Visual Abstract
Abstract
Background and objectives The prevalence of autosomal dominant polycystic kidney disease (ADPKD) remains controversial. Incidence rates in Olmsted County, Minnesota, during 1935–1980 were previously reported. The current work extends this study to 2016.
Design, setting, participants, & measurements The Rochester Epidemiology Project and radiology databases of Mayo Clinic and Olmsted Medical Center (healthcare providers for Olmsted County) were searched to identify all subjects meeting diagnostic criteria for definite, likely, and possible ADPKD. Annual incidence rates were calculated using incident cases during 1980–2016 as numerator and age- and sex-specific estimates of the population of Olmsted County as denominator. Point prevalence was calculated using prevalence cases as numerator and age- and sex-specific estimates of the population of Olmsted County on January 1, 2010 as denominator. Survival curves from the time of diagnosis were compared with expected survival of the Minnesota population.
Results The age- and sex-adjusted annual incidence of definite and likely ADPKD diagnosis during 1980–2016 was 3.06 (95% CI, 2.52 to 3.60) per 100,000 person-years, which is 2.2 times higher than that previously reported for 1935–1980 (1.38 per 100,000 person-years). The point prevalence of definite or likely ADPKD on January 1, 2010 was 68 (95% CI, 53.90 to 82.13) per 100,000 population. Much higher incidence rates and point prevalence were obtained when possible ADPKD cases were included. Contrary to the previous Olmsted County study, patient survival in this study was not different from that in the general population.
Conclusions The point prevalence of definite and likely ADPKD observed in this study is higher than those reported in the literature, but lower than genetic prevalence based on estimates of disease expectancy or on analysis of large population-sequencing databases.
- ADPKD
- epidemiology and outcomes
- polycystic kidney disease
- male
- female
- humans
- incidence
- prevalence
- autosomal dominant polycystic kidney
- confidence intervals
- Minnesota
- radiography
- nucleic acid databases
- radiology
- publications
- health personnel
Introduction
Autosomal dominant polycystic kidney disease (ADPKD) is characterized by progressive development and growth of cysts causing enlargement and distortion of the kidneys, impairment of kidney function, and in many cases ESKD. It is the fourth leading cause of ESKD in adults (1–3). Mutations to PKD1 or PKD2 are the most common cause, but mutations to genes encoding translocon proteins, chaperones, and enzymes participating in the biogenesis of polycystin-1 and of other membrane-associated proteins have been recently associated with polycystic liver disease and mild forms of ADPKD (4–6). Patients with autosomal dominant tubulointerstitial kidney diseases—characterized by progressive inflammation, fibrosis, and kidney function decline without significant enlargement—often exhibit bilateral kidney cysts and can be erroneously diagnosed as ADPKD (7–9).
The prevalence of ADPKD has been controversial, in large part due to different definitions and methods of ascertainment. Autopsy studies, with ADPKD frequencies ranging between 100 and 450 per 100,000, may include patients with acquired or other genetic cystic kidney diseases and therefore overestimate its prevalence (10–13). Clinical studies with incomplete ascertainment of populations, on the other hand, likely underestimate the prevalence because ADPKD may be mild and undiagnosed in many people (14–17). A recent analysis of two population-based studies in German and British populations estimated minimum (i.e., diagnosed cases only) point prevalence of 24 and 39 per 100,000, respectively (18–20).
Two population-based studies have estimated incidence rates of ADPKD. The incidence rate in Copenhagen during 1920–1953 was 0.8 per 100,000 patient-years (10). Three incidence rates were estimated for the Olmsted County population during 1935–1980, 1.4 (only including patients diagnosed while alive), 2.1 (also including patients diagnosed at autopsy), and 2.8 per 100,000 patient-years (assuming a 100% autopsy rate) (21). For a highly penetrant genetic disease such as ADPKD, the disease expectancy at age 80 years is a good approximation of the genetic prevalence of the disease at birth. Disease expectancies were estimated to be approximately 80 per 100,000 in Copenhagen and 100 (clinical diagnoses only) to 250 (clinical and autopsy diagnoses assuming 100% autopsy rate) per 100,000 in Olmsted County (10,11). Recently, two large, population-sequencing databases have been used to directly estimate the genetic prevalence of ADPKD (22). The overall prevalence of high-confidence pathogenic and likely pathogenic PKD1 or PKD2 mutations was 93 (68 PKD1, 26 PKD2) and 174 per 100,000 (141 PKD1, 33 PKD2), respectively.
