Unexpected effect of haemodialysis on salivary hepatocyte growth factor

Email: jborawski{at}post.pl

Sir,

Periodontal disease causing premature tooth loss is common and aggressive in younger and still dentulous patients undergoing maintenance haemodialysis (HD) [1]. Recent studies showed that hepatocyte growth factor (HGF), a pluripotential, ubiquitous and mostly regenerative cytokine, is strongly involved in the pathogenesis and progression of periodontitis in the general population [2]. In brief, HGF excessively stimulates the growth of gingival epithelial cells into the periodontal pockets and thus impairs proper regeneration of deep collagenous structures of the periodontium [2].

Recently, we showed that both unfractionated heparin and low-molecular-weight heparin enoxaparin caused a marked up-regulation of plasma HGF [3]. The increase amounted to ~1300% from baseline after 10 min of HD and to ~400% after 180 min, mostly due to HGF release from glysosaminoglycans present on the endothelial surface and within the extracellular matrix. Therefore we hypothesized that HGF released in such striking amounts into circulating blood could penetrate into the periodontium during 4–5 h of thrice weekly HD treatment and propagate periodontal disease.

We studied 26 clinically stable patients [aged 51±12 years; 7 females; dialysis for a median of 27 months (range, 2–206 months)] who underwent bicarbonate HD sessions and were anticoagulated with enoxaparin (mean dose, 0.64±0.15 mg/kg). HD session duration was 4–5 h. Each subject had at least two or more teeth which exhibited periodontitis but were not indicated for extraction in minimum one teeth-sextant, according to the WHO recommendations on the performance of periodontal studies [4]. Before the morning HD session, the patients remained fasting; then a minimum of 5 ml of unstimulated whole saliva was collected by the spit-out method into sterile vessels after 10 min oral rinsing with distilled water. Subjects were asked not to eat and drink during the last 3 h of the HD treatment. Then saliva was collected in the same way during the last hour of the HD session. The samples were kept on melting ice for no longer than 1 h; subsequently they were centrifuged at 3800 rpm for 10 min. The supernatant (middle 1/3) was collected and stored at –70°C until assay with an established immunoenzymatic HGF kit, as described previously [3].

Median pre-dialysis saliva HGF level was 1.06 (0.02–9.65) ng/ml, while for the ‘last hour’ samples we found a median value of 0.68 (0–8.72) ng/ml. The remarkable 30% decrease in salivary HGF concentration nearly reached the level of statistical significance (Wilcoxon's P = 0.055). No reciprocal relations between the above HGF values, their per-dialytic change, enoxaparin dose or HD session duration were found.

In conclusion, we saw that salivary HGF concentration normalized during HD sessions. Our working hypothesis turned out to be apparently incorrect. The specific and important quest for the cause behind periodontal disease epidemics in maintenance HD patients has just begun and should be pursued.

Conflict of interest statement. None declared.

Magdalena Wilczynska-Borawska1, Jacek Borawski2, Oksana Kovalchuk3, Lech Chyczewski3, Michal Mysliwiec2 and Wanda Stokowska1

1 Department of Stomatology and Periodontics2 Department of Nephrology and Transplantology with Dialysis Unit3 Department of Clinical Molecular Biology Medical University Bialystok Poland

References

  1. Craig RG, Spittle MA, Levin NW. Importance of periodontal disease in the kidney patient. Blood Purif 2002; 20: 113–119[CrossRef][ISI][Medline]
  2. Ohnishi T, Daikuhara Y. Hepatocyte growth factor/scatter factor in development, inflammation and carcinogenesis: its expression and role in oral tissue. Arch Oral Biol 2003; 48: 797–804[CrossRef][ISI][Medline]
  3. Borawski J, Naumnik B, Mysliwiec M. Activation of hepatocyte growth factor/activin A/follistatin system during hemodialysis: role of heparin. Kidney Int 2003; 64: 2229–2237[CrossRef][ISI][Medline]
  4. Oral Health Surveys. Basic Methods. 4th edn. World Health Organization. Geneva 1997




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