Factors associated with rapidly progressing ADPKD include overweight or obesity (BMI ≥25 kg/m²)¹, male gender, ESRD occurring ≤55 years in multiple family members with typical ADPKD, a truncating PKD1 mutation, recurrent bleeding or infection of renal cysts in patients ≤35 years, and the need for hypertension treatment in patients ≤35 years.²

Abbreviations

ADPKD, autosomal dominant polycystic kidney disease; BMI, body mass index; ESRD, end-stage renal disease.

References

1. Nowak K, et al. J Am Soc Nephrol. 2018;29:571–8.
2. Chebib FT, Torres VE. Am J Kidney Dis. 2021;78:282–92.

The Mayo imaging classification measures the intrinsic rate of TKV growth from one age-adjusted htTKV measurement. Patients with typical ADPKD (class 1) are categorized into five subclasses (1A–1E), with classes 1C–1E indicating rapid progression.¹

The PROPKD score combines clinical and genetic markers to predict ESRD before 60 years; scores >6 indicate rapid progression.¹ The PROPKD score is not applicable for patients <35 years unless they are hypertensive and have experienced urologic complications.^1,2

Abbreviations

ADPKD, autosomal dominant polycystic kidney disease; ESRD, end-stage renal disease; htTKV, height-adjusted TKV; PROPKD, predicting renal outcome in polycystic kidney disease; TKV, total kidney volume.

References

1. Chebib FT, Torres VE. Am J Kidney Dis. 2021;78:282–92.
2. Cornec-Le Gall E, et al. J Am Soc Nephrol. 2016;27:942–51.

The REPRISE trial (NCT02160145) assessed the efficacy and safety of tolvaptan in patients with later-stage ADPKD (N=1,370). Patients were randomly assigned 1:1 to receive tolvaptan or placebo for 12 months. The primary endpoint was the change in eGFR from baseline to follow-up, adjusting for the duration that each patient participated in the trial (interpolated to 1 year). Change in eGFR was −2.34 mL/min/1.73 m² (95% CI, −2.81 to −1.87) with tolvaptan and −3.61 mL/min/1.73 m² (95% CI, −4.08 to −3.14) with placebo. There was a statistically significant difference in change in eGFR between treatment groups (1.27 mL/min/1.73 m²; 95% CI, 0.86–1.68; p<0.001).

Abbreviations

ADPKD, autosomal dominant polycystic kidney disease; CI, confidence interval; eGFR, estimated glomerular filtration rate.

Reference

Torres VE, et al. N Engl J Med. 2017;377:1930–42.

The TOOL trial (NCT03541447) compared the effect of 1- and 4-week tolvaptan + octreotide-LAR treatment with tolvaptan + placebo on GFR in patients with ADPKD and normal kidney function or hyperfiltration (N=19). The reduction in median GFR was greater with tolvaptan + octreotide-LAR vs tolvaptan + placebo at 1 and 4 weeks. However, the difference was only statistically significant at 1 week
(1 week: 10 vs 3 mL/min/1.73 m² [p=0.01]; 4 weeks: 7 vs 3 mL/min/1.73 m² [p=0.28]).

Abbreviations

ADPKD, autosomal dominant polycystic kidney disease; GFR, glomerular filtration rate; LAR, long-acting release.

Reference

Trillini M, et al. Clin J Am Soc Nephrol. 2023;18:223–33.

Tolvaptan PI and SmPC contain warnings for hypernatraemia, dehydration and hypovolaemia.^1,2 To prevent and manage symptoms of aquaresis, patients are advised to increase their fluid intake by drinking throughout the day, in anticipation or at the first signs of thirst, and drinking 1–2 cups before bed regardless of perceived thirst and after each episode of nocturia.^1–3 A diet that is low in sodium and protein reduces osmolar loads and thereby helps to reduce the aquaretic burden.^3,4 Patients are also advised to monitor their body weight daily and report changes of >3% in a week as an early sign of dehydration.^1–3 

Abbreviations

PI, prescribing information; SmPC, summary of product characteristics.

References

1. FDA. Tolvaptan PI. Available at: https://bit.ly/403HhXs (accessed 26 January 2023).
2. EMA. Tolvaptan SmPC. Available at: https://bit.ly/3j4URtb (accessed 26 January 2023).
3. Chebib FT, et al. J Am Soc Nephrol. 2018;29:2458–70.
4. Amro OW, et al. Am J Kidney Dis. 2016;68:882–91.