Summary
The very heterogeneous population of glomeruli in rats with lithium-induced chronic nephropathy which includes small glomeruli without connection to a proximal tubule (atubular glomeruli) and large hypertropic glomeruli with connection to a normal proximal tubule, was studied at the ultrastructural level, using stereological methods. After 8 weeks of lithium treatment followed by 8 weeks without lithium the hypertrophic glomeruli showed no changes in their relative ultrastructural composition, including normal mesangium, basement membrane-like material and peripheral basement membrane. The absolute quantities of each component were, however, increased due to the increased volume of the glomeruli. The atubular glomeruli had increased volume fractions of mesangium, peripheral basement membrane, basement membrane-like material and epithelium, whereas the absolute quantities were decreased due to the decreased volume. The thickness of the basement membrane was within normal limits in the group of hypertrophic glomeruli but increased by 31% above controls in the group of atubular glomeruli. Both groups of glomeruli in lithium-treated animals showed normal mean foot process width, but with a slightly abnormal distribution. The atubular glomeruli showed a disproportionate large decrease in peripheral filtration surface and capillary length, compared with the reduction in glomerular volume, whereas the hypertrophic glomeruli showed changes in proportion with the increased volume.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Baddeley AJ, Gundersen HJG, Cruz-Orive LM (1986) Estimation of surface area from vertical sections. J Microsc 142:259–276
Bohle A, Thurau K (1974) Funktion und Morphologie der Niere im akuten Nierenversagen. Verh Dtsch Ges Inn Med 80:565–582
Bohle A, Grund KE, Mackensen S, Tolon M (1977) Correlations between renal interstitium and level of serum creatinine. Morphometric investigations of biopsies in perimembranous glomerulonephritis. Virchows Arch [A] 373:15–22
Bohle A, Gise H, Mackensen-Haen S, Stark-Jakob B (1981) The obliteration of the postglomerular capillaries and its influence upon the function of both glomeruli and tubuli. Functional interpretation of morphologic findings. Klin Wochenschr 59:1043–1051
Brekke IB, Gundersen HJG, Østerby R (1985) Thickening of glomerular basement membrane in rats with severe diabetes without kidney hypertrophy. Diabetic Nephropathy 4:19–22
Brenner BM (1985) Nephron adaptation to renal injury or ablation. Am J Physiol 249: F324-F337
Christensen S, Ottosen PD (1983) Lithium-induced uremia in rats — a new model of chronic renal failure. Pflügers Arch 399:208–212
Christensen S, Ottosen PD, Olsen S (1982) Severe functional and structural changes caused by lithium in the developing rat kidney. Acta Pathol Microbiol Immunol Scand Sect A 90:257–267
Gundersen HJG (1977) Notes on the estimation of the numerical density of arbitrary profiles: The edge effect. J Microsc 111:219–223
Gundersen HJG, Seefeldt T, Østerby R (1980) Glomerular epithelial foot processes in normal man and rats. Distribution of true width and its intra- and inter-individual variation. Cell Tissue Res 205:147–155
Gundersen HJG, Bagger P, Bendtsen TF, Evans SM, Korbo L, Marcussen N, Møller A, Nielsen K, Nyengaard JR, Pakkenberg B, Sørensen FB, Vesterby A, West MJ (1988a) The new stereological tools: disector, fractionator, nucleator and point sampled intercepts and their use in pathological research and diagnosis. APMIS 96:857–881
Gundersen HJG, Bendtsen TF, Korbo L, Marcussen N, Møller A, Nielsen K, Nyengaard JR, Pakkenberg B, Sørensen FB, Vesterby A, West MJ (1988b) Some new, simple and efficient stereological methods and their use in pathological research and diagnosis. APMIS 96:379–394
