Abstract
Acute kidney injury (AKI) is a widespread clinical syndrome directly associated with patient short-term and long-term morbidity and mortality. During the last decade, the incidence rate of AKI has been increasing, the repeated and severe episodes of AKI have been recognized as a major risk factor chronic kidney diseases (CKD) and end-stage kidney disease (ESRD) leading to global disease burden. Proposed pathological processes and risk factors that add to the transition of AKI to CKD and ESRD include severity and frequency of kidney injury, older age, gender, genetics and chronic health conditions like diabetes, hypertension, and obesity. Therefore, there is a great interest in learning about the mechanism of AKI leading to renal fibrosis, the ultimate renal lesions of CKD. Over the last several years, a significant attention has been given to the field of renal fibrosis with impressive progression in knowing the mechanism of renal fibrosis to detailed cellular characterization and molecular pathways implicated in tubulointerstitial fibrosis. Research and clinical trial are underway for emerging biomarkers detecting early kidney injury, predicting kidney disease progression and developing strategies to efficiently treat AKI and to minimize AKI progression to CKD and ESRD. Specific interventions to prevent renal fibrosis are still experimental. Potential therapeutic advances based on those molecular mechanisms will hopefully offer promising insights into the development of new therapeutic interventions for patients in the near future.
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References
Afsar B, Afsar RE, Dagel T, Kaya E, Erus S et al (2018) Capillary rarefaction from the kidney point of view. Clin Kidney J 11:295–301
Alge JL, Karakala N, Neely BA, Janech MG, Tumlin JA et al (2013a) Association of elevated urinary concentration of renin-angiotensin system components and severe AKI. Clin J Am Soc Nephrol 8:2043–2052
Alge JL, Karakala N, Neely BA, Janech MG, Velez JC et al (2013b) Urinary angiotensinogen predicts adverse outcomes among acute kidney injury patients in the intensive care unit. Crit Care 17:R69
Al-Lamki RS, Mayadas TN (2015) TNF receptors: signaling pathways and contribution to renal dysfunction. Kidney Int 87:281–296
Anders HJ (2016) Of inflammasomes and alarmins: IL-1beta and IL-1alpha in kidney disease. J Am Soc Nephrol 27:2564–2575
Aydin S, Yanar K, Atukeren P, Dalo E, Sitar ME et al (2012) Comparison of oxidative stress biomarkers in renal tissues of D-galactose induced, naturally aged and young rats. Biogerontology 13:251–260
Baek JH, Zeng R, Weinmann-Menke J, Valerius MT, Wada Y et al (2015) IL-34 mediates acute kidney injury and worsens subsequent chronic kidney disease. J Clin Invest 125:3198–3214
Ballermann BJ, Obeidat M (2014) Tipping the balance from angiogenesis to fibrosis in CKD. Kidney Int Suppl 4:45–52 (2011)
Basile DP (2007) The endothelial cell in ischemic acute kidney injury: implications for acute and chronic function. Kidney Int 72:151–156
Basile DP, Fredrich K, Chelladurai B, Leonard EC, Parrish AR (2008) Renal ischemia reperfusion inhibits VEGF expression and induces ADAMTS-1, a novel VEGF inhibitor. Am J Physiol Renal Physiol 294:F928–F936
