Download Epidemiology and mortality in dialysis patients with and without

ORIGINAL ARTICLE
JNEPHROL 2013; 26 ( 4) : 755- 762
DOI: 10.5301/jn.5000224
Epidemiology and mortality in dialysis patients
with and without polycystic kidney disease:
a national study in Taiwan
Pei-Wen Lee 1, Chih-Chiang Chien 2,3,4,
Wu-Chang Yang 1,5, Jhi-Joung Wang 3,
Chih-Ching Lin 1,5
Pei-Wen Lee and Chih-Chiang Chien contributed equally
as first authors to this work.
Abstract
Background: Polycystic kidney disease (PCKD) is one
of the most common inherited disorders in end-stage
renal disease patients. It is generally thought that the
survival of PCKD patients undergoing dialysis surpasses that of general dialysis patients, but the cause
of this improved survival is not clear.
Methods: Using Taiwan’s national health insurance
claims data, we performed a longitudinal cohort study
to investigate the survival and impact of comorbidities on mortality in dialysis patients with and without
PCKD. We excluded patients without diabetes mellitus
(DM) in a further analysis. A Cox proportional hazards
model was used to identify the risk factors for allcause mortality. The Kaplan-Meier method was used
to describe overall patient survival.
Results: Five hundred and one (2.25%) of 22,298 nondiabetic incident dialysis patients had PCKD. We
found no significant difference in survival rates between those with and without PCKD. Being male,
being over 65 years old and having congestive heart
failure or cerebrovascular accident were each found
to be independent predictors of mortality in the PCKD
dialysis patients.
Conclusions: Taiwan has a lower incidence rate of
PCKD than Western countries. In Taiwan, there is little
difference in the long-term survival between dialysis
patients with and without PCKD.
Division of Nephrology, Department of Medicine, Taipei
Veterans General Hospital, Taipei - Taiwan
2
Department of Nephrology, Chi-Mei Medical Center,
Tainan - Taiwan
3
Department of Medical Research, Chi-Mei Medical Center,
Tainan - Taiwan
4
Department of Food Nutrition, Chung Hwa University
of Medical Technology, Tainan - Taiwan
5
School of Medicine, National Yang-Ming University,
Taipei - Taiwan
1
Key words: End-stage renal disease, Mortality, Polycystic kidney disease, Risk factors, Survival
Introduction
Polycystic kidney disease (PCKD) is one of the most common inherited disorders found in end-stage renal disease
(ESRD) patients. Progressive expansion of multiple renal
cysts leads to deteriorated renal function (1, 2). PCKD is
found in 10% of patients with ESRD in Western countries
(3) but in only 1.60% of those in Taiwan (4). Some studies
have proposed that the survival of PCKD patients undergoing dialysis surpasses that of general dialysis patients (3,
5-7). However, most of these studies compared PCKD dialysis patients with a nondiabetic control group. The cause of
improved survival is not clear and is presumed to stem from
multiple factors, including a better hemoglobin level, which
improves cardiac function, significantly lower blood pressure and use of more antihypertensive medications, especially inhibitors of the renin-angiotensin-aldosterone system
(3, 7-9). Whether PCKD inherently contributes any risk or
benefit to survival is uncertain. Using data from the National
Health Insurance Research Database (NHIRD) in Taiwan, we
designed a longitudinal cohort study of ESRD dialysis patients to uncover any influence of PCKD on survival and to
determine the risk factors of mortality in nondiabetic maintenance dialysis patients with and without PCKD.
© 2012 Società Italiana di Nefrologia - ISSN 1121-8428
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Lee et al: Mortality in PCKD patients on dialysis
Materials and methods
Database
Taiwan’s national health insurance program, which provides
compulsory universal health insurance, was first implemented in 1995. With the exception of prison inmates, all citizens
are enrolled in the program. All contracted medical institutions must submit standard claim documents for medical
expenses on a computerized form. Patients with ESRD are
eligible for any type of renal replacement therapy free of
charge and without co-payments.
