* Clinical osteoporosis in a CKD–MBD patient is not necessarily histological osteoporosis.
III · BoneDisease spectrum
21Comprehensive Clinical Nephrology
PTH × ALP
Two numbers position the bone.
ALP → bone turnover
High PTH · High ALP
Osteitis fibrosa
SHPT, fracture risk, brown tumours
Low PTH · High ALP
Osteomalacia
Mineralisation defect — Vit D, aluminum
High PTH · Low ALP
Early SHPT
PTH rising, bone not yet fibrotic
Low PTH · Low ALP
Adynamic bone
Over-suppression — Ca-binders, calcimimetics, active Vit D
iPTH → parathyroid drive
III · CardiovascularVascular calcification
22Comprehensive Clinical Nephrology
CV mortality driver
Calcium leaves bone, lands in vessels.
Intimal calcification
Atherosclerotic plaques. Drives ischaemic events.
Medial calcification (Mönckeberg)
Vessel-wall stiffening. ↑ Pulse pressure, LVH.
Valvular & soft-tissue
Aortic / mitral valves; periarticular deposits.
Calciphylaxis (CUA)
Painful skin necrosis. High mortality.
~50%
of mortality on chronic dialysis is cardiovascular.
Drivers: hyperphosphataemia, ↑ Ca × P load, ↑ FGF-23, uremic toxins, oxidative stress. Vascular smooth-muscle cells trans-differentiate to osteoblast-like cells.
III · PathophysiologyBone–vessel axis
23
One system, two endpoints
Treating bone protects the vessel.
Bone
Resorption
High-turnover bone releases Ca/P into blood. Low-turnover (adynamic) bone cannot buffer Ca load.
⇌
Ca · P · FGF-23 · α-Klotho
Vessel
Calcification
VSMC trans-differentiation, loss of inhibitors (fetuin-A, MGP). Stiff vessels, ↑ CV events.
PART IVDiagnosis · 診斷
24
IV
Part four
診斷
KDIGO 2017 · targets · cases
IV · DiagnosisKDIGO 2017 — Calcium
252017 KDIGO CKD–MBD Guideline Update
KDIGO 2017 · 鈣
Calcium — avoid hypercalcaemia.
CKD G3a – G5D
Avoid hypercalcaemia. Mild, asymptomatic hypocalcaemia may be tolerated to avoid Ca loading.
Dialysate Ca
Suggest 1.25 – 1.50 mmol/L (2.5 – 3.0 mEq/L).
Target range · dialysis pt
2.15–2.58mM
≈ 8.5 – 10.5 mg/dL — same range as healthy adults.
IV · DiagnosisKDIGO 2017 — Phosphate
262017 KDIGO CKD–MBD Guideline Update
KDIGO 2017 · 磷
Phosphate — lower toward normal.
Dialysis target
3.5–5.5mg/dL
~ 10 % above the normal-population range (2.5 – 5.0).
Strategy
Lower elevated P toward normal — but don't drive it below.
Binder choice
Restrict the dose of Ca-based binders in adults across the CKD spectrum.
Diet
Consider source of P — limit inorganic / additives first.
IV · DiagnosisKDIGO 2017 — PTH
272017 KDIGO CKD–MBD Guideline Update
KDIGO 2017 · 副甲狀腺
PTH — keep it in the window.
Target on dialysis
2–9×ULN
≈ 150 – 650 pg/mL (assay-normalised). Trend matters more than a single value.
If progressively rising
Evaluate Ca, P, Vit D and dialysate; treat modifiable factors first.
First-line PTH therapy
Calcimimetics, calcitriol/analogues, or both — individualise.
Refractory SHPT
Consider parathyroidectomy after medical failure.
IV · DiagnosisKDIGO 2017 — Vit D & bone
282017 KDIGO CKD–MBD Guideline Update
KDIGO 2017 · 維生素D & 骨
Don't treat 25(OH)D in isolation.
Calcitriol / analogues
Reserve for severe, progressive SHPT in CKD G4–G5. Not for routine use in earlier CKD.
Nutritional Vit D
Correct deficiency as in the general population. 25(OH)D target 25 – 80 ng/mL.
BMD testing
DEXA does predict fracture in CKD G3a – G5D — measure it when results would change management.
Bone biopsy
Reasonable when knowledge of bone histology would alter therapy (e.g. before antiresorptives).
IV · DiagnosisTreatment targets · BCS
29
CKD–MBD · 生化檢測標準
The four numbers to know.
Analyte
Normal
Dialysis target
Note
Ca血鈣
2.15 – 2.58 mM 8.5 – 10.5 mg/dL
= normal range
Avoid hypercalcaemia.
P血磷
2.5 – 5.0 mg/dL
3.5 – 5.5 mg/dL
~ 10 % above normal.
iPTH
15 – 68 pg/mL
150 – 650 pg/mL
2–9× ULN.
25(OH)D維生素D
25 – 80 ng/mL
≥ 25 ng/mL
<10 severe deficiency · >80 overdose.
25(OH)D testing is out-of-pocket in Taiwan (NTD 920).
IV · DiagnosisTreatment philosophy · 個人建議
30
My approach · 個人建議
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.
IV · CasesLong-term anuric dialysis patients
31
舉例 · clinical decisions
Eight patients, eight different moves.
All are long-term, anuric haemodialysis patients on diet control. The single labs alone don't tell us what to do — clinical context does.
For each patient, the goal is to move Ca, P, and iPTH back toward target without creating a worse downstream problem (over-suppression, vascular Ca load, hungry bone).
Treatment levers
Ca-based binders
Non-Ca binders
Active Vit D
Calcimimetics
Dialysate Ca
Diet · DC binder
Parathyroidectomy (PTX)
IV · CasesPatients 1 – 4
32
Patients 1 – 4
When P is high.
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)