Lecture · Nephrology

2026 / 07

From Ca-P Imbalance to Vascular Calcification — The CKD–MBD Continuum

鈣磷失衡與血管鈣化

紀竣議醫師 · Dr. Chun-Yi Chi

腎臟科 · 臺大醫院雲林分院

Division of Nephrology · NTU Hospital Yunlin Branch

CKD–MBD · v.2026.07

CKD–MBD大綱 · Outline

大綱

Outline

CKD–MBD framework · 簡介

One disease, three lenses — biochem, bone, vessel

Hormones & Ca–P balance · 生化

PTH · Vit D · FGF-23 — and how Ca, P go off-track

III

Bone & vascular calcification · 骨頭 & 血管

ROD · VC mechanism · inhibitors · calciphylaxis

治療 · Treatment

BCS targets · ROD treatment · binders · calcimimetics · Mg · Vit K · SNF472

Cases & take-home · 臨床案例

8 dialysis patients — applying the framework

I · Introduction定義 · Definition

04Renal Pathophysiology: The Essentials

CKD–MBD = Chronic Kidney Disease - Mineral and Bone Disorder

A spectrum, not a single disease.

慢性腎病引起的礦物質與骨骼系統失衡，由生化、骨骼、與血管三個面向共同構成。

Initially asymptomatic; classic biochemical changes appear after eGFR < 30–40 mL/min/1.73m² — but FGF-23 rises far earlier (from CKD stage 2–3). A non-traditional risk factor for cardiovascular disease.

01 · Biochemistry (BCS)

Ca, P, iPTH, Vit D, FGF-23, ALP

02 · Bone abnormalities

Renal osteodystrophy (ROD) & osteoporosis

03 · Vascular / soft-tissue calcification

CV mortality driver in dialysis patients

I · Introduction架構圖 · Framework

05KDIGO 2006 / 2009 / 2017 · CKD–MBD

The three pillars

Three lenses on one disease.

BCS · 生化檢測

Biochemistry

CaCalcium
PPhosphorus
PTHParathyroid hormone
DVitamin D
FGFFGF-23
ALPAlkaline phosphatase

Bone · 骨骼

腎性骨病變 vs. 骨鬆

ROD

Renal osteodystrophy

Osteoporosis

Density & quality of bone

Bone biopsy

TMV classification (gold standard)

CV · 血管

心血管 / 軟組織鈣化

Vascular calcification

Intimal & medial (Mönckeberg)

Valvular / soft-tissue

Aortic, mitral, periarticular

Calciphylaxis

CUA — uremic small-vessel

II · BCS三個荷爾蒙 · Three hormones

07Williams Textbook of Endocrinology

三個荷爾蒙

Three hormones run the system.

PTH

Parathyroid hormone

副甲狀腺素 — responds to Ca, mobilises bone, drives renal vit-D activation.

Ca ↑ · P ↓ (腎功能不好者↑)

Target on dialysis: 約 150–650 pg/mL (2–9× ULN)

Vit D

Vitamin D (active)

活性維生素D — 1,25-(OH)₂D₃. Activated in kidney; raises gut Ca/P absorption.

Ca ↑ · P ↑ · PTH ↓

25(OH)D sufficiency: 25–80 ng/mL

FGF23

Fibroblast Growth Factor 23

A bone-derived phosphaturic hormone. Secreted by osteoblasts / osteocytes; signals through α-Klotho co-receptor.

P ↓ · active Vit D ↓

Rises earliest in CKD; suppresses 1α-hydroxylase.

All three are interdependent — dysregulation of one pulls the others off-target. As GFR falls, the cascade accelerates.

II · BCS · Hormone 1PTH

08Williams Textbook of Endocrinology

Parathyroid hormone

PTH — the calcium thermostat.

Blood 1–84 PTH = intact PTH (iPTH). Different assays give different numbers — targets are expressed as multiples of ULN.