The data for this cohort study were obtained from the
NHIRD (http://www.doh.gov.tw/statistic/index.htm [in Chinese]; http://www.doh.gov.tw/EN2006/index_EN.aspx [in
English]), which is released for research purposes by the
Taiwan National Health Research Institute. The NHIRD,
which includes nearly all (99%) inpatient and outpatient
medical benefit claims for the population of 23 million
Taiwanese, is one of the largest and most comprehensive
databases in the world and has been used extensively in
various studies (10, 11). The NHIRD provides encrypted
patient identification numbers, sex, date of birth, dates of
admission and discharge, medical institutions providing
services, the International Classification of Diseases, Ninth
Revision, Clinical Modification (ICD-9-CM) diagnostic (up
to 5) and procedure (up to 5) codes, and outcomes. After
obtaining ethics committee approval, we used the NHIRD
for ambulatory care claims and all inpatient claims, and the
updated registry for beneficiaries. All of the datasets can
be combined using each individual’s unique personal
identification number. The study was approved by the
institutional review board, and an independent data and
safety monitoring board oversaw the conduct of the trial
and reviewed the safety and efficacy data.
Patient selection and definition
Using the NHIRD, we enrolled all ESRD patients who underwent maintenance dialysis between January 1, 1999, and
December 31, 2004. A patient was defined as undergoing
maintenance dialysis if he or she had undergone dialysis for
longer than 90 days. Patients who underwent renal transplantation before initiation of dialysis and those younger
than 20 years were excluded. The remaining patients were
followed up from the day of their first dialysis treatment until
their death, kidney transplantation or the end of the followup period on December 31, 2008. Patient selection is shown
in Figure 1.
756
Fig. 1 - Patient selection. DM = diabetes mellitus; PCKD =
polycystic kidney disease.
Ascertaining the demographic and comorbidity
variables
The patients with ESRD were stratified by the presence or
absence of PCKD at the beginning of dialysis treatment.
Data collected included survival status, date of death as well
as demographic and comorbidity variables. Demographic
variables included age and sex, and modality of initial dialysis. Baseline comorbidity variables were the major comorbidities known to affect mortality, including diabetes mellitus
(DM), hypertension (HTN), congestive heart failure (CHF),
coronary artery disease (CAD), cerebrovascular accident
(CVA), peripheral artery disease (PAD) and malignancy. The
selected comorbidities were determined based on diagnostic codes recorded on claims records from ambulatory visit
or hospitalization databases at the start of the dialysis. The
ICD-9-CM codes used to define these clinical conditions are
shown in the Appendix.
Statistical analyses
Sample size estimation was performed for the whole cohort. For sample size and attrition rate, significance was set
at an alpha of 0.05 (2-tailed). The study needed a power
of 93.2% to yield a statistically significant result. All values
were expressed as incidence proportion (%). The baseline
characteristics of the groups of patients with and without
PCKD were compared using Pearson chi-square tests. Age
was entered as a categorical variable (20-44, 45-64 and 65
years or older). A p value <0.05 was considered significant.
© 2012 Società Italiana di Nefrologia - ISSN 1121-8428
JNEPHROL 2013; 26 ( 4) : 755- 762
Overall patient survival was described using the Kaplan-Meier method. To evaluate the impact of PCKD on survival, we
analyzed the differences in baseline characteristics between
the patients with and without PCKD to determine which factors qualified for entry into a Cox regression model. The Cox
proportional hazards model was used to identify risk factors
for all-cause mortality. Hazard ratios (HRs) and 95% confidence intervals (CIs) were derived from the Cox proportional
hazards models. The proportional hazards assumption was
checked using log-minus-log plots of the survival function.
The Cox models met the assumption of proportionality of
risks. To adjust for potential confounding in the relationship
between comorbidities and the risk of mortality, multivariate analysis was used to model all-cause mortality. Further
interactions were tested. The complete model, which included all of the covariates listed in Table I, was used for
the Cox regression analysis. Each interaction term was then
included separately. The p values for each interaction term
ranged from 0.134 to 0.933, none of which was significant.
We used the likelihood ratio statistic to assess the goodness
of fit of the model. The likelihood ratios of the null model
and multivariate model were 354,931.5 and 345,923.8 for
all patients and 127,048.16 and 122,467.0 for the patients
without diabetes, respectively. The R-square, which we calculated according to Schemper and Stare’s formula (1996),
was 18.9% for all patients, and 18.7% for the patients without diabetes. The data were analyzed using the Statistical
Package for the Social Sciences (Windows version 17.0;
SPSS Inc, Chicago, IL, USA).
