Introduction

Chronic kidney failure (CKF) is a worldwide public health problem with a rising prevalence and poor outcomes^1,2. CKF is defined by glomerular filtration rate (GFR) < 60 mL/min/1.73 m2 of body surface area with or without kidney damage³. Uremia, as a syndrome reflecting the organs’ functional disorder due to the acute or chronic kidney failure, is characterized by the loss of kidney homeostasis. CKF is a pathophysiological process which ends with the decrease in nephron numbers and functions; and usually has many etiological factors which cause end stage renal disease (ESRD). ESRD is characterized by irreversible loss of renal functions and develops a clinical state that requires renal replacement treatments such as dialysis and transplantation to prevent dangerous and life threatening effects of uremia. Accumulation of excretory products and disturbance of endocrine and metabolic functions are some of the clinical results commonly seen in CKF. Uremic environment occurred after disease has been associated to the immune deficiency described by lymphocyte and monocyte function defects^4,5,6,7.

As a treatment method to increase the life quality of the patients with ESRD; kidney transplantation has been considered as an enormous progress in modern medicine and it extends higher survival rates in short and long terms compared to dialysis⁸. Graft vitality rate in the first year of transplant is >85 %, whereas it declines to <55% in 10 years after transplantation. Increase in systemic inflammation has been thought to precipitate the inflammatory response to allograft and disturbance of graft functions⁹.

In the pathogenesis of periodontitis which is a chronic inflammatory disease like CKF, it is known that immuno-inflammatory response of host is critical and that response is shaped by genetic, systemic and environmental factors. For development of periodontal diseases which had infectious etiology, there must be microbial dental plaque, whereas it is not sufficient alone. Host sensitivity and inflammatory response are also required for development of the disease^{10, 11, 12, 13}. ^{There are many evidences supporting the influences of systemic diseases over periodontium and also showing that periodontitis also causes systemic inflammation14. In related studies, various mechanisms were proposed about systemic circulation involvement of the local inflammatory mediators and bacterial products which are in interaction with the host cells and trigger the inflammatory response14. Besides, due to the pathologic mechanism of periodontitis, its contribution to development and prognosis of CKF has been supported by many studies15.}

The purpose of this study is to evaluate the clinical and periodontal conditions of hemodialysis patients waiting for kidney transplantation and to determine the treatment needs.

Materials And Methods

We included 44 hemodialysis patients (15 female and 29 male) in this study who were referred to the Department of Periodontology from Organ Transplantation Center in Karadeniz Technical University, Faculty of Medicine, for the periodontal problems or routine control. The age distribution of those patients to whom renal transplantation to be performed was between 12 - 71 year old. We identified pre-transplantation clinical periodontal status of the patients using Community Periodontal Index of Treatment Needs (CPITN), and radiologic screenings. We planned the necessary periodontal treatments and also determined the systemic diseases other than chronic kidney disease and smoking and oral hygiene habits.

World Health Organization (WHO) suggested a new index system (CPITN) to determine the treatment needs of communities in 1977. Index separated the dentition into 6 units (sextant). In CPITN, examined tooth number and examination duration decrease and record system is easier. After identification of the highest values in each sextant, the highest one among those values is recorded as each individual’s score and treatment need is decided. According to this index, if a pocket in 6 mm or more depth is detected in one of teeth, then, there is no need to evaluate other teeth and sextant is given code 4. If the deepest pocket is 4-5 mm, sextant takes code 3; if there is no pocket deeper than 3 mm, it takes code 2. While no periodontal pocket or calculus is seen, if bleeding occurs after sending probe to any part of tooth in sextant; sextant is given code 1. When there is no pathologic findings are identified, code number is 0 ^{16, 17, 18} (Table 1).

After periodontal assessment, 14 patients were diagnosed with generalized gingivitis and 30 patients with chronic periodontitis (CP). All patients with gingivitis were found at code 2 score according to CPITN index. That patient group had scaling in the context of initial periodontal treatment (Phase 1) and was trained in oral hygiene. 18 of the periodontitis patients had code 2 score, 9 of them code 3 and the remaining 3 of them code 4. The patients with code 2 score had scaling and trained in oral hygiene. The patients with code 3 score had scaling plus root planning followed by, if required, subgingival curettage. In the treatment of the patients with code 4 which requires surgical periodontal treatment, appropriate surgical procedures were applied after initial periodontal treatment.

Results

When the clinical periodontal status was assessed, CP was detected in 68 % of patients, and in 32% generalized gingivitis was detected (Figure 1). Other than CKF, 51% of patients had hypertension, 9% diabetes mellitus and 4% cardiovascular diseases (Figure 2). 32 individuals had never smoked, only 3 have continued to smoke and 9 persons already quitted (Figure 3). Looking to the oral hygiene behaviors, 45% of the patients brushed their teeth for once per day, 34% 2-3 times per day and 21% from time to time (Figure 4). It was detected that none of the patients went to a dentist before having any symptoms. While all patients had scaling and root planning, 3 of them also had initial periodontal treatment and consequently, periodontal surgery (Figure 5). Once periodontal treatments were completed, the individuals were taken to maintenance phase for follow up after transplantation.

Figure 1

Table 1. Classification of treatment needs based on CPITN index.