Ca ↓

stimulates PTH release

Ca ↑

suppresses PTH

In normal kidneys, PTH is balanced. In renal failure, retained phosphate drives PTH up — but the kidney still can't excrete it, so P and iPTH keep climbing together (vicious cycle).

Sites of PTH action

①

Bone

Resorption → release Ca / P

②

Kidney

↑ Vit D activation → Gut absorption
虛線：有研究顯示 PTH 可直接促進腸道吸收

③

Tubules

↑ Ca reabsorption · ↑ P excretion

II · BCS · Hormone 2Vitamin D

09臺北市醫師公會會刊 61:10, 2017

Two forms of Vit D

營養 vs. 活性 — same vitamin, two roles.

營養維生素D · Nutritional

Cholecalciferol / ergocalciferol

From sun & diet. Metabolized by liver 25-hydroxylase to storage form = 25(OH)D₃.

25(OH)D₃ 可自費檢驗代表身體 Vit D 存量
具骨骼外多效性作用 · pleiotropic effects

活性維生素D · Active

1,25-(OH)₂D₃ / 活性前驅 1α-(OH)D₃

Activated by kidney 1α-hydroxylase. The hormone form.

U-Ca® = 1,25-(OH)₂D₃
Onealfa® = 1α-(OH)D₃
處方藥一般營養品中無此成分

II · BCS · Hormone 2Active Vit D — physiology & CKD use

11Renal Pathophysiology: The Essentials

Four sites of action

Active Vit D raises Ca/P and lowers PTH.

Activation in the kidney is driven by hypocalcaemia (via PTH) and hypophosphataemia.

Net physiological effect — raises Ca and P, feeds back to suppress PTH.

In CKD: 1α-hydroxylase activity falls → active Vit D may be used for hypocalcaemia or severe/progressive SHPT. It also raises Ca/P load — individualise dose and follow trends.

Clinical pearl · Hungry bone syndrome

After parathyroidectomy, even high-dose Ca + active Vit D may not correct severe hypoCa — without PTH, osteoclasts can't liberate Ca/P from bone.

① Small intestine

↑ Absorption of Ca / P

② Bone

↑ Resorption (+PTH)
→ release Ca / P

③ Kidney

↓ Renal Ca / P excretion

④ Parathyroid

Negative feedback → ↓ PTH

II · BCS · Hormone 3FGF-23

12Williams Textbook of Endocrinology

Fibroblast Growth Factor 23

FGF-23 — Bone speaks to the kidney.

骨頭分泌的排磷荷爾蒙 — a bone-derived phosphaturic hormone.

Stimulated by elevated phosphate; acts on kidney.
Member of FGF-19 subfamily (FGF-15/19/21/23) — no heparin-binding site, behaves like a hormone.
Secreted by osteoblasts & osteocytes — bone as an endocrine organ.
Binds FGFR with α-Klotho co-receptor for endocrine action.

Effects

Short term

↑ Renal phosphate excretion (phosphaturia)

(in normal kidney, also exerts negative feedback on PTH)

Long term

↓ 1α-hydroxylase → ↓ active Vit D → ↑ PTH

Disease links

ADHR (autosomal dominant hypophosphatemic rickets) · TIO (tumour-induced osteomalacia) · earliest BCS change in CKD

FGF-23 rises first in CKD and is the last to respond to treatment — it is simultaneously an early warning signal and the bridge between phosphate excess and cardiovascular risk.

II · Ca / PNormal Ca / P homeostasis

14basicmedicalkey.com / parathyroid-glands

A 24-hour balance

In health, what goes in comes out.

Blood Pool

Tight regulation by PTH / Vit D / FGF-23. Constant exchange with bone.

Gut & Intake

Absorption driven by active Vit D. High processed food = high P load.

Bone Reserve

99% Ca (1kg), 85% P (0.6kg). The body's primary mineral buffer.

Intake → Gut → Blood ⇌ Bone
└─ Feces └─ Urine

II · Ca / PPhosphate balance

15Tonelli M, NEJM 362:13, 2010

Health vs. kidney failure

In kidney failure, even strict diet runs positive.