Results
A total of 43,039 incident dialysis patients were evaluated in
the study. Of these 603 patients had PCKD and 42,436 had
other causes of ESRD. During the follow-up period, 2,100
non-PCKD and 42 PCKD patients underwent kidney transplantations. As can be seen in the summary of baseline characteristics in Table II, there was a lower proportion of women
among the patients with PCKD compared than those without. Patients with PCKD had significantly lower proportions
of DM and dyslipidemia, but a higher proportion of gout.
We stratified the non-DM patients into whether they had or
did not have PCKD (Tab. II). Of the 22,196 non-DM dialysis
patients, 501 patients (2.26%) had PCKD. These patients
were predominantly male (58.7%) and had a mean age of
56.4 ± 13.4 years. HTN was the most common (78.4%) comorbidity. These patients had a greater prevalence of HTN,
gout and CVA than those without PCKD.
The survival rates for all dialysis patients and for nondiabetic patients are shown in Figures 2 and 3, respectively.
The patients with PCKD had a significantly better survival
rate than those without PCKD (p<0.001, by log-rank test).
However, the adjusted mortality rates of the patients with
PCKD relative to those without PCKD were not significantly
different (Tab. III). Because DM is an important comorbidity
that greatly impacts mortality, we further excluded DM by
using the restriction method. The reanalysis showed no difference in survival curves between the 2 groups.
We also determined the risk factors for all-cause mortality among all PCKD patients and the nondiabetic PCKD
patients by multivariate analyses. Significant risk factors
for all-cause mortality in both groups were male sex, being
older than 65 years, CHF and CVA (Tab. I).
Discussion
This nationwide representative study used Taiwan`s NHIRD
to investigate the long-term survival and mortality risk of
PCKD in dialysis patients. Only 1.4% of the incident dialysis patients had PCKD. We found no significant statistical
difference in survival rate between the patients with and
without PCKD. Being male, being 65 years or older, and
having CHF or CVA were found to be independent predictors of mortality in dialysis patients with PCKD.
There were substantial differences between the patients with
and without PCKD, with regard to several prognostic indicators of death, including age, history of DM, dyslipidemia,
CHF, CAD and PAD (Tab. II). However, we inferred a different conclusion from the multivariate adjustment. Previous
reports showed that PCKD patients have a better survival
after the initiation of dialysis than control patients (3, 5-7).
Perrone et al (3), using data from the US Renal Data System,
found a lower mortality rate in PCKD dialysis patients than
in nondiabetic dialysis patients. Zeier et al (7) presumed that
such an improvement might be a result of the effects of better hemoglobin levels on cardiac function.
Our study found a significantly greater proportion of PCKD patients on dialysis had HTN and CVA, though they were younger. This finding was consistent with previous studies (12-15).
HTN is an early and common finding in PCKD, and is possibly caused by focal ischemia resulting from cyst expansion
and by increased activity of the renin-angiotensin-aldosterone
system (16-18). A neurological event was the fourth most
common cause of death in PCKD patients (12%). Aneurysm
rupture often occurs with larger aneurysms or in patients with
poorly controlled hypertension (15, 19). We also found CVA to
be a significant risk factor for all-cause mortality in the PCKD
patients on dialysis in Taiwan (Tab. I). Taken together, our multivariate findings suggest that ESRD patients with PCKD may
not have a better survival rate than those without it.