The large discordance between estimated genetic and point prevalence of ADPKD suggests that patients with mild disease are often not diagnosed and/or that significant genetic events are overestimated. With more frequent utilization and superior resolution of imaging studies, mild cases of ADPKD are increasingly recognized. Equally, genetic studies are showing that a few cysts may have a genetic cause. Therefore, the objective of our study was to revisit the epidemiology of ADPKD in Olmsted County in the last four decades, estimate the point prevalence of clinically significant ADPKD in Olmsted County, Minnesota on January 1, 2010, and provide insight on the prevalence of mild, silent ADPKD in this population.
Materials and Methods
Research Design
This is a retrospective cohort study conducted in Olmsted County, Minnesota, an area relatively isolated from other urban centers and with few healthcare providers. The Mayo Clinic, Olmsted Medical Center, and their affiliated facilities deliver most healthcare to local residents. The population of Olmsted County was 92,006 in 1980 and 144,248 in 2010. The study was conducted in accordance with the Declaration of Helsinki and approved by the institutional review boards of the Mayo Clinic and Olmsted Medical Center.
Data Sources
We used the Rochester Epidemiology Project and the Mayo Clinic and Olmsted Medical Center radiology databases to identify subjects meeting our diagnostic criteria. The Rochester Epidemiology Project is a medical records linkage system incorporating data from all medical facilities in Olmsted County, Minnesota (23–25). The reports of all imaging studies performed at a radiology department in Olmsted County have been stored in the Mayo Clinic or Olmsted Medical Center radiology databases. Abdominal computed tomography (CT) and magnetic resonance (MR) scans have been electronically available since 1997; however, before 2009 reports were only available from one site in the Rochester Epidemiology Project. We combined these data sources to provide the most powerful strategy to capture as many potential subjects with ADPKD as possible and to most accurately estimate the incidence or prevalence of ADPKD in this region.
Identification of Potential Subjects with Autosomal Dominant Polycystic Kidney Disease
We searched the Rochester Epidemiology Project for Olmsted County residents during the years 1980–2016 with diagnostic codes for polycystic kidney, polycystic liver, and related cystic disease diagnoses to capture the potential ADPKD subjects (Supplemental Figure 1). We reviewed their medical records, abdominal imaging, and/or imaging reports including excretory urograms, ultrasound (US), CT, and MR scans. Diagnostic criteria for definite, probable, and possible ADPKD are listed in Table 1 (21,26,27) and were based on the review of the medical records, radiology reports, and available imaging studies. Patients not meeting these criteria were considered not to have ADPKD.
Diagnostic criteria for definite, likely and possible ADPKD
(1) Definite: Ravine/Pei criteria in the presence of a family history of autosomal dominant polycystic kidney disease or proven pathogenic PKD1 or PKD2 mutation (26).
(2) Likely: bilaterally enlarged kidneys with innumerable cysts or more than ten cysts (≥5mm in size; parapelvic cysts excluded) in each kidney in the absence of CKD stage 4 or 5 (to exclude patients with acquired renal cystic disease) or findings suggesting a different renal cystic disease (21).
(3) Possible: normal size or mildly enlarged kidneys with a number of cysts (≥5mm in size; parapelvic cysts excluded) above the 97.5th percentile of an age- and sex-matched control population (27) in the absence of CKD stage 4 or 5, or findings suggesting a different renal cystic disease.
Values above the 97.5th percentile by age and sex are:
The identification of undiagnosed ADPKD cases occurred through the retrieval of radiology images from the Mayo Clinic and Olmsted Medical Center. The Mayo Clinic and Olmsted Medical Center Radiology databases were searched for Olmsted County residents with reports of enhanced CT or (plain or enhanced) MR scans between 1997 and 2016 which contained the words cysts and kidney or renal. We searched only subjects who underwent enhanced CT or (plain or enhanced) MR scans because these imaging studies are more sensitive and allow a clearer separation of cystic and noncystic tissue than nonenhanced CT or US scans. The diagnostic criteria are the same as described above and listed in Table 1 (21,26,27). We reviewed the imaging studies in chronologic order, starting with the first study to get an accurate incident date. If an older study had a poor imaging quality and we could not count the number of cysts, we reviewed subsequent studies to make the diagnosis. If subjects underwent multiple imaging studies, enhanced CT or plain or contrast MR were given priority.