Health · 健康人

balanced

Intake	1200 mg/day
Gut absorb	+800 mg/day
Feces	400 mg/day
Bone ↔ blood	0 mg/day (neutral)
Renal excretion	-800 mg/day

Net balance: 0

Kidney failure · 腎衰竭

positive +

Intake	900 mg/day (limited P diet)
Gut absorb	+400 mg/day （使用 CaCO₃ 4 tabs 後，600 → 400 mg）
Feces	500 mg/day （使用 CaCO₃ 4 tabs 後，300 → 500 mg）
Bone → blood	+40 mg/day 骨頭釋出
Renal excretion	0 (假設無尿)
Hemodialysis	-390 mg/day (-900 mg/session)

Net balance: +50mg/day (沉澱在心血管!)

II · Ca / PPathophysiology · the cascade

16Wolf M, JASN 21:9, 2010

時序 · 五指標

Five markers, one sequence — who moves first?

↑ FGF-23

Earliest change; phosphaturic compensation.
↓ 1,25(OH)₂D

Reduced activation in the kidney.
↑ PTH

Secondary hyperparathyroidism develops.
↑ Phosphate

Significant rise when GFR < 30 mL/min.
↓ Calcium

Stabilised by PTH; falls late (GFR < 20).

By the time P and Ca move on labs, FGF-23 has already been rising for years — start screening from CKD stage 3, don't wait for the phosphate to break range.

III · BoneROD · terminology

18Brenner and Rector's The Kidney

腎骨病變 · ROD terminology

How we describe a CKD bone.

骨切片三要素 · TMV

Turnover · 周轉

Referenced by iPTH + ALP

Mineralisation · 礦化

Defect = osteomalacia

Volume · 體積

BV/TV — bone volume fraction (biopsy)

Bone strength · 骨骼強度

= density + quality (NIH 2001)

Bone Density · 骨密度

DEXA — diagnoses osteoporosis

Bone Quality · 骨品質

Microarchitecture, turnover, mineralisation, microdamage

Bone biopsy · 骨切片

Gold standard — TMV; rarely performed clinically

III · BoneROD subtypes

192006 KDIGO CKD–MBD

Histological spectrum

ROD — five classic types, four clinical pictures.

Osteomalacia

骨質軟化 — defective mineralisation

Low turnover · ↓M

Adynamic bone

不活動型骨病變 — low turnover, normal M

↓PTH · over-suppression

HPT → OF

High-turnover spectrum

輕度病變（mild）→ 纖維囊性骨炎（osteitis fibrosa）— 涵蓋兩型，依 PTH 嚴重度漸進

↑→↑↑PTH · ± fibrosis

MUO

Mixed uremic

混合型腎性骨病變 — high turnover + ↓M

Overlap pattern

TMV biopsy is the reference — but in practice, PTH ± ALP positions most patients across this spectrum. Clinical osteoporosis in CKD is not equal to histological osteoporosis.

III · BoneRenal osteodystrophy · TMV classification

20Moe et al. Kidney Int 2006;69:1945–53

KDIGO 2006 Histomorphometry

ROD: The TMV Classification

TMV classification

Turnover · Mineralization · Volume

Each dimension may be low, normal, or high/abnormal.

How to read the bars

AD adynamic · OM osteomalacia · MUO mixed
mild HPT mild hyperpara · OF osteitis fibrosa

Clinical safeguard

iPTH and ALP estimate turnover; they do not replace bone biopsy.

Figure adapted from 2006 KDIGO CKD-MBD.

III · Vascular calcificationTwo patterns · 型態學

21Schlieper G et al, JASN 2016; Lanzer P et al, EHJ 2014

Vascular calcification · 起點

Two patterns, two stories.

In CKD, calcium leaves bone and finds the vessel wall. Where it lands changes the clinical consequence.

Intimal · 內膜型

Atherosclerotic

Lipid-rich plaque calcifies. Patchy, focal.