Basile DP, Anderson MD, Sutton TA (2012) Pathophysiology of acute kidney injury. Compr Physiol 2:1303–1353
Baum J, Duffy HS (2011) Fibroblasts and myofibroblasts: what are we talking about? J Cardiovasc Pharmacol 57:376–379
Baylis C (1994) Age-dependent glomerular damage in the rat. Dissociation between glomerular injury and both glomerular hypertension and hypertrophy. Male gender as a primary risk factor. J Clin Invest 94:1823–1829
Beausejour CM, Krtolica A, Galimi F, Narita M, Lowe SW et al (2003) Reversal of human cellular senescence: roles of the p53 and p16 pathways. EMBO J 22:4212–4222
Bellomo R, Kellum JA, Ronco C, Wald R, Martensson J et al (2017) Acute kidney injury in sepsis. Intensive Care Med 43:816–828
Bielesz B, Sirin Y, Si H, Niranjan T, Gruenwald A et al (2010) Epithelial Notch signaling regulates interstitial fibrosis development in the kidneys of mice and humans. J Clin Invest 120:4040–4054
Bolignano D, Lacquaniti A, Coppolino G, Donato V, Campo S et al (2009) Neutrophil gelatinase-associated lipocalin (NGAL) and progression of chronic kidney disease. Clin J Am Soc Nephrol 4:337–344
Bonventre JV (2012) Can we target tubular damage to prevent renal function decline in diabetes? Semin Nephrol 32:452–462
Bonventre JV (2014) Primary proximal tubule injury leads to epithelial cell cycle arrest, fibrosis, vascular rarefaction, and glomerulosclerosis. Kidney Int Suppl 4:39–44 (2011)
Bonventre JV, Yang L (2011) Cellular pathophysiology of ischemic acute kidney injury. J Clin Invest 121:4210–4221
Borges FT, Melo SA, Ozdemir BC, Kato N, Revuelta I et al (2013) TGF-beta1-containing exosomes from injured epithelial cells activate fibroblasts to initiate tissue regenerative responses and fibrosis. J Am Soc Nephrol 24:385–392
Canaud G, Bonventre JV (2015) Cell cycle arrest and the evolution of chronic kidney disease from acute kidney injury. Nephrol Dial Transplant 30:575–583
Chang FC, Chou YH, Chen YT, Lin SL (2012) Novel insights into pericyte-myofibroblast transition and therapeutic targets in renal fibrosis. J Formos Med Assoc 111:589–598
Chawla LS, Kimmel PL (2012) Acute kidney injury and chronic kidney disease: an integrated clinical syndrome. Kidney Int 82:516–524
Chawla LS, Amdur RL, Amodeo S, Kimmel PL, Palant CE (2011) The severity of acute kidney injury predicts progression to chronic kidney disease. Kidney Int 79:1361–1369
Chawla LS, Eggers PW, Star RA, Kimmel PL (2014) Acute kidney injury and chronic kidney disease as interconnected syndromes. N Engl J Med 371:58–66
Che R, Yuan Y, Huang S, Zhang A (2014) Mitochondrial dysfunction in the pathophysiology of renal diseases. Am J Physiol Renal Physiol 306:F367–F378
Chen L, Liu BC, Zhang XL, Zhang JD, Liu H, Li MX (2006) Influence of connective tissue growth factor antisense oligonucleotide on angiotensin II-induced epithelial mesenchymal transition in HK2 cells. Acta Pharmacol Sin 27:1029–1036
Chen YT, Chang FC, Wu CF, Chou YH, Hsu HL et al (2011) Platelet-derived growth factor receptor signaling activates pericyte-myofibroblast transition in obstructive and post-ischemic kidney fibrosis. Kidney Int 80:1170–1181
Chou YH, Huang TM, Chu TS (2017) Novel insights into acute kidney injury-chronic kidney disease continuum and the role of renin-angiotensin system. J Formos Med Assoc 116:652–659