The exact number of kidney cysts in all patients was recorded. Actual abdominal images were not electronically available before 1997, so we evaluated such subjects by their medical charts and radiology or autopsy reports. If there was no information on the number of cysts in the reports, the cases were excluded. Abdominal images of all patients classified as definite ADPKD, likely ADPKD, and possible ADPKD were reviewed twice by a nephrologist (T.S.) with over 10 years expertise in ADPKD and confirmed when in doubt by another nephrologist well experienced in ADPKD (V.E.T.).
Study Population and Inclusion Criteria
Incidence of ADPKD was defined as patients newly diagnosed in Olmsted County between January 1980 and December 2016. Olmsted County residents with kidney cysts meeting the diagnostic criteria for ADPKD found incidentally on imaging studies were also identified and considered to have ADPKD (Table 1). The incident date was determined as the date when the diagnostic code was entered for the patients with diagnostic codes in the Rochester Epidemiology Project. The incident date was determined as the date when the first imaging studies meeting our diagnostic criteria were performed for the patients from radiology databases. Patients with ADPKD from all age ranges were included in this study. Only patients who had been Olmsted County residents for at least 1 year before their diagnosis were considered incident cases. Anyone moving to Olmsted County to facilitate diagnosis or treatment for ADPKD was excluded. Point prevalence of ADPKD was defined as patients meeting the criteria for ADPKD (Table 1) who were Olmsted County residents on January 1, 2010. Patients who were diagnosed before 1980 and those who moved to Olmsted County after their diagnosis were also included for the point prevalence of ADPKD.
Statistical Analysis
Clinical characteristics and laboratory data of patients at diagnosis were expressed as number (percentage), mean±SD, or median (25th and 75th percentile). Logistic regression (for dichotomous variables) and generalized linear models (for creatinine) were used to ascertain differences between definite, likely, and possible ADPKD after adjustment for age and sex.
Annual incidence rates of ADPKD per 100,000 person-years were calculated using incident cases of ADPKD as the numerator and age- and sex-specific estimates of the population of Olmsted County, Minnesota as the denominator. The population at risk was estimated using United States Census data from 1980, 1990, 2000, and 2010, with linear interpolation for intercensus years. Overall incidence rates were age and sex standardized (using direct standardization) to the United States 2010 white population. Incidence rates were also estimated separately for men and women and by age group. Estimates were provided for definite, definite and likely, and definite and likely and possible diagnoses. In addition, incidence rates were estimated for patients with a diagnostic code as well as all patients (patients with a diagnostic code and those with radiology reports only). Annual incidence rates were estimated averaging across 5-year calendar periods. We created jitter plots to show the distribution of the number of cysts by age group and sex among the patients with ADPKD who met “possible” diagnostic criteria.Point prevalence of ADPKD was calculated using prevalent cases of ADPKD on January 1, 2010 as the numerator and age- and sex-specific estimates of the population of Olmsted County, Minnesota on January 1, 2010 as the denominator, as determined from the Rochester Epidemiology Project census (25). Prevalence was age and sex standardized (using direct standardization) to the United States 2010 white population. Prevalence was also estimated separately for men and women and by age group. Estimates were provided for likely alone and likely and possible diagnoses.
Survival for each of the groups (definite, likely, possible) and the expected survival (based on the Minnesota total population) for each group was compared by plotting Kaplan–Meier curves. The survival curves start follow-up at the date of diagnosis of ADPKD until death or date of last follow-up visit. Expected survival was derived by applying the age-, sex-, and calendar year–specific mortality rates for the state of Minnesota to the ADPKD cohort. The observed and expected survivals were compared using a one-sample log-rank test.
