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2017 ; 24
(2
): 107-116
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The Tubulointerstitial Pathophysiology of Progressive Kidney Disease
#MMPMID28284376
Schnaper HW
Adv Chronic Kidney Dis
2017[Mar]; 24
(2
): 107-116
PMID28284376
show ga
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.