Full text of DOI:10.1016/S0272-6386(00)70042-4

Gender Difference in the Mean Age at the Induction of Hemodialysis
in Patients With Autosomal Dominant Polycystic Kidney Disease
Isao Ishikawa, MD, Kenji Maeda, MD, Shigeru Nakai, MD, and Yoshindo Kawaguchi, MD
● Male patients with autosomal dominant polycystic kidney disease (ADPKD) begin hemodialysis earlier than
female patients. The rate of progression of many other renal diseases is also faster in men than women. In this
study, gender difference in ADPKD was compared with that in other diseases, such as chronic glomerulonephritis,
diabetic nephropathy, and nephrosclerosis, using the data obtained from an annual statistical survey of the
Japanese Society for Dialysis Therapy. The male-female ratio in ADPKD (n ؍ 8,176) was 1.17:1 and closer to 1.0:1
than the other diseases. Men with ADPKD started hemodialysis therapy 1.3 years earlier than women (male age,
55.9 ؎ 12.4 years versus female age, 57.2 ؎ 11.5 years), and the age difference was less than that in other diseases.
These results suggest that the prognosis in women with ADPKD is relatively worse than that in men with ADPKD or
that women are not well protected against the progression of this disease compared with other renal diseases. In
conclusion, men with ADPKD are introduced to hemodialysis therapy earlier than women; however, the age
difference was small compared with other common renal diseases.
ꢀ 2000 by the National Kidney Foundation, Inc.
INDEX WORDS: Autosomal dominant polycystic kidney disease (ADPKD); diabetic nephropathy; gender; glomeru-
lonephritis; hemodialysis (HD).
therapy were the same for men and women during these time
periods, and there was no exclusion or refusal of treatment,
ALE PATIENTS WITH autosomal domi-
nant polycystic kidney disease (ADPKD)
M
as a general rule in Japan. The indication and timing of the
start of hemodialysis was the same for chronic glomerulone-
phritis, ADPKD, and nephrosclerosis, although patients with
diabetic nephropathy tended to be introduced to hemodialy-
sis earlier than other diseases. The male-female ratio was
calculated to determine the influence of gender on the
prevalence of renal disease. Gender differences in mean age
distribution at the introduction of dialysis were compared among
various diseases. There was no distinction made between PKD1
or PKD2 in patients with ADPKD, and specific features of the
ADPKD population were not analyzed because these data
were not available from the registry.
undergo hemodialysis earlier than female pa-
tients with ADPKD.1-4 Although many other
chronic renal diseases also show this tendency,
ie, the rate of progression of chronic renal dis-
ease is faster in men than women,5-7 we studied
gender differences concerning the prognosis of
renal diseases using accumulated data in Japan.
This study was performed to determine whether
men with ADPKD are more disadvantaged con-
cerning the start and prevalence of dialysis
therapy than women with ADPKD compared
with other renal diseases.
Data are expressed as mean Ϯ SD. Statistical treatment of
the data included testing for significant differences between
means by non-paired Student’s t-test.
MATERIALS AND METHODS
RESULTS
Data were obtained from an annual statistical survey of
the Japanese Society for Dialysis Therapy between 1983 and
1997,8 and permission for use was obtained by the Patient
Registration Committee of the Japanese Society for Dialysis
Therapy. The registration procedure has been described
previously.8 This is a retrospective study using combined
multicenter data for each year.
The male-female ratios at the start of dialysis
for chronic glomerulonephritis (n ϭ 134,202),
diabetic nephropathy (n ϭ 82,163), nephrosclero-
sis (n ϭ 15,614), and ADPKD (n ϭ 8,176) were
1.51:1, 1.75:1, 1.67:1, and 1.17:1, respectively
(Fig 1). The male-female ratio was the lowest in
ADPKD and highest in diabetic nephropathy.
Figure 1 shows that for every disease, men
started dialysis at an earlier age than women.
Men with chronic glomerulonephritis began di-
alysis 1.9 years earlier than women (male age,
55.9 Ϯ 15.7 versus female age, 57.8 Ϯ 15.7
years; P Ͻ 0.0001). Men with diabetic nephropa-
thy started dialysis therapy 1.8 years earlier than
women (male age, 60.3 Ϯ 10.5 versus female
age, 62.1 Ϯ 11.9 years; P Ͻ 0.0001). Men with
nephrosclerosis started on dialysis therapy 2.2
years earlier than women (male age, 69.9 Ϯ 11.6
The timing and indications for starting hemodialysis
From the Department of Internal Medicine, Division of
Nephrology, Kanazawa Medical University, Uchinada, Ja-
pan, and the Japanese Society for Dialysis Therapy.
Received August 11, 1999; accepted in revised form
December 10, 1999.
Address reprint requests to Isao Ishikawa, MD, Division
of Nephrology, Department of Internal Medicine, Kanazawa
Medical University, Uchinada, Kahoku, Ishikawa, 920-0293
Japan. E-mail: isikawai@kanazawa-med.ac.jp
ꢀ 2000 by the National Kidney Foundation, Inc.
0272-6386/00/3506-0008$3.00/0
doi:10.1053/ajkd.2000.7464
1072
American Journal of Kidney Diseases, Vol 35, No 6 (June), 2000: pp 1072-1075

