Assessing kidney size can help predict the rate of future kidney function decline1,2

Measuring kidney function alone may not reveal how ADPKD is progressing1,3

Kidney Function and TKV Over Time
Kidney Function and TKV Over Time

Adapted from Grantham JJ, et al. Nat Rev Nephrol. 2011;7(10):556-566.

Changes in kidney size often precede kidney function decline

  • Patients with ADPKD may remain asymptomatic for years while the disease progresses, likely due to compensatory hyperfiltration1,4
  • Enlarging cysts compress surrounding nephrons and may be causing damage even when kidney function remains normal1
  • The rate of progression in ADPKD is variable from patient to patient1

Patients presenting with a rapid decline in eGFR are already experiencing rapid disease progression5,6*

*eGFR decline ≥5 mL/min/1.73 m2 within 1 year or eGFR decline of ≥2.5 mL/min/1.73 m2 per year over a period of 5 years.5

Half of ADPKD patients will reach end-stage kidney disease by age 60

Nearly 50% of patients with ADPKD will reach end-stage kidney disease (ESKD) by age 607

ADDITIONAL FACTORS TO CONSIDER REGARDING ADPKD PROGRESSION

Even though ADPKD impacts all races, research shows that patient outcomes, such as early diagnosis and treatment of ADPKD, may vary by race and ethnicity attributed to social determinants of health (SDOH). Though more extensive research is needed, based on the available data, it's important to consider the following:

  • In a nearly 10-year (2004-2013) retrospective cohort study that included 23,647 patients with ADPKD, Black patients with ADPKD reached ESKD approximately 1.5 years faster (54.4 ± 13 years of age) than White patients with ADPKD (55.9 ± 12.8 years of age)8
  • In one study evaluating the onset of ESKD in patients with ADPKD, Black patients who also had the sickle cell trait reached ESKD approximately 10 years earlier (n=l3; range 28-50, averaging 38.2 years of age) than Black patients without the sickle cell trait (n=9; range 36-57, averaging 48.1 years of age)9

IDENTIFY RISK FACTORS ASSOCIATED WITH THE RISK OF RAPID PROGRESSION

If a patient presents with any of these independently validated risk factors, they could be appropriate for treatment.10

Identifying Factors of Patients at Risk for Rapid Disease Progression
Identifying Factors of Patients at Risk for Rapid Disease Progression

ADPKD=autosomal dominant polycystic kidney disease; eGFR=estimated glomerular filtration rate; ESKD=end-stage kidney disease; TKV=total kidney volume.

  1. 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.
  2. 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.
  3. Grantham JJ, Mulamalla S, Swenson-Fields KI. Why kidneys fail in autosomal dominant polycystic kidney disease. Nat Rev Nephrol. 2011;7(10):556-566.
  4. Ness B, Stovall K. Current recommendations for treating autosomal dominant polycystic kidney disease. JAAPA. 2016;29(12):24-28.
  5. Gansevoort RT, Arici M, Benzing T, et al. Recommendations for the use of tolvaptan in autosomal dominant polycystic kidney disease: a position statement on behalf of the ERA-EDTA Working Groups on Inherited Kidney Disorders and European Renal Best Practice. Nephrol Dial Transplant. 2016;31(3):337-348.
  6. Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney Intern Suppl. 2013;3(1):1-150.
  7. Chebib FT, Torres VE. Autosomal dominant polycystic kidney disease: core curriculum 2016. Am J Kidney Dis. 2016;67(5):792-810.
  8. Murphy EL, Dai F Blount KL, Droher ML, et al. Revisiting racial differences in ESRD due to ADPKD in the United States. BMC Nephrol. 2019;20(1):55.
  9. Yium J, Gabow P, Johnson A, et al. Autosomal dominant polycystic kidney disease in Blacks: clinical course and effects of sickle-cell hemoglobin. J Am Soc Nephrol. 1994;4:1670-1674.
  10. Rastogi A, Ameen KM, Al-Baghdadi M, et al. Autosomal dominant polycystic kidney disease: updated perspectives. Ther Clin Risk Manag. 2019;15:1041-1052.
  11. Chapman AB, Bost JE, Torres VE, et al. Kidney volume and functional outcomes in autosomal dominant polycystic kidney disease. Clin J Am Soc Nephrol. 2012;7(3):479-486.
  12. Yu ASL, Shen C, Landsittel DP, et al. Baseline total kidney volume and the rate of kidney growth are associated with chronic kidney disease progression in autosomal dominant polycystic kidney disease. Kidney Int. 2018;93(3):691-699.
  13. Nowak K, You Z, Gitomer B, et al. Overweight and obesity are predictors of progression in early autosomal dominant polycystic kidney disease. J Am Soc Nephrol. 2018;29(2):571-578.
  14. Cornec-Le Gall E, Audrézet MP, Rousseau A, et al. The PROPKD score: a new algorithm to predict renal survival in autosomal dominant polycystic kidney disease. J Am Soc Nephrol. 2016;27(3):942-951.
  15. Bhutani H, Smith V, Rahbari-Oskoui F, et al; for the CRISP Investigators. A comparison of ultrasound and magnetic resonance imaging shows that kidney length predicts chronic kidney disease in autosomal dominant polycystic kidney disease. Kidney Int. 2015;88(1):146-151.
Measuring TKV, Icon

