The most common inherited kidney disease is autosomal dominant polycystic kidney disease (ADPKD), which is characterized by progressive enlargement of the kidneys with multiple bilateral cysts, leading to eventual loss of kidney function and development of end-stage renal disease in middle age.
ADPKD is the primary diagnosis for 10% of patients on renal replacement therapy in the United Kingdom and in 5% in the United States.
Polycystic liver is a common extrarenal manifestation of ADPKD, with the prevalence of liver cysts in patients with ADPKD increasing with age. More than 90% of patients with ADPKD >40 years of age have at least one liver cyst. Liver cysts are more common and numerous in premenopausal women than in men. Other abdominal manifestations associated with ADPKD include colonic diverticular disease, abdominal wall hernias, and pancreatic cysts.
Less well recognized in ADPKD are clinically significant biliary tract complications. Parminder K. Judge, MD, and colleagues at a tertiary center in the United Kingdom observed that in addition to the infective and comprehensive complications caused by polycystic livers, several ADPKD patients had repeated hospitalizations for biliary tract disease. The researchers conducted a systematic literature search that found no reports describing the range of presentations of biliary tract disease in patients with ADPKD, nor were there any that quantified any excess risk of clinically significant biliary tract disease in ADPKD.
To test the hypothesis that there is an association between ADPKD and biliary tract disease, the researchers designed a disease association study. They used routinely collected English hospital inpatient data from 1998 to 2012 to compare hospitalization rates for biliary tract disease among patients with ADPKD with rates in non-ADPKD control populations. Study results were reported in the Journal of the American Society of Nephrology [2017;28(9):2738-2748].
The study utilized England Hospital Episode Statistics (HES) data to identify 23,454 people with ADPKD and 6,412,754 hospital controls, identified from an admission for one of a variety of minor conditions with no mention of polycystic kidney disease in any admission. Of the ADPKD population, median age at the start of follow-up was 58 years, 46% (n=10,789) were women, and 85% (n=20,011) were white. In 4% (n=906), a history of diabetes was recorded, and 7% (n=1747) had a recorded history of vascular disease. On average, the hospital controls were younger (median age, 48 years) and less likely to have diabetes (3%, n=189,858) or vascular disease (3%; n=181,832).
Following adjustment for age, sex, ethnicity, social deprivation, region, prior diabetes, prior vascular disease or cancer, and year of first admission, the rates of admission for a series of disease outcomes were compared among those with ADPKD with those without ADPKD (ADPKD versus non-ADPKD rate ratios [RRs]). The adjusted rates of ESRD were 112 times higher in patients with ADPKD compared with hospital controls (2.82% vs 0.03% per year; RR, 112; 95% confidence interval [CI], 109-116).
The rates of admission for biliary tract disease were 2.2 times higher in the
ADPKD population than in the hospital controls (1.31% vs 0.59% per year; RR, 2.24; 95% CI, 2.16-2.33) and 4.7 times higher than for serious liver complications (0.31% vs 0.07% per year, RR, 4.67; 95% CI, 4.35-5.02).
The RRs attenuated substantially in analyses restricted to patients on maintenance dialysis or with a kidney transplant, but the association between ADPKD and biliary tract disease remained (RR, 1.19; 95% CI, 1.08-1.31). The ADPKD versus non-ADPKD RRs for biliary tract disease were larger for men than women (heterogeneity P<.001); RRs for serious liver complications appeared higher in women (heterogeneity P<.001).
There was an absolute excess risk of biliary tract disease associated with ADPKD of 0.73% per year (95% CI, 0.68%-0.78% per year). That risk was larger than the absolute excess risk for serious liver disease (0.24% per year; 95% CI, 0.21%-0.28% per year), as well as for cerebral aneurysms (0.11% per year; 95% CI, 0.09%-0.14% per year), inguinal hernias (0.11% per year; 95% CI, 0.08%-0.14% per year), or abdominal wall hernias (0.35% per year; 95% CI, 0.32%-0.38% per year). The risk was similar to that of colonic diverticular disease and much less than for urinary tract infections.
The researchers cited some limitations to the study, including predialysis CKD stages not well recorded in the HES database and a lack of laboratory data. In addition, there was no information on body mass index available for adjustment, and the rates of infection from particular sources may have been underestimated due to the difficulty in distinguishing sources of infection in admissions for sepsis. Finally, there was no direct confirmation of the definitions of ADPKD.
The researchers summarized by saying, “We raised and tested the hypothesis that ADPKD is associated with clinically significant biliary tract disease as well as serious liver complications. We found that women with ADPKD are at higher relative risk of a liver complication that men, but the reverse was observed for the positive association between ADPKD and biliary tract disease, suggesting that liver and biliary complications of
ADPKD have distinct disease mechanisms. The absolute excess risks of biliary tract complications in people with ADPKD are similar to the absolute excess risks of some of the better established complications, and therefore, biliary tract disease should be a key differential diagnosis in patients with ADPKD presenting with abdominal pain or sepsis.”