Results
We reviewed medical charts, radiology reports, and abdominal images of 2131 subjects in the Rochester Epidemiology Project with diagnostic codes of polycystic or related cystic kidney disease and of 2765 subjects in the Mayo Clinic or Olmsted Medical Center radiology databases with citation of multiple kidney or renal cysts in the radiology reports (Supplemental Table 1). A total of 364 patients were identified with definite (n=85), likely (n=45), or possible (n=234) ADPKD (199 from diagnostic codes and 165 from radiology reports and imaging review) between 1980 and 2016 (Supplemental Table 2).
Demographics and Clinical Characteristics
The demographic and clinical characteristics of the patients by the type of diagnosis are summarized in Table 2. The subjects with definite ADPKD were younger and their total kidney volumes were larger (median, 1085; interquartile range [IQR], 740–3011 ml) than those of the patients with likely (median, 766; IQR, 408–1000 ml) and possible ADPKD (median, 375; IQR, 279–444 ml). Differences between the groups in the frequency of manifestations associated with ADPKD were NS when adjusted by age and sex, except for depression which was less common in the patients with a definite diagnosis. Of the 85 patients with definite ADPKD, genotype was confirmed in 66 individuals from 33 families (42%, 27%, 27%, and 3% of the families with PKD1 truncating, PKD1 nontruncating, PKD2, and GANAB mutations, respectively). Only two patients in the likely and one patient in the possible ADPKD groups had genetic testing with no mutation detected.
Characteristics of patients with definite, likely, and possible autosomal dominant polycystic kidney disease at diagnosis
Incidence Rate
The annual incidence rate of definite ADPKD was 1.79 (95% CI, 1.40 to 2.17) per 100,000 and the annual incidence of definite or likely ADPKD was 3.06 (95% CI, 2.52 to 3.60) per 100,000 through the study period (Figure 1, A and B, Table 3). These were similar in males and females and showed similar trends throughout the study period, regardless of the source of identification (Supplemental Figure 2). The annual incidence of ADPKD was markedly higher (9.44 per 100,000; 95% CI, 8.45 to 10.44) when subjects with possible ADPKD identified using imaging criteria were included after 1997 (Figure 1B, Table 3). These rates showed similar trends for males and females throughout the study period, regardless of the source of identification (Supplemental Figure 2). Annual incidence rates of possible ADPKD increased progressively since 1997, probably reflecting the increasing utilization of CT and MR scans, particularly in older populations (Supplemental Figure 3).
Annual incidence rates of ADPKD are higher when likely and possible cases are included. Trends in age- and sex-adjusted annual incidence of autosomal dominant polycystic kidney disease (ADPKD) per 100,000 person-years over time, by diagnostic criteria using (A) only diagnostic codes or (B) both diagnostic codes and radiology reports to identify cases. D, definite; D/L, definite or likely; D/L/P, definite, likely or possible.
Annual incidence rates per 100,000 by age and sex in Olmsted County, 1980–2016
Incidences of definite ADPKD and of definite or likely ADPKD, whether identified from diagnosis codes or from radiology reports and imaging review, were lowest for the age group 0–17 and remained relatively constant across age groups over time (Figure 2, A–D). On the other hand, incidences were greater in older groups than younger groups when possible ADPKD cases were added, likely due to the higher utilization of CT and MR scans in older subjects (Figure 2, E and F). The number of cysts in the subjects with possible ADPKD increased with age in part because higher numbers of cysts were required in older individuals to meet the diagnostic imaging criteria (Figure 3).
Incidences rates of definite or likely ADPKD across age groups have been relatively constant over time, while rates of possible cases have increased likely due to the higher utilization of CT and MR scans. Trends in age-specific annual incidence of ADPKD per 100,000 over time, separately for each diagnostic criterion: (A) definite ADPKD, only diagnostic codes used to identify subjects; (B) definite ADPKD, diagnostic codes and radiology used to identify subjects; (C) definite or likely ADPKD, only diagnostic codes used to identify subjects; (D) definite or likely ADPKD, diagnostic codes and radiology used to identify subjects; (E) definite, likely, or possible ADPKD, only diagnostic codes used to identify subjects; and (F) definite, likely, or possible ADPKD, diagnostic codes and radiology used to identify subjects.
