotal nephrectomy

Remuzzi, Andrea; Mazerska, Maria; Gephardt, Gordon N.; Novick, Andrew C.; Brenner, Barry M.; Remuzzi, Giuseppe

doi:10.1038/ki.1995.279

Cited by 59 publications

(27 citation statements)

References 5 publications

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“…In all of the studies described above, quantification of sclerosis was based on semiquantitative scores. Yet 2D analysis of a single section of a biopsy specimen overestimates the number of normal glomeruli and underestimates the actual extent of glomerulosclerosis (106,107). Thus one cannot currently tell what volume of glomerular capillaries is actually affected by sclerosis and to what extent the sclerosis volume is effectively reduced by treatment.…”

Section: Animals Studies Help Clarify the Significance Of Human Findingsmentioning

confidence: 99%

Mechanisms of progression and regression of renal lesions of chronic nephropathies and diabetes

Remuzzi

Benigni

Remuzzi³

2006

Journal of Clinical Investigation

539

419

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The incidence of chronic kidney diseases is increasing worldwide, and these conditions are emerging as a major public health problem. While genetic factors contribute to susceptibility and progression of renal disease, proteinuria has been claimed as an independent predictor of outcome. Reduction of urinary protein levels by various medications and a low-protein diet limits renal function decline in individuals with nondiabetic and diabetic nephropathies to the point that remission of the disease and regression of renal lesions have been observed in experimental animals and even in humans. In animal models, regression of glomerular structural changes is associated with remodeling of the glomerular architecture. Instrumental to this discovery were 3D reconstruction studies of the glomerular capillary tuft, which allowed the quantification of sclerosis volume reduction and capillary regeneration upon treatment. Regeneration of capillary segments might result from the contribution of resident cells, but progenitor cells of renal or extrarenal origin may also have a role. This review describes recent advances in our understanding of the mechanisms and mediators underlying renal tissue repair ultimately responsible for regression of renal injury.

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Section: Animals Studies Help Clarify the Significance Of Human Findingsmentioning

confidence: 99%

Mechanisms of progression and regression of renal lesions of chronic nephropathies and diabetes

Remuzzi

Benigni

Remuzzi³

2006

Journal of Clinical Investigation

539

419

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“…The complex three-dimensional structure of the glomerular capillary bed has been studied using serial section microtomy (16,50,76,90). However, the method generally has not been practical for studying the overall renal vascular architecture because of physical problems relating to the alignment and registration of adjacent sections, lost or distorted sections, and time and effort involved in the preparation and analysis of the sections.…”

Section: Three-dimensional Analysis Of Serial Sectionsmentioning

confidence: 99%

The use of microcomputed tomography to study microvasculature in small rodents

Bentley

Ortiz

Ritman

et al. 2002

American Journal of Physiology-Regulatory, Integrative and Comp

135

109

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The use of microcomputed tomography to study microvasculature in small rodents. Am J Physiol Regulatory Integrative Comp Physiol 282: R1267-R1279, 2002 10.1152/ajpregu.00560.2001.-Appropriate nephron function is dependent on the intrarenal arrangement of blood vessels. The preferred and primary means to study the architecture of intrarenal circulation has been by filling it with opaque substances such as india ink, radio-opaque contrast material, or various polymers for study by light or scanning electron microscopy. With such methodologies, superficial vessels may obscure deep vessels and little quantitative information may be obtained. Serial-section microtomy has not been practical because of problems relating to alignment and registration of adjacent sections, lost sections, and preparation time and effort. Microcomputed tomography (micro-CT) overcomes such limitations and provides a means to study the three-dimensional architecture of filled vessels within an intact rodent kidney and to obtain more quantitative information. As an example of micro-CT's capabilities, we review the use of micro-CT to study the alterations in renal microvasculature caused by the development of liver cirrhosis after chronic bile duct ligation. In this example, micro-CT evidence shows a selective decrease in cortical vascular filling in the kidney, with a maintenance of medullary vascular filling. These changes may contribute to the salt and water retention that accompanies cirrhosis. These results indicate that micro-CT is a promising method to evaluate renal vascular architecture in the intact rodent kidney relative to physiological and pathological function. kidney; imaging; microcirculation; vasculature APPROPRIATE NEPHRON FUNCTION appears to be dependent on the detailed three-dimensional interrelationship of blood vessels with the tubular components. Many techniques and/or methods have been developed to examine the microanatomic arrangement of pre-and postglomerular vasculature (4,29,36,40,54,55,59,71,98). In this respect, such efforts were prompted by early studies showing that urinary excretion varied in relation to the intrarenal environment and was dependent on the coupling of renal microcirculation and tubular components. In 1947, Trueta and colleagues (96), studying the crush syndrome in rabbits, observed that there was a shift of blood flow from the renal cortex to the medulla during hemorrhage. They suggested this shift to be the major explanation for the lack of urine flow, despite a preservation of renal blood flow (RBF). The shift of blood flow within the renal cortex from superficial short nephrons to deep long nephrons was later observed in sodium-retaining states such as cardiac insufficiency, hepatic cirrhosis, or hypovolemia (1,18,53,104). showed that changes in renal perfusion pressure, within a range (75-130 mmHg) in which RBF remains unchanged (RBF autoregulation), were followed by dramatic changes in sodium excretion. This situation is comparable to that seen in the early stages Address for reprint requ...