Population: general adults · diabetes · early CKD

Consequence: plaque rupture → MI · stroke · limb ischaemia

Medial · 中層型 (Mönckeberg)

Osteogenic

Diffuse circumferential "pipe-stem" calcification.

Population: CKD · dialysis · diabetes

Consequence: arterial stiffness → ↑ PWV · LVH · diastolic HF · CV mortality

Clinical pearl · Most dialysis patients have both, but medial calcification is the CKD-specific driver — and the one Ca-P imbalance accelerates.

III · Vascular calcificationMechanism · VSMC switch

22Shanahan CM et al, Circ Res 2011; Paloian & Giachelli, AJP-Renal 2014

Why Ca-P matters

The vessel becomes bone.

High phosphate actively reprograms vascular smooth muscle cells (VSMCs) — this is not passive precipitation.

Phosphate enters

Pit-1 / Pit-2 import phosphate into the VSMC.

Pit-1 / Pit-2 = type III Na–Pi cotransporters (SLC20A1/2)

Cell becomes osteogenic

↓ SM22α, ↑ RUNX2 / BMP-2 → osteoblast-like VSMC.

SM22α = smooth-muscle marker (lost) · RUNX2 / BMP-2 = osteogenic drivers

Vesicles form crystals

High Ca/P → apoptosis + matrix vesicles → hydroxyapatite.

Brakes fail; VC spreads

↓ Fetuin-A · matrix Gla protein (MGP) · pyrophosphate (PPi) → more vesicles, more VC.

VC in CKD is an active, programmed disease of the vessel wall — not just calcium falling out of solution. Once established, the goal is to halt, not reverse.

III · Vascular calcificationDrivers — what tips the balance

23Vervloet M & Cozzolino M, Kidney Int 2017

Promoters & protectors

A balance, not a single villain.

Promoters · 加速因子

↑ Phosphate + Ca load
dietary P · Ca binders · high-Ca dialysate · active Vit D

↑ FGF-23 + ↓ α-Klotho
early CKD signal / impaired protection

Toxins + inflammation
oxidative stress · diabetes · age

Protectors · 抑制因子

Fetuin-A
CPP chaperone

MGP + PPi
local crystal-growth brakes; MGP needs Vit K

Mg + α-Klotho
protective signals; therapeutic role still emerging

CKD shifts the equilibrium: promoters rise, protectors fall. Targeting VC means moving both arms of the balance.

III · Vascular calcificationBiomarker · CPP & T50

24Pasch A et al, JASN 2012; Smith ER et al, JASN 2014; Bostom A et al, JAHA 2018

From snapshot to propensity

Serum Ca-P doesn't tell the whole story.

CPP and T50 estimate calcification propensity beyond a single Ca-P result.

Calciprotein particles (CPP)

Fetuin-A chaperones excess Ca · P — a protective buffer.

CPP-I — amorphous / soluble

CPP-II — crystalline / pro-calcifying

CKD accelerates CPP-I → CPP-II — high P, low fetuin-A.

T50 — serum calcification propensity

Time to half-maximal CPP-I → CPP-II transformation.
Shorter T50 = higher calcification propensity.

↓ T50

Associates with all-cause & CV mortality.

Research tool: influenced by Mg, P and bicarbonate.

Not yet routine clinical care — but T50 is moving from research to bedside, and it reframes how we think about Ca-P targets.

III · Vascular calcificationImaging · 影像 & prognosis

25Kauppila LI et al, Atherosclerosis 1997; Block GA et al, KI 2007; Adragao T et al, NDT 2004

Look for it · measure it

Calcification seen predicts mortality.

