台大雲林分院腎臟科 · Nephrology Clinical Sharing

Clinical Experience of Tolvaptan
for ADPKD and NHI Pre-Approval Process

Two Cases — Tips for Navigating Taiwan NHI Coverage

台大雲林分院腎臟科 紀竣議

Nephrology Division, National Taiwan University Hospital Yunlin Branch

Jun 2026

ADPKD — The Progressive Burden

1:500
Most common hereditary kidney disease — one of the most frequent life-threatening monogenic disorders worldwide
~50%
Reach end-stage renal disease by age 60, driven by progressive bilateral renal cyst growth and kidney enlargement
TKV
Total Kidney Volume (htTKV) is the primary imaging biomarker of disease progression — Mayo 1A–1E risk stratification
100 200 500 1000 2000 5000 15 20 30 40 50 60 70 Age (years) htTKV (mL/m) 1A 1B 1C 1D 1E Mayo Classification TKV growth / yr ΔeGFR (mL/min/yr) 1A < 1.5% − 0.2 1B 1.5 – 3.0% − 1.7 1C 3.0 – 4.5% − 2.7 1D 4.5 – 6.0% − 3.8 1E > 6.0% − 5.5 Irazabal MV et al. JASN 2015;26:160–172
Mayo Class 1E — the highest-risk subgroup — predicts >6% annual eGFR decline without treatment. Both patients in this series carry this classification.

REFERENCES

1. Irazabal MV, et al. Imaging Classification of Autosomal Dominant Polycystic Kidney Disease: A Simple Model for Selecting Patients for Clinical Trials. J Am Soc Nephrol. 2015;26(1):160–172.

2. Mayo Clinic PKD Center. ADPKD Classification. mayo.edu/research/documents/pkd-center-adpkd-classification/doc-20094754

Tolvaptan (Jinarc) — Mechanism & Evidence

Mechanism of Action

Vasopressin V2 receptor antagonist → reduces cAMP-driven cyst epithelial proliferation and fluid secretion → slows kidney enlargement

TEMPO 3:4 Trial

3.1% vs 5.5% annual TKV growth; significantly slower eGFR decline over 3 years in CKD Stage 1–3 patients

REPRISE Trial

Confirmed benefit in patients with eGFR 25–65 mL/min/1.73m² (CKD Stage 3–4); slowed decline ~1.3 mL/min/year vs placebo

Taiwan NHI Coverage

NHI approved reimbursement for Jinarc in ADPKD patients meeting eligibility criteria — first covered in 2023


Requires pre-approval (事前審查) and annual renewal (申請展延). Administered via hospital NHI portal.

Key safety consideration: Hepatotoxicity risk — mandatory regular LFT monitoring. Contraindicated in cataracts and hepatic impairment.

Taiwan NHI Eligibility Criteria

CriterionRequirementNotes
DiagnosisConfirmed ADPKDImaging or genetic confirmation required
Mayo ClassificationClass 1C, 1D, or 1EDerived from height-adjusted TKV (htTKV) via CT imaging
Renal FunctioneGFR ≥ 25 mL/min/1.73m²CKD-EPI equation; both cases applied at eGFR 30–35
Liver FunctionAST/ALT ≤ 3× ULN, no hepatic diseaseRecent lab report required; hepatotoxicity is key concern
OphthalmologyNo cataract; IOP within normal limitsOphthalmology exam report must be attached to application
Skin EvaluationNo skin tumorsClinical documentation in narrative sufficient
Metabolic PanelUA and electrolytes (Na, K) within rangeIncluded in standard lab panel — attach report with date
Both cases in this series: Mayo 1E, eGFR 30–35 mL/min at application, all safety criteria documented — approved within one week of submission.

Pre-Approval Workflow — 事前審查

01

Lab Panel

Cr, eGFR, AST/ALT, UA, Na/K, CBC, urine PCR — all within 3 months of submission

02

CT Imaging

Abdominal CT → measure TKV + htTKV → determine Mayo class 1C/D/E (within 12 months)

03

Ophthalmology

IOP measurement, cataract evaluation — written report required as supporting document

04

Narrative + Submit

Write clinical narrative with all key elements. Upload via hospital NHI portal (送核) for all 3 dose tiers.

05

Approval

同意備查 — typically 2–7 days. Prescribe and begin titration: 45+15 → 60+30 → 90+30 mg.

Key tip: Apply for all three dose tiers simultaneously (45+15, 60+30, 90+30 mg) — this covers the full titration period under a single application cycle, as demonstrated in both cases.

