Characteristics of Patients with End-Stage Kidney Disease in ADPKD

Abstract

Introduction Cystic expansion damaging the parenchyma is thought to lead to end-stage kidney disease (ESKD) in autosomal dominant polycystic kidney disease (ADPKD). Here we characterized genotypic and phenotypic attributes of ADPKD at time of ESKD. Methods This is a retrospective cross-sectional study of patients with ADPKD with ESKD evaluated at Mayo Clinic with available abdominal computed tomography (CT) or magnetic resonance imaging (MRI). Kidney volumes were measured (total kidney volume adjusted for height [HtTKV]), Mayo Image Class (MIC) calculated, ADPKD genotype determined, and clinical and laboratory features obtained from medical records. Results Differences in HtTKV at ESKD were associated with patient age and sex; older patients and women had smaller HtTKV at ESKD. HtTKV at ESKD was observed to be 12.3% smaller with each decade of age ( P < 0.01); but significant only in women (17.8%, P < 0.01; men 6.9%, P = 0.06). Patients with onset of ESKD at <47, 47–61, or >61 years had different characteristics, with a shift from youngest to oldest in male to female enrichment, MIC from 1D/1E to 1B/1C, likely fully penetrant PKD1 mutations from 95% to 42%, and presence of macrovascular disease from 8% to 40%. Macrovascular disease was associated with smaller kidneys in female patients. Conclusion HtTKV at ESKD was smaller with advancing age in patients with ADPKD, particularly in women. These novel findings provide insight into possible underlying mechanisms leading to ESKD, which differ between younger and older individuals. Cystic growth is the predominant mechanism in younger patients with ESKD, whereas aging-related factors, including vascular disease, becomes potentially important as patients age.

Rapidly Progressing to ESRD in an Individual with Coexisting ADPKD and Masked Klinefelter and Gitelman Syndromes

“…Therefore, discordance between cyst burden and renal function decline trajectories that could be explained by lower cyst growth and remarkably slowed kidney enlargement in this ADPKD patient. In the present study, it was hypothesized that coexisting ADPKD with masked KS and GS may have a synergistic effect on the stimulation of rapid evolution to ESRD, and their synergistic effect may be the result of regulation of multiple signaling pathways, including vascular disease [ 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 ] (see Figure 2 ).…”

“…Moreover, activation of the mTOR pathway and increased vascular endothelial apoptosis in KS [66] and ADPKD could affect the intracranial aneurysm growth in our patient [23,24,67]. Finally, other possible factors that could affect ADPKD progression and the growth of the intracranial aneurysm in this patient include also an increased RAAS stimulation, apoptosis, fibrosis, and vascular disease [26,27,68]. On the other hand, in both ADPKD and KS there is an elevated frequency of intracranial aneurysms and, in the case of associated variants in PKD1 protein and KS, it is expected to have at least additive intracranial aneurysms in disease presentation [21,49,50,55].…”

“…Moreover, activation of the mTOR pathway and increased vascular endothelial apoptosis in KS [ 66 ] and ADPKD could affect the intracranial aneurysm growth in our patient [ 23 , 24 , 67 ]. Finally, other possible factors that could affect ADPKD progression and the growth of the intracranial aneurysm in this patient include also an increased RAAS stimulation, apoptosis, fibrosis, and vascular disease [ 26 , 27 , 68 ].…”

Management of autosomal dominant polycystic kidney disease in the era of disease-modifying treatment options

“…In fact, 50% of the patients reached ESKD by age of 54 years and 75% by age of 62 years in a recent study with a large tertiary care center cohort [ 18 ]. It has also been demonstrated that, within a family, despite shared mutations, there is wide variability in the age at which a family member reaches ESKD [ 19 ]. Given the wide heterogeneity and phenotypic variability of ADPKD, it is prudent to identify the group of patients who are at risk of rapid progression toward ESKD to initiate disease-modifying treatment early to slow the progression of the kidney disease.…”

Asymptomatic Pyuria as a Prognostic Biomarker in Autosomal Dominant Polycystic Kidney Disease

“…1,2 It is a phenotypically variable disease with patients progressing to kidney failure from relentless kidney growth. 3 Disease severity stratification using genetic, clinical, and radiological biomarkers is used to predict the rate of ADPKD progression. 4 Height-adjusted total kidney volume (Ht-TKV) has been recognized as a prognostic biomarker of cystic burden and disease severity.…”