Abstract: SA-PO274
Nephropathic Cystinosis: A Distinct Model of CKD-MBD
Session Information
- Bone and Mineral Metabolism: Calcium, Magnesium, Kidney Stones
November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Bone and Mineral Metabolism
- 402 Bone and Mineral Metabolism: Clinical
Authors
- Florenzano, Pablo, Pontificia Universidad Catolica de Chile, Santiago, Chile
- Ferreira, Carlos R., NHGRI, Bethesda, Maryland, United States
- Jimenez, Macarena, Pontificia Universidad Católica de Chile, Santiago, Chile
- Tella, Sri harsha, University of South Carolina, Columbia, South Carolina, United States
- Gafni, Rachel, NIH, Bethesda, Maryland, United States
- Wolf, Myles, Duke University, Durham, North Carolina, United States
- Gahl, William, National Institutes of Health, Bethesda, Maryland, United States
- Salusky, Isidro B., Mattel Children's Hospital, Los Angeles, California, United States
- Collins, Michael, NIHI, Bethesda, Maryland, United States
Background
Cystinosis is a rare autosomal recessive lysosomal storage disorder. Nephropathic cystinosis (NC) presents with Fanconi syndrome and CKD. Persistent phosphate wasting is a prominent feature; however, its impact on CKD-MBD has not been described. Thus, we compare CKD-MBD in NC (n=53) vs. non-NC (n=97).
Methods
eGFR, Ca, P, PTH, 1,25D, FGF23, and TRP were assessed. C-terminal FGF23 was measured by ELISA (Quidel), S-PTH and 1,25D by immunoassay. Subjects were grouped according to CKD stage; CKD 4 and 5 were analyzed together. Dialysis pts. were excluded. All NC patients were treated with cysteamine, phosphate supplementation, and 1,25D; non-NC with 1,25D and binders as needed. Statistical analysis included Spearman correlations and the Mann-Whitney U test.
Results
Age and eGFR were similar between the groups (Table). In NC across all CKD stages, TRP and FGF23 were lower, and 1,25D higher (Figure). PTH and S-PO4 were lower in NC stage 3. In NC, FGF23 was inversely associated with eGFR (r=-0.30, p<0.05) and positively associated with S-PO4(r=0.53, p<0.001). All hypophosphatemic NC subjects had normal FGF23 levels, independent of eGFR.
Conclusion
NC is characterized by a distinct CKD-MBD, with lower FGF23 and higher 1,25D levels. Persistent phosphate wasting may lead to this phenotype. Such findings may: 1) explain the long-term musculoskeletal complications and 2) support the concept for induction of phosphate excretion in non-NC pts. to lower FGF23 and raise 1,25D levels.
Funding
- NIDDK Support