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Kidney Week

ASN / Education & Meetings / Kidney Week /
Abstract: SA-PO601

Kidney Outcome in Primary Hyperoxaluria Type 3

Session Information

Category: Genetic Diseases of the Kidney

  • 802 Non-Cystic Mendelian Diseases

Authors

  • McIntosh, Mary I., Mayo Clinic, Rochester, Minnesota, United States
  • Harris, Peter C., Mayo Clinic, Rochester, Minnesota, United States
  • Mehta, Ramila A., Mayo Clinic, Rochester, MN, Rochester, Minnesota, United States
  • Olson, Julie B., Mayo Clinic, Rochester, Minnesota, United States
  • Seide, Barbara M., Mayo Clinic, Rochester, Minnesota, United States
  • Enders, Felicity T., Mayo Clinic, Rochester, Minnesota, United States
  • Sas, David J., Mayo Clinic, Rochester, Minnesota, United States
  • Lieske, John C., Mayo Clinic, Rochester, Minnesota, United States
  • Milliner, Dawn S., Mayo Clinic, Rochester, Minnesota, United States

Group or Team Name

  • Rare Kidney Stone Consortium
Background

Primary hyperoxaluria type 3 (PH3) is caused by HOGA1 gene mutations. Little is known of the mechanism of hyperoxaluria, long term outcome, or genotype effects.

Methods

PH3 patients were identified (n=47) from the Rare Kidney Stone Consortium (RKSC) PH Registry and categorized by HOGA1 mutations. In addition to demographics and baseline laboratory data, eGFR and urine oxalate (Uox) were compared at diagnosis (dx) and last followup (f/u). Comparisons between groups were by Chi-square test for categorical variables and Kruskal-Wallis test for continuous variables.

Results

Most frequent mutations were the splicing change p.Leu233_Gly234ins17, n=10 homozygotes (Leu233), and the inframe deletion p.Glu315del, n=9 homozygotes (Glu315). Comparisons were made between these and all other combinations (n = 28). Among PH3 overall, eGFR declined with age (r2=.30, p= .0001). Among patients < 20 yrs of age, median eGFR at dx for Leu233 was 125.3 ml/min/1.73m2 vs. 115.7 in Glu315 and 86.3 among all others (p=0.057).

There were no significant differences among genotype groups for age at dx or f/u yrs [median 4.5(1.1,11.7)]. There was a trend toward lower Uox and higher eGFR in the Leu233 group at dx and at f/u, though statistically significant only for Uox at f/u (p=0.02) and eGFR at dx (p=0.047). Urine HOG did not correlate with urine glycerate in PH3 overall (r=.39, p=0.12).

Conclusion

PH3 patients show decreasing eGFR over time. Lower Uox and higher eGFR trends were seen in Leu233 homozygotes, though patient numbers were small. HOG suppression of GRHPR as a mechanism for the hyperoxaluria, predicted to elevate d-glycerate, is not supported by this data. Further study is needed to understand genotype effects and outcome of PH3.

PH3 Patient Characteristics
 Total (n=47)Leu233 (n=10)Glu315 (n=9)Others (n=28)P
Age at diagnosis (dx), yrs5.8(2.3,19.8)3.8(2.1,4.8)3.2(1.4,46.8)6.9(4.2,27.1)0.15
Uox at dx11.11(0.9,1.4)1.05(0.91,1.33)1.03(0.85,1.12)1.18(0.94,1.44)0.49
UHOG, mg/gm creat276.4(39.7,108.0)102.4(99.2,108.0)42.4(38.6,100.6)44.3(27.7,150.3)0.41
Uglycerate, mg/gm creat33.0(0.83,13.17)23.1(10.3,44.0)3.8(0.66,3.9)1.3(0.15,7.9)0.09
eGFR at dx93.9(67.1,107.4)101.0(94.6,134.6)102.2(74.1,104.2)77.9(62.9,95.0)0.047
Uox at f/u0.98(0.7,1.3)0.62(0.53,0.96)1.06(0.82,1.16)1.13(0.81,1.35)0.03
eGFR at f/u95.1(69.7,109.2)98.0(85.4,133.3)96.6(65.5,104.1)86.2(68.1,108.8)0.40

Values are median(Q1,Q3); 1Uox, mm/BSA/day, normal < 0.45; 2Urine HOG, normal < 5 mg/gm creat; 3Urine glycerate, normal < 55 mg/gm creat <10 yrs of age then <25

Funding

  • NIDDK Support