Effect of non-surgical periodontal therapy on renal function in chronic kidney disease patients with periodontitis: a systematic review and meta-analysis of interventional studies

  • Dan Zhao
  • Abrar Tahir Khawaja
  • Lijian Jin
  • Kam Wa Chan
  • Maurizio Tonetti
  • Sydney Chi Wai Tang
  • George PelekosEmail author
Original Article



This systematic review evaluated the impacts of non-surgical periodontal therapy (NSPT) in patients with chronic kidney disease (CKD) and periodontitis in order to explore causality and assess the potential benefits of co-management.


This systematic review and meta-analyses were conducted by searching MEDLINE, EMBASE, PubMed, Cochrane Library, and Open GREY. Interventional studies of adult patients suffering from CKD and periodontitis were investigated. Effect of NSPT on renal function was analyzed.


A total of 109 participants from four case-series studies and 97 participants from one randomized controlled trial were included in this review. Sixty percent of the eligible studies (3/5) aimed at the effect of NSPT on nutritional status and systemic inflammation in dialysis patients. The other two studies concluded a beneficial impact of NSPT on estimated glomerular filtration rate (eGFR) in patients with CKD stages 2–4. Moreover, two meta-analyses were accomplished on eGFR and serum creatinine to evaluate the changes between baseline and 3-month follow-up. The pooled mean of eGFR was not significantly different pre- and post-NSPT using random and fixed-effect models. The change for creatinine was not significant using the random effect model but was significant when the fixed effect model was used (p < 0.001).


There is insufficient evidence to conclude the potential benefit of NSPT on renal function in CKD patients with periodontitis.

Clinical relevance

Periodontitis contributes to the inflammatory burden and has been associated with impaired kidney function in many observational studies. However, well-designed clinical trials in pre-dialysis patients investigating the impact of NSPT on renal function–related parameters are missing.


Chronic kidney disease Renal function Periodontitis Non-surgical periodontal therapy Systematic review Meta-analysis 


Funding information

This review was supported by The University of Hong Kong, Hong Kong SAR, China.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Informed consent

For this type of study, formal consent is not required.

Supplementary material

784_2019_3066_MOESM1_ESM.pdf (25 kb)
ESM 1 (PDF 25 kb)
784_2019_3066_MOESM2_ESM.pdf (150 kb)
ESM 2 (PDF 150 kb)
784_2019_3066_MOESM3_ESM.pdf (249 kb)
ESM 3 (PDF 248 kb)
784_2019_3066_MOESM4_ESM.pdf (183 kb)
ESM 4 (PDF 183 kb)
784_2019_3066_MOESM5_ESM.pdf (179 kb)
ESM 5 (PDF 178 kb)


