Skip to main content
SpringerLink
Log in

Formation of atubular glomeruli in the developing kidney following chronic urinary tract obstruction

  • Review
  • Published:
Pediatric Nephrology Aims and scope Submit manuscript

Abstract

Congenital urinary tract obstruction is a major cause of progressive renal disease in children. We developed a model of partial unilateral ureteral obstruction (UUO) in the neonatal mouse, in which nephrogenesis at birth is similar to that of the midtrimester human fetus. The proximal tubule responds to UUO by undergoing apoptosis and necrosis, likely due to mitochondrial sensitivity to hypoxia and reactive oxygen species in the face of reduced endogenous antiapoptotic factors such as eNOS. Damage to the glomerulotubular junction is followed by scission and formation of atubular glomeruli and aglomerular tubules. This is an orchestrated process, with atubular glomeruli surrounded by a continuous layer of regenerated parietal epithelial cells. Relief of UUO at 7 days of age results in remodeling of the renal parenchyma by adulthood. In contrast to proximal tubular destruction, collecting ducts remain dilated and patent, with remodeling due to apoptosis and proliferation (a process associated with recruitment of intercalated cells as progenitor cells following UUO in the fetal monkey). Formation of atubular glomeruli occurs in other renal disorders (congenital nephrotic syndrome and cystinosis), and may represent a maladaptive response to proximal tubular injury reflecting an evolutionary adaptation by an ancestor we share with aglomerular marine fish.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Thornhill BA, Forbes MS, Marcinko ES, Chevalier RL (2007) Glomerulotubular disconnection in neonatal mice after relief of partial ureteral obstruction. Kidney Int 72:1103–1112

    Article  CAS  Google Scholar 

  2. Chevalier RL, Thornhill BA, Forbes MS, Kiley SC (2010) Mechanisms of renal injury and progression of renal disease in congenital obstructive nephropathy. Pediatr Nephrol 25:687–697

    Article  Google Scholar 

  3. Hall AM, Unwin RJ, Parker N, Duchen MR (2009) Multiphoton imaging reveals differences in mitochondrial function between nephron segments. J Am Soc Nephrol 20:1293–1302

    Article  CAS  Google Scholar 

  4. Ohse T, Pippin JW, Chang AM, Krofft RD, Miner JH, Vaughan MR, Shankland SJ (2009) The enigmatic parietal epithelial cell is finally getting noticed: a review. Kidney Int 76:1225–1238

    Article  Google Scholar 

  5. Ronconi E, Sagrinati C, Angelotti ML, Lazzeri E, Mazzinghi B, Ballerini L, Parente E, Becherucci F, Gacci M, Carini M, Maggi E, Serio M, Vannelli GB, Lasagni L, Romagnani S, Romagnani P (2009) Regeneration of glomerular podocytes by human renal progenitors [see comment]. J Am Soc Nephrol 20:322–332

    Article  CAS  Google Scholar 

  6. Venkatachalam MA, Griffin KA, Lan R, Geng H, Saikumanr P, Bidani AK (2010) Acute kidney injury: a springboard for progression in chronic kidney disease. Am J Physiol 298:F1078–F1094

    CAS  Google Scholar 

  7. Chevalier RL, Forbes MS (2008) Generation and evolution of atubular glomeruli in the progression of renal disorders. J Am Soc Nephrol 19:197–206

    Article  Google Scholar 

  8. Forbes MS, Thornhill BA, Park MH, Chevalier RL (2007) Lack of endothelial nitric-oxide synthase leads to progressive focal renal injury. Am J Pathol 170:87–99

    Article  CAS  Google Scholar 

  9. Silverstein DM, Travis BR, Thornhill BA, Schurr JS, Kolls JK, Leung JC, Chevalier RL (2003) Altered expression of immune modulator and structural genes in neonatal unilateral ureteral obstruction. Kidney Int 64:25–35

    Article  CAS  Google Scholar 

  10. Valles P, Pascual L, Manucha W, Carrizo L, Ruttler M (2003) Role of endogenous nitric oxide in unilateral ureteropelvic junction obstruction in children. Kidney Int 63:1104–1115

    Article  CAS  Google Scholar 

  11. Butt MJ, Tarantal AF, Jimenez DF, Matsell DG (2007) Collecting duct epithelial-mesenchymal transition in fetal urinary tract obstruction. Kidney Int 72:936–944