The number of cysts in the subjects with possible ADPKD increased with age in part because higher numbers of cysts were required to meet the diagnostic imaging criteria for ADPKD. (A) Female patients. (B) Male patients.
Point Prevalence
For the prevalence of ADPKD in Olmsted County on January 1, 2010, we found 136 patients who were Olmsted County residents on January 1, 2010 and were given diagnostic codes before 2010 among the patients enrolled for incidence study. We found five additional subjects given diagnostic codes before 1980 in Olmsted County who were Olmsted County residents on January 1, 2010. Twenty additional subjects who had been diagnosed outside Olmsted County were Olmsted County residents on January 1, 2010. As a result, 161 patients with ADPKD (definite, 65; likely, 26; possible, 70) lived in Olmsted County on January 1, 2010 (Table 4). The point prevalence of definite ADPKD was 47 (95% CI, 35 to 59); of definite or likely ADPKD was 68 (95% CI, 54 to 82); and of definite, likely, or possible ADPKD was 124 (95% CI, 105 to 143) per 100,000 population on January 1, 2010.
Prevalence per 100,000 population by age and sex in Olmsted County on January 1, 2010
Patient Survival and Survival Free of Kidney Death
One patient was diagnosed at autopsy and excluded from the survival analyses. Thus, 363 patients were included in the plots for death. The median (IQR) follow-up of these patients was 6.0 (2.7–12.1) years with a range of 0 days to 37.7 years (three patients were lost to follow-up at the date of diagnosis and thus have 0 days of follow-up). Patient survival after diagnosis of ADPKD was better for individuals with definite ADPKD than those with likely or possible ADPKD (Figure 4A), but the average age at diagnosis in the definite ADPKD group was about 20 years younger than in the other two groups (Table 2). The survival rate of patients after a definite diagnosis of ADPKD was not different from that of the general population. Patient survival rates after a likely or possible diagnosis of ADPKD tended to be lower compared with the general population, although the P values were NS.
Survival rates from the date of diagnosis of ADPKD were not significantly different from those of the general population, nor different between 1980–1996 and 1997–2016. (A) Patient survival of patients with definite, likely, or possible ADPKD (solid lines) compared with expected survival based on the Minnesota total population (dashed lines); and (B) for patients diagnosed in 1980–1996 compared with those diagnosed in 1997–2016; survival by time period included just the definite and likely cases.
A total of 6 of 85 patients with definite ADPKD died at a mean age of 61±11 years, compared with 15 of 44 patients with likely ADPKD at a mean age of 74±13 years and 44 of 234 patients with possible ADPKD at a mean age of 77±15 years. Causes of death included cardiovascular (23%), neoplastic (23%), infectious (17%), neurologic (15%), and other disorders (22%) and were not different between the groups. One death was caused by thoracic aortic dissection; no deaths were due to rupture of an intracranial aneurysm.
For the composite end point of kidney death/death outcome, 16 patients were excluded (one who was diagnosed at autopsy and 15 with unknown kidney death status). Thus 348 patients were included in the analysis. The median (IQR) follow-up of these patients was 5.7 (2.7–11.2) years. Survival rate free of kidney death/death after diagnosis appeared better in patients with definite ADPKD than in those with likely ADPKD who were 20 years older at the time of diagnosis, although it was not statistically significant (Supplemental Figure 4A). Survival rate free of kidney death/death with age rather than time from diagnosis as the x axis showed lower survival in the patients with definite compared with likely or possible ADPKD (Supplemental Figure 4B).
A total of 24 of 84 patients with definite ADPKD reached ESKD at a mean age of 49±11 years compared with 7 of 44 patients with likely ADPKD at a mean age of 63±13 years. Only 5 of 222 patients with possible ADPKD reached ESKD at a mean age of 51±27 years.
Patient survival and patient survival free of kidney death rates were not different between 1980–1996 and 1997–2016 (Figure 4B, Supplemental Figure 4C).
