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Acute and chronic effects of metabolic acidosis on renal function and structure

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Abstract

Background

Emerging evidence suggests that chronic metabolic acidosis (CMA) may have significant implications in terms of worsening renal disease in CKD patients, but the effect of CMA on renal function and structure has not been fully elucidated.

Method

We studied the acute and chronic consequences of an acid load (AL) on glomerular filtration rate (GFR) and renal histology in C57BL/6 mice. FITC-inulin clearance was performed at several time points; markers of renal fibrosis were studied at mRNA and protein levels; finally, kidney expression of candidate molecules triggering changes in renal function was studied.

Results

Glomerular hyperfiltration occurred within 1–3 days from AL; after 1 week, the GFR returned to baseline and then declined progressively within 15–21 days. The GFR decline was accompanied by the onset of renal fibrosis, as shown by Masson trichrome staining. Markers of renal fibrosis, namely α-smooth muscle actin and collagen-1, increased after 1 day of acid loading in both mRNA and protein levels and remained higher than baseline for up to 21 days. Well-known mediators of renal fibrosis, including transforming growth factor (TGF)-β and the intrarenal renin–angiotensin system (RAS) axis, were increased even before the decline of the GFR.

Conclusion

Acid load caused hyperfiltration acutely and a progressive decline of the GFR chronically; the evidence of renal fibrosis indicates that structural and not only functional renal changes occurred. The concomitant upregulation of TGF-β and intrarenal RAS axis indicates that those factors may be potentially involved in the progression of kidney disease in this setting.

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Author information

Author notes

  1. Gennaro Tammaro and Miriam Zacchia have equally contributed to this paper.

Authors and Affiliations

  1. Division of Nephrology, Department of Cardio-thoracic and Respiratory Sciences, University of Campania “Luigi Vanvitelli”, Naples, Italy

    Gennaro Tammaro, Miriam Zacchia, Enrica Zona, Enza Zacchia & Giovambattista Capasso

Authors
  1. Gennaro Tammaro
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  2. Miriam Zacchia
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  3. Enrica Zona
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  4. Enza Zacchia
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  5. Giovambattista Capasso
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Corresponding author

Correspondence to Miriam Zacchia.

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All applicable international, national and institutional guidelines for the care and use of animals were followed. This article does not contain any studies with humans participants.

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40620_2018_493_MOESM1_ESM.pptx

Supplementary material 1 (PPTX 83 KB). Supplementary figure 1. Acute effect of HCl loading on the GFR. HCl addition to the food caused metabolic acidosis (left panel) and glomerular hyperfiltration (right panel). N = 6. *p < 0.05 versus control.

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Tammaro, G., Zacchia, M., Zona, E. et al. Acute and chronic effects of metabolic acidosis on renal function and structure. J Nephrol 31, 551–559 (2018). https://doi.org/10.1007/s40620-018-0493-3

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  • DOI: https://doi.org/10.1007/s40620-018-0493-3

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