Lateral abdominal X-ray — AAC

Kauppila 0–24 · score ≥7 = high CV risk

腹主動脈鈣化 · L1–L4(4節)× 前後壁(2)× 0–3 = 0–24

Pelvis & hand X-ray

Adragão 0–8 · peripheral VC

周邊動脈鈣化 · 髂/股/橈/指(4區)× 左右(2)× 有=1 = 0–8

CT — CACS

Agatston score · 面積 × 密度係數 · most sensitive

冠狀動脈鈣化 · HU 130–199=1, 200–299=2, 300–399=3, ≥400=4

Functional — PWV

Carotid-femoral PWV · arterial stiffness / CV risk

動脈硬化度 · 頸–股距離 ÷ 脈波傳導時間(m/s)· >10 m/s = 異常

Prognostic weight

2–4×

CV mortality in dialysis patients with high VC burden vs. low.

KDIGO 2017 (3.3.1)

Lateral abdominal X-ray is a reasonable CT alternative to detect VC. (2C)

Find it once — it changes how you weigh every subsequent Ca, P, Vit D, and binder decision.

III · Vascular calcificationBone–vessel axis

26Vervloet M & Cozzolino M, Kidney Int 2017

One system, two endpoints

Treating bone protects the vessel.

Bone · 骨骼

↑ High turnover

Excess Ca & P released into blood → vessel loading

↓ Low turnover · adynamic

Cannot buffer Ca load → Ca spills to vessel wall

Adynamic bone + Ca loading = highest VC risk

⇌

Ca ↑

P ↑

FGF-23 ↑

Klotho ↓

Vessel · 血管

VSMC trans-differentiation

Smooth muscle → osteoblast-like; loss of MGP, PPi, fetuin-A

↑ Arterial stiffness

Intimal & medial calcification → ↑ CV events & mortality

Optimising bone turnover is not just about fracture prevention — correcting adynamic bone is associated with slower VC progression.

III · Vascular calcificationClinical impact of VC

27Kauppila LI et al, Atherosclerosis 1997; London GM et al, NDT 2003; Foley RN et al, AJKD 1998

Why it matters · 臨床後果

Stiff vessels steal from the heart.

Hemodynamic cascade

Medial calcification → ↑ Arterial stiffness

↑ Pulse wave velocity · loss of Windkessel buffer function

↑ Pulse pressure → LVH → HFpEF

↑ LV afterload; ↓ diastolic BP → subendocardial ischaemia, arrhythmia

Intimal calcification → Plaque instability

Atherosclerotic lesions more prone to rupture → ACS, stroke

Outcome data · 腎臟病患

~50%

of HD patient deaths are cardiovascular

10–30× higher CV mortality than age-matched general population

Aortic calcification score predicts CV death independently

Kauppila score ≥ 7 → ↑ all-cause & CV mortality in ESRD

PWV independently predicts mortality in CKD

Each 1 m/s rise in aortic PWV → ↑14% CV mortality risk

Vascular calcification is not a bystander — it is a direct mediator of the excess cardiovascular mortality seen in CKD.

III · Vascular calcificationEndogenous inhibitors

28Luo G et al, Nature 1997 (MGP); Ketteler M et al, Lancet 2003 (fetuin-A); Lomashvili KA et al, JASN 2005 (PPi); Hu MC et al, JASN 2011 (Klotho)

What normally protects vessels

CKD dismantles the anti-calcification system.

MGP

Vit K–dependent local brake

Inhibits local crystal growth.

dp-ucMGP = dephosphorylated–uncarboxylated MGP

CKD: ↑ dp-ucMGP = inactive MGP, vascular Vit K deficit

Fetuin-A

Circulating CPP chaperone

Buffers Ca-P; falls with inflammation.

CKD: ↓ fetuin-A → ↓ buffering

Pyrophosphate

Endogenous crystal blocker

Blocks hydroxyapatite growth.

ENPP1 = ectonucleotide pyrophosphatase/phosphodiesterase 1 (makes PPi from ATP)

CKD: ↓ ENPP1; ↑ ALP degrades PPi

Klotho

FGF-23 co-receptor

Supports phosphate handling; anti-calcific.

CKD: falls early

Simultaneous loss of all four inhibitors creates a calcification-permissive milieu — even before mineral levels visibly rise on lab tests.

