Tags

Type your tag names separated by a space and hit enter

Activity and functional significance of the renal kallikrein-kinin-system in polycystic kidney disease of the rat.
Kidney Int. 2002 Jun; 61(6):2149-56.KI

Abstract

Activity and functional significance of the renal kallikrein-kinin-system in polycystic kidney disease of the rat.

BACKGROUND

The kallikrein-kinin-system is a complex multienzymatic system that has been implicated in the control of systemic blood pressure, glomerular filtration rate, and proteinuria. The present study investigated its functional role in rat polycystic kidney disease (PKD), which is characterized by progressive renal failure and proteinuria in the absence of systemic hypertension and stimulated renin-angiotensin-system.

METHODS

Kallikrein and bradykinin levels were measured in plasma and urine of rats with polycystic kidneys and compared to non-affected controls (SD) and rats with reduced renal mass. The functional relevance of the kallikrein-kinin system (KKS) was assessed by the effects of a short-term treatment with either a selective bradykinin (BK) B1-receptor antagonist (des-Arg9-[Leu8]-BK), a B2-receptor antagonist (HOE 140), an angiotensin converting enzyme inhibitor (ramipril), or an angiotensin II-receptor blocker (HR 720) on systemic and renal parameters.

RESULTS

Urine levels of kallikrein were increased threefold in 9-month-old PKD, and BK excretion was increased tenfold in 3-month and 30-fold in 9-month-old PKD compared to age-matched SD rats. Blood pressure in 9-month-old PKD rats was decreased to the same degree by ramipril and HR 720. In contrast, only ramipril and HOE 140 significantly reduced proteinuria and albuminuria, independent from creatinine clearance. This effect was accompanied by an increased excretion of bradykinin. The B1 receptor antagonist had no influence on functional renal parameters.

CONCLUSIONS

The present study demonstrates an age-dependent activation of the renal KKS in rats with polycystic kidney disease. The bradykinin B2-receptor is involved in the pathogenesis of proteinuria, independent from systemic blood pressure or creatinine clearance. The antiproteinuric effect of ramipril in this model is angiotensin II-independent and related to its influence on the renal KKS.

Authors+Show Affiliations

V. Department of Medicine (Nephrology/Endocrinology/Rheumatology), University Hospital Mannheim, Germany. BraunC@verw.ma.uni-heidelberg.deNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

12028455

Citation

Braun, Claude, et al. "Activity and Functional Significance of the Renal Kallikrein-kinin-system in Polycystic Kidney Disease of the Rat." Kidney International, vol. 61, no. 6, 2002, pp. 2149-56.
Braun C, Kleemann T, Hilgenfeldt U, et al. Activity and functional significance of the renal kallikrein-kinin-system in polycystic kidney disease of the rat. Kidney Int. 2002;61(6):2149-56.
Braun, C., Kleemann, T., Hilgenfeldt, U., Riester, U., Rohmeiss, P., & van der Woude, F. J. (2002). Activity and functional significance of the renal kallikrein-kinin-system in polycystic kidney disease of the rat. Kidney International, 61(6), 2149-56.
Braun C, et al. Activity and Functional Significance of the Renal Kallikrein-kinin-system in Polycystic Kidney Disease of the Rat. Kidney Int. 2002;61(6):2149-56. PubMed PMID: 12028455.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Activity and functional significance of the renal kallikrein-kinin-system in polycystic kidney disease of the rat. AU - Braun,Claude, AU - Kleemann,Thomas, AU - Hilgenfeldt,Ulrich, AU - Riester,Udo, AU - Rohmeiss,Peter, AU - van der Woude,Fokko J, PY - 2002/5/25/pubmed PY - 2002/10/22/medline PY - 2002/5/25/entrez SP - 2149 EP - 56 JF - Kidney international JO - Kidney Int. VL - 61 IS - 6 N2 - UNLABELLED: Activity and functional significance of the renal kallikrein-kinin-system in polycystic kidney disease of the rat. BACKGROUND: The kallikrein-kinin-system is a complex multienzymatic system that has been implicated in the control of systemic blood pressure, glomerular filtration rate, and proteinuria. The present study investigated its functional role in rat polycystic kidney disease (PKD), which is characterized by progressive renal failure and proteinuria in the absence of systemic hypertension and stimulated renin-angiotensin-system. METHODS: Kallikrein and bradykinin levels were measured in plasma and urine of rats with polycystic kidneys and compared to non-affected controls (SD) and rats with reduced renal mass. The functional relevance of the kallikrein-kinin system (KKS) was assessed by the effects of a short-term treatment with either a selective bradykinin (BK) B1-receptor antagonist (des-Arg9-[Leu8]-BK), a B2-receptor antagonist (HOE 140), an angiotensin converting enzyme inhibitor (ramipril), or an angiotensin II-receptor blocker (HR 720) on systemic and renal parameters. RESULTS: Urine levels of kallikrein were increased threefold in 9-month-old PKD, and BK excretion was increased tenfold in 3-month and 30-fold in 9-month-old PKD compared to age-matched SD rats. Blood pressure in 9-month-old PKD rats was decreased to the same degree by ramipril and HR 720. In contrast, only ramipril and HOE 140 significantly reduced proteinuria and albuminuria, independent from creatinine clearance. This effect was accompanied by an increased excretion of bradykinin. The B1 receptor antagonist had no influence on functional renal parameters. CONCLUSIONS: The present study demonstrates an age-dependent activation of the renal KKS in rats with polycystic kidney disease. The bradykinin B2-receptor is involved in the pathogenesis of proteinuria, independent from systemic blood pressure or creatinine clearance. The antiproteinuric effect of ramipril in this model is angiotensin II-independent and related to its influence on the renal KKS. SN - 0085-2538 UR - https://www.unboundmedicine.com/medline/citation/12028455/Activity_and_functional_significance_of_the_renal_kallikrein_kinin_system_in_polycystic_kidney_disease_of_the_rat_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0085-2538(15)48464-9 DB - PRIME DP - Unbound Medicine ER -