Figure 2

Figure 1.Evaluation of clinical periodontal status for age and sex within and between the groups

Figure 3

Figure 2. Evaluation of systemic disease status within and between the groups

Figure 4

Figure 3. Evaluation of smoking habits within and between the groups

Figure 5

Figure 4. Evaluation of tooth brushing habits within and between the groups

Figure 6

Figure 5.Evaluation of periodontal treatment methods within and between the groups

Discussion

Disturbances of the immune system in CKF involve both innate and adaptive immunities¹⁹. ^{T cells which play an important role in the control of the immune system- associated mechanisms, is also one of the main components of the immune response to periodontal infections. These cells control the functional activity of both innate and also adaptive immune responses20. CD4 T-cells were initially subdivided into two subsets as Th1 and Th2, on the basis of the patterns of their cytokine production. Dysfunctional maturation of T helper lymphocytes in CKF patients may cause delays in immune response and sensitivity to infections21. Functional abnormalities of monocytes, neutrophils and dendritic cells are directly linked to the infection risk in this patient population22, 23.}

Several different mechanisms have been proposed in the literature to explain the high inflammatory status in this population, including the deterioration of renal function which leads to low urinary IL-6 excretion and increased serum cytokine levels, overproduction of pro-inflammatory cytokines caused by an elevated number of circulating monocytes, increased oxidative stress, the accumulation of advanced glycation end-products (AGEs) caused by decreased renal clearance which can trigger an inflammatory response and the presence of co-morbid factors such as diabetes^24-28. In addition to all those findings, there are some findings showing that periodontal diseases may also play a role in the etiopathogenesis of CKF¹⁵.

Among the dentate individuals, 427 (12.3%) were diagnosed with periodontitis. Based on the cut-off point of 0.3 mg/dL, 41.8% of individuals with periodontitis had high serum CRP levels compared to 27.1% of those without periodontitis¹. Moreover, in a study based on the negative effects of uremia on innate and adaptive immune response, the presence of higher CP prevalence in CKF patients was claimed compared to those without CKF and that was also proven with the obtained results²⁹. 68% rate of CP findings in that study which we investigated limited number of patients, as anticipated in the studies above; make us to think that CP findings may also be a factor in the etiology of CKF in those patients. Even though we think that smoking habits, poor oral hygiene and presence of systemic diseases other than CKF in our patients may play a crucial role not only in CKF but also in the etiopathogenesis of periodontal diseases; recent studies have shown that both diseases have similar mechanisms^{15, 29}. Besides, gingivitis in those patients may turn into periodontitis in such a period that host sensitivity increases and oral hygiene deteriorates. It also may negatively affect CKF and general health after transplantation.

Chronic inflammation may play a crucial role not only in the etiology of CKF, but also in the short and long term success of kidney transplantation. The main pathogenetic mechanism for the deterioration of chronic transplants is inflammation, which is modulated by alloimmune-dependent (human leukocyte antigen [HLA] mismatches, panel reactive antibody [PRA] scores and acute rejection) and alloimmune-independent factors (cold ischemic time, ischemia/reperfusion injury, smoking, diabetes and live versus cadaveric donors). Clinically, serum and urine IL-6 levels are indicators of acute rejection episodes and the successful anti-rejection therapy reduces serum IL-6 levels. Similarly, C-reactive protein (CRP) was shown as a predictor of renal allograft survival³⁰. However, different studies reported that inflammatory parameters mentioned above can also increase in periodontal diseases. The findings have shown that higher levels of IL-6 were produced in diseased periodontal tissues compared to healthy gingival tissues and serum CRP levels increase in the patients with periodontitis. When the significance of IL-6 and CRP in transplantation and the association between periodontitis and systemic inflammatory markers are considered; it may be thought that the diagnosis and treatment of periodontal disease may be effective on the transplantation success³⁰.

Health of periodontal tissues is crucial not only for transplantation success but also in post-transplantation period. To prevent post-transplantation organ rejection, the patients take immunosuppressive drugs and those drugs can cause gingival hyperplasia^31-33. According to the recent data, the incidence of gingival hyperplasia induced by cyclosporine taken by renal transplantation patients varies between 22% and 58%³¹. While the mechanism of gingival hyperplasia after cyclosporine treatment has not been known completely; cell culture studies have shown that it has a direct effect on gingival proliferation, protein synthesis and collagen production³⁴. Gingival hyperplasia due to cyclosporine starts from papillae and can expand through the occlusal of tooth. Most studies report that gingival hyperplasia is associated with increased cyclosporine dosage, the presence of increased plaque and gingival inflammation and is more commonly seen in the young^{31, 32, 35}. It has been shown that good oral hygiene decreases the incidence of gingival hyperplasia or delays its development^{33, 35}. ^{Besides, immunosuppressive agents affect gingival hyperplasia in different rates. In the past 10 years, tacrolimus has been increasingly favored over cyclosporine as an immunosuppressive drug, especially in younger renal transplant recipients. The incidence of gingival hyperplasia in renal transplant patients receiving tacrolimus is typically less than those reported for cyclosporine, generally between 0% and 15%31.}

Gingival hyperplasia should be treated for continuance of the periodontal tissue health. Besides, since gingival hyperplasia makes the oral hygiene difficult; it is certain that possible development of periodontal infection has a negative effect on renal transplantation success. Thus, during the reevaluation of the CKF patients in terms of oral and gingival health after transplantation, gingivectomy or flap operations should be applied for hyperplasia treatment.

In conclusion, due to the strong association between periodontitis and systemic inflammation, periodontal evaluation of CKF patients has a crucial role in terms of gingival health and also general health of the patients. Moreover, continuance of gingival health is also required for long term success of transplantation. Thus, renal transplantation patients should be evaluated in terms of oral and gingival health during treatment and after treatment and if necessary, they should be treated