Kidney Week

Abstract: SA-PO299

Low Expression of Renal Claudin-2 Increases Medullary Pro-Inflammatory Macrophages and Calcification in Nephrectomy Patients with a History of Urinary Stone Disease

Session Information

• Bone and Mineral Metabolism: Stones, Calcifications, Case Reports
  November 04, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Bone and Mineral Metabolism

• 502 Bone and Mineral Metabolism: Clinical

Authors

• Jayachandran, Muthuvel, Mayo Clinic College of Medicine and Science, Rochester, Minnesota, United States

Muthuvel Jayachandran,

• Delbusso, Miles, Mayo Clinic College of Medicine and Science, Rochester, Minnesota, United States

Miles Delbusso,

• Herrera Hernandez, Loren Paola, Mayo Clinic College of Medicine and Science, Rochester, Minnesota, United States

Loren Paola Herrera Hernandez,

• Haskic, Zejfa, Mayo Clinic College of Medicine and Science, Rochester, Minnesota, United States

Zejfa Haskic,

• Rule, Andrew D., Mayo Clinic College of Medicine and Science, Rochester, Minnesota, United States

Andrew D. Rule,

• Koo, Kevin, Mayo Clinic College of Medicine and Science, Rochester, Minnesota, United States

Kevin Koo,

• Lieske, John C., Mayo Clinic College of Medicine and Science, Rochester, Minnesota, United States

John C. Lieske,

Background

The transmembrane protein claudin-2 (Clnd2) is highly expressed in the proximal tubule and descending thin limb where it is key for ~70% of filtered Ca²⁺ reabsorption. Men with a rare missense mutation in Clnd2 manifest hypercalciuria and urinary stone disease (USD). However, the relationship of Clnd2 expression to renal calcification and interstitial cellular responses is not known. Thus, we examined Cldn2 expression, interstitial calcification, and pro- and anti-inflammatory macrophages (Mφ’s) in nephrectomy samples from patients with and without a USD history.

Methods

Non-cancerous kidney tissue sections from patients with (n=31 stone formers (SFs); 10F/21M) and without (n=50 non-stone formers (NSFs); 16F/34M) a history of USD were used for immunohistochemical analyses. Data are presented as median (25^th, 75^th percentile) and analyzed by Wilcoxon rank-sum test to identify statistically significant (P<0.05) differences between groups.

Results

Expression of Clnd2 protein in both cortex and medulla of kidneys was significantly (P=0.02) lower in SFs than NSFs. Renal medullary calcification (% calcification) and populations of M1 Mφ’s (proinflammatory) were significantly (p<0.001) greater in SFs. There were no differences in the renal tissue population of M2 Mφ’s (anti-inflammatory), age, body mass index, hypertension before surgery, serum creatinine, and eGFR between groups.

Conclusion

These results suggest that SFs have decreased expression of Clnd2 protein in the proximal tubule and thin descending limb of Henle’s loop. This in turn may increase the formation of interstitial calcifications and populations of pro-inflammatory Mφ’s in USD formers. NIDDK (DK135097) and Mayo Foundation.

Funding

• NIDDK Support