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

Outline · 大綱

I

ADPKD & Tolvaptan

Epidemiology, Mayo classification, TEMPO & REPRISE evidence

Slides 03 – 04

II

Taiwan NHI Process

Eligibility criteria · pre-approval workflow · documentation checklist

Slides 05 – 07

III

Clinical Cases

Case 1 (M, 44y · since 2023) · Case 2 (F, 44y · since 2024) · comparison

Slides 08 – 17

IV

2025 KDIGO Guideline

Tolvaptan indications · split-dose titration & safety · BP & lifestyle

Slides 19 – 22

Tips section (slide 18) bridges clinical cases and KDIGO guideline — practical workflow pearls extracted from the two cases.

ADPKD — The Progressive Burden

1 : 500

Most common monogenic kidney disease — among the most prevalent life-threatening inherited disorders

~50%

Reach ESRD by age 60, driven by progressive bilateral renal cyst growth and kidney enlargement

5 Classes

Mayo Class 1A–1E stratified by htTKV and age — primary imaging biomarker for progression risk

> 5% / yr

eGFR decline in Class 1E — the highest-risk subgroup and primary target for Tolvaptan therapy

100 200 400 600 1,000 2,000 4,000 6,000 10,000 15 20 25 30 35 40 45 50 55 60 65 70 75 80 Patient Age (Years) HtTKV (mL/m) Class 1E Class 1D Class 1C Class 1B Class 1A
htTKV = height-adjusted Total Kidney Volume (mL/m)

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 renal cysts enlargement

TEMPO 3:4 Trial

2.8% 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 2019-07

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. Hepatic impairment is an absolute contraindication; glaucoma is a Taiwan NHI exclusion criterion.

Torres VE, et al. TEMPO 3:4. N Engl J Med 2012;367:2407–2418
Torres VE, et al. REPRISE. N Engl J Med 2017;377:1930–1942

Taiwan NHI Eligibility Criteria

① 處方規範　限腎臟專科醫師處方　·　須經事前審查核准後使用　·　每日至多使用 2 粒　·　每年檢附評估資料重新申請
②

初次使用條件

下列須全部符合（initial use）
✓18–50 歲
✓第 3 期 CKD（eGFR 30–59），且已出現病情迅速惡化跡象
✓確診 ADPKD，腎臟影像呈雙側／瀰漫性水泡
✓並符合下列至少一項：
(1) eGFR 下降：1 年內 ↓ ≥ 5.0，或 5 年內每年 ↓ ≥ 2.5 mL/min/1.73m²　（須排除脫水、藥物、感染、阻塞等原因）
(2) htTKV 符合 Mayo 1C–1E disease
💡 Mayo 分期可請放射科發報告，首次申請附圖說明
③

用藥前確認

確認下列條件及病史（pre-treatment）
✓用藥前肝功能正常
✓血清尿酸 ≤ 7 mg/dL
✓無青光眼，或眼科證實眼壓控制良好
✓無皮膚腫瘤病史
✓無電解質異常
✓排除懷孕、哺乳、脫水、尿路阻塞、肝損傷病史
💡 眼科轉介附病歷即可　·　皮膚免專科背書　·　尿酸可藥物控制
④

停藥條件

出現下列情況時停用（discontinue）
✕藥物調整後，肝功能指數仍 > 3× 正常上限
✕使用滿 1 年後，eGFR 下降仍 ≥ 5 mL/min/1.73m²
✕出現明顯副作用，有危害健康疑慮

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 — 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) — 廠商建議第一年申請 4 / 4 / 5 盒 方便調整，後續每年申請 12 盒。
TEMPO 3:4 final-dose distribution (reference for box quantities): 120 mg — 55%　·　90 mg — 21%　·　60 mg — 24%

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, glaucoma evaluation
  • ✓
    Skin examination: no tumors (note in clinical narrative)
  • ✦
    Clinical narrative — diagnosis, Mayo class, eGFR, all safety checks passed, proposed titration plan with quantity
Key tip — 我的申請範本：多囊腎病人，目前肌肝酸 XX mg/dL，eGFR=XX mL/min/1.73m²，肝功能正常，尿酸正常，電解質正常 (附報告 日期)，無皮膚腫瘤。TKV=XX mL, htTKV=XX mL/m (附 CT 報告 日期), Mayo classification 1X，眼壓正常 (附門診紀錄 日期)。請惠予給付 JINARC 使用，減緩腎功能惡化。預計一年使用：45mg+15mg 四盒，60mg+30mg 四盒，90mg+30mg 五盒。
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, 41 at application · 44 now  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 months