III · Vascular calcificationCalciphylaxis · CUA

29Nigwekar SU et al, NEJM 2018; Brandenburg VM et al, Nat Rev Nephrol 2018; Sinha S et al (CALCIPHYX trial), eClinicalMedicine 2024

Extreme form · 急性重症

Calciphylaxis — VC at its most lethal.

Calcific Uremic Arteriolopathy (CUA)

Subcutaneous arteriole calcification → occlusion → painful ischaemic skin necrosis. Incidence 1–4%; mortality 40–80%, often from sepsis.

Risk factors

Mineral imbalance

↑ Ca/P · SHPT · excess Ca or active Vit D

Warfarin use

↓ Vit K–dependent MGP activation

Patient factors

Female · obesity · DM · low albumin · liver disease

Lesion distribution

Proximal trunk/thigh lesions = worse prognosis

Management

Stop / reduce

Warfarin · Ca-based binder · excess active Vit D

Optimise dialysis

Adequate HD · ↓ dialysate Ca · control P · avoid hyperCa

Add / coordinate

Sodium thiosulfate (STS) 25 g IV 3×/wk, last 30–60 min of HD · cinacalcet if SHPT

Wound care · pain control · infection management

SNF472 (CALCIPHYX): neutral for wound healing and pain; numerically fewer deaths.

Think calciphylaxis early: painful, violaceous, indurated skin lesions in a dialysis patient with warfarin or uncontrolled mineral balance — biopsy confirms, early action saves lives.

IV · TreatmentTreatment targets · BCS

31KDIGO 2017 CKD–MBD guideline

CKD–MBD · 生化檢測標準

The four numbers — NTUH target + trend.

Analyte	Normal	NTUH target	Note
Ca 血鈣	2.12 – 2.58 mM 8.5 – 10.3 mg/dL	= normal range	Interpret albumin-corrected / ionized Ca when needed.
P 血磷	2.5 – 5.0 mg/dL	3.5 – 5.5 mg/dL	NTUH practical range; act on persistent elevation and trend.
iPTH	15 – 68 pg/mL	約 150 – 650 pg/mL	≈2–9× assay ULN; act on marked change, not a single value.
25(OH)D 維生素D	25 – 80 ng/mL	≥ 30 ng/mL (充足) / ≥ 20 可接受	NTUH pragmatic target; KDIGO has no CKD-specific numeric target.

NTUH targets are practical local targets. ★ KDIGO 2017: measure 25(OH)D selectively, correct deficiency / insufficiency using general-population strategies, and base Ca / P / PTH treatment on serial values considered together.

IV · TreatmentTreatment philosophy · 個人建議

Guiding principles

Treat patients, not Ca × P.

BCS first · diagnose by the numbers

Bone disease is hard to confirm — biopsy is rare. Combine biochemistry with clinical inference.
Diet control for (almost) every dialysis patient

Phosphate-additives, protein source, and adherence drive the lab numbers.
Read each value, then read the whole picture

Know what the patient is already on — dose, pill count, dialysate. Adjust stepwise; follow the trend. Don't fixate on Ca × P.
Treat the parathyroid & the bone

Manage the symptoms and the disease — not just the analyte.
Look for VC — let it tighten every Ca decision

Once vascular calcification is documented (lateral X-ray, Kauppila), shift away from Ca-based binders, lower dialysate Ca, and reassess active Vit D dosing.

IV · Targeting VCStrategy · five levers

33KDIGO 2017 CKD–MBD guideline

Targeting vascular calcification

Five places to push.

Established VC is largely irreversible — so the goal is to slow progression. Every CKD-MBD decision can be re-framed as "does this add to, or subtract from, the vascular Ca-P load?"

Lower P ★

A major modifiable lever.

Diet · additives · binders · NHE3 inhibitor (tenapanor) · adequate dialysis.

Limit Ca load

Restrict Ca-binder dose · cautious active Vit D · individualised dialysate Ca.