Discussion
The overall age- and sex-adjusted annual incidence of ADPKD diagnosis in Olmsted County during 1935–1980 was estimated to be 1.38 per 100,000 person-years (21). The present study indicates that definite and likely ADPKD has been diagnosed 2.2 times more frequently during 1980–2016 (3.06 per 100,000 person-years). The point prevalence of definite or likely ADPKD on January 1, 2010 in Olmsted County was 68 per 100,000 population, which is higher than that recently estimated in European populations, between 24 and 39 per 100,000 (18), possibly due to a more comprehensive ascertainment of a population served by only two medical centers. These prevalence rates are lower than the genetic prevalence estimated through calculations of disease expectancy in Copenhagen and Olmsted County (80–250 per 100,000 population) (10,11) and that directly estimated from large population-sequence databases (267 per 100,000 population, including pathogenic and likely pathogenic PKD1 or PKD2 mutations only) (22).
To provide insight into the cause for the large discrepancy between the estimated point and genetic prevalence of ADPKD, we systematically reviewed the radiology reports from the Mayo Clinic and Olmsted Medical Center radiology databases and the corresponding archived images to identify additional Olmsted County residents with possible ADPKD. These patients all had normal size or mildly enlarged kidneys with a number of cysts exceeding the 97.5th percentile of a control population matched by sex and age (27) in the absence of CKD stage 4 or stage 5, or findings suggesting a different cystic kidney disease. With the addition of these possible ADPKD cases, the incidence of ADPKD increased from 3.06 to 9.44 per 100,000 patient-years and the point prevalence in 2010 increased from 68 to 124 per 100,000 population, still lower than the estimated genetic prevalence from population-sequencing databases (22). It seems likely that many or possibly most of the patients with possible ADPKD could have weak PKD1 or PKD2 mutations or mutations to other ADPKD or autosomal dominant polycystic liver disease genes recently identified (4–6) or yet to be identified, or nongenetic forms of polycystic kidney disease. Interestingly, only 18% of the patients with high-confidence pathogenic mutations in the study by Lanktree et al. had PKD1-truncating mutations, (22) compared with 51% of the patients enrolled into the HALT-PKD clinical trial (28). These data suggest that mild ADPKD is likely to be underestimated and underdiagnosed. Young individuals are also underdiagnosed because they rarely require imaging studies.Contrary to the previous study of the epidemiology of ADPKD in Olmsted County during 1935–1980, patient survival of the patients with ADPKD in this study is not different from that in the general population. Many factors may account for this observation, including diagnosis of milder cases and improvements in the treatment of hypertension and KRTs. Whereas in the previous study patient survival improved between 1935–1955 and 1956–1980, no further improvement occurred between 1980–1996 and 1997–2016 in this study. It is of interest that only one patient suffered an intracranial aneurysm rupture and this preceded a possible diagnosis of ADPKD. No deaths were due to intracranial aneurysm rupture, although one death was due to a thoracic aortic dissection, a vascular association of ADPKD (11).
This study has a number of limitations. Definite and likely diagnoses of ADPKD are based on robust criteria and likely denote clinically significant disease. We required family history or positive genetic tests for a definite diagnosis of ADPKD; therefore, the incidence of definite ADPKD might have been underestimated because family history was not adequately recorded in some patients. Cases of possible ADPKD were mostly identified from radiology databases. Many Olmsted County residents did not have abdominal imaging studies, and reports for those who had them were electronically available since 1997. We searched only subjects who underwent enhanced CT or MR imaging. Therefore, the prevalence of possible ADPKD has likely been underestimated. On the other hand, the imaging diagnostic criteria used in our study are not foolproof and inclusion of patients with other cystic diseases could have led to an overestimation of disease prevalence. Point prevalence of definite or likely ADPKD included only diagnosed cases, but not patients with the disease who have not yet been or will never be diagnosed, and therefore underestimate the overall prevalence of ADPKD. There might be some patients who moved to Olmsted County to receive medical service from the Mayo Clinic, therefore point prevalence of ADPKD might be overestimated. Survival curves were estimated from the date of diagnosis of ADPKD (not from birth) to avoid immortal time bias (29,30). As a result, survival curves started at the different baseline characteristics in each group (definite, likely, and possible ADPKD). Finally, Olmsted County represents a relatively small geographic area, which limits the generalizability of the results to the broader population.