Measuring TKV can help predict kidney disease progression1,2

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predicting the rate of progression

INDICATION and IMPORTANT SAFETY INFORMATION

INDICATION:

JYNARQUE is indicated to slow kidney function decline in adults at risk of rapidly progressing autosomal dominant polycystic kidney disease (ADPKD).

IMPORTANT SAFETY INFORMATION:

WARNING: RISK OF SERIOUS
LIVER INJURY

WARNING: RISK OF SERIOUS LIVER INJURY

  • JYNARQUE® (tolvaptan) can cause serious and potentially fatal liver injury. Acute liver failure requiring liver transplantation has been reported
  • Measure transaminases (ALT, AST) and bilirubin before initiating treatment, at 2 weeks and 4 weeks after initiation, then monthly for the first 18 months and every 3 months thereafter. Prompt action in response to laboratory abnormalities, signs, or symptoms indicative of hepatic injury can mitigate, but not eliminate, the risk of serious hepatotoxicity
  • Because of the risks of serious liver injury, JYNARQUE is available only through a Risk Evaluation and Mitigation Strategy program called the JYNARQUE REMS Program

CONTRAINDICATIONS:

  • History, signs or symptoms of significant liver impairment or injury. This contraindication does not apply to uncomplicated polycystic liver disease
  • Taking strong CYP3A inhibitors
  • With uncorrected abnormal blood sodium concentrations
  • Unable to sense or respond to thirst
  • Hypovolemia
  • Hypersensitivity (e.g., anaphylaxis, rash) to JYNARQUE or any component of the product
  • Uncorrected urinary outflow obstruction
  • Anuria

Serious Liver Injury: JYNARQUE can cause serious and potentially fatal liver injury. Acute liver failure requiring liver transplantation has been reported in the post-marketing ADPKD experience. Discontinuation in response to laboratory abnormalities or signs or symptoms of liver injury (such as fatigue, anorexia, nausea, right upper abdominal discomfort, vomiting, fever, rash, pruritus, icterus, dark urine or jaundice) can reduce the risk of severe hepatotoxicity. To reduce the risk of significant or irreversible liver injury, assess ALT, AST and bilirubin prior to initiating JYNARQUE, at 2 weeks and 4 weeks after initiation, then monthly for 18 months and every 3 months thereafter.

Hypernatremia, Dehydration and Hypovolemia: JYNARQUE therapy increases free water clearance which can lead to dehydration, hypovolemia and hypernatremia. Instruct patients to drink water when thirsty, and throughout the day and night if awake. Monitor for weight loss, tachycardia and hypotension because they may signal dehydration. Ensure abnormalities in sodium concentrations are corrected before initiating therapy. If serum sodium increases above normal or the patient becomes hypovolemic or dehydrated and fluid intake cannot be increased, suspend JYNARQUE until serum sodium, hydration status and volume status parameters are within the normal range.

Inhibitors of CYP3A: Concomitant use of JYNARQUE with drugs that are moderate or strong CYP3A inhibitors (e.g., ketoconazole, itraconazole, lopinavir/ritonavir, indinavir/ritonavir, ritonavir, and conivaptan) increases tolvaptan exposure. Use with strong CYP3A inhibitors is contraindicated; dose reduction of JYNARQUE is recommended for patients taking moderate CYP3A inhibitors. Patients should avoid grapefruit juice beverages while taking JYNARQUE.

Adverse Reactions: Most common observed adverse reactions with JYNARQUE (incidence >10% and at least twice that for placebo) were thirst, polyuria, nocturia, pollakiuria and polydipsia.

Other Drug Interactions:

  • Strong CYP3A Inducers: Co-administration with strong CYP3A inducers reduces exposure to JYNARQUE. Avoid concomitant use of JYNARQUE with strong CYP3A inducers
  • V2-Receptor Agonist: Tolvaptan interferes with the V2-agonist activity of desmopressin (dDAVP). Avoid concomitant use of JYNARQUE with a V2-agonist

Pregnancy and Lactation: Based on animal data, JYNARQUE may cause fetal harm. In general, JYNARQUE should be discontinued during pregnancy. Advise women not to breastfeed during treatment with JYNARQUE.

