Kidney Week

Abstract: TH-PO0126

Clinical and Genetic Characterization of an Autosomal Dominant Tubulointerstitial Kidney Disease Brazilian Cohort

Session Information

• Integrative Genomics and Multi-Omics in Noncystic Genetic Kidney Disease
  October 22, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Genetic Diseases of the Kidneys

• 1202 Genetic Diseases of the Kidneys: Non-Cystic (Complex and Non-Cystic Monogenic)

Authors

• Silva, Jukelson Barbosa, Universidade de Sao Paulo, São Paulo, SP, Brazil

Jukelson Barbosa Silva

• Watanabe, Elieser H., Universidade de Sao Paulo, São Paulo, SP, Brazil

Elieser H. Watanabe, MD, PhD

• Murata, Gilson Masahiro, Universidade de Sao Paulo, São Paulo, SP, Brazil

Gilson Masahiro Murata, DrPH

• Neves, Precil D., Universidade de Sao Paulo, São Paulo, SP, Brazil

Precil D. Neves, MD, PhD

• Schlesinger, David, Mendelics, São Paulo, SP, Brazil

David Schlesinger, MD, PhD

• Santos, Bibiana Amelia, Mendelics, São Paulo, SP, Brazil

Bibiana Amelia Santos

• Clementino, Andre, Universidade de Sao Paulo, São Paulo, SP, Brazil

Andre Clementino

• Teles, Milena, Universidade de Sao Paulo, São Paulo, SP, Brazil

Milena Teles, MD, PhD

• Onuchic, Luiz F., Universidade de Sao Paulo, São Paulo, SP, Brazil

Luiz F. Onuchic, MD, PhD

Background

Autosomal dominant tubulointerstitial kidney disease (ADTKD) is the second or third most commonly diagnosed monogenic kidney disease in some populations, however data on its genetic profile and clinical features are scarce in developing countries.

Methods

We performed a retrospective and prospective observational study on patients from a highly admixed Brazilian population with suspected or confirmed ADTKD followed at a single center, and their affected family members. Clinical, laboratory, imaging, and histopathological (in some cases) data were collected. Genetic diagnosis in suspected cases used targeted tests (Sanger sequencing, MLPA, NGS-based panel and MUC1 SNaPshot minisequencing and/or nanopore long-read sequencing) or WES to identify causative variants in UMOD, MUC1, HNF1B, REN, or SEC61A1, as well as in other rare or potentially novel disease-causing genes.

Results

The cohort included 110 patients from 19 families: ADTKD-UMOD (n=80; 12 families), ADTKD-MUC1 (n=22; 3 families), and ADTKD-HNF1B (n=8; 4 families). In ADTKD-UMOD, end-stage kidney disease (ESKD) occurred at 46 (IQR 40-57) years. Gout affected 33.3% of these patients, manifesting at 17.5 (IQR 16-22) years and associating with reduced uric acid fractional excretion (6.5±4.5%). In contrast, ADTKD-MUC1 cases reached ESKD at 51.3 (IQR 37-55) years and did not display gout. ADTKD-HNF1B was associated with diabetes/MODY5 (5/8 patients), pancreatic anomalies (6/8), genital tract malformations (4/8), hypomagnesemia (5/8), and ESKD (1/8 at age 40). UMOD variants included p.Gly55Ser (6 families); p.Tyr286Cys (1); p.Gly88Asp (1); p.Cys248Arg (1); p.Tyr193Cys (1), p.Glu304Asp (1), and p.Asn85Ile (1), classified as likely pathogenic or pathogenic according to ACMG. All MUC1 families presented a 27dupC frameshift variant. Among HNF1B families, half presented whole-gene deletions, while the others harbored the p.Gln182Ter or p.Arg295His variants.

Conclusion

ADTKD-UMOD was the prevailing ADTKD subtype, with early-onset gout as a clinical hallmark, aligning with international cohorts. Half of the ADTKD-UMOD families displayed the p.Gly55Ser variant and all ADTKD-MUC1 families harbored a 27dupC frameshift variant, while half of the ADTKD-HNF1B families had whole-gene deletions. Genetic diagnosis was essential for disease subclassification, avoided kidney biopsy and allowed genetic counseling and evaluation of family members as potential transplant donors.