Kidney Week

Abstract: TH-PO0113

Proteomic Discovery of Urinary Myoglobin as a Noninvasive Biomarker for Chronic Benign Proteinuria Caused by CUBN Variants

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

• Inoki, Yuta, Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Hyogo Prefecture, Japan

Yuta Inoki, MD, MEd

• Horinouchi, Tomoko, Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Hyogo Prefecture, Japan

Tomoko Horinouchi, MD, PhD

• Sakakibara, Nana, Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Hyogo Prefecture, Japan

Nana Sakakibara, MD, PhD

• Nishimura, Ryo, Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Hyogo Prefecture, Japan

Ryo Nishimura

• Baba, Minato, Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Hyogo Prefecture, Japan

Minato Baba

• Fujiwara, Ayako, Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Hyogo Prefecture, Japan

Ayako Fujiwara

• Yamamoto, Asahi, Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Hyogo Prefecture, Japan

Asahi Yamamoto, MD

• Kimura, Yuka, Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Hyogo Prefecture, Japan

Yuka Kimura, MD

• Aoyama, Shuhei, Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Hyogo Prefecture, Japan

Shuhei Aoyama, MD

• Ichikawa, Yuta, Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Hyogo Prefecture, Japan

Yuta Ichikawa

• Yamamura, Tomohiko, Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Hyogo Prefecture, Japan

Tomohiko Yamamura, MD, PhD

• Ishimori, Shingo, Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Hyogo Prefecture, Japan

Shingo Ishimori, MD, PhD

• Iijima, Kazumoto, Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Hyogo Prefecture, Japan

Kazumoto Iijima, MD, PhD

• Nagano, China, Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Hyogo Prefecture, Japan

China Nagano, MD, PhD

• Nozu, Kandai, Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Hyogo Prefecture, Japan

Kandai Nozu, MD, PhD

Group or Team Name

• Department of Pediatrics, Kobe University Graduate School of Medicine

Background

Chronic benign proteinuria (PROCHOB) is a tubular disorder caused by biallelic C-terminal CUBN variants. Impaired cubilin-mediated proximal tubular reabsorption causes urinary albumin leakage, resulting in moderate albuminuria. Because conventional tubular markers, including urinary β2-microglobulin (uBMG) and α1-microglobulin, remain unelevated, it closely mimics early-stage glomerular diseases. Despite a highly favorable prognosis requiring only observation without treatment, this misleading clinical profile frequently subjects patients to unnecessary kidney biopsies and ineffective angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers before genetic testing is considered.

Methods

We performed high-throughput aptamer-based urinary proteomics (SomaScan) on a discovery cohort (7 PROCHOB, 7 idiopathic nephrotic syndrome, 6 Alport syndrome) to identify a disease-specific screening biomarker for PROCHOB diagnostics. The top candidate was subsequently validated using a chemiluminescent enzyme immunoassay in an independent cohort of 25 PROCHOB patients, 33 with moderate proteinuric glomerular diseases, 6 with Dent disease, and 10 controls.

Results

Proteomics identified 23 upregulated proteins in PROCHOB; myoglobin was selected for validation as a plausible cubilin/megalin ligand. In the validation cohort, the urinary myoglobin-to-creatinine (uMB/Cr) ratio was significantly elevated in PROCHOB compared to moderate proteinuric glomerular diseases (median 260.5 vs. 2.5 ng/mgCr; P<0.001). uMB/Cr robustly distinguished PROCHOB from these diseases (AUC=0.998); a 22.2 ng/mgCr cutoff yielded 100% sensitivity, 94.0% specificity, 92.6% positive predictive value, and 100% negative predictive value. Although Dent disease also exhibited increased urinary myoglobin, uBMG/Cr perfectly differentiated it from PROCHOB (cutoff 15.23 µg/mgCr; 100% sensitivity and specificity).

Conclusion

We established a highly accurate, noninvasive diagnostic algorithm utilizing a profile of high uMB/Cr and low uBMG/Cr ratios. This reliably differentiates PROCHOB from early-stage glomerular diseases and Dent disease. This algorithm helps prioritize genetic testing and simplifies diagnosis. Ultimately, it allows patients to avoid unnecessary biopsies and treatments, safely guiding them to simple observation.

Funding

• Other NIH Support