Hirose K, Østerby R, Nozawa M, Gundersen HJG (1982) Development of glomerular lesions in experimental long-term diabetes in rats. Kidney Int 21:689–695
Hostetter TH (1984) The hyperfiltering glomerulus. Med Clin North Am 68:387–398
Hostetter TH, Meyer TW, Rennke HG, Brenner BM, Noddin JA, Sandstrom DJ (1986) Chronic effects of dietary protein in the rat with intact and reduced renal mass. Kidney Int 30:509–517
Jensen EB, Gundersen HJG, Østerby R (1979) Determination of membrane thickness distribution from orthogonal intercepts. J Microsc 115:19–33
Kramp RA, MacDowell M, Gottschalk CW, Oliver JR (1974) A study by microdissection and micropuncture of the structure and function of the kidneys and nephrons of rats with chronic renal damage. Kidney Int 5:147–176
Mackensen-Haen S, Bader R, Grund KE, Bohle A (1981) Correlations between renal cortical interstitial fibrosis, atrophy of the proximal tubules and impairment of the glomerular filtration rate. Clin Nephrol 15:167–171
Marcussen N, Olsen TS (1990) Atubular glomeruli in patients with chronic pyelonephritis. Lab Invest 62:467–473
Marcussen N, Ottosen PD, Christensen S, Olsen TS (1989) Atubular glomeruli in lithium induced chronic nephropathy in rats. Lab Invest 61:295–302
Maunsbach AB (1966) The influence of different fixatives and fixation methods on the ultrastructure of rat kidney proximal tubule cells. I. Comparison of different perfusion fixation methods and of glutaraldehyde, formaldehyde and osmium tetroxide fixatives. J Ultrastruct Res 15:242–282
Møller JC, Skriver E (1985) Quantitative ultrastructure of human proximal tubules and cortical interstitium in chronic renal disease (hydronephrosis). Virchows Arch [A] 406:389–406
Møller JC, Skriver E, Olsen S, Maunsbach AB (1984) Ultrastructural analysis of human proximal tubules and cortical interstitium in chronic renal disease (Hydronephrosis). Virchows Arch [A] 402:209–237
Ottosen PD, Sigh B, Kristensen J, Olsen S, Christensen S (1984) Lithium induced interstitial nephropathy associated with chronic renal failure. Acta Pathol Microbiol Immunol Scand Sect A 92:447–454
Østerby R (1973) A quantitative electron microscopic study of mesangial regions in glomeruli from patients with short term juvenile diabetes mellitus. Lab Invest 29:99–110
Østerby R, Gundersen HJG (1980) Fast accumulation of basement membrane material and the rate of morphological changes in acute experimental diabetic glomerular hypertrophy. Diabetologia 18:493–500
Seefeldt T, Bohman S-O, Gundersen HJG, Maunsbach AB, Petersen VP, Olsen S (1981) Quantitative relationship between glomerular foot process width and proteinuria in glomerulonephritis. Lab Invest 44:541–546
Shea SM, Raskova J, Morrison AB (1978) A stereologic study of glomerular hypertrophy in the subtotally nephrectomized rat. Am J Pathol 90:201–210
Steinhardt GF, Ramon G, Salinas-Madrigal L (1988) Glomerulosclerosis in obstructive uropathy. J Urol 140:1316–1318
Sterio DC (1984) The unbiased estimation of number and sizes of arbitrary particles using the disector. J Microsc 134:127–136
Weibel ER (1979) Stereological methods: practical methods for biological morphometry, vol 1. Academic Press, New York
Yoshida Y, Fogo A, Shiraga H, Glick AD, Ichikawa I (1988) Serial micropuncture analysis of single nephron function in subtotal renal ablation. Kidney Int 33:855–867
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Marcussen, N., Ottosen, P.D. & Christensen, S. Ultrastructural quantitation of atubular and hypertrophic glomeruli in rats with lithium-induced chronic nephropathy. Vichows Archiv A Pathol Anat 417, 513–522 (1990). https://doi.org/10.1007/BF01625732
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01625732