The Tubulointerstitial Pathophysiology of Progressive Kidney Disease

H. William Schnaper*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

50 Scopus citations


Accumulating evidence suggests that the central locus for the progression of CKD is the renal proximal tubule. As injured tubular epithelial cells dedifferentiate in attempted repair, they stimulate inflammation and recruit myofibroblasts. At the same time, tissue loss stimulates remnant nephron hypertrophy. Increased tubular transport workload eventually exceeds the energy-generating capacity of the hypertrophied nephrons, leading to anerobic metabolism, acidosis, hypoxia, endoplasmic reticulum stress, and the induction of additional inflammatory and fibrogenic responses. The result is a vicious cycle of injury, misdirected repair, maladaptive responses, and more nephron loss. Therapy that might be advantageous at one phase of this progression pathway could be deleterious during other phases. Thus, interrupting this downward spiral requires narrowly targeted approaches that promote healing and adequate function without generating further entry into the progression cycle.

Original languageEnglish (US)
Pages (from-to)107-116
Number of pages10
JournalAdvances in Chronic Kidney Disease
Issue number2
StatePublished - Mar 1 2017


  • CKD
  • Fibrosis
  • Proximal tubule
  • Remnant nephron

ASJC Scopus subject areas

  • Nephrology


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