© 2012 Società Italiana di Nefrologia - ISSN 1121-8428
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Lee et al: Mortality in PCKD patients on dialysis
TABLE I
RISK FACTORS FOR ALL-CAUSE MORTALITY IN ALL AND NONDIABETIC DIALYSIS PATIENTS WITH PCKD
All dialysis patients with PCKD
Covariate
Nondiabetic dialysis patients with PCKD
Univariate
analysis
Multivariate
analysis
Univariate
analysis
Multivariate
analysis
HR (95% CI)
HR (95% CI)
HR (95% CI)
HR (95% CI)
1.711 (1.269-2.307)*
1.975 (1.430-2.727)*
1.734 (1.231-2.443)*
2.014 (1.415-2.865)*
1
1
1
1
45-64
1.434 (0.865-2.378)
1.391 (0.827-2.339)
1.306 (0.757-2.254)
1.273 (0.732-2.211)
≥65
4.630 (2.837-7.555)*
4.536 (2.687-7.659)*
4.458 (2.637-7.536)*
4.419 (2.555-7.645)*
Diabetes mellitus
(yes vs. no)
1.755 (1.268-2.430)*
1.397 (0.999-1.954)
-
-
Hypertension
(yes vs. no)
1.279 (0.884-1.850)
0.993 (0.678-1.454)
1.379 (0.909-2.091)
-
Dyslipidemia
(yes vs. no)
0.738 (0.402-1.357)
0.544 (0.293-1.010)
0.540 (0.221-1.317)
-
Gout (yes vs. no)
1.222 (0.894-1.670)
0.924 (0.659-1.295)
1.092 (0.754-1.583)
-
Congestive heart failure
(yes vs. no)
2.377 (1.648-3.429)*
2.336 (1.551-3.518)*
2.468 (1.593-3.823)*
2.481 (1.550-3.970)*
Coronary artery disease
(yes vs. no)
1.881 (1.359-2.603)*
1.045 (0.733-1.492)
1.862 (1.265-2.740)*
1.031 (0.686-1.551)
Cerebrovascular accident
(yes vs. no)
1.770 (1.212-2.585)*
1.685 (1.140-2.429)*
1.896 (1.225-2.934)*
1.871 (1.205-2.905)*
Peripheral arterial disease
(yes vs. no)
1.561 (0.580-4.203)
1.177 (0.429-3.228)
1.833 (0.679-4.952)
-
Chronic lung disease
(yes vs. no)
1.873 (1.248-2.812)*
1.051 (0.677-1.633)
1.697 (1.049-2.746)*
0.918 (0.555-1.518)
Chronic liver disease
(yes vs. no)
1.349 (0.962-1.891)
1.350 (0.957-1.905)
1.235 (0.832-1.833)
-
Cancer (yes vs. no)
1.627(0.884-2.993)
1.308 (0.691-2.476)
1.261 (0.590-2.696)
-
Sex (male vs. female)
Age at initiation of dialysis
20-44 (reference)
CI = confidence interval; HR = hazard ratio; PCKD = polycystic kidney disease.
*p<0.05.
758
© 2012 Società Italiana di Nefrologia - ISSN 1121-8428
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TABLE II
PATIENT BASELINE CHARACTERISTICS
All dialysis patients
Nondiabetic dialysis patients
Without PCKD
(n = 42,436)
With PCKD
(n = 603)
Without PCKD
(n = 21,695)
With PCKD
(n = 501)
No. (%)
No. (%)
No. (%)
No. (%)
20,033 (47.2)
355 (58.9)†
9,945 (45.8)
294 (58.7)†
20-44
6,777(16)
113(18.7)*
5264 (24.3)
104 (20.8) †
45-64
18,644(43.9)
289(47.9)*
8317 (38.3)
244 (48.7) †
≥65
17,015(40.1)
201(33.3)*
8114 (37.4)
153 (30.5) †
Mean age
59.15 ± 14.42
57.40 ± 13.33
56.81 ± 16.41
56.36 ± 13.40
HD
38,635 (91.1)
549 (91)
19,050 (87.9)
453 (90.4)
Diabetes mellitus
20,741 (48.9)
102 (16.9)†
-
-
Hypertension
33,373 (78.6)
484 (80.3)
14,859 (68.5)
393 (78.4)†
Dyslipidemia
6,366 (15)
43 (7.1)†
1,642 (7.6)
26 (5.2)*
Gout
5,607 (13.2)
114 (23.9)†
3,242 (14.9)
116 (23.2)†
Congestive heart failure
8,383 (19.8)
66 (10.9)†
2,559 (11.8)
47 (9.4)
Coronary artery disease
9,946 (23.4)
100 (16.6)†
3,238 (14.9)
72 (14.4)
Cerebrovascular accident
5,322 (12.5)
71 (11.8)
1,635 (7.5)
53 (10.6)*
Peripheral arterial disease
1,380 (3.3)
9 (1.5)*
524 (2.4)
8 (1.6)
Chronic lung disease
4,707 (11.1)
54 (9)
2,201 (10.1)
42 (8.4)
Chronic liver disease
7,716 (18.2)
105 (17.4)
3,812 (17.6)
83 (16.6)
Cancer
2,182 (5.1)
24 (4)
1340 (6.2)
19 (3.8)*
Male sex
Age, years
HD = hemodialysis; PCKD = polycystic kidney disease.