Chung AC, Lan HY (2015) MicroRNAs in renal fibrosis. Front Physiol 6:50
Coca SG, Yusuf B, Shlipak MG, Garg AX, Parikh CR (2009) Long-term risk of mortality and other adverse outcomes after acute kidney injury: a systematic review and meta-analysis. Am J Kidney Dis 53:961–973
Coca SG, Singanamala S, Parikh CR (2012) Chronic kidney disease after acute kidney injury: a systematic review and meta-analysis. Kidney Int 81:442–448
Cruz-Solbes AS, Youker K (2017) Epithelial to mesenchymal transition (EMT) and endothelial to mesenchymal transition (EndMT): role and implications in kidney fibrosis. Results Probl Cell Differ 60:345–372
Ding H, Zhou D, Hao S, Zhou L, He W et al (2012) Sonic hedgehog signaling mediates epithelial-mesenchymal communication and promotes renal fibrosis. J Am Soc Nephrol 23:801–813
Fabian SL, Penchev RR, St-Jacques B, Rao AN, Sipila P et al (2012) Hedgehog-Gli pathway activation during kidney fibrosis. Am J Pathol 180:1441–1453
Farris AB, Alpers CE (2014) What is the best way to measure renal fibrosis?: a pathologist’s perspective. Kidney Int Suppl 4:9–15 (2011)
Ferenbach DA, Bonventre JV (2015) Mechanisms of maladaptive repair after AKI leading to accelerated kidney ageing and CKD. Nat Rev Nephrol 11:264–276
Fine LG, Orphanides C, Norman JT (1998) Progressive renal disease: the chronic hypoxia hypothesis. Kidney Int Suppl 65:S74–S78
Fiorentino M, Grandaliano G, Gesualdo L, Castellano G (2018) Acute kidney injury to chronic kidney disease transition. Contrib Nephrol 193:45–54
Freedman BI, Volkova NV, Satko SG, Krisher J, Jurkovitz C et al (2005) Population-based screening for family history of end-stage renal disease among incident dialysis patients. Am J Nephrol 25:529–535
Funk JA, Schnellmann RG (2012) Persistent disruption of mitochondrial homeostasis after acute kidney injury. Am J Physiol Renal Physiol 302:F853–F864
Galvan DL, Green NH, Danesh FR (2017) The hallmarks of mitochondrial dysfunction in chronic kidney disease. Kidney Int 92:1051–1057
Geng H, Lan R, Singha PK, Gilchrist A, Weinreb PH et al (2012) Lysophosphatidic acid increases proximal tubule cell secretion of profibrotic cytokines PDGF-B and CTGF through LPA2- and Galphaq-mediated Rho and alphavbeta6 integrin-dependent activation of TGF-beta. Am J Pathol 181:1236–1249
Gerstung M, Roth T, Dienes HP, Licht C, Fries JW (2007) Endothelin-1 induces NF-kappaB via two independent pathways in human renal tubular epithelial cells. Am J Nephrol 27:294–300
Gewin L, Vadivelu S, Neelisetty S, Srichai MB, Paueksakon P et al (2012) Deleting the TGF-beta receptor attenuates acute proximal tubule injury. J Am Soc Nephrol 23:2001–2011
Gewin L, Zent R, Pozzi A (2017) Progression of chronic kidney disease: too much cellular talk causes damage. Kidney Int 91:552–560
Go AS, Parikh CR, Ikizler TA, Coca S, Siew ED et al (2010) The assessment, serial evaluation, and subsequent sequelae of acute kidney injury (ASSESS-AKI) study: design and methods. BMC Nephrol 11:22
Goldstein SL, Jaber BL, Faubel S, Chawla LS, Acute Kidney Injury Advisory Group of American Society of Nephrology (2013) AKI transition of care: a potential opportunity to detect and prevent CKD. Clin J Am Soc Nephrol 8:476–483
