Thread by @sashapannu

1/ Hi #MedTwitter Let’s chat about Chronic Kidney Disease (CKD) - Mineral Bone Disorder (MBD) in pediatric patients. #ASPNFOAM group #NephTwitter #tweetorial #PedNeph
@ASPNeph

2/ What are some consequences of CKD-MBD?

3/ Answer all of the above! What is CKD-MBD? Systemic disorder of mineral & bone metabolism from CKD. Involves ≥1, per 2006 KDIGO:
1. Abnormalities of Ca, phos, PTH, FGF23, vit D metabolism
2. Bone abnormalities
3. Extraskeletal calcification

4/ Beginning CKD stage 3: Hyperphosphatemia, ⬆️ PTH, ⬇️calcitriol, ⬆️FGF23

Prior belief: precipitating event was hyperphosphatemia from ⬇️ filtered load due to a low GFR

More recently: ⬆️ FGR-23 is the initiating event to CKD-MBD 🦴🫘

5/ One of the earliest detectable biomarkers of CKD-MBD is FGF23. FGF23 is a hormone secreted by osteoblasts & osteocytes. FGF23 increases renal excretion of phosphate & inhibits 1-α hydroxylase, decreasing calcitriol synthesis

6/ Calcitriol acts to ⬆️ calcium & phosphate absorption at the small intestine. At the parathyroid gland, hypocalcemia and hyperphosphatemia stimulate PTH. Calcium, 1,25 Vitamin D, & FGF23 each have direct inhibitory effects on PTH secretion

7/ Advancing stages of CKD ⬆️FGF23, PTH, phos but ⬇️calcitriol
🦴FGF23 suppresses PTH secretion but the parathyroid gland becomes resistant to⬆️ FGF23 & PTH levels rise
🦴FGF23 prevents hyperphos in early stages of CKD. Later CKD stages, FGF23 is unable to compensate & phos ⬆️

8/ 🦴Calcitriol deficiency occurs initially from inhibition of 1-α hydroxylase by FGF23
🦴As CKD advances, hyperphos & loss of renal tissue also contribute to ⬇️calcitriol
🦴Calcitriol ⬆️Ca & phos absorption from small intestine, but with ⬇️ calcitriol there is ⬇️Ca absorption

9/⬇️Calcium, ⬇️calcitriol, hyperphos contribute to excessive PTH secretion
⬆️PTH causes calcium mobilization from bone & osteitis fibrosa (high turnover bone disease)
Pic 1 Bone histology high bone turnover
Pic 2 IF high bone turnover. Yellow = double tetracycline labelling

10/ KDIGO guidelines recommend monitoring calcium, phosphate, PTH, & alkaline phosphatase in pediatric patients beginning in CKD stage 2. There are several global and regional guidelines with variable target values.

11/ ESPN Guidelines

12/ Assessment of 🦴 turnover is the most important diagnostic tool for management of CKD-MBD Bone turnover is the process of resorption by osteoclasts followed by formation of new bone by osteoblasts.

13/ Bone biopsy is gold standard to assess🦴turnover Bone biopsies are underutilized bc invasive, laborious, require special equipment/ expertise
🦴Instead use phos, Ca, alk phosp (AP), bone specific AP, PTH, 25VitD
🦴These biomarkers aren't precise predictors of bone histology

14/ ⬆️PTH lead to ⬆️bone turnover & osteitis fibrosa lesions

⬇️PTH levels lead to ⬇️bone turnover. This happens when PTH is excessively suppressed by meds

Advanced CKD or on dialysis➡️require ⬆️PTH to maintain similar level of bone turnover vs those with normal🫘function

15/ PTH is a poor surrogate marker for bone turnover as its secretion varies with changes in Ca++. Thus PTH levels fluctuate rapidly

🦴Bone turnover is a much slower process, with high bone turnover taking weeks to occur & adynamic bone disease taking months to years to occur

16/ CKD-associated hyperphosphatemia treatment ➡️dietary restrictions & phosphate binders

🦴Normal phos for age + PTH is > goal range for CKD stage ➡️ limit dietary phos to Dietary Reference Intake (DRI)

🦴⬆️phos + ⬆️ PTH ➡️limit dietary phosp to 80% of DRI

17/ What if diet alone is insufficient to control hyperphos and/or PTH?

🦴Phos binders ➡️bind to phos in the GI tract forming an insoluble complex or bind phos into a resin

🦴Phos is not absorbed & secreted into the feces

🦴Phos binders are either calcium or non-calcium-based

18/ Newest of the phos binders is ferric citrate. It ⬇️phos & improves iron status

Ferric Citrate & Chronic Kidney Disease in Children (FIT4KiD) study➡️investigating effects of ferric citrate on FGF23 in Peds CKD 3-4 patients

Ferric citrate is hypothesized to ⬇️FGF-23 levels

19/ Tx Secondary Hyperparathyroidism? Calcitriol & other VitD sterols
🦴Calcitriol binds to VitD receptor on the parathyroid glands with ❌feedback on PTH synthesis
🦴In CKD ➡️endogenous calcitriol is ⬇️
🦴Treatment: Calcitriol
🦴Adverse effects of VitD sterols: ⬆️Ca/Phos/FGF23

20/ Cinacalcet (calcimimetic)- also Tx secondary hyperparathyroidism

🦴⬆️sensitivity of calcium-sensing receptor on parathyroid glands to extracellular Ca++ to ⬇️PTH release & levels immediately

🦴Cinacalcet avoids hyperCal, hyperphos, ⬆️FGF23 Adverse effect: Hypocalcemia

21/ FGF23 has other implications for health besides bone mineralization & CKD-MBD
FGF23 levels ⬆️ mortality in patients with & without CKD
Multiple factors stimulate FGF23, including iron deficiency which is common amongst CKD patients

22/ Currently, no guidelines regarding strategies to reduce FGF23 levels in CKD
🦴Phos is a major driver of ⬆️FGF23
🫘Phos reduction may lead to ⬇️FGF23
🦴Dietary phos restriction, phos binders, & intensified dialysis may improve phos status & have beneficial effects on FGF23

23/ Compared to standard dialysis, intensified dialysis & renal transplant have better cardiovascular outcomes for ESRD Peds pts ♥️🩺

Both can improve factors that contribute to cardiovascular disease, like fluid overload, HTN, anemia, secondary hyperparathyroidism, ⬆️FGF23

Thank you for scrolling till the end. Signing off for now .. until next time!! All the past #ASPNFOAM group tweetorials are available for free access at thanks to #ASPNFOAM
@drM_sudha
@nefron1310
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