*p<0.05; †p<0.001.
DM is the leading cause of ESRD (35.3%) in Taiwan. ESRD
patients with DM have a poorer survival rate than non-DM
patients (20). ESRD patients with diabetic nephropathy frequently have multiple comorbid conditions that are mainly
vascular in nature, including retinopathy, neuropathy and
cardiovascular complications (21, 22). Our PCKD group had
a much smaller proportion of DM than our non-PCKD group.
After excluding the DM patients, we found no significant difference in survival rates between the 2 nondiabetic groups.
The incidence of ESRD resulting from PCKD is reported to
range from 6 to 8 patients per million population (PMP) in
the United States (23), but only approximately 5.02 PMP in
Taiwan (4). PCKD is the fourth most common cause (2.4%)
of ESRD in the United States, preceded by DM (44.0%),
HTN (27.9%) and chronic glomerulonephropathy (CGN)
(6.7%) (10). In Taiwan, ESRD secondary to PCKD is much
rarer (1.4%), and is the fifth largest cause, preceded by DM
(37.31%), CGN (31.92%), HTN (6.15%) and gout (2.69%)
© 2012 Società Italiana di Nefrologia - ISSN 1121-8428
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Lee et al: Mortality in PCKD patients on dialysis
TABLE III
COX REGRESSION ESTIMATES OF THE ASSOCIATION
BETWEEN PCKD AND ALL-CAUSE MORTALITY FOR ALL
PATIENTS AND NONDIABETIC PATIENTS
Subgroup
All dialysis patients
Without PCKD
(reference)
With PCKD
Fig. 2 - Kaplan-Meier survival curves for all dialysis patients
with or without polycystic kidney disease (PCKD). The logrank test showed a significant difference between patients
with or without PCKD (p<0.001, by log-rank test). DM = diabetes mellitus.
Nondiabetic patients
Without PCKD
(reference)
With PCKD
Univariate
analysis
Multivariate
analysis
HR (95% CI)
HR (95% CI)
1
1
0.719
(0.625-0.826)*
0.954
(0.829-1.098)†
1
1
0.982
(0.836-1.154)
1.040
(0.885-1.222) ‡
CI = confidence interval; HR = hazard ratio; PCKD = polycystic
kidney disease.
*p<0.05.
†
Adjusted for sex, age, dialysis modality, diabetes mellitus,
hypertension, dyslipidemia, congestive heart failure, coronary
artery disease, cerebrovascular accident, peripheral artery disease, lung disease, liver disease and cancer.
‡
Adjusted for sex, age, dialysis modality, hypertension, dyslipidemia, congestive heart failure, coronary artery disease, cerebrovascular accident, peripheral artery disease, lung disease,
liver disease and cancer.
Fig. 3 - Comparison of 10-year survival curves for nondiabetic dialysis patients with or without polycystic kidney disease
(PCKD; p = 0.825, by log-rank test).
(4). The prevalence of PCKD in another Asian country, Japan, is 2.1% among men and 2.7% among women (24).
There may be several reasons for the difference in outcomes
in ESRD patients with PCKD between Taiwan and Western
countries. First, Taiwan has a lower prevalence of PCKD.
In addition, the difference may be due to differences in
ethnicity and a lower prevalence of diabetic nephropathy in
760
Taiwan. The possible effect of these variables on the generalizability of our results should be taken into consideration.
It has been demonstrated that in affected males, female
carriers and cardiac variant men with Anderson-Fabry
disease, renal cysts are usually detected (25). Pisani et al
reported the first case with simultaneous presence of multiple liver and kidney cysts in patients with genetically confirmed Anderson-Fabry disease (26). This could be a new
association that can confound and delay the diagnosis of
Anderson-Fabry disease.
