Summary
In ultrafiltrated plasma (molecular weight <50,000) obtained from four patients with multiple muscular trauma and acute post-traumatic renal failure, it was possible to verify a subcomponential specific digestion of the subunits alpha and gamma of phosphorylase kinase isolated from rabbit skeletal muscle. The activity of free proteolytic enzymes in ultrafiltrated plasma as well as an increase of plasma alpha1-antitrypsin values were correlated with the severity and unfavourable course of the illness. In contrast, the plasma levels of alpha2-macroglobulin were drastically lowered. The mean total protein concentration in the sera of patients with post-traumatic ARF was lowered, whereas the mean ultrafiltrate protein concentration was significantly enhanced. In ultrafiltrated plasma of two patients with hyperuricaemic ARF, three patients with ARF after drug over-dosage, one patient with acute pancreatic necrosis combined with acute renal failure and one patient with chronic pancreatitis, no proteolytic activity could be detected using phosphorylase kinase as substrate. Studies on the trypsin binding capacity of the plasma protease inhibitors revealed a significantly lowered level in patients with post-traumatic acute renal failure as compared to healthy controls, patients with chronic renal insufficiency and patients on regular dialysis treatment. Proteolytic activity was found in ca. 100-fold concentrated diafiltrates (molecular weight >10,000) of patients on regular dialysis treatment. Our data suggest a participation of proteases on protein catabolism in hypercatabolic states. Whilst the blood coagulation system can largely be excluded as a source of proteases, it is possible that proteolytic enzymes may be released from muscle lysosomes and/or macrophages after multiple muscular trauma.
Zusammenfassung
Im ultrafiltrierten Plasma (Molekulargewicht <50 000) von vier Patienten mit Polytrauma und akutem posttraumatischen Nierenversagen gelang der Nachweis einer proteolytischen Verdauung der Untereinheiten alpha und gamma von Phosphorylase-Kinase, isoliert aus Skelettmuskulatur von Kaninchen. Es bestand eine Beziehung zwischen der Aktivität der freien proteolytischen Enzyme im ultrafiltrierten Plasma und dem Anstieg der Plasma-Alpha1-Antitrypsin-Werte mit der Schwere und dem ungünstigen Verlauf der Erkrankung. Die Plasma-Alpha2-Macroglobulin-Spiegel waren bei Patienten mit posttraumatischem akuten Nierenversagen deutlich erniedrigt. Im Serum von Patienten mit posttraumatischem akuten Nierenversagen war die Gesamtproteinkonzentration erniedrigt, im Plasmaultrafiltrat signifikant erhöht. Bei zwei Patienten mit akuter hyperurikämischer Nephropathie und drei Patienten mit medikamentös induziertem akuten Nierenversagen, einem Patienten mit akuter Pankreasnekrose und akutem postoperativen Nierenversagen sowie einem Patienten mit chronischer Pankreatitis und Zustand nach Whipple-Operation konnten dagegen im ultrafiltrierten Plasma keine freien proteolytischen Enzyme mit Phosphorylase-Kinase als Substrat entdeckt werden. Die Titration der Plasmaproteaseninhibitoren mit Trypsin ergab eine signifikant verminderte Bindungskapazität bei Patienten mit posttraumatischem akuten Nierenversagen im Vergleich zu Patienten mit chronischer Niereninsuffizienz oder regelmäßiger Hämodialyse und gesunden Kontrollen. Proteolytische Aktivität fanden wir bei chronisch urämischen Dauerdialysepatienten im 100fach ankonzentrierten Diafiltrat (Molekulargewicht >10 000). Unsere Daten lassen an eine Beteiligung von Proteasen am Eiweißkatabolismus denken. Während das Blutgerinnungssystem als mögliche Quelle von Proteasen weitgehend ausgeschlossen werden konnte, ist es möglich, daß proteolytische Enzyme nach Polytrauma aus Lysosomen und/oder Makrophagen der Skelettmuskulatur freigesetzt werden.
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Abbreviations
- SDS:
-
sodium dodecyl sulfate
- TCA:
-
trichloroacetic acid (10%)
- RDT:
-
regular dialysis treatment
- ARF:
-
acute renal failure
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This work was supported by the Deutsche Forschungsgemeinschaft (Ho 781/1)
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Hörl, W.H., Stepinski, J., Gantert, C. et al. Evidence for the participation of proteases on protein catabolism during hypercatabolic renal failure. Klin Wochenschr 59, 751–759 (1981). https://doi.org/10.1007/BF01721263
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DOI: https://doi.org/10.1007/BF01721263