Control PTH

Choose calcimimetic, Vit D analog, or both from Ca / P / PTH trends.

Boost protectors

Mg · Vit K: promising mechanisms, but not routine anti-VC therapy.

Mg: serum level guides dialysate & binder. Vit K: no routine assay — INR will not show it.

Novel direct anti-VC

SNF472: investigational; surrogate imaging data, no hard-outcome indication.

IV · Targeting VCBinders & calcimimetics — does it change VC?

34Treat-to-Goal 2002 · DCOR 2007 · ADVANCE 2011 · EVOLVE 2012 · IMPROVE-CKD 2020 · LANDMARK 2021

Evidence · what the trials show

The Ca-vs-non-Ca question.

Trial	Comparison	VC endpoint	Result	Signal
Treat-to-Goal Chertow 2002	Sevelamer vs Ca-based	CACS & aortic CT	+	Less CACS progression with sevelamer
DCOR Suki 2007	Sevelamer vs Ca-based	All-cause mortality	—	Neutral; signal in age ≥ 65 subgroup
ADVANCE Raggi 2011	Cinacalcet + low-dose Vit D vs Vit D alone	CACS, aortic CT	+	Attenuated CACS progression
EVOLVE Chertow 2012	Cinacalcet vs placebo (HD, SHPT)	CV death & MACE	±	Neutral (ITT); signal in lag-censored analysis
IMPROVE-CKD Toussaint 2020	Lanthanum vs placebo (CKD 3b–4)	PWV, aortic CT	—	Neutral — P-lowering pre-dialysis did not slow VC
LANDMARK Ogata 2021	Lanthanum vs Ca carbonate (HD)	Composite CV events	—	No difference between binder types

Take-home · Some non-Ca binder trials slowed VC imaging progression, but definitive CV-outcome benefit remains unproven. Select binder and PTH therapy from Ca / P / PTH trends and total Ca load.

Binders · 非鈣 — sevelamer · 碳酸鑭 lanthanum · 檸檬酸鐵 ferric citrate · sucroferric oxyhydroxide ｜含鈣 — 醋酸鈣／碳酸鈣｜鋁劑限短期

IV · Targeting VCEmerging — Magnesium · Vit K · SNF472

35MAGiCAL-CKD · JASN 2023; iPACK-HD · NDT 2023; VitaVasK · CKJ 2022; CALIPSO · Circulation 2020

What's next

Emerging anti-calcification approaches.

Magnesium

Mg²⁺

Mechanism: competes with Ca for crystal nucleation · stabilises CPP · lengthens T50.

Evidence: low serum Mg predicts mortality & VC in dialysis. MAGiCAL-CKD — Mg supplementation did not slow CACS progression in CKD 3–4 (neutral, JASN 2023).

Not routine VC therapy: consider only under local protocol with Mg monitoring; avoid hypermagnesaemia.

Vitamin K

K1 / K2

Mechanism: activates MGP via γ-carboxylation — MGP is the local VC brake.

Evidence: dp-ucMGP elevated in CKD = subclinical Vit K deficiency. VitaVasK · iPACK-HD · K4Kidneys (trials mostly K1) — biomarker improves; hard VC endpoints mixed-to-neutral.

Not routine VC therapy. Do not supplement Vit K in a patient on warfarin without anticoagulation oversight.

SNF472

IP6

Mechanism: IV myo-inositol hexaphosphate (phytate) — binds growing hydroxyapatite crystals, blocks growth.

Evidence: CALIPSO — slowed coronary & aortic valve CACS progression in HD over 52 wk. Calciphylaxis trial neutral on primary endpoint.

Investigational: not approved for VC and without demonstrated hard-outcome benefit.

Promising biology, but clinical outcomes and approvals remain to be established.

IV · Targeting boneRenal osteodystrophy — treatment

36KDIGO 2017 CKD-MBD guideline; Jamal SA et al, JBMR 2011 (denosumab in CKD); Block GA et al, JAMA 2017 (etelcalcetide)

ROD · 骨骼疾病治療

Treat bone by its type, not just the PTH.

