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
Gingival hyperplasia, calcium antagonists
From:Department of Nephrology, Saitama Medical School, Saitama, Japan.
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:
- The patient had been taking antihypertensive agents for at least a month.
- The patient had been performing CAPD for end-stage renal failure.
- The patient had been taking no other medications that could cause gingival hyperplasia.
- The patient had not been switched from one calcium antagonist to another while included in this study.
- 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).
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.
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
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.