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Disease progression

Methods for measuring disease progression

For patients in earlier stages of the disease, measuring estimated glomerular filtration rate (eGFR) may not reveal the ongoing damage caused by autosomal dominant polycystic kidney disease (ADPKD).1,2

  • eGFR and serum creatinine levels are important indicators of kidney function, but alone may not be reliable indicators of early-stage ADPKD2
  • eGFR may remain steady over many years while the kidneys increase in volume by 400%, to 1500 cm3 1

Compensatory renal hypertrophy and glomerular hyperfiltration can mask the underlying destruction of the surrounding renal parenchyma.3,4

Serum creatinine levels rise late in the course of the disease, only after the parenchyma has incurred serious, irreversible damage.2

By the time serum creatinine levels start to rise appreciably,

more than 50% of functional renal tissue may have already been destroyed3

An increase in total kidney volume (TKV) can precede a drop in eGFR levels5-7

Move the slider to advance stage of ADPKD.

eGFR

Creatinine levels

Healthy kidney

Early stages of ADPKD

Early stages of ADPKD

Later stages of ADPKD

Later stages of ADPKD

End-stage renal disease

  • Normal TKV
  • Normal eGFR
  • Normal creatinine levels
  • Increasing TKV
  • Normal eGFR
  • Normal to slightly elevated creatinine levels
  • Increasing TKV
  • Normal eGFR
  • Normal to slightly elevated creatinine levels
  • Continued TKV growth
  • Severely decreased GFR
  • Increasingly high creatinine levels
  • Continued TKV growth
  • Severely decreased GFR
  • Increasingly high creatinine levels
  • TKV up to 1500cm3
  • GFR <15 mL/min/1.73 m2 or dialysis
  • High creatinine levels

The role of TKV

TKV can provide an important predictor of early-stage disease progression and future renal decline even before eGFR levels begin to drop. TKV provides an indicator of progression in early-stage ADPKD, as it can be used to evaluate patients with normal eGFR levels.2,5,6

In 2016, the FDA provided a recommendation for the use of TKV, measured at baseline, as a prognostic enrichment biomarker to select patients with ADPKD at a high risk of a progressive decline in renal function.8

eGFR should continue to be used concomitantly

to monitor renal function in your patients with ADPKD1,2,7

  1. Braun WE. Autosomal dominant polycystic kidney disease: emerging concepts of pathogenesis and new treatments. Cleve Clin J Med. 2009;76(2):97-104.

  2. Grantham JJ, Chapman AB, Torres VE. Volume progression in autosomal dominant polycystic kidney disease: the major factor determining clinical outcomes. Clin J Am Soc Nephrol. 2006;1(1):148-157.

  3. Grantham JJ. Autosomal dominant polycystic kidney disease. N Engl J Med. 2008;359(14):1477-1485.

  4. Grantham JJ, Mulamalla S, Swenson-Fields KI. Why kidneys fail in autosomal dominant polycystic kidney disease. Nat Rev Nephrol. 2011;7(10):556-566.

  5. Grantham JJ, Torres VE. The importance of total kidney volume in evaluating progression of polycystic kidney disease. Nat Rev Nephrol. 2016;12(11):667-677.

  6. Perrone RD, Neville J, Chapman AB, et al. Therapeutic area data standards for autosomal dominant polycystic kidney disease: a report from the Polycystic Kidney Disease Outcomes Consortium (PKDOC). Am J Kidney Dis. 2015;66(4):583-590.

  7. Johnson CA, Levey AS, Coresh J, Levin A, Lau J, Eknoyan G. Clinical practice guidelines for chronic kidney disease in adults: part I. definition, disease stages, evaluation, treatment, and risk factors. Am Fam Physician. 2004;70(5):869-876.

  8. US Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER). Qualification of biomarker—total kidney volume in studies for treatment of autosomal dominant polycystic kidney disease: guidance for industry. https://www.fda.gov/downloads/Drugs/Guidances/UCM458483.pdf. Published September 2016. Accessed October 3, 2018.