Low turnover · Adynamic

Goal: let PTH rise toward target — stop suppressing further

Reduce Ca load: non-Ca binder · dialysate Ca 1.25 mmol/L

If PTH oversuppressed: reduce active Vit D / cinacalcet

Never raise P deliberately: adynamic bone cannot buffer P → VC risk↑.

High turnover · SHPT

Calcimimetics — ↓ PTH, Ca, P; cinacalcet PO / etelcalcetide IV

Active Vit D — calcitriol / paricalcitol; monitor Ca & P

Combination — complementary; permits lower doses of each

PTX — refractory SHPT despite maximal therapy; consider if persistent iPTH >800, uncontrolled Ca/P or progressive VC

Fracture prevention · 骨折預防 = 建議骨質疏鬆治療

Denosumab (RANKL inhibitor) — not preferred in ESRD. Consider only after specialist CKD-MBD / turnover assessment; correct hypoCa and closely monitor Ca for weeks after dose; avoid if adynamic bone suspected.

Bisphosphonates — CKD 1–3 with normal PTH: as general population; CKD 4–5D: individualise by CKD-MBD severity, fracture risk and possible bone biopsy.

Bone biopsy is the gold standard for ROD typing; in practice, PTH trend + ALP + clinical context guide the decision.

V · CasesLong-term anuric HD · Patients 1 – 8

舉例 · clinical decisions

Eight patients, eight different moves.

All long-term, anuric HD patients on diet control. Labs alone don't decide — clinical context, trend, and medication history drive the move.

Pt	Ca (mM)	P (mg/dL)	iPTH (pg/mL)	Treatment suggestion
1	1.90	5.7	500	Ca-based binder (low Ca) ≥ non-Ca binder
2	2.20	6.0	350	Non-Ca binder > Ca-based binder
3	2.20	5.3	900	Active Vit D or calcimimetics
4	2.70	5.3	350	Low-Ca dialysate + ↓ Ca binder dose (or switch to non-Ca)
5	2.70	6.5	350	Low-Ca dialysate + non-Ca binder
6	2.70	6.5	1000	Calcimimetics + low-Ca dialysate ± non-Ca binder or consider PTX
7	1.90	2.5	650	Active Vit D
8	1.90	2.5	30	Stop binder · diet ± high-Ca dialysate · (post-PTX: high-Ca dialysate + Ca + Vit D)

HIGH P

P > 5.5 — pick binder by Ca status.

HIGH Ca

Ca > 2.58 — stop Ca load, lower dialysate Ca.

HIGH PTH

iPTH > 600 — Vit D or calcimimetics. (See Ca/P)

Same numbers, different patient → different plan. Trend, medications and clinical state must inform the move.

ClosingKey takeaways · 重點回顧

Key takeaways

What to carry home.

VC strongly predicts cardiovascular risk

CV mortality is substantial in dialysis. Medial calcification is the CKD-specific pattern.

Ca-P drives VC actively

High P switches VSMC to osteoblast-like cells. Not passive precipitation — a programmed phenotype change.

Control the BCS numbers first

P · Ca · PTH — diet, binders, dialysate, adequate dialysis. Doable today; the rest is not yet routine.

Look for VC — it informs risk and care

Lateral abdominal X-ray or echocardiography are reasonable CT alternatives. Known VC should tighten Ca-load decisions.

Treat bone by type; limit mineral burden

Adynamic bone: ↓ Ca load, let PTH recover. SHPT: individualise calcimimetic / Vit D analog / combination. Restrict Ca-binder dose.

Emerging therapies — and know calciphylaxis

Mg · Vit K · SNF472 remain investigational for VC. Painful ischaemic skin in dialysis: urgent multidisciplinary assessment; review warfarin, optimise wound/pain/infection care, consider STS case-by-case.

鈣磷失衡 與 血管鈣化