Documentation Checklist — Initial Application

Lab Reports (within 3 months)

  • Serum creatinine & eGFR (CKD-EPI)
  • AST, ALT — full liver function panel
  • Uric acid, serum Na, serum K
  • Urine protein-creatinine ratio (UPCR)
  • CBC (hemoglobin, platelet count)

Imaging, Clinical & Narrative

  • Abdominal CT: TKV and htTKV measurements (within 12 months)
  • Mayo classification documentation (1C / 1D / 1E)
  • Ophthalmology report — IOP, cataract evaluation
  • Skin examination: no tumors (note in clinical narrative)
  • Clinical narrative — diagnosis, Mayo class, eGFR, all safety checks passed, proposed titration plan with quantity
Case Presentation · 01

Case 1 — Male, 44 Years Old
ADPKD · Mayo 1E · Jinarc since May 2023

Three years of continuous treatment — initial application, dose titration, and three successful annual renewals

Case 1 — Patient Profile & Baseline

Demographics

Male, 44 years old  ADPKD


Comorbidities

CKD Stage 3 → 4  ·  Hypertension  ·  Gout


Medications

Aspirin  ·  Carvedilol  ·  Doxazosin  ·  Olmesartan/Amlodipine (Sevikar)


Jinarc started May 19, 2023

Baseline at Application — Feb 2023

35.2
eGFR (mL/min/1.73m²)
2.2
Creatinine (mg/dL)
2,939
TKV (mL)
1,781
htTKV (mL/m)
1E

Mayo Classification

Highest-risk group · htTKV > 1,500 mL/m

LFT normal  ·  UA normal  ·  Electrolytes normal  ·  IOP normal  ·  No skin tumors

Case 1 — Initial NHI Application

1

Feb 23, 2023

Lab workup + CT imaging completed — Cre 2.2, eGFR 35.2, TKV 2,939 mL, htTKV 1,781 mL/m

2

Apr 24, 2023

Applications submitted for 45+15 mg and 60+30 mg tiers (titration doses)

3

Apr 25, 2023

Application submitted for 90+30 mg tier (maintenance dose)

4

Apr 26–28, 2023

All three tiers approved (同意備查) — within 2 to 4 days

5

May 19, 2023

Jinarc initiated at 45+15 mg → escalated to 60+30 → 90+30 mg over 8 weeks

Dose TierPurposeQuantity
45+15 mgTitration Week 1–44 boxes (112 tabs each)
60+30 mgTitration Week 5–84 boxes (112 tabs each)
90+30 mgMaintenance5 boxes (140 tabs each)

Sample Clinical Narrative (translated)

"ADPKD patient. Cre 2.2 mg/dL, eGFR 35.2 mL/min. LFT/UA/electrolytes normal (lab report 2023/02/23). No skin tumors. TKV 2,939 mL, htTKV 1,781 mL/m (CT 2023/02/23). Mayo class 1E. IOP normal (ophtho note 2023/04/24). Request NHI coverage for Jinarc to slow CKD progression. Year 1 plan: 45+15 ×4 boxes, 60+30 ×4 boxes, 90+30 ×5 boxes."

Tip: Apply for all dose tiers simultaneously — all approved in a single cycle, no gaps in coverage during titration.

Case 1 — Renal Function Over 3 Years on Jinarc

eGFR Trend

35.2

Baseline 2023

17.3

Recent 2026

← older                                       newer →

Stabilized at 31–35 mL/min for ~2 years on Jinarc · CT Jul 2025: no significant TKV change

Creatinine Trend

2.2

Baseline (mg/dL)

4.1

Recent (mg/dL)

← older                                       newer →

Cre stable at 2.2–2.5 mg/dL for ~2 years on Jinarc  ·  recent CKD stage 4 progression noted 2025–2026

Case 1 — Three Annual Renewals

May 2023

Jinarc initiated → titration complete → stable on 90+30 mg

1

Feb 22, 2024 — 1st Renewal

90+30 mg × 336 tabs submitted & approved Feb 23 — within 1 day

2

Feb 21, 2025 — 2nd Renewal

90+30 mg × 336 tabs — approved Feb 26, 2025

3

Jan 22, 2026 — 3rd Renewal

90+30 mg × 336 tabs — approved Jan 27, 2026

Renewal Narrative — Key Elements

  • Confirm ongoing Mayo 1E classification
  • State Jinarc start date (e.g. 2023/05/19)
  • Current dose: 90+30 mg
  • Renal stability: "Cre 2.2–2.3 mg/dL" (provide recent value range)
  • Proteinuria stable: "最近 160 mg/day"
  • Request: 90+30 mg × 12 boxes for continuation
Renewal tip: No CT required. Submit 30–60 days before expiry. Approval consistently within 1–7 days for this patient.
Case Presentation · 02

Case 2 — Female, 44 Years Old
ADPKD · Mayo 1E · Jinarc since Sep 2024

Strong family history · larger kidneys · concurrent anemia management alongside Jinarc