Gomez-Garre D, Largo R, Tejera N, Fortes J, Manzarbeitia F, Egido J (2001) Activation of NF-kappaB in tubular epithelial cells of rats with intense proteinuria: role of angiotensin II and endothelin-1. Hypertension 37:1171–1178
Goodarzi AA, Block WD, Lees-Miller SP (2003) The role of ATM and ATR in DNA damage-induced cell cycle control. Prog Cell Cycle Res 5:393–411
Grande MT, Sanchez-Laorden B, Lopez-Blau C, De Frutos CA, Boutet A et al (2016) Erratum: Snail1-induced partial epithelial-to-mesenchymal transition drives renal fibrosis in mice and can be targeted to reverse established disease. Nat Med 22:217
Granger DN, Kvietys PR (2015) Reperfusion injury and reactive oxygen species: the evolution of a concept. Redox Biol 6:524–551
Grynberg K, Ma FY, Nikolic-Paterson DJ (2017) The JNK signaling pathway in renal fibrosis. Front Physiol 8:829
Haase VH (2012) Hypoxia-inducible factor signaling in the development of kidney fibrosis. Fibrogenesis Tissue Repair 5:S16
Haase M, Devarajan P, Haase-Fielitz A, Bellomo R, Cruz DN et al (2011) The outcome of neutrophil gelatinase-associated lipocalin-positive subclinical acute kidney injury: a multicenter pooled analysis of prospective studies. J Am Coll Cardiol 57:1752–1761
Hall AM, Schuh CD (2016) Mitochondria as therapeutic targets in acute kidney injury. Curr Opin Nephrol Hypertens 25:355–362
Henderson NC, Mackinnon AC, Farnworth SL, Kipari T, Haslett C et al (2008) Galectin-3 expression and secretion links macrophages to the promotion of renal fibrosis. Am J Pathol 172:288–298
Heung M, Chawla LS (2014) Acute kidney injury: gateway to chronic kidney disease. Nephron Clin Pract 127:30–34
Hewitson TD, Boon WC, Simpson ER, Smith ER, Samuel CS (2016) Estrogens do not protect, but androgens exacerbate, collagen accumulation in the female mouse kidney after ureteric obstruction. Life Sci 158:130–136
Hewitson TD, Holt SG, Smith ER (2017) Progression of tubulointerstitial fibrosis and the chronic kidney disease phenotype—role of risk factors and epigenetics. Front Pharmacol 8:520
Horbelt M, Lee SY, Mang HE, Knipe NL, Sado Y, Kribben A et al (2007) Acute and chronic microvascular alterations in a mouse model of ischemic acute kidney injury. Am J Physiol Renal Physiol 293:F688–F695
Hosohata K (2016) Role of oxidative stress in drug-induced kidney injury. Int J Mol Sci 17:1826
Hsu CY (2012) Yes, AKI truly leads to CKD. J Am Soc Nephrol 23:967–969
Huang XR, Chung AC, Wang XJ, Lai KN, Lan HY (2008) Mice overexpressing latent TGF-beta1 are protected against renal fibrosis in obstructive kidney disease. Am J Physiol Renal Physiol 295:F118–F127
Huen SC, Huynh L, Marlier A, Lee Y, Moeckel GW, Cantley LG (2015) GM-CSF promotes macrophage alternative activation after renal ischemia/reperfusion injury. J Am Soc Nephrol 26:1334–1345
Hultstrom M, Becirovic-Agic M, Jonsson S (2018) Comparison of acute kidney injury of different etiology reveals in-common mechanisms of tissue damage. Physiol Genomics 50:127–141
Humphreys BD, Xu F, Sabbisetti V, Grgic I, Movahedi Naini S et al (2013) Chronic epithelial kidney injury molecule-1 expression causes murine kidney fibrosis. J Clin Invest 123:4023–4035
Ishani A, Xue JL, Himmelfarb J, Eggers PW, Kimmel PL, Molitoris BA et al (2009) Acute kidney injury increases risk of ESRD among elderly. J Am Soc Nephrol 20:223–228