    Article  CAS  Google Scholar 

  12. Konda R, Orikasa S, Sakai K, Ota S, Kimura N (1996) The distribution of renin containing cells in scarred kidneys. J Urol 156:1450–1454

    Article  CAS  Google Scholar 

  13. El-Dahr SS, Gomez RA, Gray MS, Peach MJ, Carey RM, Chevalier RL (1990) In situ localization of renin and its mRNA in neonatal ureteral obstruction. Am J Physiol 258:F854–F862

    CAS  PubMed  Google Scholar 

  14. Cohen EP, Regner K, Fish BL, Moulder JE (2000) Stenotic glomerulotubular necks in radiation nephropathy. J Pathol 190:484–488

    Article  CAS  Google Scholar 

  15. Benigni A, Gagliardini E, Remuzzi A, Corna D, Remuzzi G (2001) Angiotensin-converting enzyme inhibition prevents glomerular-tubule disconnection and atrophy in passive Heymann nephritis, an effect not observed with a calcium antagonist. Am J Pathol 159:1743–1750

    Article  CAS  Google Scholar 

  16. Marcussen N, Olsen TS (1990) Atubular glomeruli in patients with chronic pyelonephritis. Lab Invest 62:467–473

    CAS  PubMed  Google Scholar 

  17. Thoene JG (2007) A review of the role of enhanced apoptosis in the pathophysiology of cystinosis. Molec Genet Metab 92:292–298

    Article  CAS  Google Scholar 

  18. Vats AN, Costello B, Mauer M (2003) Glomerular structural factors in progression of congenital nephrotic syndrome. Pediatr Nephrol 18:234–240

    PubMed  Google Scholar 

  19. Najafian B, Kim Y, Crosson JT, Mauer M (2003) Atubular glomeruli and glomerulotubular junction abnormalities in diabetic nephropathy. J Am Soc Nephrol 14:908–917

    Article  Google Scholar 

  20. Brezniceanu M-L, Liu F, Wei C-C, Tran S, Sachetelli S, Zhang S-L, Guo D-F, Filep JG, Ingelfinger JR, Chan JSD (2007) Catalase overexpression attenuates angiotensinogen expression and apoptosis in diabetic mice. Kidney Int 71:912–923

    Article  CAS  Google Scholar 

  21. Oliver J, Luey AB (1935) Plastic studies in abnormal renal architecture. Arch Pathol 19:1–23

    Google Scholar 

  22. Marcussen N (2000) Tubulointerstitial damage leads to atubular glomeruli: significance and possible role in progression. Nephrol Dial Transplant 15(Suppl 6):74–75

    Article  Google Scholar 

  23. Thornhill BA, Burt LA, Chen C, Forbes MS, Chevalier RL (2005) Variable chronic partial ureteral obstruction in the neonatal rat: A new model of ureteropelvic junction obstruction. Kidney Int 67:42–52

    Article  Google Scholar 

  24. Chevalier RL, Thornhill BA, Chang AY (2000) Unilateral ureteral obstruction in neonatal rats leads to renal insufficiency in adulthood. Kidney Int 58:1987–1995

    Article  CAS  Google Scholar 

  25. Grantham JJ, Wallace DP (2002) Return of the secretory kidney. Am J Physiol 282:F1–F9

    Article  CAS  Google Scholar 

  26. Smith HW (1953) From fish to philosopher. Little, Brown, Boston

    Google Scholar 

  27. Grafflin AL (1933) Glomerular degeneration in the kidney of the daddy sculpin (Myoxocephalus scorpius). Anat Rec 57:59–78

    Article  Google Scholar 

  28. Beyenbach KW (2003) Kidneys sans glomeruli. Am J Physiol 286:F811–F827

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pediatrics, University of Virginia Health System, Box 800386, Charlottesville, VA, 22908, USA

    Robert L. Chevalier, Michael S. Forbes & Barbara A. Thornhill

Authors
  1. Robert L. Chevalier
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Michael S. Forbes
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Barbara A. Thornhill
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Robert L. Chevalier.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chevalier, R.L., Forbes, M.S. & Thornhill, B.A. Formation of atubular glomeruli in the developing kidney following chronic urinary tract obstruction. Pediatr Nephrol 26, 1381–1385 (2011). https://doi.org/10.1007/s00467-010-1748-y

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00467-010-1748-y

Keywords

Search

Navigation