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Defects of these proteins lead to the formation of distinctive fluid-filled cysts in the kidneys, as is the case for other heritable polycystic kidney diseases.⁴ ADPKD is complex in its interaction of genetic heterogeneity, allelic heterogeneity, and environmental effects, leading to large phenotypic variability and a wide range of age at onset.^2,4 ADPKD is generally diagnosed via family history and imaging testing to detect renal cysts. There are no pharmacologic treatments currently indicated for ADPKD, but testing may be beneficial for family planning and for early detection and treatment of disease

complications.²

ADPKD is a systemic disease, with cysts developing in other organs as well—most frequently, in the liver and pancreas. Additional extrarenal manifestations associated with ADPKD include cardiac disease and intracranial aneurysms.^2,5-7 Progression of the disease leads to an increase in the number and volume of cysts and an increase in kidney volume, which lead to a decline in renal function,8 renal inflammation, fibrosis, and ESRD.⁹ By the time there is a decline in renal function, the enlarged kidney is distorted, with little recognizable parenchyma.² Along with renal decline, disease complications include polycystic liver disease, cardiac disease, hypertension, hematuria, urinary tract infections, renal stones, and renal pain.^2,5

ADPKD is a chronic disease that evolves over a lifetime. Mild symptoms in early stages typically go undiagnosed as ADPKD. The majority of cases are due to PKD1mutations, and by definition, progress more rapidly.^3,10 The symptoms caused by ADPKD contribute to substantial morbidity and impairment of quality of life, as well as costs to society, as these undiagnosed symptoms progress. Although few studies have investigated the impact of symptoms on quality of life in patients with ADPKD, chronic pain is evidently a significant complication; therefore, pain management is an important consideration in patients with ADPKD.^11,12 A recent study of patients with early ADPKD from the Polycystic Kidney Disease Treatment Network (the HALT PKD Trial) demonstrated that symptoms relating to abdominal fullness and pain are greater in patients with more advanced disease, possibly due to organ enlargement.¹³ Similarly, little has been reported on the economic burden of ADPKD.¹⁴ In contrast, chronic kidney disease (CKD) has been investigated extensively and is recognized as a source of substantial morbidity and economic burden with clear associations between kidney dysfunction and adverse outcomes, leading to hospitalizations, resource utilization, and mortality.¹⁵

As ADPKD is both among the leading causes of ESRD and the leading heritable cause,^2,16,17 it is important for US healthcare payers to understand this genetic disorder and the healthcare resource utilization and costs associated with it. Here we review the available ADPKD literature, published between 2003 and 2013, to characterize the impact of ADPKD on patients and healthcare systems, and to assess any current gaps in the available evidence that hinder either a better understanding of the disease or the need for effective therapies, as there is currently no treatment for ADPKD. Better understanding and earlier diagnosis of the disease may lead to improved treatment of complications. Information on ADPKD incidence and prevalence, diagnostic criteria and risk factors, and the humanistic and economic burden of this genetic disorder are summarized.

METHODS

Search Parameters

PubMed and EMBASE databases from January 2003 to March 2013 were searched for potentially relevant articles published in English. Search terms included “autosomal dominant polycystic kidney disease” and “ADPKD” alone and in combination with “chronic kidney disease,” “CKD,” or “chronic renal insufficiency,” and “polycystic kidney disease” and “PKD/polycystic.”

Study Inclusion/Exclusion Criteria

Studies were included for screening if they were identified as a study of either ADPKD or PKD. As ADPKD is a disease subset of PKD, both search terms were used in the screening process to ensure that all ADPKD studies would be included, even those classified as “PKD.” Studies removed from the analysis through screening included studies that were: 1) not in English; 2) not conducted in human patients; 3) not conducted in a population generalizable to the United States, Canada, France, Germany, Italy, Spain, or the United Kingdom; or 4) not full-text articles.

Studies excluded from eligibility for analysis were those that were: 1) not ADPKD studies (to eliminate any studies on only PKD); 2) limited to analysis of basic science or genetic risk factors only; 3) case studies (with samples of ?20 patients); or 4) unrelated to the specific topics of the review: incidence/prevalence, diagnostic criteria and risk factors, humanistic burden, and economic burden. Any information on treatment patterns, treatment adherence and compliance, symptoms, and comorbidities was noted while analyzing articles based on the 4 specific topics of the review.

Data Extraction and Qualitative Assessment

A single reviewer evaluated publications for inclusion and performed data extraction, and a second reviewer performed a quality check of included studies and extracted data for accuracy. For the selected publications, data extracted included information on publication details, study design and methods, study population size and characteristics, diagnostic criteria, disease progression, quality of life, costs, and study outcomes. All data were analyzed qualitatively. The estimates of the rates of prevalence, incidence, and disease progression were extracted and summarized as reported without adjustment.

RESULTS

Through the initial search, 2459 articles were identified, with 1835 remaining after the removal of duplicates (Figure). In the course of study review, 379 articles were removed through an initial screening, and 1401 were removed through assessment for eligibility, leaving 55 studies included in the qualitative synthesis (eAppendix Table, available at www.ajmc.com).

Epidemiology of ADPKD: Incidence and Prevalence

No primary epidemiology studies for ADPKD, including incidence and prevalence or other important measures (ie, age at onset, disease severity by age, mortality by age) were conducted during the period covered in this analysis (January 2003 to March 2013). ADPKD prevalence rates were cited frequently, but few articles referenced a primary study, and many had no citation (Table 1,^18-62 bottom section).

Only 3 primary research studies were cited in the articles covered in this review (Table 1, top section).^18-20The majority of papers that included a reference cited 2 primary studies, which were conducted in Denmark¹⁹ in 1957 and in the United States¹⁸ in 1983. The US study was the only one to investigate incidence; the estimated incidence of symptomatic and family-screen cases was 1.38 per 100,000 person-years and the incidence of observed and estimated cases based on autopsy was 2.75 per 100,000 person-years. The Danish study found prevalence rates of 1:773 (adult autopsy) and 2.2:1000 (newborn autopsy) in comparing hospital statistics of PKD with relevant population figures. The other primary research study cited in the selected articles was a study conducted in Wales in 1991,²⁰ which found a prevalence rate of 1:2459 in a population study using a genetic register of all known cases of ADPKD.

Characteristics of the geographic regions and periods in which these primary studies were conducted most likely contributed to the variance of rates reported. Diagnostic criteria for ADPKD were developed in 1994 and refined in 2009, occurring in each case after the ADPKD incidence and prevalence studies were published.^1,63Additional studies in more globally diverse populations using the updated ADPKD diagnostic criteria are needed to establish a more accurate estimate of the prevalence of ADPKD.

ADPKD Diagnostic Criteria/Risk Factors for Progression

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