Kang DH, Anderson S, Kim YG, Mazzalli M, Suga S et al (2001) Impaired angiogenesis in the aging kidney: vascular endothelial growth factor and thrombospondin-1 in renal disease. Am J Kidney Dis 37:601–611
Kida Y, Tchao BN, Yamaguchi I (2014) Peritubular capillary rarefaction: a new therapeutic target in chronic kidney disease. Pediatr Nephrol 29:333–342
Kimura M, Asano M, Abe K, Miyazaki M, Suzuki T, Hishida A (2005) Role of atrophic changes in proximal tubular cells in the peritubular deposition of type IV collagen in a rat renal ablation model. Nephrol Dial Transplant 20:1559–1565
Kitching AR (2014) Dendritic cells in progressive renal disease: some answers, many questions. Nephrol Dial Transplant 29:2185–2193
Ko GJ, Grigoryev DN, Linfert D, Jang HR, Watkins T et al (2010) Transcriptional analysis of kidneys during repair from AKI reveals possible roles for NGAL and KIM-1 as biomarkers of AKI-to-CKD transition. Am J Physiol Renal Physiol 298:F1472–F1483
Kobori H, Nangaku M, Navar LG, Nishiyama A (2007) The intrarenal renin-angiotensin system: from physiology to the pathobiology of hypertension and kidney disease. Pharmacol Rev 59:251–287
Kok HM, Falke LL, Goldschmeding R, Nguyen TQ (2014) Targeting CTGF, EGF and PDGF pathways to prevent progression of kidney disease. Nat Rev Nephrol 10:700–711
Kokeny G, Nemeth Z, Godo M, Hamar P (2010) The Rowett rat strain is resistant to renal fibrosis. Nephrol Dial Transplant 25:1458–1462
Kramann R, Humphreys BD (2014) Kidney pericytes: roles in regeneration and fibrosis. Semin Nephrol 34:374–383
Kramann R, Schneider RK, DiRocco DP, Machado F, Fleig S et al (2015) Perivascular Gli1+ progenitors are key contributors to injury-induced organ fibrosis. Cell Stem Cell 16:51–66
Kriz W, Kaissling B, Le Hir M (2011) Epithelial-mesenchymal transition (EMT) in kidney fibrosis: fact or fantasy? J Clin Invest 121:468–474
Lamouille S, Xu J, Derynck R (2014) Molecular mechanisms of epithelial-mesenchymal transition. Nat Rev Mol Cell Biol 15:178–196
Le Clef N, Verhulst A, D’Haese PC, Vervaet BA (2016) Unilateral renal ischemia-reperfusion as a robust model for acute to chronic kidney injury in mice. PLoS ONE 11:e0152153
LeBleu VS, Taduri G, O’Connell J, Teng Y, Cooke VG et al (2013) Origin and function of myofibroblasts in kidney fibrosis. Nat Med 19:1047–1053
Leemans JC, Kors L, Anders HJ, Florquin S (2014) Pattern recognition receptors and the inflammasome in kidney disease. Nat Rev Nephrol 10:398–414
Leonard EC, Friedrich JL, Basile DP (2008) VEGF-121 preserves renal microvessel structure and ameliorates secondary renal disease following acute kidney injury. Am J Physiol Renal Physiol 295:F1648–F1657
Leung KC, Tonelli M, James MT (2013) Chronic kidney disease following acute kidney injury-risk and outcomes. Nat Rev Nephrol 9:77–85
Lewington AJ, Cerda J, Mehta RL (2013) Raising awareness of acute kidney injury: a global perspective of a silent killer. Kidney Int 84:457–467
Li J, Qu X, Bertram JF (2009) Endothelial-myofibroblast transition contributes to the early development of diabetic renal interstitial fibrosis in streptozotocin-induced diabetic mice. Am J Pathol 175:1380–1388
