Liver Involvement in Early Autosomal-Dominant Polycystic Kidney Disease

Abstract

Background & Aims Polycystic liver disease (PLD), the most common extra-renal manifestation of autosomal-dominant polycystic kidney disease (ADPKD), has become more prevalent due to increased life expectancy, improved renal survival, reduced cardiovascular mortality, and renal replacement therapy. No studies have fully characterized PLD in large cohorts. We investigated whether liver and cyst volumes associate with volume of the hepatic parenchyma, results from liver laboratory tests, and patient-reported outcomes. Methods We performed a cross-sectional analysis of baseline liver volumes, measured by magnetic resonance imaging, and their association with demographics, results from liver laboratory and other tests, and quality of life. The data were collected from a randomized, placebo-controlled trial underway at 7 tertiary-care medical centers to determine whether the combination of an angiotensin I converting enzyme inhibitor and angiotensin II receptor blocker was superior to the inhibitor alone, and whether low blood pressure (<110/75mmHg) was superior to standard blood pressure (120–130/70–80mmHg), in delaying renal cystic progression in 558 patients with ADPKD, stage 1–2 chronic kidney disease, and hypertension (15–49 years old). Results We found hepatomegaly to be common among patients with ADPKD. Cysts and parenchyma contributed to hepatomegaly. Cysts were more common and liver and cyst volumes were greater in women, increasing with age. Patients with advanced disease had relative loss of liver parenchyma. We observed small abnormalities in results from liver laboratory tests, and that splenomegaly and hypersplenism associated with the severity of PLD. Higher liver volumes were associated with lower quality of life. Conclusions Hepatomegaly is common even in early-stage ADPKD and not accounted for by cysts alone. Parenchymal volumes are larger, compared with liver volumes of patients without ADPKD or with those predicted by standardized equations—even among patients without cysts. The severity of PLD is associated with altered biochemical and hematologic features, as well as quality of life.

Biliary Tract and Liver Complications in Polycystic Kidney Disease

“…1,8,24,25 However, liver enlargement in ADPKD results from both cystic change and increased liver parenchymal volume, and men with ADPKD have been found to have relatively increased height-adjusted liver parenchymal volume compared to women. 23 The differing patterns of associations in our subgroup analyses by age and sex suggest that cystic change in the liver-which has been reported to cause obstructive jaundice [17][18][19][20][21][22] -is not the key cause of biliary tract complications in ADPKD. Polycystin complexes localize to primary cilia in the kidney and biliary tract.…”

“…23 Common bile duct dilation was present in 17% of the cohort, but it was the only biliary tract abnormality described. These data corroborate earlier observations from a Japanese study of 55 people with ADPKD, where the prevalence of common bile duct dilation was 40% compared with 7% in controls.…”

“…Other ADPKD studies, including the HALT-PKD-A, have also found that the prevalence of liver cysts is higher in women with ADPKD compared with men. 9,23 Estrogen receptors are expressed in the epithelium of liver cysts, 1,8,24,25 and in women, exogenous estrogen use and pregnancy both seem to increase cyst cell proliferation and liver cyst size. 1,8,24,25 However, liver enlargement in ADPKD results from both cystic change and increased liver parenchymal volume, and men with ADPKD have been found to have relatively increased height-adjusted liver parenchymal volume compared to women.…”

Predicted Mutation Strength of Nontruncating PKD1 Mutations Aids Genotype-Phenotype Correlations in Autosomal Dominant Polycystic Kidney Disease

“…27 TKV and eGFR may not be ideal measures to compare men with women, but because our data included sex correction factors in the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation and TKV correction by height to account for men having larger kidneys, it suggests that these results likely reflect real sex differences. 22,27 The greater liver cyst burden in women is known, 28 but we have shown that this is only significant in the larger PKD1 population.…”

Pancreatic Cysts in Autosomal Dominant Polycystic Kidney Disease: Prevalence and Association withPKD2Gene Mutations

“…In the HALT Progression of Polycystic Kidney Disease, or HALT-PKD, study, a multicenter clinical trial of antihypertensive drug treatment in ADPKD in which MR imaging was limited to the coronal plane, pancreatic cysts were identified at baseline in only 1.8% of 560 patients with ADPKD, with 62% having only one cyst (29). By contrast, in our study, 36% of all patients with ADPKD (40 of 110) had at least one pancreatic cyst; 63% of those patients (25 of 40) had more than one cyst.…”