  1. 1.
    Vos T et al (2016) Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet 388(10053):1545–1602. CrossRefGoogle Scholar
  2. 2.
    Jha V, Garcia-Garcia G, Iseki K, Li Z, Naicker S, Plattner B, Saran R, Wang AY, Yang CW (2013) Chronic kidney disease: global dimension and perspectives. Lancet 382(9888):260–272. CrossRefPubMedGoogle Scholar
  3. 3.
    Webster AC, Nagler EV, Morton RL, Masson P (2017) Chronic kidney disease. Lancet 389(10075):1238–1252. CrossRefPubMedGoogle Scholar
  4. 4.
    Honeycutt AA, Segel JE, Zhuo X, Hoerger TJ, Imai K, Williams D (2013) Medical costs of CKD in the Medicare population. J Am Soc Nephrol 24(9):1478–1483. CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Kahn LS, Vest BM, Madurai N, Singh R, York TR, Cipparone CW, Reilly S, Malik KS, Fox CH (2015) Chronic kidney disease (CKD) treatment burden among low-income primary care patients. Chronic Illn 11(3):171–183. CrossRefPubMedGoogle Scholar
  6. 6.
    Levin A, Foley RN (2000) Cardiovascular disease in chronic renal insufficiency. Am J Kidney Dis 36(6 Suppl 3):S24–S30CrossRefGoogle Scholar
  7. 7.
    Ene-Iordache B, Perico N, Bikbov B, Carminati S, Remuzzi A, Perna A, Islam N, Bravo RF, Aleckovic-Halilovic M, Zou H, Zhang L, Gouda Z, Tchokhonelidze I, Abraham G, Mahdavi-Mazdeh M, Gallieni M, Codreanu I, Togtokh A, Sharma SK, Koirala P, Uprety S, Ulasi I, Remuzzi G (2016) Chronic kidney disease and cardiovascular risk in six regions of the world (ISN-KDDC): a cross-sectional study. Lancet Glob Health 4(5):e307–e319. CrossRefPubMedGoogle Scholar
  8. 8.
    Kassebaum NJ, Bernabe E, Dahiya M, Bhandari B, Murray CJ, Marcenes W (2014) Global burden of severe periodontitis in 1990-2010: a systematic review and meta-regression. J Dent Res 93(11):1045–1053. CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Page RC, Offenbacher S, Schroeder HE, Seymour GJ, Kornman KS (1997) Advances in the pathogenesis of periodontitis: summary of developments, clinical implications and future directions. Periodontol 2000 14:216–248CrossRefGoogle Scholar
  10. 10.
    Hajishengallis G, Lambris JD (2012) Complement and dysbiosis in periodontal disease. Immunobiology 217(11):1111–1116. CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Cobb CM (1996) Non-surgical pocket therapy: mechanical. Ann Periodontol 1(1):443–490. CrossRefPubMedGoogle Scholar
  12. 12.
    Darveau RP, Tanner A, Page RC (1997) The microbial challenge in periodontitis. Periodontol 14:12–32CrossRefGoogle Scholar
  13. 13.
    Cobb CM (2002) Clinical significance of non-surgical periodontal therapy: an evidence-based perspective of scaling and root planing. J Clin Periodontol 29(Suppl 2):6–16PubMedGoogle Scholar
  14. 14.
    Zhao D, Khawaja AT, Jin L, Li KY, Tonetti M, Pelekos G (2018) The directional and non-directional associations of periodontitis with chronic kidney disease: a systematic review and meta-analysis of observational studies. J Periodontal Res 53:682–704. CrossRefPubMedGoogle Scholar
  15. 15.
    Kshirsagar AV, Offenbacher S, Moss KL, Barros SP, Beck JD (2007) Antibodies to periodontal organisms are associated with decreased kidney function. The Dental Atherosclerosis Risk in Communities study. Blood Purif 25(1):125–132. CrossRefPubMedGoogle Scholar
  16. 16.
    Fisher MA, Taylor GW, Papapanou PN, Rahman M, Debanne SM (2008) Clinical and serologic markers of periodontal infection and chronic kidney disease. J Periodontol 79(9):1670–1678. CrossRefPubMedGoogle Scholar
  17. 17.
    Salimi S, Ng N, Seliger SL, Parsa A (2014) Periodontal disease, renal dysfunction and heightened leukocytosis. Nephron Clin Pract 128(1–2):107–114. CrossRefPubMedGoogle Scholar