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

申請內容

"多囊腎病人，目前肌肝酸2.2 mg/dL，eGFR=35.2 mL/min/1.73m²，肝功能正常，尿酸正常，電解質正常(附報告2023/02/23)，無皮膚腫瘤。TKV=2939 mL, height adjusted TKV=1781 mL/m (附CT報告2023年初) Mayo classification 1E，眼壓正常。請惠予給付JINARC使用，減緩腎功能惡化。預計一年使用，45mg+15mg四盒，60mg+30mg四盒，90mg+30mg五盒。"

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

← oldernewer →
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)

← oldernewer →
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 per strength submitted & approved Feb 23 — within 1 day

2

Feb 21, 2025 — 2nd Renewal

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

3

Jan 22, 2026 — 3rd Renewal

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

Renewal Narrative — Key Elements

  • ✓
    Confirm ongoing Mayo 1E classification
  • ✓
    State Jinarc start date (2023/05/19)
  • ✓
    Current dose: 90+30 mg
  • ✓
    Renal stability: recent Cre & eGFR range

申請內容

"多囊腎病人，Mayo classification 1E，於2023/05/19開始使用JINARC減緩腎功能惡化至今，目前服用90mg+30mg，腎功能穩定(Cre 2.2–2.5 mg/dL)，欲申請新一年90mg+30mg十二盒，繼續使用以減緩腎功能惡化，懇請給予核准。"

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, 42 at application · 44 now  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 glaucoma 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 months

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

申請內容（與 Case 1 同模板）

"多囊腎病人，目前肌肝酸2.2 mg/dL，eGFR=30.8 mL/min/1.73m²，肝功能正常，尿酸正常，電解質正常(附報告2024/08/23)，無皮膚腫瘤。TKV=3679.8 mL, height adjusted TKV=2257.5 mL/m (附CT報告2024/07/04) Mayo classification 1E，眼壓正常。請惠予給付JINARC使用，減緩腎功能惡化。預計一年使用，45mg+15mg四盒，60mg+30mg四盒，90mg+30mg五盒。"

Case 2 — Renal Function Trend

eGFR Trend

37.6

Earliest (2022)

20.4

Recent (2026)

← 20222026 →
eGFR declining pre-Jinarc (37.6 → 18.9) · Stabilized in 20–23 range since treatment start (single 30.8 post-treatment value reflects measurement variability)

Creatinine Trend

1.6

Earliest (mg/dL)

2.85

Recent (mg/dL)

← 20222026 →
Active challenge: Severe IDA (Hb 6.7–8.0 g/dL, Ferritin <12, TSAT 3%) — requires ESA therapy (Recormon) and IV iron alongside Jinarc
1st Annual Renewal: Jul 29, 2025 submitted → approved Aug 7, 2025 · 90+30 mg × 336 tabs per strength

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

首次申請廠商建議三種劑量各 4 / 4 / 5 盒。注意有些醫院 (如敝院) 要一次送兩筆，因為 30 mg 健保碼相同但分在兩種劑型中 (60+30 跟 90+30)，有疑問請詢問貴單位熟悉申報相關人員。

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.

2025 KDIGO ADPKD — Tolvaptan 適應症

Rec 4.1.1.1

1B

"We recommend"

eGFR ≥ 25 mL/min/1.73m²

+

Rapid Progression（符合任一）：
► Mayo Class 1C–1E（MIC by MRI 優先，CT 可替代）
► eGFR 年下降 ≥ 3 mL/min/1.73m²