This study has several limitations. First, the diagnosis of comorbidities in this study relied on claims data and ICD-9-CM
diagnosis codes, which may result in potential disease misclassification. Second, we assessed comorbidities on the
basis of a simple classification (presence/absence), which
does not take into account disease severity. Third, our study
© 2012 Società Italiana di Nefrologia - ISSN 1121-8428
JNEPHROL 2013; 26 ( 4) : 755- 762
APPENDIX
ICD-9-CM CODES USED TO IDENTIFY CLINICAL CONDITIONS
Conditions
ICD-9-CM
Polycystic kidney
disease
753.12-753.14
Diabetes mellitus (DM)
250.xx, 357.2, 362.0x, 366.41
Hypertension
362.11, 401.x-405.x, 437.2
Dyslipidemia
272.0, 272.2, 272.4
Gout
274.0-274.9
Congestive heart failure
(CHF)
428.0-428.43, 428.9, 398.91
Coronary artery disease
(CAD)
410.xx- 414.xx
Cerebrovascular
accident/TIA
430-438.xx
Peripheral arterial
disease (PAD)
440.0-440.9, 38.13-38.18,
39.22-39.26, 39.28
Chronic lung disease
490-496x, 500-505x, 506.4x
Chronic liver disease
571.x
Cancer
140-208
Taiwan has a low proportion of PCKD cases. The long-term
survival outcomes of dialysis patients with and without
PCKD are similar in Taiwan. The risk factors for mortality
in PCKD dialysis patients are being male, being older than
65 years and having CHF or CVA.
Financial support: This study was supported by grant CMFHR10177
from the Chi-Mei Medical Center and grant NHRI-NHIRD-99182
from the National Health Research Institutes in Taiwan.
Address for correspondence:
Chih-Ching Lin, MD
Division of Nephrology and Department of Medicine
Taipei Veterans General Hospital
No. 201, Sec. 2, Shih-Pai Road
Taipei, Taiwan 112, Republic of China
[email protected]
3.
References
2.
Conclusion
Conflict of interest: None.
x or xx can indicate any number or no number.
ICD-9-CM = International Classification of Diseases, Ninth Revision, Clinical Modification; TIA = transient ischemic attack.
1.
lacked data on the duration and treatment regimens of the
diseases, biochemical data and socioeconomic characteristics. These variables may exert some influence on mortality
and should be considered as confounders in future studies.
Torres VE, King BF, Chapman AB, et al. Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease (CRISP).
Magnetic resonance measurements of renal blood flow and
disease progression in autosomal dominant polycystic kidney disease. Clin J Am Soc Nephrol. 2007;2(1):112-120.
King BF, Torres VE, Brummer ME, et al. Consortium for
Radiologic Imaging Studies of Polycystic Kidney Disease
(CRISP). Magnetic resonance measurements of renal blood
flow as a marker of disease severity in autosomal-dominant
polycystic kidney disease. Kidney Int. 2003;64(6):2214-2221.
4.
5.
6.
Perrone RD, Ruthazer R, Terrin NC. Survival after end-stage
renal disease in autosomal dominant polycystic kidney disease: contribution of extrarenal complications to mortality.
Am J Kidney Dis. 2001;38(4):777-784.
Hwang SJ, Yang WC, Che HH. 1999 National Dialysis Surveillance in Taiwan. Acta Neurol (Napoli). 2000;14:139-228.
Abbott KC, Agodoa LY. Polycystic kidney disease at endstage renal disease in the United States: patient characteristics and survival. Clin Nephrol. 2002;57(3):208-214.
Hadimeri H, Nordén G, Friman S, Nyberg G. Autosomal
dominant polycystic kidney disease in a kidney transplant
population. Nephrol Dial Transplant. 1997;12(7):14311436.
© 2012 Società Italiana di Nefrologia - ISSN 1121-8428
761
Lee et al: Mortality in PCKD patients on dialysis
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
762
Zeier M, Jones E, Ritz E. Autosomal dominant polycystic
kidney disease: the patient on renal replacement therapy.
Nephrol Dial Transplant. 1996;11(Suppl 6):18-20.
Patch C, Charlton J, Roderick PJ, Gulliford MC. Use of
antihypertensive medications and mortality of patients with
autosomal dominant polycystic kidney disease: a population-based study. Am J Kidney Dis. 2011;57(6):856-862.