  18. 18.
    Borrell LN, Papapanou PN (2005) Analytical epidemiology of periodontitis. J Clin Periodontol 32(Suppl 6):132–158. CrossRefPubMedGoogle Scholar
  19. 19.
    Elihimas Junior UF, Elihimas HC, Lemos VM, Leao Mde A, Sa MP, Franca EE, Lemos A, Valente LM, Markman Filho B (2014) Smoking as risk factor for chronic kidney disease: systematic review. J Bras Nefrol 36(4):519–528. CrossRefPubMedGoogle Scholar
  20. 20.
    Ritz E, Rychlik I, Locatelli F, Halimi S (1999) End-stage renal failure in type 2 diabetes: a medical catastrophe of worldwide dimensions. Am J Kidney Dis 34(5):795–808. CrossRefPubMedGoogle Scholar
  21. 21.
    Kshirsagar AV, Craig RG, Moss KL, Beck JD, Offenbacher S, Kotanko P, Klemmer PJ, Yoshino M, Levin NW, Yip JK, Almas K, Lupovici EM, Usvyat LA, Falk RJ (2009) Periodontal disease adversely affects the survival of patients with end-stage renal disease. Kidney Int 75(7):746–751. CrossRefPubMedGoogle Scholar
  22. 22.
    de Souza CM, Braosi AP, Luczyszyn SM, Olandoski M, Kotanko P, Craig RG, Trevilatto PC, Pecoits-Filho R (2014) Association among oral health parameters, periodontitis, and its treatment and mortality in patients undergoing hemodialysis. J Periodontol 85(6):e169–e178. CrossRefPubMedGoogle Scholar
  23. 23.
    Tonetti MS, D’Aiuto F, Nibali L, Donald A, Storry C, Parkar M, Suvan J, Hingorani AD, Vallance P, Deanfield J (2007) Treatment of periodontitis and endothelial function. N Engl J Med 356(9):911–920. CrossRefPubMedGoogle Scholar
  24. 24.
    Chambrone L, Foz AM, Guglielmetti MR, Pannuti CM, Artese HP, Feres M, Romito GA (2013) Periodontitis and chronic kidney disease: a systematic review of the association of diseases and the effect of periodontal treatment on estimated glomerular filtration rate. J Clin Periodontol 40(5):443–456. CrossRefPubMedGoogle Scholar
  25. 25.
    Deschamps-Lenhardt S, Martin-Cabezas R, Hannedouche T, Huck O (2019) Association between periodontitis and chronic kidney disease: systematic review and meta-analysis. Oral Dis 25(2):385–402. CrossRefPubMedGoogle Scholar
  26. 26.
    Lee CF, Lin CL, Lin MC, Lin SY, Sung FC, Kao CH (2014) Surgical treatment for patients with periodontal disease reduces risk of end-stage renal disease: a nationwide population-based retrospective cohort study. J Periodontol 85(1):50–56. CrossRefPubMedGoogle Scholar
  27. 27.
    Graziani F, Cei S, La Ferla F, Vano M, Gabriele M, Tonetti M (2010) Effects of non-surgical periodontal therapy on the glomerular filtration rate of the kidney: an exploratory trial. J Clin Periodontol 37(7):638–643. CrossRefPubMedGoogle Scholar
  28. 28.
    Vilela EM, Bastos JA, Fernandes N, Ferreira AP, Chaoubah A, Bastos MG (2011) Treatment of chronic periodontitis decreases serum prohepcidin levels in patients with chronic kidney disease. Clinics (Sao Paulo) 66(4):657–662CrossRefGoogle Scholar
  29. 29.
    Guo N, Lin G (2017) Effects of nonsurgical periodontal therapy on serum inflammatory factor levels in patients with chronic kidney disease and periodontitis. Biomedical Research (India) 28(9):3899–3902Google Scholar
  30. 30.
    Moher D, Liberati A, Tetzlaff J, Altman DG, Group P (2010) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Int J Surg 8(5):336–341. CrossRefGoogle Scholar
  31. 31.
    Higgins JP, Altman DG, Gotzsche PC, Juni P, Moher D, Oxman AD, Savovic J, Schulz KF, Weeks L, Sterne JA, Cochrane Bias Methods G, Cochrane Statistical Methods G (2011) The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ 343:d5928. CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Higgins JPT, Altman DG, Sterne JAC (editors). Chapter 8: assessing risk of bias in included studies. In: Higgins JPT, Green S (editors). Cochrane handbook for systematic reviews of interventions version 5.1.0 (updated march 2011). The Cochrane Collaboration, 2011. Available from
