1

1. Parathyroid gland function and
dysfunction in dialysis patients
Amr El-Husseini Mohamed
MD, FACP, FASN
Professor of Medicine
Medical Director
University of Kentucky
July 25th 2018

2. Disclosure
• Nothing to disclose
• Salaried UK employee

3. How many organs in our body
do we have 4 copies of ?

4. Parathyroid Gland

6. Amount of daily PTH secretion
9,43kDa (PTH molecaular weight) = 1.57 exp-08 pg/molc
50 pg/mL/ 1.57 exp-08 pg/molecules = 3,184 exp 6 molecules
3184 millions of PTH molecules in 50pg/mL.
3184.000.000 X 3500 X 6 X 24
1.337.280.000.000.000 Molecules

7. Why does PTH go up
in our patient?

10. What is the order of sequences
• Hyperphosphatemia
• Hypocalcemia
• Decrease Calcitriol level
• Increase PTH level
• Increase FGF-23 level

13. Calcitriol Decline and iPTH Elevation
as CKD Progresses
N = 150.
iPTH = intact PTH.
eGFR (mL/min/1.73 m2)
152535455565758595105
100
200
300
400
0
10
20
30
40
50
iPTH(pg/mL)
Calcitriol
1,25(OH)2D3(pg/mL)
Stage 3
7.4 million
Stage 2
5.7 million
Stage 4
300,000
CKD Stage 1
5.6 million
25
65
Low-Normal
Calcitriol
High-Normal
PTH
© 2005 The Johns Hopkins University School of Medicine.

15. Proceedings of the National Academy of Sciences. 1963; 49: 613-617
Berson et al., discovered single polyclonal
antibody against epitopes in the carboxy-
terminal end of the PTH molecule.
This was an innovation and opened the
door for a revolution in PTH
measurements.

18. Kevin Martin DiaSorin 2015
900
800
700
600
500
400
300
200
100
Total I-PTH = 1000 pg/ml

20. El-Husseini et al. (Semin Nephrol 2018, in press)

21. El-Husseini et al. (Semin Nephrol 2018, in press)

23. Why do we need to
treat SPTH ?

26. CKD-MBD

27. Population Attributable Risk of All
Cause Mortality in CKD 5D
• 17.5% Mineral metabolism abnormalities
(Phosphorus > 5.0 mg/dl, Calcium >
10 mg/dl, intact PTH > 600 pg/ml)
• 11.3% Anemia (hgb < 11 g/dl)
• 5.1% Inefficient Dialysis (URR < 65%)
We should be able to significantly improve
mortality of CKD patients by improving
control of CKD-MBD.
Block et al JASN 2004

28. Vascular Calcification and CKD
Patient Without CKD
Intimal Calcification
Secondary to
Atherosclerosis
Medial Calcification
Secondary to CKD
Patients With CKD
Rib
Vertebra
EBCT Indicating Coronary
Calcification
Raggi P. Clin Nephrol. 2000;54:325-333.
EBCT=electron beam computed tomography.

31. Renal osteodystrophy pattern based on bone biopsy.
K/DOQI-recommended iPTH levels do not prevent LTB disease in HD patients
Barreto et al., Kidney International, 2008
82%
64%
37%
60%
37%
62%

32. Renal osteodystrophy: Analysis of 630
bone biopsies
Malluche et al., JBMR 2011
40%
36%
62%
20%
PTH level was not a significant predictor of BT in Blacks.
58%
24%
18%

34. Tentori et al., AJKD 2015

35. Sprague et al., AJKD 2016

36. Felix Mandl in Vienna, performed the first documented
parathyroidectomy in 1925 on a 34-year-old man with
compensatory parathyroid hyperplasia in OFC

37. Parathyroidectomy improves laboratory
parameters in resistant hyperparathyroidism
with the assumption that clinical outcomes
will also improve.
However, no RCT to demonstrate the
benefits of parathyroidectomy.

38. Floege et al., NDT 2011
iPTH and mortality

39. What is a successful
parathyroidectomy ?
A decrease of iPTH levels > 80 %
A decrease of iPTH levels > 90 %
No need for another surgery

40. PTH levels were not significantly lower in the TPTX group until 36 months
MeanPTHatdischarge
54ng/L
MeanPTHat3years
24versus75ng/L
Schlosser et al., Ann Surg. 2016
52
48
PTH was < 75 ng/L in >90 %

41. Successful PTX was defined if iPTH was <300 pg/mL
Zhang et al., Sci Rep. 2016
90%
10%
501 patients

42. iPTH levels after PTx
0
100
200
300
400
500
600
700
800
900
1000
Category 1
Preop iPTH
Postop iPTH
3 months iPTH147 pg/mL
16–498 47 pg/mL
1–515
Roshan et al., Clin Otolaryngol 2006
932 pg/mL
58–1808
Preop iPTH Postop iPTH 3 Months iPTH

43. El-Husseini et al. (Nephron Clinical Practice, 2018)
31 % of the patients were readmitted within 90 days
mostly because of hypocalcemia (74%).
> 80% of patients had iPTH < 150 pg/mL overtime
N = 87

44. Do we need Bone biopsy prior to PTX ?
Prior to PTX, aluminum toxicity and adynamic bone disease should be
excluded particularly if PTH is not severely elevated.
Parathyroidectomy can worsen symptoms of aluminum and nonaluminum-
related adynamic bone disease, especially if hypoparathyroidism is induced.
El-Husseini and Sawaya, Semin Dial. 2014

47. May 2017

48. PLoS One. 2017 Apr 6;12 (4): e0174811

49. Tentori et al., AJKD 2015

50. 89% had ≥ 30% reduction in PTH.
A mean 53.6% decrease in PTH level.
Bushinsky et al., Am J Nephrol. 2015
Etelcalcitide

51. Benefits
Cure
Definitive
Less expensive
Avoid long term
meds SE
Minimally invasive
Risks
Hypoparathyroid
No return
Trash vital organ
Needs long term
meds
Complications

52. No RCT
Need long-term follow up after PTX
Assay and target PTH levels in ESRD
Be ready to treat hypoparathyroidism

53. Your enemy today can be your friend tomorrow. Hopefully, we are not killing our
tomorrow's friend.