Liu Y (2004) Epithelial to mesenchymal transition in renal fibrogenesis: pathologic significance, molecular mechanism, and therapeutic intervention. J Am Soc Nephrol 15:1–12
Liu Y (2010) New insights into epithelial-mesenchymal transition in kidney fibrosis. J Am Soc Nephrol 21:212–222
Liu BC, Chen L, Sun J, Huang HQ, Ma KL, Liu H et al (2006) Connective tissue growth factor-mediated angiotensin II-induced hypertrophy of proximal tubular cells. Nephron Exp Nephrol 103:e16–e26
Liu S, Soong Y, Seshan SV, Szeto HH (2014) Novel cardiolipin therapeutic protects endothelial mitochondria during renal ischemia and mitigates microvascular rarefaction, inflammation, and fibrosis. Am J Physiol Renal Physiol 306:F970–F980
Liu M, Ning X, Li R, Yang Z, Yang X, Sun S et al (2017) Signalling pathways involved in hypoxia-induced renal fibrosis. J Cell Mol Med 21:1248–1259
Lopez-Hernandez FJ, Lopez-Novoa JM (2012) Role of TGF-beta in chronic kidney disease: an integration of tubular, glomerular and vascular effects. Cell Tissue Res 347:141–154
Lorz C, Ortiz A, Justo P, Gonzalez-Cuadrado S, Duque N et al (2000) Proapoptotic Fas ligand is expressed by normal kidney tubular epithelium and injured glomeruli. J Am Soc Nephrol 11:1266–1277
Lovisa S, Zeisberg M, Kalluri R (2016) Partial epithelial-to-mesenchymal transition and other new mechanisms of kidney fibrosis. Trends Endocrinol Metab 27:681–695
Lozano R, Naghavi M, Foreman K, Lim S, Shibuya K et al (2012) Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 380:2095–2128
Maarouf OH, Aravamudhan A, Rangarajan D, Kusaba T, Zhang V et al (2016) Paracrine Wnt1 drives interstitial fibrosis without inflammation by tubulointerstitial cross-talk. J Am Soc Nephrol 27:781–790
Macconi D, Remuzzi G, Benigni A (2014) Key fibrogenic mediators: old players. Renin-angiotensin system. Kidney Int Suppl 4:58–64 (2011)
Machida Y, Kitamoto K, Izumi Y, Shiota M, Uchida J et al (2010) Renal fibrosis in murine obstructive nephropathy is attenuated by depletion of monocyte lineage, not dendritic cells. J Pharmacol Sci 114:464–473
Mack M, Yanagita M (2015) Origin of myofibroblasts and cellular events triggering fibrosis. Kidney Int 87:297–307
Meng XM, Tang PM, Li J, Lan HY (2015) TGF-beta/Smad signaling in renal fibrosis. Front Physiol 6:82
Menke J, Iwata Y, Rabacal WA, Basu R, Yeung YG et al (2009) CSF-1 signals directly to renal tubular epithelial cells to mediate repair in mice. J Clin Invest 119:2330–2342
Moonen L, D’Haese PC, Vervaet BA (2018) Epithelial cell cycle behaviour in the injured kidney. Int J Mol Sci 19:2038
Mosser DM, Edwards JP (2008) Exploring the full spectrum of macrophage activation. Nat Rev Immunol 8:958–969
Munoz-Espin D, Serrano M (2014) Cellular senescence: from physiology to pathology. Nat Rev Mol Cell Biol 15:482–496
Murea M, Park JK, Sharma S, Kato H, Gruenwald A et al (2010) Expression of Notch pathway proteins correlates with albuminuria, glomerulosclerosis, and renal function. Kidney Int 78:514–522
Nastase MV, Zeng-Brouwers J, Wygrecka M, Schaefer L (2018) Targeting renal fibrosis: Mechanisms and drug delivery systems. Adv Drug Deliv Rev 129:295–307
Nath KA (1992) Tubulointerstitial changes as a major determinant in the progression of renal damage. Am J Kidney Dis 20:1–17
