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Corrigendum Open Access | 10.1172/JCI193824

Crystal deposition triggers tubule dilation that accelerates cystogenesis in polycystic kidney disease

Jacob A. Torres, Mina Rezaei, Caroline Broderick, Louis Lin, Xiaofang Wang, Bernd Hoppe, Benjamin D. Cowley Jr., Vincenzo Savica, Vicente E. Torres, Saeed Khan, Ross P. Holmes, Michal Mrug, and Thomas Weimbs

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Published May 1, 2025 - More info

Published in Volume 135, Issue 9 on May 1, 2025
J Clin Invest. 2025;135(9):e193824. https://doi.org/10.1172/JCI193824.
© 2025 Torres et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published May 1, 2025 - Version history
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Crystal deposition triggers tubule dilation that accelerates cystogenesis in polycystic kidney disease
Jacob A. Torres, … , Michal Mrug, Thomas Weimbs
Jacob A. Torres, … , Michal Mrug, Thomas Weimbs
Research Article Nephrology

Crystal deposition triggers tubule dilation that accelerates cystogenesis in polycystic kidney disease

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Abstract

The rate of disease progression in autosomal-dominant polycystic kidney disease (ADPKD) has high intrafamilial variability, suggesting that environmental factors may play a role. We hypothesized that a prevalent form of renal insult may accelerate cystic progression and investigated tubular crystal deposition. We report that calcium oxalate (CaOx) crystal deposition led to rapid tubule dilation, activation of PKD-associated signaling pathways, and hypertrophy in tubule segments along the affected nephrons. Blocking mTOR signaling blunted this response and inhibited efficient excretion of lodged crystals. This mechanism of “flushing out” crystals by purposefully dilating renal tubules has not to our knowledge been previously recognized. Challenging PKD rat models with CaOx crystal deposition or inducing calcium phosphate deposition by increasing dietary phosphorus intake led to increased cystogenesis and disease progression. In a cohort of patients with ADPKD, lower levels of urinary excretion of citrate, an endogenous inhibitor of calcium crystal formation, were correlated with increased disease severity. These results suggest that PKD progression may be accelerated by commonly occurring renal crystal deposition that could be therapeutically controlled by relatively simple measures.

Authors

Jacob A. Torres, Mina Rezaei, Caroline Broderick, Louis Lin, Xiaofang Wang, Bernd Hoppe, Benjamin D. Cowley Jr., Vincenzo Savica, Vicente E. Torres, Saeed Khan, Ross P. Holmes, Michal Mrug, Thomas Weimbs

×

Original citation: J Clin Invest. 2019;129(10):4506-4522. https://doi.org/10.1172/JCI128503

Citation for this corrigendum: J Clin Invest. 2025;135(9):e193824. https://doi.org/10.1172/JCI193824

The dosing of a drug in the Methods and figure legends was incorrect. The corrected sentences are below.

A high dose of NaOx (70 mg/kg) was initially used to induce acute, severe nephrolithiasis in the mice, which led to rapid, abundant crystal deposition that appeared to be exclusively luminal (Figure 2, A and B).

WT male and female C57BL/6 mice (Charles River Laboratories), 8–10 weeks of age and weighing between 20 and 30 g, were challenged with a single i.p. injection of 0.22 M NaOx in 0.9% saline, sterile filtered and administered at 30 mg/kg (low dose), and euthanized at 6 hours (n = 4), 1 day (n = 12), 3 days (n = 8), and 7 days (n = 10); or at 70 mg/kg (high dose), and animals were euthanized at 3 hours (n = 4) and 1 day (n = 9) to induce acute CaOx crystal deposition.

Eight-week-old Sprague Dawley rats weighing between 200 and 300 g (Charles River Laboratories) were challenged with a single i.p. injection of 0.22 M NaOx in 0.9% saline, sterile filtered and administered at 70 mg/kg and were analyzed after 6 hours (n = 5), 1 day (n = 5), 3 days (n = 5), or 7 days (n = 3).

To induce moderate, reversible crystal deposition, we next administered a low dose of NaOx (30 mg/kg), which resulted in CaOx crystal deposition as early as 6 hours after injection, peaking at 24 hours, with excretion of most crystals by day 3 (Figure 2D).

Figure 2. (A) H&E-stained kidney sections 1 day after administration of 70 mg/kg NaOx, visualized by normal and polarized light microscopy.

Figure 2. (C) Immunoblot of total kidney lysates for p-S6 (Ser235/236), p-STAT3 (Tyr705), and total proteins 3 hours (n = 4) and 1 day (n = 9) after 70 mg/kg NaOx treatment.

Figure 2. (D) Polarized light micrographs of kidney sections from mice treated with 30 mg/kg NaOX, 6 hours (n = 4), 1 day (n = 12), 3 days (n = 8), and 7 days (n = 13) after treatment.

Figure 2. (E) Immunofluorescence staining of p-S6 (Ser235/236) and p-STAT3 (Tyr705) in mice treated with 30 mg/kg NaOx. Images of animals treated with 30 mg/kg NaOx are representative of 5 experiments.

Figure 3. (A) Polarized microscopic images of H&E-stained renal sections from rats treated with 70 mg/kg NaOx, 6 hours (n = 5), 24 hours (n = 5), 3 days (n = 5), and 7 days (n = 3) after treatment.

The authors regret the errors.

Footnotes

See the related article at Crystal deposition triggers tubule dilation that accelerates cystogenesis in polycystic kidney disease.

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