In summary, this study has shown that the incidence of clinically significant, definite or likely, ADPKD has remained almost unchanged throughout the last four decades, but was higher than in the previous four decades, likely due to increased recognition of the disease. On the other hand, the incidence of possible, mostly asymptomatic ADPKD, detected incidentally with the increasing utilization and quality of radiologic imaging, has increased dramatically. Further studies using genetic testing will be needed to determine to what extent these possible ADPKD cases are due to mutations in the ADPKD or other cystogenic genes. The prevalence of definite or likely ADPKD was higher than the results of most of other studies based on patients clinically diagnosed with ADPKD, possibly because of a more comprehensive ascertainment of a population served by only two medical centers.
Disclosures
Dr. Chamberlain is supported by funding from EpidStat Institute for research in collaboration with Amgen. Dr. Cornec-Le Gall reports speaker fees from Otsuka Pharmaceuticals. Dr. Harris reports receiving grants and/or research reagents from Amgen, Bayer AG, Genzyme Corporation, GlaxoSmithKline, Mitobridge, Otsuka Pharmaceuticals, Palladio Biosciences, Regulus Therapeutics, and Vertex Pharmaceuticals, all outside the submitted work. Dr. Harris also reports a position on the Clinical Advisory Board of Mironid, honoraria from Otsuka Pharmaceuticals and Vertex Pharmaceuticals, and other fees from Otsuka Pharmaceuticals. Dr. Torres reports grants and/or other fees from Acceleron Pharma, Blueprint Medicines, Mironid, Otsuka Pharmaceuticals, Palladio Biosciences, Sanofi Genzyme, Regulus Therapeutics, and Vertex Pharmaceuticals, all outside the submitted work. Dr. Chebib, Dr. Hogan, Ms. Killian, Ms. Edwards, Mr. Madsen, Ms. Senum, Dr. Shukoor, and Dr. Suwabe have nothing to disclose.
Funding
This study has been supported by the Mayo Clinic Robert M. and Billie Kelley Pirnie Translational Polycystic Kidney Disease Center (DK090728). Ms. Senum and Dr. Torres are supported by a grant from the National Institute of Diabetes and Digestive and Kidney Diseases (P30 DK090728).
Supplemental Material
This article contains the following supplemental material online at http://cjasn.asnjournals.org/lookup/suppl/doi:10.2215/CJN.05900519/-/DCSupplemental.
Supplemental Table 1. List of diagnostic codes related to polycystic kidney, polycystic liver in the Rochester Epidemiology Project.
Supplemental Table 2. Number of patients with ADPKD.
Supplemental Figure 1. Identification of ADPKD cases from diagnostic codes in the Rochester Epidemiology Database between 1980 and 2016.
Supplemental Figure 2. Trends in age-adjusted annual incidence of ADPKD per 100,000 over time, by diagnostic criteria and sex.
Supplemental Figure 3. Trends in age-specific annual utilization of abdominal contrast-CT and MR scans per 100,000 over time in Olmsted County.
Supplemental Figure 4A. Survival free of kidney death or patient death for definite, likely, and possible ADPKD groups from the time of diagnosis.
Supplemental Figure 4B. Survival free of kidney death or patient death for definite, likely, and possible ADPKD groups from birth.
Supplemental Figure 4C. Survival free of kidney death or patient death for definite, likely, and possible ADPKD groups for patients diagnosed in 1980–1996 compared with those diagnosed in 1997–2016.
Acknowledgments
We thank Dr. Ziad Zoghby (Nephrology) and Ms. Vicki C. Schmidt (Radiology) for their assistance in the collection of clinical data, and we thank Mr. Scott M. Brue (programmer) and Mr. Joseph J Larson (statistician) for their help in analyzing the data. We thank Mr. Andrew J. Metzger (Nephrology) for measuring the kidney or liver volumes of the enrolled patients. We also thank Walter K. Kremers for providing assistance with the study design. This project was performed within the Master’s program supported by Grant Number UL1 TR002377 from the National Center for Advancing Translational Sciences and the Mayo Clinic Graduate School.
Footnotes
Published online ahead of print. Publication date available at www.cjasn.org.
- Received May 14, 2019.
- Accepted October 31, 2019.
- Copyright © 2020 by the American Society of Nephrology
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