Role of obstruction in autosomal dominant polycystic kidney disease in rats

George A. Tanner, Norbert Gretz, Bret A. Connors, Andrew Evan, Michael Steinhausen

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Kidney micropuncture and microdissection studies were carried out on heterozygous 2- to 4-month-old female and male Han:SPRD rats with autosomal dominant polycystic kidney disease (ADPKD) and on normal controls, to determine whether cysts are obstructed. Pressures in proximal tubules and cysts were determined using a servo null device and were recorded before, during, and after intraluminal infusion of an isotonic equilibrium solution at 15 and 50 nl/min. Initial cyst pressures in nine cystic rats averaged 18.5 ± 5.9 (SD) mm Hg, N = 49, significantly (P <0.01) higher than in normal proximal tubules in four control rats, 14.3 ± 1.6 mm Hg, N = 36. Pressures in non-cystic tubules in cystic rats, 16.8 ± 4.4 mm Hg, N = 25, were not significantly different from pressures in control kidneys or in cysts. When proximal tubules were microinfused at 15 nl/min in control rats, tubule pressure increased by 3.8 ± 1.2 mm Hg, N = 24. In cysts, the response was highly variable. Twenty out of 33 microinfused cysts (61%) showed responses similar to normal tubules and were considered to be nonobstructed; 13 (39%) showed large pressure increases upon microinfusion, sometimes to values over 100 mm Hg (obstructed cysts). Left kidney inulin clearance (in μl/min · 100 g body wt) averaged 335 ± 65 (N = 4) in control rats and 344 ± 144 (N = 9) in cystic rats; at this early stage of the disease no decline in GFR was seen. Weights of cystic kidneys were twice those of normal animals. Microdissection and scanning electron microscopy revealed the presence of intraluminal casts and debris and constrictions between cysts that would impede fluid flow. We conclude that obstruction is a frequent, early event in PKD and, when present, promotes cyst enlargement. Since many cysts are not obstructed, we suggest that factors other than fixed obstruction initiate cyst formation.

Original languageEnglish (US)
Pages (from-to)873-886
Number of pages14
JournalKidney International
Volume50
Issue number3
StatePublished - 1996
Externally publishedYes

Fingerprint

Autosomal Dominant Polycystic Kidney
Cysts
Pressure
Microdissection
Kidney
Cystic Kidney Diseases
Isotonic Solutions
Inulin
Punctures
Constriction
Electron Scanning Microscopy

ASJC Scopus subject areas

  • Nephrology

Cite this

Tanner, G. A., Gretz, N., Connors, B. A., Evan, A., & Steinhausen, M. (1996). Role of obstruction in autosomal dominant polycystic kidney disease in rats. Kidney International, 50(3), 873-886.

Role of obstruction in autosomal dominant polycystic kidney disease in rats. / Tanner, George A.; Gretz, Norbert; Connors, Bret A.; Evan, Andrew; Steinhausen, Michael.

In: Kidney International, Vol. 50, No. 3, 1996, p. 873-886.

Research output: Contribution to journalArticle

Tanner, GA, Gretz, N, Connors, BA, Evan, A & Steinhausen, M 1996, 'Role of obstruction in autosomal dominant polycystic kidney disease in rats', Kidney International, vol. 50, no. 3, pp. 873-886.
Tanner GA, Gretz N, Connors BA, Evan A, Steinhausen M. Role of obstruction in autosomal dominant polycystic kidney disease in rats. Kidney International. 1996;50(3):873-886.
Tanner, George A. ; Gretz, Norbert ; Connors, Bret A. ; Evan, Andrew ; Steinhausen, Michael. / Role of obstruction in autosomal dominant polycystic kidney disease in rats. In: Kidney International. 1996 ; Vol. 50, No. 3. pp. 873-886.
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