The rate of renal disease progression varies widely among patients with autosomal dominant polycystic kidney disease (ADPKD), necessitating optimal patient selection for enrollment into clinical trials. Patients from the Mayo Clinic Translational PKD Center with ADPKD (n=590) with computed tomography/magnetic resonance images and three or more eGFR measurements over $6 months were classified radiologically as typical (n=538) or atypical (n=52). Total kidney volume (TKV) was measured using stereology (TKVs) and ellipsoid equation (TKVe). Typical patients were randomly partitioned into development and internal validation sets and subclassified according to height-adjusted TKV (HtTKV) ranges for age (1A-1E, in increasing order). Consortium for Radiologic Imaging Study of PKD (CRISP) participants (n=173) were used for external validation. TKVe correlated strongly with TKVs, without systematic underestimation or overestimation. A longitudinal mixed regression model to predict eGFR decline showed that log 2 HtTKV and age significantly interacted with time in typical patients, but not in atypical patients. When 1A-1E classifications were used instead of log 2 HtTKV, eGFR slopes were significantly different among subclasses and, except for 1A, different from those in healthy kidney donors. The equation derived from the development set predicted eGFR in both validation sets. The frequency of ESRD at 10 years increased from subclass 1A (2.4%) to 1E (66.9%) in the Mayo cohort and from 1C (2.2%) to 1E (22.3%) in the younger CRISP cohort. Class and subclass designations were stable. An easily applied classification of ADPKD based on HtTKV and age should optimize patient selection for enrollment into clinical trials and for treatment when one becomes available.

Autosomal dominant polycystic kidney disease (ADPKD) is a common cause of ESRD. Affected individuals inherit a defective copy of either PKD1 or PKD2, which encode polycystin-1 (PC1) or polycystin-2 (PC2), respectively. PC1 and PC2 are secreted on urinary exosome-like vesicles (ELVs) (100-nm diameter vesicles), in which PC1 is present in a cleaved form and may be complexed with PC2. Here, label-free quantitative proteomic studies of urine ELVs in an initial discovery cohort (13 individuals with PKD1 mutations and 18 normal controls) revealed that of 2008 ELV proteins, 9 (0.32%) were expressed at significantly different levels in samples from individuals with PKD1 mutations compared to controls (P,0.03). In samples from individuals with PKD1 mutations, levels of PC1 and PC2 were reduced to 54% (P,0.02) and 53% (P,0.001), respectively. Transmembrane protein 2 (TMEM2), a protein with homology to fibrocystin, was 2.1-fold higher in individuals with PKD1 mutations (P,0.03). The PC1/TMEM2 ratio correlated inversely with height-adjusted total kidney volume in the discovery cohort, and the ratio of PC1/TMEM2 or PC2/TMEM2 could be used to distinguish individuals with PKD1 mutations from controls in a confirmation cohort. In summary, results of this study suggest that a test measuring the urine exosomal PC1/TMEM2 or PC2/TMEM2 ratio may have utility in diagnosis and monitoring of polycystic kidney disease. Future studies will focus on increasing sample size and confirming these studies. The data were deposited in the ProteomeXchange (identifier PXD001075).

BACKGROUND Partial hepatectomy and cyst fenestration (PHCF) selectively provides clinical benefit in highly symptomatic patients with polycystic liver disease (PLD). This study aims to ascertain whether the reduction in liver volume (LV) achieved by PHCF is sustained long term. STUDY DESIGN Clinical data were retrieved from the electronic records of all patients with PLD who underwent PHCF between 1985 and 2014. Preoperative LVs (LV1), postoperative LVs (LV2), and late follow-up LVs (LV3) were measured from magnetic resonance or CT images. RESULTS Among 186 patients who underwent PHCF, 91% were Caucasian women with autosomal dominant polycystic kidney disease with a mean age of 49 years. Major perioperative complications (Clavien III/IV) occurred in 21% of the patients. Operative mortality (<90 days) was 2.7%. Eleven patients had liver failure develop, received liver transplants, or had liver-related deaths. Overall survival was 95.7%, 93.3%, 85.6%, and 77.7% at 1, 5, 10, and 15 years respectively. Imaging records for volumetry were unavailable in 32 patients. Of the remaining 154 patients, 34 had imaging for 1 LV, 64 for 2 LVs, and 55 for all 3 LVs. Median LV was 6,781 mL (interquartile range 4,903 to 8,341 mL) preoperatively and 2,502 mL (interquartile range 2,089 to 3,136 mL) after PHCF, leading to a median postoperative LV reduction of 61%. At follow-up (mean 8 years), median LV was 2,519 mL (interquartile range 2,083 to 3,752 mL). Interestingly, 33 of 62 patients with available LV2 and LV3 showed additional regression in LV at follow-up (median –14.1%), and the rest showed mild growth of 9.9%. Overall volumetric comparison of preoperative with follow-up liver imaging showed sustained LV reduction (median 61%). CONCLUSIONS Sustained long-term reductions in LV after PHCF can be achieved in selected patients with severe, highly symptomatic PLD. In our experience, liver-related death and subsequent liver transplantation are infrequent after PHCF.