To report SUSPECTED ADVERSE REACTIONS, contact Otsuka America Pharmaceutical, Inc. at 1-800-438-9927 or FDA at 1-800-FDA-1088 (www.fda.gov/medwatch).

Please see FULL PRESCRIBING INFORMATION, including BOXED WARNING.

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INDICATION and IMPORTANT SAFETY INFORMATION
INDICATION and IMPORTANT SAFETY INFORMATION

INDICATION:

JYNARQUE is indicated to slow kidney function decline in adults at risk of rapidly progressing autosomal dominant polycystic kidney disease (ADPKD).

IMPORTANT SAFETY INFORMATION:

WARNING: RISK OF SERIOUS
LIVER INJURY

WARNING: RISK OF SERIOUS LIVER INJURY

  • JYNARQUE® (tolvaptan) can cause serious and potentially fatal liver injury. Acute liver failure requiring liver transplantation has been reported
  • Measure transaminases (ALT, AST) and bilirubin before initiating treatment, at 2 weeks and 4 weeks after initiation, then monthly for the first 18 months and every 3 months thereafter. Prompt action in response to laboratory abnormalities, signs, or symptoms indicative of hepatic injury can mitigate, but not eliminate, the risk of serious hepatotoxicity
  • Because of the risks of serious liver injury, JYNARQUE is available only through a Risk Evaluation and Mitigation Strategy program called the JYNARQUE REMS Program

CONTRAINDICATIONS:

  • History, signs or symptoms of significant liver impairment or injury. This contraindication does not apply to uncomplicated polycystic liver disease
  • Taking strong CYP3A inhibitors
  • With uncorrected abnormal blood sodium concentrations
  • Unable to sense or respond to thirst
  • Hypovolemia
  • Hypersensitivity (e.g., anaphylaxis, rash) to JYNARQUE or any component of the product
  • Uncorrected urinary outflow obstruction
  • Anuria

Serious Liver Injury: JYNARQUE can cause serious and potentially fatal liver injury. Acute liver failure requiring liver transplantation has been reported in the post-marketing ADPKD experience. Discontinuation in response to laboratory abnormalities or signs or symptoms of liver injury (such as fatigue, anorexia, nausea, right upper abdominal discomfort, vomiting, fever, rash, pruritus, icterus, dark urine or jaundice) can reduce the risk of severe hepatotoxicity. To reduce the risk of significant or irreversible liver injury, assess ALT, AST and bilirubin prior to initiating JYNARQUE, at 2 weeks and 4 weeks after initiation, then monthly for 18 months and every 3 months thereafter.

Hypernatremia, Dehydration and Hypovolemia: JYNARQUE therapy increases free water clearance which can lead to dehydration, hypovolemia and hypernatremia. Instruct patients to drink water when thirsty, and throughout the day and night if awake. Monitor for weight loss, tachycardia and hypotension because they may signal dehydration. Ensure abnormalities in sodium concentrations are corrected before initiating therapy. If serum sodium increases above normal or the patient becomes hypovolemic or dehydrated and fluid intake cannot be increased, suspend JYNARQUE until serum sodium, hydration status and volume status parameters are within the normal range.

Inhibitors of CYP3A: Concomitant use of JYNARQUE with drugs that are moderate or strong CYP3A inhibitors (e.g., ketoconazole, itraconazole, lopinavir/ritonavir, indinavir/ritonavir, ritonavir, and conivaptan) increases tolvaptan exposure. Use with strong CYP3A inhibitors is contraindicated; dose reduction of JYNARQUE is recommended for patients taking moderate CYP3A inhibitors. Patients should avoid grapefruit juice beverages while taking JYNARQUE.

Adverse Reactions: Most common observed adverse reactions with JYNARQUE (incidence >10% and at least twice that for placebo) were thirst, polyuria, nocturia, pollakiuria and polydipsia.

Other Drug Interactions:

  • Strong CYP3A Inducers: Co-administration with strong CYP3A inducers reduces exposure to JYNARQUE. Avoid concomitant use of JYNARQUE with strong CYP3A inducers
  • V2-Receptor Agonist: Tolvaptan interferes with the V2-agonist activity of desmopressin (dDAVP). Avoid concomitant use of JYNARQUE with a V2-agonist

Pregnancy and Lactation: Based on animal data, JYNARQUE may cause fetal harm. In general, JYNARQUE should be discontinued during pregnancy. Advise women not to breastfeed during treatment with JYNARQUE.

To report SUSPECTED ADVERSE REACTIONS, contact Otsuka America Pharmaceutical, Inc. at 1-800-438-9927 or FDA at 1-800-FDA-1088 (www.fda.gov/medwatch).

Please see FULL PRESCRIBING INFORMATION, including BOXED WARNING.