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Abstract: SA-PO545

Diagnostic Yield of Exome Sequencing in Early Onset Hypertensive Nephropathy in Adults

Session Information

  • Genetic Diseases: Diagnosis
    November 05, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
    Abstract Time: 10:00 AM - 12:00 PM

Category: Genetic Diseases of the Kidneys

  • 1102 Genetic Diseases of the Kidneys: Non-Cystic

Authors

  • Serre, Justine, Assistance Publique - Hopitaux de Paris, Paris, France
  • Doreille, Alice, Assistance Publique - Hopitaux de Paris, Paris, Île-de-France, France
  • Serveaux Dancer, Marine, Eurofins Biomnis Lyon, Lyon, France
  • Raymond, Laure, Eurofins Biomnis Lyon, Lyon, France
  • Rafat, Cedric, Assistance Publique - Hopitaux de Paris, Paris, Île-de-France, France
  • Mesnard, Laurent, Assistance Publique - Hopitaux de Paris, Paris, France

Group or Team Name

  • Service de néphrologie Hôpital Tenon
Background

Hypertensive nephropathy (HN) is one of the most frequent causes of chronic kidney disease (CKD). However, the very existence of HN has been called into question. Its diagnostic framework is based on non-specific criteria.
Next generation sequencing with exome sequencing (ES) has emerged as a comprehensive tool to detect Mendelian diseases in nephrology. ES has yet to be consistently incorporated in the diagnostic workup of patients with presumed HN.

Methods

We retrospectively collected the ES performed in the context of HN between September 2018 and February 2021. The diagnosis of HN was established if patients had an eGFR of less than 60ml/min/1.73m2, combined with hypertension, if no other cause of kidney disease could be identified, and a urinary protein to creatinine ratio of less than 2.5 was required.

Results

A total of 128 patients (Table 1) were sequenced in the context of HN.We detected pathogenic / likely pathogenic variants in 20 of the 128 patients (16%) encompassing 14 different monogenic disorders with Nephronophthisis and Alport syndrome accounting for more than half of it.
Consanguinity and extra-renal disease possibly linked to the renal phenotype were significantly associated with ES positivity.
The diagnostic yield of ES was lower in patients of African ancestry (8% versus 30% in non-African ancestry patients, p<0.01). There were significantly more variant of uncertain significance in patients with African (56%) compared to non-African ancestry (22%) (p=0.04) but less co-segregation data, with significantly more ES performed in solo, only proband (96%, compared to 80% in non-African ancestry patients, p<0.01).

Conclusion

The high diagnostic yield of ES (16%) in a population of patients thought to have HN casts further doubts on the validity of the existing diagnosis criteria.
Our results argue for more consistent implementation of ES in patients supposed to have HN.

Patient characteristics and diagnostic yield
 All patients
n = 128
Positive results
n = 20
Negative results
n = 108
p
Age, median [Q25-75]
41.5 [35.0; 51.0]
40.0 [31.8; 47.5]
42.0 [36.0; 51.0]
0.37
Sex (male), n (%)
99 (77)
13 (65)
86 (80)
0.16
CKD Stage V – Transplanted, n (%)
86 (67)
17 (81)
69 (64)
0.4
First-degree nephropathy, n (%)
38 (30)
9 (45)
29 (27)
0.1
Consanguinity, n (%)
8 (6.3)
4 (20)
4 (3.7)
0.021
Extra-Renal diseases, n (%)
30 (23)
11 (55)
19 (18)
<0.001
African ancestry, n (%)
84 (66)
7 (35)
77 (71)
<0.01