Nelson PJ, Rees AJ, Griffin MD, Hughes J, Kurts C, Duffield J (2012) The renal mononuclear phagocytic system. J Am Soc Nephrol 23:194–203
Ninichuk V, Gross O, Segerer S, Hoffmann R, Radomska E et al (2006) Multipotent mesenchymal stem cells reduce interstitial fibrosis but do not delay progression of chronic kidney disease in collagen4A3-deficient mice. Kidney Int 70:121–129
Nogueira A, Pires MJ, Oliveira PA (2017) Pathophysiological mechanisms of renal fibrosis: a review of animal models and therapeutic strategies. Vivo 31:1–22
Ohtomo S, Nangaku M, Izuhara Y, Takizawa S, Strihou C, Miyata T (2008) Cobalt ameliorates renal injury in an obese, hypertensive type 2 diabetes rat model. Nephrol Dial Transplant 23:1166–1172
Parikh CR, Jani A, Melnikov VY, Faubel S, Edelstein CL (2004) Urinary interleukin-18 is a marker of human acute tubular necrosis. Am J Kidney Dis 43:405–414
Rodrigues-Diez RR, Garcia-Redondo AB, Orejudo M, Rodrigues-Diez R, Briones AM et al (2015) The C-terminal module IV of connective tissue growth factor, through EGFR/Nox1 signaling, activates the NF-kappaB pathway and proinflammatory factors in vascular smooth muscle cells. Antioxid Redox Signal 22:29–47
Sanz AB, Sanchez-Nino MD, Ortiz A (2011) TWEAK, a multifunctional cytokine in kidney injury. Kidney Int 80:708–718
Sanz AB, Izquierdo MC, Sanchez-Nino MD, Ucero AC, Egido J et al (2014) TWEAK and the progression of renal disease: clinical translation. Nephrol Dial Transplant 29(Suppl 1):i54–i62
Schmiedt CW, Brainard BM, Hinson W, Brown SA, Brown CA (2016) Unilateral renal ischemia as a model of acute kidney injury and renal fibrosis in cats. Vet Pathol 53:87–101
Schrijvers BF, Flyvbjerg A, Tilton RG, Rasch R, Lameire NH, De Vriese AS (2005) Pathophysiological role of vascular endothelial growth factor in the remnant kidney. Nephron Exp Nephrol 101:e9–e15
Sharfuddin AA, Molitoris BA (2011) Pathophysiology of ischemic acute kidney injury. Nat Rev Nephrol 7:189–200
Sturmlechner I, Durik M, Sieben CJ, Baker DJ, van Deursen JM (2017) Cellular senescence in renal ageing and disease. Nat Rev Nephrol 13:77–89
Sun YB, Qu X, Caruana G, Li J (2016) The origin of renal fibroblasts/myofibroblasts and the signals that trigger fibrosis. Differentiation 92:102–107
Susantitaphong P, Siribamrungwong M, Doi K, Noiri E, Terrin N, Jaber BL (2013) Performance of urinary liver-type fatty acid-binding protein in acute kidney injury: a meta-analysis. Am J Kidney Dis 61:430–439
Takaori K, Nakamura J, Yamamoto S, Nakata H, Sato Y et al (2016) Severity and frequency of proximal tubule injury determines renal prognosis. J Am Soc Nephrol 27:2393–2406
Tan RJ, Zhou D, Zhou L, Liu Y (2014) Wnt/beta-catenin signaling and kidney fibrosis. Kidney Int Suppl 4:84–90 (2011)
Tanaka T, Matsumoto M, Inagi R, Miyata T, Kojima I et al (2005) Induction of protective genes by cobalt ameliorates tubulointerstitial injury in the progressive Thy1 nephritis. Kidney Int 68:2714–2725
Tang WW, Ulich TR, Lacey DL, Hill DC, Qi M et al (1996) Platelet-derived growth factor-BB induces renal tubulointerstitial myofibroblast formation and tubulointerstitial fibrosis. Am J Pathol 148:1169–1180
Tang Z, Lu B, Hatch E, Sacks SH, Sheerin NS (2009) C3a mediates epithelial-to-mesenchymal transition in proteinuric nephropathy. J Am Soc Nephrol 20:593–603
