Abstract: TH-PO723
Cardiac Oxalosis in Primary Hyperoxaluria
Session Information
- Genetic Diseases of the Kidneys: Non-Cystic - I
October 25, 2018 | Location: Exhibit Hall, San Diego Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidney
- 1002 Genetic Diseases of the Kidney: Non-Cystic
Authors
- Milliner, Dawn S., Mayo Clinic, Rochester, Minnesota, United States
- Pellikka, Patricia A., Mayo Clinic, Rochester, Minnesota, United States
- Mehta, Ramila A., Mayo Clinic, Rochester, Minnesota, United States
- Manggaard, Jennifer, Mayo Clinic, Rochester, Minnesota, United States
- Lieske, John C., Mayo Clinic, Rochester, Minnesota, United States
- Sas, David J., Mayo Clinic, Rochester, Minnesota, United States
- Dehmel, Bastian, OxThera AB, Thousand Oaks, California, United States
- Enders, Felicity T., Mayo Clinic, Rochester, Minnesota, United States
Group or Team Name
- Rare Kidney Stone Consortium
Background
Primary hyperoxaluria (PH) is an inherited disease characterized by increased hepatic production of oxalate (ox). Renal excretion of excess ox causes kidney stones, nephrocalcinosis, and renal damage. As GFR declines plasma ox (Pox) increases and can cause systemic calcium oxalate deposits (oxalosis). Cardiac involvement results in conduction abnormalities and infiltrative cardiomyopathy. However, epidemiology of cardiac oxalosis in PH is not well defined.
Methods
The PH registry of the Rare Kidney Stone Consortium was queried for information regarding cardiac function. Among 128 PH subjects with Pox available prior to transplant, 101 had type 1 (PH1), 14 PH2, and 13 PH3. ECG studies (n=433 from 52 subjects), echocardiograms (n= 92 from 40), Pox (nl < 1.6 umol/L), and urine ox (Uox, nl < 0.46 mmol/24 hrs) at initial evaluation and during follow-up were analyzed. E/e' was used for diastolic function (nl <13). LV strain nl < -18%.
Results
At diagnosis mean (median) age was 18.6 (11.5) yrs, eGFR 75 (65) ml/min/1.73m2, urine oxalate (Uox) 1.9 (1.7) mmol/1.73m2/day, and Pox 21.3 (6.1) umol/L. At diagnosis 1/52 ECGs were abnormal, with atrial fibrillation (afib) in a subject with eGFR 66. Subjects were followed for 14.1 (11.4) yrs. Pox increased as eGFR declined (p<0.0001) as expected. Overall 14/52 PH subjects had 48 abnormal ECGs showing 1st degree or variable AV block (n=6), bundle branch block (3), afib (5), and LVH (4). Abnormal ECG studies did not differ across eGFR groups (p=0.22). Table 1 shows clinical characteristics and echo at last followup.
Conclusion
Using standard clinical tests, most PH subjects demonstrate good cardiac function, even at eGFR < 30 when Pox increases significantly. Whether more sensitive monitoring tools will demonstrate earlier manifestions of cardiac oxalosis remains to be established.
Clinical findings at last follow-up
| eGFR <29, ESRD | eGFR 30-59 | eGFR 60-89 | eGFR > 90 | Total | p value | |
| n=52 | n=19 | n=31 | n=26 | n=128 | ||
| eGFR, mean (SD) | 10.5 (6.3) | 46.8 (7.8) | 72.08 (7.8) | 227 (436) | 76 (211) | <0.0001 |
| Age follow-up (yrs) | 35.5 (19.4) | 38.3 (21.2) | 30.1 (16.4) | 25.8 (14.5) | 32.6 (18.4) | 0.08 |
| Years follow-up | 11.4 (13.3) | 12.8 (12.8) | 15.3 (12.0) | 19.1 (12.4) | 14.1 (13.0) | 0.01 |
| Pox, umol/L | 58.6 (50.2) | 13.9 (26.7) | 4.0 (3.3) | 3.8 (6.8) | 26.9 (41.9) | <0.0001 |
| LV EF, % | 59 (6) | 60 (6) | 57 (9) | 54 (2) | 58 (7) | 0.10 |
| Diastolic function, E/e' | 10.5 (4.6) | 9.6 (2.4) | 11.6 (3.7) | 8.8 (2.5) | 10.6 (3.8) | 0.10 |
| LV Strain, % | -20.6 (0.8) | -19 (2.1) | -18.9 (2.0) | -17.8 (1.9) | -19.2(1.9) | 0.06 |
Funding
- NIDDK Support – OxThera