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Post-heparin lipoprotein lipase activity is similar in patients on peritoneal dialysis compared to patients on haemodialysis
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
(English)In: BMC Nephrology, ISSN 1471-2369Article, review/survey (Other academic) Submitted
Abstract [en]

Background: Lipoprotein lipase (LPL) activity is known to be reduced in patients with chronic kidney disease (CKD). Heparin, given as a bolus at start of the haemodialysis(1), induces a release of LPL from its binding sites at endothelial surfaces of capillaries to blood. It is not clear if the levels of endothelial LPL between dialysis sessions remains lowered in patients on HD due to the necessary frequent heparinizations. The aim of this study was to see if the pool of heparin-releasable LPL activity differed between patients on HD compared to those on PD that do not need anticoagulation during dialysis.

The study included 16 patients each on chronic PD or HD.  All patients received a bolus of low molecular weight heparin (tinzaparin 75 units/kg) intravenously to estimate the endothelial pool of LPL. Blood samples were drawn for analysis of LPL activity and triglycerides (TG) before and 40 and 180 minutes after the tinzaparin bolus.

Results: The increase in median LPL activity at 40 min after tinzaparin was similar in PD and HD patients. At 180 minutes a slightly higher median level of LPL activity was noted in the PD patients (6.1 mU/mL (n=6) versus 3.4 mU/mL (n=16), p=0.005). The TG concentration in plasma at 40 min was reduced relatively more in the PD patients than in the HD patients. At 180 min TG had returned to start levels in HD patients while they were still below the start level in PD patients.

Conclusion: Post-heparin LPL activity is similar in PD as in HD patients. This indicates that the endothelial LPL pool is not exhausted by repeated loss during each HD session.

Keyword [en]
Peritoneal dialysis, haemodialysis, lipoprotein lipase, triglyceride, tinzaparin, anticoagulation.
National Category
Urology and Nephrology
Research subject
Medical Biochemistry
URN: urn:nbn:se:umu:diva-62720OAI: diva2:577665
Available from: 2012-12-17 Created: 2012-12-15 Last updated: 2013-01-03Bibliographically approved
In thesis
1. Lipoprotein lipase activity is reduced in dialysis patients. Studies on possible causal factors.
Open this publication in new window or tab >>Lipoprotein lipase activity is reduced in dialysis patients. Studies on possible causal factors.
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Cardiovascular disease is a major cause of mortality and morbidity in patients on chronic haemodialysis (HD). One main contributing factor is renal dyslipidaemia, characterized by an impaired catabolism of triglyceride (TG)-rich lipoproteins with accumulation of atherogenic remnant particles. The enzyme lipoprotein lipase (LPL) is a key molecule in the lipolysis of TG-rich lipoproteins into free fatty acids. The activity of LPL is reduced in HD-patients. This study was performed to elucidate various conditions and factors that may have an impact on LPL-related lipid metabolism.

I. The functional pool of LPL is located at the vascular surface. The enzyme is released by heparin and low molecular weight heparins (LMWH) into the circulating blood and extracted and degraded by the liver. Heparin and LMWH are used for anticoagulation during HD to avoid clotting in the extracorporeal devices. This raises a concern that the LPL system may become exhausted by repeated administration of LMWH in patients on HD. In a randomized cross over designed study twenty patients on chronic HD were switched from a primed infusion of heparin to a single bolus of LMWH (tinzaparin).  The LPL activity in blood was higher on HD with LMWH at 40 minutes but lower at 180 minutes compared to HD with heparin. These values did not change during the 6-month study period. With heparin a significant TG reduction was found at 40 minutes and a significantly higher TG value at 180 and 210 minutes than at start. TG was higher during the HD-session with tinzaparin than with heparin. Our data demonstrate that repeated HD with heparin or with LMWH does not exhaust the LPL-system in the long term but does disturb the LPL system and TG metabolism during every HD session.

II. In this study HD patients were compared with patients on peritoneal dialysis (PD) in a case control fashion. PD patients showed the same reaction of the LPL system to LMWH as HD patients. This confirmed that both HD and PD patients had the same, reduced, heparin-releasable LPL pool. The main difference was that in PD patients the TG continued to be cleared effectively even at 180 minutes after the bolus of LMWH injection. This may be due to a slower removal of the released LPL by the liver in PD patients. 

III. In recent years, citrate (Citrasate) in the dialysate has been used in Sweden as a local anticoagulant for chronic HD. We performed a randomized cross over study that included 23 patients (16 men and 7 women) to investigate if citrate in the dialysate is safe and efficient enough as anticoagulant. The study showed that citrate anticoagulation eliminated the need of heparin or LMWH as anticoagulation for HD in half of the patients. However, individual optimization of doses of anticoagulants used together with citrate have to be made.

IV. Recently angiopoietin-like proteins, ANGPTL3 and 4 have emerged as important modulators of lipid metabolism as potent inhibitors of LPL. Twenty-three patients on chronic HD and 23 healthy persons were included as case and controls to investigate the levels of these proteins in plasma of HD-patients and to evaluate if HD may alter these levels. The data showed that plasma levels of ANGPTL3 and 4 were increased in patients with kidney disease compared to controls. This may lead to inactivation of LPL. High flux-HD, but not low flux-HD, reduced the levels of ANGPTL4, while the levels of ANGPTL3 were not significantly influenced.  On HD with local citrate as anticoagulant, no LPL activity was released into plasma during dialysis in contrast to the massive release of LPL with heparin (LMWH). Citrate HD was not associated with a significant drop in plasma TG at 40 minutes, while both HD with citrate and heparin resulted in significantly increased TG levels at 180 minutes compared to the start values.

Conclusions:  Citrate as a local anticoagulant during haemodialysis eliminates the need of heparin or LMWH in about half of the HD patients. Citrate does not induce release of LPL from its endothelial binding sites. We have shown that although HD with heparin causes release of the endothelial pool of LPL during each dialysis session, the basal pool is similarly low in PD patients that do not receive heparin. This indicates that the LPL pool is lowered as a consequence of the uraemia, per se. One explanation could be the increased levels of ANGPTL3 and 4. HD with high flux filters can temporarily lower the levels of ANGPTL4. Further studies are, however, needed to understand why LPL activity is low in patients with kidney disease.

Place, publisher, year, edition, pages
Umeå: Umeå universitet, 2012. 62 p.
Umeå University medical dissertations, ISSN 0346-6612 ; 1540
Haemodialysis, lipoprotein lipase, ANGPTL3, ANGPTL4, citrate dialysate, dialyzer.
National Category
Urology and Nephrology
Research subject
urn:nbn:se:umu:diva-62733 (URN)978-91-7459-541-3 (ISBN)
Public defence
2013-01-24, Sal E04, Norrlands Universitetssjukhus, Umeå, 09:00 (Swedish)
Available from: 2013-01-03 Created: 2012-12-16 Last updated: 2013-01-03Bibliographically approved

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