  33. 33.
    Sterne JA, Hernan MA, Reeves BC, Savovic J, Berkman ND, Viswanathan M, Henry D, Altman DG, Ansari MT, Boutron I, Carpenter JR, Chan AW, Churchill R, Deeks JJ, Hrobjartsson A, Kirkham J, Juni P, Loke YK, Pigott TD, Ramsay CR, Regidor D, Rothstein HR, Sandhu L, Santaguida PL, Schunemann HJ, Shea B, Shrier I, Tugwell P, Turner L, Valentine JC, Waddington H, Waters E, Wells GA, Whiting PF, Higgins JP (2016) ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions. BMJ 355:i4919. CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Kokotovic D, Burcharth J, Helgstrand F, Gogenur I (2017) Systemic inflammatory response after hernia repair: a systematic review. Langenbeck's Arch Surg 402:1023–1037. CrossRefGoogle Scholar
  35. 35.
    The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) Working Group (2013) Handbook for grading the quality of evidence and the strength of recommendations using the GRADE approach. Available at: Updated October 2013
  36. 36.
    Ryan R, Hill S (2016) How to GRADE the quality of the evidence. Cochrane Consumers and Communication Group, available at Version 3.0 December 2016
  37. 37.
    Luo D, Wan X, Liu J, Tong T (2016) Optimally estimating the sample mean from the sample size, median, mid-range, and/or mid-quartile range. Stat Methods Med Res 27:1785–1805. CrossRefPubMedGoogle Scholar
  38. 38.
    Wan X, Wang W, Liu J, Tong T (2014) Estimating the sample mean and standard deviation from the sample size, median, range and/or interquartile range. BMC Med Res Methodol 14:135. CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Fu R, Vandermeer BW, Shamliyan TA, O'Neil ME, Yazdi F, Fox SH, Morton SC (2013) Handling Continuous Outcomes in Quantitative Synthesis. Methods Guide for Comparative Effectiveness Reviews. (Prepared by the Oregon Evidence-based Practice Center under Contract No. 290-2007-10057-I) AHRQ Publication No. 13-EHC103-EF. Rockville, MD: Agency for Healthcare Research and Quality.
  40. 40.
    Higgins JPT, Deeks JJ (editors) (2011) Chapter 7: selecting studies and collecting data. In: Higgins JPT, Green S (editors), Cochrane handbook for systematic reviews of interventions version 5.1.0 (updated march 2011). The Cochrane Collaboration, . Available from
  41. 41.
    DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7(3):177–188CrossRefGoogle Scholar
  42. 42.
    Borenstein M, Hedges LV, Higgins JP, Rothstein HR (2010) A basic introduction to fixed-effect and random-effects models for meta-analysis. Res Synth Methods 1(2):97–111. CrossRefPubMedGoogle Scholar
  43. 43.
    Deeks JJ, Higgins JPT, Altman DG (editors) (2011) Chapter 9: Analysing data and undertaking meta-analyses. In: Higgins JPT, Green S (editors). Cochrane handbook for systematic reviews of interventions version 5.1.0 (updated march 2011). The Cochrane Collaboration, 2011. Available from
  44. 44.
    Fang F, Wu B, Qu Q, Gao J, Yan W, Huang X, Ma D, Yue J, Chen T, Liu F, Liu Y (2015) The clinical response and systemic effects of non-surgical periodontal therapy in end-stage renal disease patients: a 6-month randomized controlled clinical trial. J Clin Periodontol 42(6):537–546. CrossRefPubMedGoogle Scholar
  45. 45.
    Almeida S, Figueredo CM, Lemos C, Bregman R, Fischer RG (2017) Periodontal treatment in patients with chronic kidney disease: a pilot study. J Periodontal Res 52(2):262–267CrossRefGoogle Scholar
  46. 46.