GENDER DIFFERENCE IN ADPKD
1073
Fig 1. Gender differences of age distribu-
tion when starting hemodialysis in patients
with glomerulonephritis (GN), diabetic ne-
phropathy (DM), ADPKD, and nephrosclero-
sis. The prevalence of females was the great-
est in ADPKD and the least in DM, and the
difference in mean age was the least in ADPKD
and the greatest in nephrosclerosis.
versus female age, 72.1 Ϯ 11.5 years; P Ͻ
0.0001). In men with ADPKD, dialysis began 1.3
years earlier than for women (male age, 55.9 Ϯ
12.4 versus female age, 57.2 Ϯ 11.5 years; P Ͻ
0.0001). In ADPKD, the mean age of women at
the start of dialysis therapy was slightly younger
than that for other diseases.
The ages of both men and women in all
diseases showed normal distribution curves, ex-
cept for women with chronic glomerulonephritis,
which showed a bumpy curve (Fig 1).
faster in men than women, and men begin hemo-
dialysis therapy at an earlier age than women for
conditions such as immunoglobulin A nephropa-
thy, chronic glomerulonephritis, diabetic ne-
phropathy, and nephrosclerosis. Men with ESRD
showed a standardized mortality rate twice that
of women.11 Men had a 22% greater risk for
death than women, attributable to a greater risk
for death from acute myocardial infarction, car-
diac complications, and malignancy.12
With one exception,13 all studies reported that
the rate at which renal failure progresses is faster
in men than women with ADPKD.1-4,13 Survival
analysis of age at renal death showed a signifi-
cant gender difference: median age at renal death
was 53.5 years in men and 58.0 years in women,1
and the mean age at ESRD was 50.6 years in men
and 55.1 years in women.4 However, in this
study, the mean age was 55.9 years in men and
57.2 years in women. The difference in age was
1.3 years, in contrast to 4.5 years.1,4
DISCUSSION
The overall prevalence of end-stage renal dis-
ease (ESRD) is greater in men than women. A
greater incidence of ESRD in men was described
in glomerulonephritis,9 and a greater incidence
of ESRD was detected in white men, but not in
black men, with diabetic nephropathy. The male-
female ratio was 1.6:1 for ESRD caused by
glomerulonephritis and 2.2:1 for immunoglobu-
lin A nephropathy.10 In this study, the male-
female ratio was 1.17:1 for ADPKD. This ratio
was closer to 1:1 compared with the male-female
ratio at the start of dialysis; 1.51:1 for chronic
glomerulonephritis, 1.75:1 for diabetic nephropa-
thy, and 1.67:1 for nephrosclerosis. The male-
female prevalence of ADPKD was almost equal,
showing that women with ADPKD were not
strongly protected against this disease.
One study,3 a nationwide registration, showed
that more men than women with ADPKD (630
men, 527 women) enter ESRD programs be-
tween the ages of 25 and 44 years and 65 and 74
years, respectively, although the prevalence in
both sexes was similar for the ages of 45 to 64
years. In our study, the male-female ratios at the
start of dialysis for the ages of 25 and 44 years
(n ϭ 1,127), 45 and 64 years (nϭ 4,936), and 65
and 74 years (nϭ 1,453) were 1.84:1, 1.07:1, and
The progression of chronic renal disease is

1074
ISHIKAWA ET AL
1.10:1, respectively, suggesting that more men
than women with ADPKD had entered ESRD
programs only between the ages of 25 and 44
years. Unfortunately, our study only indicates
age at onset of ESRD and does not give informa-
tion on the rate of progression of the disease.
Female gender did not show protection against
the progression of ADPKD compared with other
renal diseases in this study. The precise mecha-
nisms underlying gender differences in the pro-
gression of chronic diseases remain to be eluci-
dated. Deterioration of renal function in patients
with chronic renal disease is faster in men than
women14,15 independent of the presence of hyper-
tension or hyperlipidemia. However, many
mechanisms of renal injury have been proposed
by using animal experiments related to the pro-
gression of chronic renal disease. One mecha-
nism involves genetic changes in structure and
function between men and women. Sex hor-
mones16 may be related to mesangial prolifera-
tion and extracellular matrix formation through
the release of cytokines, vasoactive agents, and
growth factors. Recently, Torres et al17 reported
that female Han:Sprague-Dawley rats had greater
renal concentrations of ␣-tocopherol and less
severe renal cystic disease. Estrogens show po-
tent antioxidant activity, unlike testosterone. Men
ingest more protein and phosphate than women,
resulting in hyperfiltration in glomerular filtra-
tion.18 Therefore, sex hormones may be the main
cause for this gender difference and poorer out-
comes in men.
However, sex hormones and acquired environ-
mental factors that prevent the progression of
renal diseases in women may be less effective in
ADPKD. Although ADPKD is an autosomal
dominant disease, hereditary factors equally dis-
advantageous to both genders may be more im-
portant for the progression of ADPKD than ac-
quired aggravating environmental factors. This
theory suggests that the prognosis in women
with ADPKD is worse than that in men with
ADPKD if ADPKD is compared with other renal
diseases.
Significant gender differences were observed
in terms of more pronounced progression in
women with autosomal recessive polycystic kid-
ney disease19 and in terms of a greater incidence
of renal cell carcinoma in male dialysis pa-
tients.20 No gender difference was found for age
at renal death in prepubertal patients with cysti-
nosis or nephronophthisis,1 and only a slight
male dominance was observed in patients with
ADPKD.
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