Polycystic kidney disease
Polycystic kidney disease (PKD) is an inherited disorder characterised by cyst formation and enlargement primary in the kidney. PKD may impair kidney function and eventually cause kidney failure (Figure 1).
Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary renal disease, with an incidence between 1:400 and 1:1000 live births. 2 and accounts for 7–10% of all patients requiring renal replacement therapy. Therefore, an early and high accurate diagnosis is needed. The diagnosis of ADPKD is usually based on the observation of kidney cysts by ultrasound in patients with positive family history for ADPKD. However, ultrasound imaging has limited sensitivity in children and young adults, before the age of 30 years. Furthermore molecular diagnosis by genetic testing has been hampered by the genetic complexity of ADPKD, and only 65% of ADPKD patients exhibit definitive pathogenic (i.e. truncating) mutations. On the other hand, the biopsy in human ADPKD with preserved kidney function is contraindicated, because renal tissue is rarely available. Proteomic analysis of urine offers a non-invasive means to simultaneously detect changes in the expression and processing of multiple proteins. The urinary peptide based classifier shows high diagnostics accuracy (Figure 2A) and also a correlation (Figure 2B) to the height adjusted total kidney volume (htTKV)1;2 that has been considered the best prognostic marker in ADPKD. However, accurate determination of htTKV is time-consuming, requires quantitative imaging algorithms and is not universally accessible. In addition, monitoring response to therapy by TKV requires relatively long follow-up times to allow for accurate determination of TKV changes over time.
Moreover, urinary peptidomic biomarkers reliably predict progression to end stage renal disease (ESRD) in ADPKD patients based on a single baseline urine sample 3. The urinary peptide based classifier allows stratification of ADPKD patients according to their risk to develop ESRD within the next 10–13 years (Figure 3).
1. Kistler AD, Mischak H, Poster D, Dakna M, Wuthrich RP, Serra AL. Identification of a unique urinary biomarker profile in patients with autosomal dominant polycystic kidney disease. Kidney Int 2009; 76: 89-96
2. Kistler AD, Serra AL, Siwy J et al. Urinary proteomic biomarkers for diagnosis and risk stratification of autosomal dominant polycystic kidney disease: a multicentric study. PLoS One 2013; 8: e53016
3. Pejchinovski M, Siwy J, Metzger J et al. Urine Peptide Markers Predicts Esrd Risk in Adpkd and Reveal Proteolytic Patways Involved in Progression. Nephrology Dialysis Transplantation 2016; 31: 22