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Abstract: SA-PO1012

Gene Expression in Kidney Tissue From CKDu Patients in Central America and Sri Lanka

Session Information

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

Category: CKD (Non-Dialysis)

  • 2203 CKD (Non-Dialysis): Mechanisms

Authors

  • Wijkstrom, Julia, Karolinska Institutet, Stockholm, Sweden
  • Schwarz, Angelina, Karolinska Institutet, Stockholm, Stockholm, Sweden
  • Gonzalez, Marvin Antonio, Universidad Nacional Autonoma de Nicaragua Leon, Leon, León, Nicaragua
  • Leiva, Ricardo A., Universidad de El Salvador, San Salvador, El Salvador
  • Cruz, Zulma Carolina, Hospital Nacional Rosales, San Salvador, El Salvador
  • Jayasumana, Channa, Ministry of Health Sri Lanka, Colombo, Western , Sri Lanka
  • Elinder, Carl G., Karolinska Institutet, Stockholm, Sweden
  • Wernerson, Annika, Karolinska Institutet, Stockholm, Sweden
Background

Chronic kidney disease of unknown etiology (CKDu) or Mesoamerican Nephropathy was first reported from Central America and later from other countries such as Sri Lanka and India. CKDu in Central America and Sri Lanka have many clinical and morphological similarities, but if the disease has the same etiology or pathophysiological mechanisms has not been firmly established.
We have previously conducted kidney biopsy studies in El Salvador, Nicaragua and Sri Lanka, where we have stored tissue for RNA-sequencing. In the current study we have analyzed the different gene expression in Central America and Sri Lanka and compared with healthy controls.

Methods

Kidney biopsy tissue stored in RNAlater™ from previous studies in El Salvador (n=7), Nicaragua (n=11), and Sri Lanka (n=10) and control tissue from Swedish living kidney donors (n=11) were microdissected into glomerular and tubulointerstitial fractions and RNA-sequencing was performed.

Results

Principal component analysis displayed a distinct separation of glomerular and tubulointerstitial fractions. RNA profiles of the tubulointerstitial fractions from Central America (El Salvador and Nicaragua) compared to Sri Lanka did not show any significant difference, i.e. genes in the tubules display similar expression. The glomerular fraction displayed some difference in the RNA profile between Central America and Sri Lanka but not as pronounced as between cases and controls. Preliminary results from differentially expressed gene analysis indicates significant differences in genes expression in both glomerular and tubulointerstitial fractions in cases compared to controls. Upregulated genes are involved in inflammation like the complement system and chemokine signaling. Further analysis of the results is ongoing.

Conclusion

Tubulointerstitial fractions in kidney biopsies from Central America and Sri Lanka show a strikingly similar gene expression. However, the glomerular fractions show some differences that will be further explored.
The gene expression profile in this study suggests that the pathophysiological mechanisms behind CKDu in Central America and Sri Lanka are the same and a joint etiology is probable. Preliminary analysis of upregulated genes shows involvement in inflammatory pathways.

Funding

  • Private Foundation Support