Schrier RW, McFann KK, Johnson AM. Epidemiological
study of kidney survival in autosomal dominant polycystic
kidney disease. Kidney Int. 2003;63(2):678-685.
Chen HF, Chen P, Li CY. Risk of malignant neoplasms of liver
and biliary tract in diabetic patients with different age and
sex stratifications. Hepatology. 2010;52(1):155-163.
Chen HF, Ho CA, Li CY. Age and sex may significantly interact with diabetes on the risks of lower-extremity amputation
and peripheral revascularization procedures: evidence from
a cohort of a half-million diabetic patients. Diabetes Care.
2006;29(11):2409-2414.
Gonzalo A, Gallego A, Rivera M, Orte L, Ortuño J. Influence of
hypertension on early renal insufficiency in autosomal dominant polycystic kidney disease. Nephron. 1996;72(2):225230.
Bardají A, Martinez-Vea A, Valero A, et al. Cardiac involvement
in autosomal-dominant polycystic kidney disease: a hypertensive heart disease. Clin Nephrol. 2001;56(3):211-220.
Himmelfarb J, Stenvinkel P, Ikizler TA, Hakim RM. The elephant
in uremia: oxidant stress as a unifying concept of cardiovascular disease in uremia. Kidney Int. 2002;62(5):1524-1538.
Ring T, Spiegelhalter D. Risk of intracranial aneurysm
bleeding in autosomal-dominant polycystic kidney disease.
Kidney Int. 2007;72(11):1400-1402.
Gabow PA, Chapman AB, Johnson AM, et al. Renal structure
and hypertension in autosomal dominant polycystic kidney
disease. Kidney Int. 1990;38(6):1177-1180.
Barrett BJ, Foley R, Morgan J, Hefferton D, Parfrey P.
Differences in hormonal and renal vascular responses
between normotensive patients with autosomal dominant
polycystic kidney disease and unaffected family members.
Kidney Int. 1994;46(4):1118-1123.
18. Ecder T, Schrier RW. Hypertension in autosomal-dominant
polycystic kidney disease: early occurrence and unique aspects. J Am Soc Nephrol. 2001;12(1):194-200.
19. Schievink WI, Torres VE, Piepgras DG, Wiebers DO. Saccular intracranial aneurysms in autosomal dominant polycystic
kidney disease. J Am Soc Nephrol. 1992;3(1):88-95.
20. Yang WC, Hwang SJ. Taiwan Society of Nephrology. Incidence, prevalence and mortality trends of dialysis endstage renal disease in Taiwan from 1990 to 2001: the
impact of national health insurance. Nephrol Dial Transplant.
2008;23(12):3977-3982.
21. Schroijen MA, Dekkers OM, Grootendorst DC, et al.
NECOSAD Study Group. Survival in dialysis patients is not
different between patients with diabetes as primary renal disease and patients with diabetes as a co-morbid condition.
BMC Nephrol. 2011;12(1):69.
22. Rodríguéz JA, Clèries M, Vela E. Registry Committee R;
Renal Registry Committee. Diabetic patients on renal replacement therapy: analysis of Catalan Registry data.
Nephrol Dial Transplant. 1997;12(12):2501-2509.
23. Collins AJ, Foley RN, Herzog C, et al. US Renal Data
System 2010 annual data report. Am J Kidney Dis. 2011;
57(1)(A8):e1-e526.
24. Wakai K, Nakai S, Kikuchi K, et al. Trends in incidence of
end-stage renal disease in Japan, 1983-2000: age-adjusted
and age-specific rates by gender and cause. Nephrol Dial
Transplant. 2004;19(8):2044-2052.
25. Glass RB, Astrin KH, Norton KI, et al. Fabry disease:
renal sonographic and magnetic resonance imaging findings in affected males and carrier females with the classic
and cardiac variant phenotypes. J Comput Assist Tomogr.
2004;28(2):158-168.
26. Pisani A, Riccio E, Cianciaruso B, Imbriaco M. Simultaneous multicystic kidney and Anderson-Fabry disease: 2 separate entities or same side of the coin. J Nephrol. 2011;24(6):
806-808.
Accepted: August 22, 2012
© 2012 Società Italiana di Nefrologia - ISSN 1121-8428