Incidence of Gingival Hyperplasia Caused by Calcium Antagonists in Continuous Ambulatory Peritoneal Dialysis Patients

Junko Shouda, Hidetomo Nakamoto, Souichi Sugahara, Hirokazu Okada, Hiromichi Suzuki

Calcium antagonists are widely used for the treatment of cardiovascular diseases in patients receiving dialysis therapy. The incidence of gingival hyperplasia has been reported as 10% - 20% in patients treated with calcium antagonists in the general population. However, precise reports examining the incidence or pathogenesis of gingival hyperplasia in continuous ambulatory peritoneal dialysis (CAPD) patients are lacking. We recruited 54 CAPD patients. Three patients treated with long-acting nifedipine and one patient treated with felodipine were reported by a periodontist to have gingival hyperplasia. No patients were taking amlodipine and other calcium antagonists. After discontinuation of calcium antagonists, gingival hyperplasia disappeared within 1 month. Based on these results, we suggest that it is important to examine whether the gingiva is overgrown in CAPD patients taking calcium antagonists.

Key words

Gingival hyperplasia, calcium antagonists

From:

Department of Nephrology, Saitama Medical School, Saitama, Japan.

Introduction

The long-term prognosis for continuous ambulatory peritoneal dialysis (CAPD) patients depends on cardiac status (1). Adequate control of blood pressure is most important for prevention of cardiovascular events. Recent studies show that close to 80% of continuous ambulatory peritoneal dialysis (CAPD) patients have hypertension (defined as systolic blood pressure > 140 mmHg or diastolic pressure > 90 mmHg) (2). It is therefore mandatory to apply antihypertensive agents for decreasing blood pressure in CAPD patients. According to a European Dialysis and Transplant Association (EDTA) report, calcium antagonists are the agents most frequently employed, followed in decreasing order by beta blockers, angiotensin converting enzyme (ACE) inhibitors, centrally acting agents, a1-antagonists, and vasodilators (3). Dihydropyridines are extensively metabolized; their half-life is not altered by renal failure; they are not eliminated by dialysis; and no dosage adjustment is required (4). For these reasons, dihydropyridines are the most widely studied and used agents in end-stage renal disease patients (3). However, several studies have described gingival hyperplasia induced by calcium antagonists (5-10).

Our study was conducted from April 1995 to March 1998 at the Kidney Disease Center, Saitama Medical School, Saitama, Japan, to study the incidence of gingival hyperplasia induced by calcium antagonists in CAPD patients.

Patients and methods

We studied 54 patients who were being treated in the outpatient CAPD clinic and who were referred to the outpatient dental clinic. Medical histories were taken, and the patients' medical charts were examined.

Patients were included in the study if:
  1. The patient had been taking antihypertensive agents for at least a month.
  2. The patient had been performing CAPD for end-stage renal failure.
  3. The patient had been taking no other medications that could cause gingival hyperplasia.
  4. The patient had not been switched from one calcium antagonist to another while included in this study.
  5. The patient had received no periodontal therapy within the 6 months before inclusion in this study.

Patients who qualified were sent to the staff periodontist for oral examination. The examination included probing depths and grading gingival hyperplasia of the remaining dentition for each patient. Hyperplasia was measured from the cemento-enamel junction to the free gingival margin. The hyperplasia was graded according to the gingival overgrowth index described by McGaw, Lam, and Coates (11): 0 = no overgrowth, feather-edged gingival margin; 1 = blunting of gingival margin; 2 = moderate gingival overgrowth (< 1/3 of crown length); 3 = marked gingival overgrowth (> 1/3 of crown length).

Results

The results of this study are presented in Tables I and II. Table I shows the characteristics of patients in this study with gingival hyperplasia. Typical gingival hyperplasia is shown in Figure 1.

Gingival hyperplasia occurred in 9.7% of male and 4.5% of female patients receiving antihypertensive agents, and it was found in the patients using calcium antagonists (Table II). Among the calcium antagonists, only nifedipine and felodipine induced gingival hyperplasia.

Discussion

The purpose of this study was to examine whether calcium antagonists produce gingival hyperplasia in CAPD patients, as reports or literature examining the incidence of gingival hyperplasia in CAPD patients are lacking. Moreover, although gingival hyperplasia is seen in patients taking phenytoin and cyclosporine (12), no cases in patients maintaining CAPD are reported in Western literature.

The incidence of gingival hyperplasia induced by calcium antagonists varies by report: in Japan, the incidence is 3% - 20% in hypertensive subjects receiving calcium antagonists; in Europe and the U.S.A., it is 0.5% - 83% (8,10). In the present study, the incidence of gingival hyperplasia in patients on CAPD was 7.4% (4 of 54 patients). From these data, it is difficult to determine whether the incidence of gingival hyperplasia is lower or higher in CAPD patients compared to hypertensive subjects receiving calcium antagonists. Our present study has clearly demonstrated, for the first time, that calcium antagonists induce gingival hyperplasia in patients on CAPD.

Figure 1: Nifedipine-associated gingival hyperplasia.

The mechanisms by which calcium antagonists induce gingival hyperplasia have yet to be fully explained (13). Among the several proposed mechanisms, the best hypothesis so far is that calcium antagonists inhibit the influx of calcium ions that is needed for degradation and synthesis of collagen (14). The accumulated collagen and other extracellular matrix not degraded owing to inhibition of calcium influx by calcium antagonists are suggested to produce gingival hyperplasia. In addition to this mechanism, the importance of good oral hygiene for prevention of gingival hyperplasia is emphasized (12). In the present study, we did not examine the condition of oral hygiene; however, it is unlikely that patients on CAPD have poorer oral hygiene than the general population.

In the present study, 3 cases of gingival hyperplasia occurred among 18 patients taking nifedipine, and 1 case occurred in the 1 patient taking felodipine. No cases were found among the 27 patients taking amlodipine. The reason why cases of gingival hyperplasia were most prevalent among nifedipine users might be explained as follows: Nifedipine is the lowest calcium antagonist that has total clearance. It is known to dilate the arterioles much more than amlodipine does (15). These actions may produce unbalance of the gingival tissue and create edema. Indeed, the incidence of gingival overgrowth is 3% with amlodipine (16). In this pathological process, inflammation and inhibition of calcium influx owing to use of calcium antagonist stimulate collagen synthesis. Then, gingival hyperplasia is formed.

In conclusion, gingival hyperplasia owing to the adverse effects of dihydropyridines should be carefully examined when these agents are used for treatment of hypertension in CAPD patients.

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Corresponding author:

Hiromichi Suzuki, md, Department of Nephrology, Saitama Medical School, 38 Moroyama-machi, Iruma-gun, Saitama 350-0495 Japan.