Piret Lab


Our overall aim is to understand the molecular and cellular changes that occur in kidney proximal tubules in acute kidney injury (AKI) and progression of AKI to chronic kidney disease (CKD).

Specifically, we are investigating the roles of members of the Krüppel-like factor (KLF) family of transcription factors, in controlling cellular metabolism in normal kidney, and during AKI and CKD.

Why is this important?

  • In 2014, there were almost 4 million hospitalizations with AKI in people aged 20 and older
  • Of patients aged 66 and older who were hospitalized with AKI in 2018, >8% died in hospital. Of those that were discharged, the cumulative 1-year incidence of recurrent hospitalization with AKI was >26%, and of death was >31%. Of those who did not have CKD before AKI, >50% went on to develop CKD after 1 year
  • Of patients aged 20 and older that started outpatient dialysis for AKI treatment in 2018, the cumulative incidence of death at 1 year was >34%
  • Patients in the ICU may have an incidence of AKI ranging from 20%–50%
  • There are currently no therapies to treat AKI, reverse its effects, or prevent transition to CKD

Why the proximal tubule?

  • The proximal tubule is the powerhouse for reabsorption of solutes and proteins by the kidney
  • AKI may result from diverse causes such as drugs (e.g. chemotherapeutics), environmental toxins, sepsis, ischemia (lack of oxygen). All of these primarily affect the proximal tubule.
  • Many cellular changes occur in damaged proximal tubules, including changes in morphology, cell cycle, secretome, and cellular metabolism
  • We have shown that proximal tubular KLFs are critical for determining the cellular response to injury
  • Mice lacking proximal tubular KLF6 are protected from AKI whereas mice lacking KLF15 have worsened AKI – our current research aims to understand the mechanisms of these effects

    figure 1                         


Project 1: Role of KLF6 and KLF15 in control of PT cellular metabolism

Our previous data has shown that KLF6 is likely to transcriptionally repress expression of genes involved in branched chain amino acid (BCAA; Val, Leu, Ile) catabolism. and that KLF15 likely cooperates with PPARα to control fatty acid oxidation (FAO). We are studying the mechanisms by which KLF6 and KLF15 may co-operate to regulate BCAA catabolism and FAO, either directly and/or through mTORC1 signaling.

Project 2: Role of BCAA catabolism in severity of and recovery after AKI

BCAA are catabolized in the kidney to generate TCA cycle intermediates, but the significance of these metabolic pathways for kidney function have not previously been explored. We have shown that expression of genes encoding BCAA catabolic enzymes is reduced in various forms of AKI and CKD. We now aim to understand the significance of BCAA catabolism in AKI by undertaking studies in vitro and in vivo to determine whether loss of BCAA catabolism results in increased susceptibility to AKI and/or CKD; and whether activation of BCAA catabolism can protect against AKI and/or CKD.

figure 2



Dr. Piret graduated with an honors degree in Biochemistry (MBiochem) from the University of Oxford in 2003, and went on to gain her DPhil (PhD) with Professor Rajesh Thakker at the University of Oxford.  Her thesis focused on the role of uromodulin in the thick ascending limb of the nephron, and elucidated mechanisms by which uromodulin mutations cause the monogenic renal disorder autosomal dominant tubulointerstital kidney disease. She then stayed in the lab of Prof. Thakker to undertake post-doctoral research, broadening her studies to include mechanisms of the inherited kidney stone disorder Dent’s disease, as well as disorders of calcium homeostasis, including those due to mutations in the calcium-sensing receptor pathway. Dr Piret joined Stony Brook University in 2017.


Horne SJ, Vasquez JM, Guo Y, Ly V, Piret SE, Leonardo AR, Ling J, Revelo MP, Bogenhagen D, Yang VW, He JC, Mallipattu SK. Podocyte-specific loss of Krüppel-Like Factor 6 Increases Mitochondrial Injury in Diabetic Kidney Disease.  Diabetes (2018) 67: 2420-33.

Piret SE, Olinger E, Reed AAC, Nesbit MA, Hough TA, Bentley L, Devuyst O, Cox RD, Thakker RV. Mouse model for inherited renal fibrosis associated with endoplasmic reticulum stress. Disease Models and Mechanisms (2017) 10: 773-86.

Piret SEa, Gorvin CMa, Pagnamenta AT, Howles SA, Cranston T, Rust N, Nesbit MA, Glaser B, Taylor JC, Buchs AE, Hannan FM, Thakker RV. Identification of a G-protein Subunit-11 Gain-of-Function Mutation, Val340Met, in a Family With Autosomal Dominant Hypocalcemia Type 2 (ADH2). J Bone Miner Res (2016) 31: 1207-14. ajoint first authors

Piret SE, Esapa CT, Gorvin CM, Head R, Loh NY, Devuyst O, Thomas G, Brown SDM, Brown M, Croucher P, Cox R, Thakker RV. A mouse model of early-onset renal failure due to a xanthine dehydrogenase nonsense mutation. PLoS One (2012) 7: e45217.

Williams SE, Reed AAC, Galvanovskis J, Antignac C, Goodship T, Karet FE, Kotanko P, Lhotta K, Morinière V. Williams P, Wong W, Rorsman P, Thakker RV.  Uromodulin mutations causing Familial Juvenile Hyperuricaemic Nephropathy lead to protein maturation defects and retention in the endoplasmic reticulum. Hum Mol Genet (2009) 18: 2963-74. [published using maiden name]

Full list of publications: NIH Publications - Piret Bibliography


KidneyCure (American Society of Nephrology) Joseph V. Bonventre Research Scholar Grant (2020-2022)

UAB-UCSD O’Brien Center for Acute Kidney Injury Research Pilot & Feasibility Grant (2018-2020)

Stony Book Department of Medicine Pilot Project Grant (2018)