Role of the Kallikrain-Kinin System in Human Pancreatitis

Uehara, Soichiro; K, Honjyo; Furukawa, Shoei; Hirayama, Akio; Sakamoto, Wataru

doi:10.1007/978-1-4615-9546-5_106

Cited by 19 publications

(9 citation statements)

References 13 publications

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“…Patients with acute pancreatitis had six-fold higher plasma renin values than normal, which could be attributed to hypovolemia (22). However, plasma trypsin and kallikrein activate prorenin to renin, which in turn increases angiotensin II levels, leading to increased kidney vascular resistance, decreased effective kidney blood flow, and decline in GFR (22,23).…”

Section: Vascular Effects Of Acute Pancreatitismentioning

confidence: 99%

AKI Associated with Acute Pancreatitis

Nassar

Qunibi

2019

CJASN

111

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Acute pancreatitis is a common disorder of the pancreas. It is the most frequent gastrointestinal cause for hospitalization and one of the leading causes of in-hospital deaths. Its severity ranges from mild self-limited disease to severe acute necrotizing pancreatitis characterized by systemic complications and multiorgan failure. Severe acute pancreatitis develops in about 20% of patients with acute pancreatitis and may be associated with multiorgan failure (respiratory, cardiovascular, and kidney). AKI is a frequent complication of severe acute pancreatitis and develops late in the course of the disease, usually after the failure of other organs. It carries a very poor prognosis, particularly if kidney replacement therapy is required, with mortality rates exceeding 75%. The exact pathophysiology of AKI in acute pancreatitis remains unclear but appears to result from initial volume depletion followed by complex vascular and humoral factors. Here, we provide an overview of the epidemiology, pathogenesis, causes, and management of AKI in patients with severe acute pancreatitis.

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Section: Vascular Effects Of Acute Pancreatitismentioning

confidence: 99%

AKI Associated with Acute Pancreatitis

Nassar

Qunibi

2019

CJASN

111

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“…However, it is not known at present, which enzymes are responsible for the actual generation of kinins. Earlier clinical observations have indicated that both tissue kallikrein and plasma kallikrein may be activated during acute pancreatitis (Uehara et al ., 1989). In addition to kallikreins, the specific kininogenases, also other enzymes which may be activated during pancreatitis such as trypsin, cathepsins, plasmin and others have the potential for cleavage of kininogens and release of kinins (Prado, 1970).…”

Section: Discussionmentioning

confidence: 99%

Involvement of tissue kallikrein but not plasma kallikrein in the development of symptoms mediated by endogenous kinins in acute pancreatitis in rats

Griesbacher

Rainer

Tiran

et al. 2002

British J Pharmacology

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In order to investigate the mechanism of kinin release leading to vascular symptoms in acute interstitial‐oedematous pancreatitis, the novel, selective inhibitors of tissue kallikrein, (2S,2′R)‐2‐(2′‐amino‐3′‐(4′‐chlorophenyl)propanoylamino)‐N‐(3‐guanidinopropyl)‐3‐(1‐naphthyl)propanoamide (FE999024, CH‐2856), and of plasma kallikrein, (2′S,2′′R)‐4‐(2′‐(2′′(carboxymethylamino)‐3′′‐cyclohexyl‐propanoylamino)‐3′‐phenyl‐propanoylamino)piperidine‐1‐carboxamidin (FE999026, CH‐4215), were used in experimental caerulein‐induced pancreatitis in rats. Oedema formation and plasma protein extravasation during the 2 h infusion of caerulein were inhibited in a dose‐dependent manner by i.p. pretreatment with FE999024 (7–60 μmol kg−1) while FE999026 had no effect at the same doses. Haemoconcentration and hypovolaemia associated with the pancreatic oedema formation during pancreatitis were significantly attenuated by FE999024 at a dose of 20 μmol kg−1. The reduction in circulating plasma volume was not affected by FE999026. Accumulation of amylase and lipase in the pancreas was dose‐dependently reduced by FE999024 while enzyme activities in the blood serum were increased by FE999024 at 60 μmol kg−1 indicating improved enzyme removal from the tissue. Enzyme activities in the tissue and in the blood remained unaffected by FE999026. FE999024 (20 μmol kg−1) largely inhibited increased tissue kallikrein‐like activity in the pancreas during acute pancreatitis and also strongly attenuated influx of plasma kallikrein into the tissue. FE999026 (20 μmol kg−1) significantly inhibited plasma kallikrein‐like activity in the pancreas but had no effect on tissue kallikrein‐like activity. In conclusion, vascular kinin‐mediated symptoms observed during oedematous pancreatitis in the rat are caused by the action of tissue kallikrein in the pancreas whereas an involvement of plasma kallikrein seems to be unlikely. British Journal of Pharmacology (2002) 137, 692–700. doi:

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“…Zusätzlich zu der vasokonstriktiven Wirkung von Endothelin-1 (siehe oben) induziert die Freisetzung der Peptidase Trypsin und der Protease Kallikrein die Aktivierung des Renin-Angiotensin-Aldosteron-Systems (RAAS) [50,51].…”

Section: Vaskuläre Und Hämodynamische Effekteunclassified

Pankreatitisbedingte akute Nierenschädigung (AP-AKI): Definition, Pathophysiologie, Diagnostik und Therapie

et al. 2020

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ZusammenfassungDie akute Pankreatitis (AP) stellt die häufigste gastrointestinale Ursache für Krankenhausaufnahmen dar. Die Mortalität liegt bei 5 %, kann jedoch in Abhängigkeit vom Schweregrad auf bis zu 40 % ansteigen. Insbesondere schwere Verlaufsformen sind mit einem Multiorganversagen vergesellschaftet und haben eine schlechte Prognose. In diesem Zusammenhang kann es bei bis zu 10 % der Patienten zum akuten Nierenversagen (Acute kidney injury, AKI) kommen, das sich meistens spät nach dem Versagen anderer Organe entwickelt, aber auch initial oder isoliert auftreten kann. Darüber hinaus bestimmt das AKI als Komplikation der schweren Pankreatitis maßgeblich die Prognose, da die Mortalität, vor allem bei dialysepflichtigem AKI, auf bis zu 75 % dramatisch ansteigen kann.Im Vergleich zu anderen intensivmedizinisch assoziierten AKIs (z. B. Volumenmangel, kardiales Pumpversagen, Sepsis oder Intoxikationen) weist das mit einer AP assoziierte AKI (AP-AKI) viele Gemeinsamkeiten, aber auch deutliche Unterschiede auf. Die zwei existierenden Formen des AP-AKI (initiale prärenale Schädigung aufgrund eines Volumenmangels, intrarenale Schädigung in der Spätphase) können aufeinander folgend, aber auch unabhängig voneinander auftreten. Obwohl die Pathophysiologie gänzlich unverstanden ist, scheint eine systemische und lokale entzündliche Reaktion eine wichtige Rolle zu spielen. Die frühe Diagnose und die rechtzeitige Einleitung einer effektiven supportiven und ätiopathogenetisch gerichteten Therapie kann die Prognose deutlich verbessern. Ungeachtet dessen finden sich derzeit nur wenige Studien, die sich explizit mit AKI und Pankreatitis befassen.In der vorliegenden Übersicht konzentrieren wir uns – unter Verwendung der aktuellsten Literatur – auf die zugrunde liegenden pathophysiologischen Mechanismen des AP-AKI, untersuchen in dieser Hinsicht den diagnostischen und prognostischen Stellenwert alter und neuer Serum- und Urinmarker und diskutieren die für die AP-AKI empfohlenen Behandlungsansätze inklusive möglicher Nierenersatzverfahren.

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Role of the Kallikrain-Kinin System in Human Pancreatitis

Cited by 19 publications

References 13 publications

AKI Associated with Acute Pancreatitis

AKI Associated with Acute Pancreatitis

Involvement of tissue kallikrein but not plasma kallikrein in the development of symptoms mediated by endogenous kinins in acute pancreatitis in rats

Pankreatitisbedingte akute Nierenschädigung (AP-AKI): Definition, Pathophysiologie, Diagnostik und Therapie

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