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“…Thus, while only an average of 29% of glomeruli were scored as affected by glomerulosclerosis in the adriamycin model on single sections, serial-section reconstructions revealed that 92% of glomeruli on average actually showed sclerotic changes. Similar results have been obtained in the analysis of human kidney biopsies (14). To accurately establish to what extent AII antagonism can effectively reduce the sclerotic areas, and the volume of glomerular capillary tuft eventually regenerated, more extensive investigation, focused at the individual glomerular level, is needed.…”

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confidence: 55%

Is Regression of Chronic Nephropathies a Therapeutic Target?

Remuzzi

2005

Journal of the American Society of Nephrology

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M ost kidney diseases lead to progressive deterioration of renal function, but the rate of progression differs among different disease types and even among individual patients with the same disease. Experimental studies and clinical research over the last few decades have identified several plausible mechanisms for progression of renal disease in various animal models and in human disease. These observations have led directly to studies establishing the fact that loss of renal function can be limited by certain antihypertensive medications (1). Thus, drugs that counteract the action of angiotensin II (AII)-the angiontensin-converting enzyme (ACE) inhibitors and the AII receptor antagonists-modify glomerular hemodynamics, lower proteinuria, and slow the rate of disease progression (2). Whether these drugs given in higher doses than those required to normalize BP can not only slow or halt progresssion but also induce regression of established glomerulosclerosis and tubular interstitial lesions has been debated. Evidence of reversal of proteinuria and glomerulosclerosis by combining a low-protein diet with an ACE inhibitor was first provided by Marinides et al. in 1990 in the puromycin aminonucleoside rat model (3). Ten years later, attention was again drawn to this topic by the work of Ma et al. (4). Although at that time glomerular structural changes were still considered irreversible, these authors showed regression of glomerulosclerosis in aging rats given an AII receptor antagonist. In this study, reversal of glomerular and vascular lesions was associated with modulation of plasminogen activator inhibitor-1 (PAI-1). The efficacy of AII antagonism in inducing regression of structural changes has also been demonstrated in a genetic model of progressive kidney disease, the male Munich Wistar Fromter (MWF) rat (5,6). In these rats, which develop proteinuria and glomerulosclerosis spontaneously with age, combined treatment with an ACE inhibitor and an AII receptor antagonist induced complete regression of proteinuria and favorably affected glomerulosclerosis. Thus, glomerular structural changes were ameliorated in those glomeruli with sclerosis involving Ͻ25% of the tuft area, while more extensive lesions remained unaltered. Interestingly, although GFR was not improved by treatment, the glomerular ultrafiltration coefficient increased (5). Recently, similar observations have also been reported in the renal ablation model by Adamczak and coworkers (7,8). In this classical model of glomerular disease progression, delayed treatment with an ACE inhibitor induced partial reversal of glomerular as well as interstitial and vascular lesions. Reversal of glomerular structural lesions was associated with remodeling of glomerular capillary microvasculature, as estimated by morphometric analysis, with a reduction in mean glomerular volume and reversal of the increase in total capillary surface area observed after renal mass ablation (8). Despite the beneficial effect of treatment on glomerulosclerosis in these animals, plasma...

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Three-dimensional analysis of glomerular morphology in patients with subtotal nephrectomy

Cited by 59 publications

References 5 publications

Mechanisms of progression and regression of renal lesions of chronic nephropathies and diabetes

Mechanisms of progression and regression of renal lesions of chronic nephropathies and diabetes

The use of microcomputed tomography to study microvasculature in small rodents

Is Regression of Chronic Nephropathies a Therapeutic Target?

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