    Siribamrungwong M, Yothasamutr K, Puangpanngam K (2014) Periodontal treatment reduces chronic systemic inflammation in peritoneal dialysis patients. Ther Apher Dial 18(3):305–308PubMedGoogle Scholar
  47. 47.
    Siribamrungwong M, Puangpanngam K (2012) Treatment of periodontal diseases reduces chronic systemic inflammation in maintenance hemodialysis patients. Ren Fail 34(2):171–175CrossRefGoogle Scholar
  48. 48.
    Artese HP, Sousa CO, Luiz RR, Sansone C, Torres MC (2010) Effect of non-surgical periodontal treatment on chronic kidney disease patients. Braz Oral Res 24(4):449–454CrossRefGoogle Scholar
  49. 49.
    Borah MF, Schoenfeld PY, Gotch FA, Sargent JA, Wolfsen M, Humphreys MH (1978) Nitrogen balance during intermittent dialysis therapy of uremia. Kidney Int 14(5):491–500CrossRefGoogle Scholar
  50. 50.
    Ikizler TA, Pupim LB, Brouillette JR, Levenhagen DK, Farmer K, Hakim RM, Flakoll PJ (2002) Hemodialysis stimulates muscle and whole body protein loss and alters substrate oxidation. Am J Physiol Endocrinol Metab 282(1):E107–E116. CrossRefPubMedGoogle Scholar
  51. 51.
    Ghebremichael-Weldeselassie Y, Whitaker HJ, Farrington CP (2014) Self-controlled case series method with smooth age effect. Stat Med 33(4):639–649. CrossRefPubMedGoogle Scholar
  52. 52.
    Petersen I, Douglas I, Whitaker H (2016) Self controlled case series methods: an alternative to standard epidemiological study designs. BMJ 354:i4515. CrossRefPubMedGoogle Scholar
  53. 53.
    Chen LP, Chiang CK, Chan CP, Hung KY, Huang CS (2006) Does periodontitis reflect inflammation and malnutrition status in hemodialysis patients? Am J Kidney Dis 47(5):815–822. CrossRefPubMedGoogle Scholar
  54. 54.
    Inker LA, Astor BC, Fox CH, Isakova T, Lash JP, Peralta CA, Kurella Tamura M, Feldman HI (2014) KDOQI US commentary on the 2012 KDIGO clinical practice guideline for the evaluation and management of CKD. Am J Kidney Dis 63(5):713–735. CrossRefPubMedGoogle Scholar
  55. 55.
    Kocyigit I, Yucel HE, Cakmak O, Dogruel F, Durukan DB, Korkar H, Unal A, Sipahioglu MH, Oymak O, Gurgan CA, Tokgoz B (2014) An ignored cause of inflammation in patients undergoing continuous ambulatory peritoneal dialysis: periodontal problems. Int Urol Nephrol 46(10):2021–2028CrossRefGoogle Scholar
  56. 56.
    Grubbs V, Garcia F, Jue BL, Vittinghoff E, Ryder M, Lovett D, Carrillo J, Offenbacher S, Ganz P, Bibbins-Domingo K, Powe NR (2017) The Kidney and Periodontal Disease (KAPD) study: a pilot randomized controlled trial testing the effect of non-surgical periodontal therapy on chronic kidney disease. Contemp Clin Trials 53:143–150. CrossRefPubMedGoogle Scholar
  57. 57.
    Sharma P, Cockwell P, Dietrich T, Ferro C, Ives N, Chapple ILC (2017) INfluence of successful periodontal intervention in REnal disease (INSPIRED): study protocol for a randomised controlled pilot clinical trial. Trials 18(1):535. CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Jamieson L, Skilton M, Maple-Brown L, Kapellas K, Askie L, Hughes J, Arrow P, Cherian S, Fernandes D, Pawar B, Brown A, Boffa J, Hoy W, Harris D, Mueller N, Cass A (2015) Periodontal disease and chronic kidney disease among aboriginal adults; an RCT. BMC Nephrol 16:181. CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    Teeuw WJ, Slot DE, Susanto H, Gerdes VE, Abbas F, D'Aiuto F, Kastelein JJ, Loos BG (2014) Treatment of periodontitis improves the atherosclerotic profile: a systematic review and meta-analysis. J Clin Periodontol 41(1):70–79. CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Periodontology, Faculty of DentistryThe University of Hong KongHong KongChina
  2. 2.Department of Medicine, Li Ka Shing Faculty of MedicineThe University of Hong KongHong KongChina

Personalised recommendations