Abstract: SA-PO705
An Examination of Multiple Explanations for Secondary Hyperparathyroidism
Session Information
- Bone and Mineral Metabolism: Clinical - II
October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Bone and Mineral Metabolism
- 402 Bone and Mineral Metabolism: Clinical
Authors
- Phelps, Kenneth R., Stratton VAMC, Albany, New York, United States
- Mason, Darius, Methodist South Hospital, Memphis, Tennessee, United States
Background
We have advanced the tradeoff-in-the-nephron hypothesis to explain the evolution of secondary hyperparathyroidism (SHPT) in CKD (Nutrients 2017;9:pii:E427). The hypothesis states that a high phosphate (P) concentration in the cortical distal nephron ([P]CDN) limits availability of calcium (Ca) for reabsorption and necessitates high [PTH] for maintenance of normocalcemia. With assumptions, P excreted per volume of filtrate (EP/Ccr) is a surrogate for [P]CDN to which [PTH] can be compared. In the present study, we used contemporaneous data to assess our hypothesis and others.
Methods
Fasting specimens of serum (s), plasma, and urine (u) were obtained from 30 patients with stages 3 or 4 CKD (mean eGFR 29.5 mL/min/1.73m2). Concentrations of creatinine ([cr]), P, Ca, and ionized calcium ([Ca]i) were measured with standard methods. [PTH]1-84 and intact [FGF23] were measured with ELISAs (Scantibodies and Immutopics), [25OHD] with an enzyme immunoassay (immunodiagnosticsystems), and [1,25(OH)2D] with a radioimmunoassay (Labcorp). EP/Ccr and ECa/Ccr were calculated as [P]u[cr]s/[cr]u and [Ca]u[cr]s/[cr]u. Simple linear regressions were performed to examine theories of SHPT (see table).
Results
[PTH] varied directly with 100/eGFR, ECa/Ccr, [FGF23], and EP/Ccr. Other regressions were not significant.
Conclusion
The direct relationship of [PTH] to ECa/Ccr undermines the theory of skeletal resistance to PTH. The relationship to [FGF23] probably reflects dependence of FGF23 synthesis on PTH (Kidney Int 2017;92:165). The regression of [PTH] on EP/Ccr supports the tradeoff-in-the-nephron hypothesis. The regression also explains the inverse relationship of [PTH] to eGFR and the historic observation that influx of P determines [PTH] in CKD. Our data do not support other explanations for SHPT.
| EXPLANATION FOR INCREASED PTH SECRETION | REGRESSION(S) EXAMINED | R2 | p |
| CKD causes SHPT | [PTH] on 100/eGFR | 0.33 | < 0.001 |
| Original tradeoff hypothesis (in plasma) | [PTH] on [Ca]i;[PTH] on [P]s | 0.06; 0.09 | 0.21; 0.11 |
| Skeletal resistance to PTH | [PTH] on [Ca]i; [PTH] on ECa/Ccr | 0.06; 0.12 | 0.21; 0.015 |
| Deficiency of 1,25(OH)2D | [PTH] on [1,25(OH)2D] | 0.03 | 0.34 |
| Direct effect of hyperphosphatemia | [PTH] on [P]s | 0.09 | 0.11 |
| Parent vitamin D insufficiency | [PTH] on [25OHD] | 0.001 | 0.85 |
| Loss of suppression by FGF23 | [PTH] on [FGF23] | 0.13 | 0.05 |
| Tradeoff in the nephron | [PTH] on EP/Ccr | 0.28 | 0.003 |
Funding
- Veterans Affairs Support – Sanofi-Genzyme