年齡 >55 歲 → 個別化共同決策

即使符合快速進展標準，55 歲以上患者仍須與病人共同討論風險效益，因效益隨年齡遞減。

PROPKD Score >6 → 補強佐證

MIC 或 eGFR 下降速率不確定時（尤其 1B/1C 邊界），PROPKD >6 可提供快速進展的額外依據。

PROPKD Score（0–9分）：男性（+1）、基因型（PKD2=0、PKD1非截斷=2、PKD1截斷=4）、35歲前高血壓（+2）、35歲前泌尿道事件（+2）；預測進入透析之年齡（中位數）： >6分=49歲、4~6分=57歲、<4分=71歲。

治療中 eGFR 降至 <25 仍可繼續

已開始使用者，eGFR 低於 25 不必停藥——持續至腎替代療法（KRT）開始前才停用。

排除其他 eGFR 下降原因

啟動前應先排除血管病變、糖尿病腎病、蛋白尿 ≥1 g/d 或 AKI 等急慢性因素，確認 ADPKD 為主因。

Devuyst O, et al. KDIGO 2025 Clinical Practice Guideline for ADPKD. Kidney Int. 2025;107(Suppl 2S):S1–S239
Cornec-Le Gall E, et al. The PROPKD Score. J Am Soc Nephrol. 2016;27(3):942–951

2025 KDIGO ADPKD — 劑量滴定與安全監測

劑量滴定（Split-Dose Regimen）

45+15

起始劑量

45 mg 晨起 + 15 mg 8 小時後；最低推薦劑量，讓患者適應利尿效應（≥ 1 週）

60+30

中間劑量

視耐受性升階；亦可從此劑量再上調（≥ 1 週）

90+30

目標劑量

90 mg 晨起 + 30 mg 8 小時後；除非不耐受或藥物交互作用，否則以此為治療目標

停藥時機：妊娠前、哺乳期、KRT 開始前。CYP3A 強效抑制劑合用需考慮降階。

監測要求

肝功能監測（強制，不可省略）

基線 → 第1、2、4、8、12、18個月 → 之後每3個月。ALT/AST 升高伴症狀（黃疸、倦怠、腹痛）立即停藥。

Sick-Day Plan — 體液流失時暫停

嘔吐、腹瀉、發燒、高溫環境、長途飛行等情境需暫停 Jinarc®，以降低急性腎損傷（AKI）風險。

利尿效應衛教

預期每日尿量增加，感到口渴時應飲水補充；低鈉飲食可小幅減少利尿量。不建議常規使用 thiazide 利尿劑對抗利尿效應。

尿酸上升 — 痛風患者謹慎

Tolvaptan 可升高血尿酸；有痛風病史者應積極監測並治療（本系列兩個案均有痛風或高尿酸記錄）。

Devuyst O, et al. KDIGO 2025 Clinical Practice Guideline for ADPKD. Kidney Int. 2025;107(Suppl 2S):S1–S239

2025 KDIGO ADPKD — 血壓管理與生活調整

適用族群血壓目標等級備註
18–49歲，CKD G1–G2
且 BP >130/85 mmHg		 ≤ 110/75 mmHg (if tolerated)
居家血壓計測量		 1D HALT-PKD Trial A：積極降壓組腎臟保護效益顯著
≥50歲，任何 CKD 分期 SBP < 120 mmHg
標準化診間量測		 2C 依 KDIGO BP in CKD 指引；如可耐受，應積極達標
第一線降壓藥 RASi（ACEi 或 ARB） 1C ADPKD 腎素-血管緊張素系統活化，RASi 為首選抗高血壓藥
⚠ 禁忌：雙重 RAS 阻斷 避免 ACEi / ARB / DRI 合用 1B 組合無額外效益，增加 AKI 與高鉀血症風險
補充水分（未服用 Tolvaptan 者）：每日攝取 2.5–3 L 以上水分，藉由抑制 AVP 分泌來減緩囊腫生長。以尿液滲透壓 <300 mOsm/kg 作為監測指標。
生活調整：低鈉飲食（<2 g/天）改善血壓；維持健康體重（腎臟重量可修正 BMI）；避免 NSAIDs（CKD G3+）；規律有氧運動。

Devuyst O, et al. KDIGO 2025 Clinical Practice Guideline for ADPKD. Kidney Int. 2025;107(Suppl 2S):S1–S239

Summary

Both Cases

Both 44 y, Mayo 1E.
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