Case 2 — Patient Profile & Baseline

Demographics

Female, 44 years old  ADPKD


Comorbidities

CKD Stage 4  ·  Hypertension (onset age 32)  ·  Iron-deficiency Anemia  ·  Gout


Family History

Mother: ADPKD + Hypertension

Brother: CKD  ·  Sister: affected  ·  Father: HTN

Classic autosomal dominant pedigree


Medications

Ferrous  ·  Indapamide  ·  Azilsartan (Edarbi)  ·  Nebivolol

Jinarc started Sep 25, 2024

Baseline at Application — Aug 2024

30.8
eGFR (mL/min/1.73m²)
2.2
Creatinine (mg/dL)
3,680
TKV (mL)
2,258
htTKV (mL/m)
1E

Mayo Classification

htTKV 2,258 mL/m — significantly enlarged

Larger kidneys than Case 1 (TKV 3,680 vs 2,939 mL)  ·  Ophthalmology Jul 2024: no cataract confirmed

Case 2 — Initial NHI Application

1

Jul 4, 2024

Abdominal CT confirmed TKV 3,679.8 mL; polycystic kidneys and liver documented

2

Aug 23, 2024

Full lab workup — Cre 2.2, eGFR 30.8, LFT/UA/electrolytes within normal limits

3

Aug 29–30, 2024

All three dose tiers submitted simultaneously: 45+15, 60+30, 90+30 mg

4

Sep 2–4, 2024

All tiers approved (同意備查) within 3 to 6 days

5

Sep 25, 2024

Jinarc initiated at 45+15 mg → titrated to 90+30 mg over 8 weeks

Dose TierPurposeQuantity
45+15 mgTitration Week 1–44 boxes (112 tabs each)
60+30 mgTitration Week 5–84 boxes (112 tabs each)
90+30 mgMaintenance5 boxes (140 tabs each)
Same strategy as Case 1: all three tiers submitted in one cycle — confirmed as efficient and consistently approved without issue.

Jul 29, 2025 — 1st Renewal

90+30 mg × 336 tabs  ·  approved Aug 7, 2025

Case 2 — Renal Function Trend

eGFR Trend

37.6

Earliest (2022)

20.4

Recent (2026)

← 2022                                       2026 →

eGFR declining pre-Jinarc (37.6 → 18.9) · Stabilized in 20–23 range since treatment start

Creatinine Trend

1.6

Earliest (mg/dL)

2.85

Recent (mg/dL)

← 2022                                       2026 →

Active challenge: Severe IDA (Hb 6.7–8.0 g/dL, Ferritin <12, TSAT 3%) — requires ESA therapy (Recormon) and IV iron alongside Jinarc

Comparing Both Cases

FeatureCase 1 — Male, 44yCase 2 — Female, 44y
Mayo Classification1E1E
TKV at application2,939 mL3,680 mL
htTKV at application1,781 mL/m2,258 mL/m
eGFR at application35.2 mL/min/1.73m²30.8 mL/min/1.73m²
Jinarc startedMay 2023Sep 2024
Duration / renewals~3 years · 3 annual renewals~1.5 years · 1 annual renewal
Approval time (initial)2–4 days3–6 days
Notable comorbidityGout, HTNIron-deficiency anemia, HTN, strong FHx
Renal outcomeStable ~2yr on Jinarc; recent CKD stage 4 progressioneGFR decline arrested; stabilized 20–23

Clinical Tips for NHI Pre-Approval

1

Apply all dose tiers simultaneously

Submit 45+15, 60+30, and 90+30 mg in the same cycle. Both cases confirm this — all tiers approved together within one week, covering full titration.

2

Confirm lab recency before submitting

All labs must be within 3 months; CT within 12 months. Coordinate lab draw, CT, and ophthalmology in the same clinical window when possible.

3

Schedule ophthalmology early

Ophtho appointments can have long waits. Book the evaluation in advance — the written report must be available at time of NHI submission.

4

Write a complete clinical narrative

Include: diagnosis, Cre/eGFR, LFT/UA/electrolyte status, TKV + htTKV, Mayo class, IOP, no skin tumors, and full dose plan. Completeness avoids delays.

5

Renewal is simple — plan 30–60 days ahead

No CT required. Submit current dose, start date, recent Cr/eGFR/proteinuria, and a brief stability statement. Consistently approved within 1–7 days.

6

Comorbidities don't disqualify — manage in parallel

Case 2 had severe anemia and active gout — neither contraindicated Jinarc. Monitor LFTs closely; address concurrent conditions alongside treatment.

Summary

Both Cases

Mayo 1E patients, eGFR 30–35 at application — all NHI tiers approved rapidly. Maintained on 90+30 mg Jinarc long-term.

Renal Outcomes

Case 1: eGFR stable ~33 for 2 years; CT showed no structural progression. Case 2: eGFR decline arrested after treatment initiation.

NHI Process

Pre-approval within 2–7 days when documentation is complete. Annual renewals are straightforward — no CT required, approved in 1–7 days.

Key Takeaway

Apply all three dose tiers simultaneously. Prepare documentation proactively. A complete narrative = fast approval and seamless titration.

台大雲林分院腎臟科 紀竣議 · Nephrology Division, NTUH Yunlin Branch · June 2026