Increased activity of the renal kallikrein–kinin system in autosomal dominant polycystic kidney disease in rats, but not in humans
Autor: | Udo Riester, Rainer Birck, Carsten Tschöpe, Peter Rohmeiss, Thomas Kleemann, Ulrich Hilgenfeldt, Fokko J. van der Woude, Claude Braun |
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Rok vydání: | 2002 |
Předmět: |
Adult
Male Aging medicine.medical_specialty Kallikrein-Kinin System Urinary system Immunology Autosomal dominant polycystic kidney disease Bradykinin urologic and male genital diseases Excretion chemistry.chemical_compound Species Specificity Internal medicine medicine Polycystic kidney disease Animals Humans Immunology and Allergy Aged Pharmacology Creatinine urogenital system Rats Inbred Strains Kallikrein Middle Aged Kinin Polycystic Kidney Autosomal Dominant medicine.disease Rats Endocrinology chemistry Kallikreins Kidney disease |
Zdroj: | International Immunopharmacology. 2:1949-1956 |
ISSN: | 1567-5769 |
DOI: | 10.1016/s1567-5769(02)00171-6 |
Popis: | The kallikrein–kinin system (KKS) was investigated in autosomal dominant polycystic kidney disease (ADPKD)-affected rats (PKD) and compared to unaffected controls (SD) and 5/6 nephrectomized rats (5/6 Nx). In addition, patients with ADPKD compared to patients with nonpolycystic kidney disease and healthy controls have been investigated. Plasma and urine samples for determination of creatinine, protein, kallikrein (KAL) and bradykinin (BK) were taken in male 3- and 9-month-old PKD, SD and 9-month-old 5/6 Nx. The same parameters were determined in young (age: 20–40 years) and old (41–65 years) male patients with ADPKD and compared to age-matched patients with nonpolycystic kidney disease and age-matched healthy controls. Plasma and urine KAL were measured by chromogenic peptide substrate, and kinins were determined by radioimmunoassay. Urine KAL and BK levels were increased in PKD compared to age-matched SD. No differences with respect to serum KAL were found between PKD and SD. In 5/6 Nx, urinary BK levels showed a trend towards higher compared to old SD ( p =0.06). KAL and BK were not increased in serum and urine of patients with ADPKD, in contrast to rats. Urinary KAL excretion was reduced in patients with ADPKD and advanced renal failure. Our results demonstrate an age-dependent activation of the renal KKS in rats with ADPKD, whereas the KKS is not activated in patients with ADPKD and advanced renal failure. These data indicate that there are fundamental differences in the factors influencing the course of the disease in human and rat ADPKD. |
Databáze: | OpenAIRE |
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