Tsai YC, Chiu YW, Tsai JC, Kuo HT, Lee SC et al (2014) Association of angiopoietin-2 with renal outcome in chronic kidney disease. PLoS ONE 9:e108862
Venkatachalam MA, Griffin KA, Lan R, Geng H, Saikumar P, Bidani AK (2010) Acute kidney injury: a springboard for progression in chronic kidney disease. Am J Physiol Renal Physiol 298:F1078–F1094
Vinuesa E, Hotter G, Jung M, Herrero-Fresneda I, Torras J, Sola A (2008) Macrophage involvement in the kidney repair phase after ischaemia/reperfusion injury. J Pathol 214:104–113
Wang S, Diao H, Guan Q, Cruikshank WW, Delovitch TL et al (2008) Decreased renal ischemia-reperfusion injury by IL-16 inactivation. Kidney Int 73:318–326
Wang Y, Chang J, Yao B, Niu A, Kelly E et al (2015) Proximal tubule-derived colony stimulating factor-1 mediates polarization of renal macrophages and dendritic cells, and recovery in acute kidney injury. Kidney Int 88:1274–1282
Weisheit CK, Engel DR, Kurts C (2015) Dendritic cells and macrophages: sentinels in the kidney. Clin J Am Soc Nephrol 10:1841–1851
Wirthensohn G, Guder WG (1986) Renal substrate metabolism. Physiol Rev 66:469–497
Wolf G, Ziyadeh FN, Stahl RA (1999) Angiotensin II stimulates expression of transforming growth factor beta receptor type II in cultured mouse proximal tubular cells. J Mol Med (Berl) 77:556–564
Wong WK, Robertson H, Carroll HP, Ali S, Kirby JA (2003) Tubulitis in renal allograft rejection: role of transforming growth factor-beta and interleukin-15 in development and maintenance of CD103+ intraepithelial T cells. Transplantation 75:505–514
Wu H, Craft ML, Wang P, Wyburn KR, Chen G et al (2008) IL-18 contributes to renal damage after ischemia-reperfusion. J Am Soc Nephrol 19:2331–2341
Wu CF, Chiang WC, Lai CF, Chang FC, Chen YT et al (2013) Transforming growth factor beta-1 stimulates profibrotic epithelial signaling to activate pericyte-myofibroblast transition in obstructive kidney fibrosis. Am J Pathol 182:118–131
Yan M, Tang C, Ma Z, Huang S, Dong Z (2016) DNA damage response in nephrotoxic and ischemic kidney injury. Toxicol Appl Pharmacol 313:104–108
Yang L, Besschetnova TY, Brooks CR, Shah JV, Bonventre JV (2010) Epithelial cell cycle arrest in G2/M mediates kidney fibrosis after injury. Nat Med 16:535–543
Yang Y, Zhang ZX, Lian D, Haig A, Bhattacharjee RN, Jevnikar AM (2015) IL-37 inhibits IL-18-induced tubular epithelial cell expression of pro-inflammatory cytokines and renal ischemia-reperfusion injury. Kidney Int 87:396–408
Yano T, Nozaki Y, Kinoshita K, Hino S, Hirooka Y et al (2015) The pathological role of IL-18Ralpha in renal ischemia/reperfusion injury. Lab Invest 95:78–91
Yard BA, Daha MR, Kooymans-Couthino M, Bruijn JA, Paape ME et al (1992) IL-1 alpha stimulated TNF alpha production by cultured human proximal tubular epithelial cells. Kidney Int 42:383–389
Yu M, Ryu DR, Kim SJ, Choi KB, Kang DH (2010) Clinical implication of metabolic syndrome on chronic kidney disease depends on gender and menopausal status: results from the Korean National Health and Nutrition Examination Survey. Nephrol Dial Transplant 25:469–477
Zager RA, Johnson AC, Andress D, Becker K (2013) Progressive endothelin-1 gene activation initiates chronic/end-stage renal disease following experimental ischemic/reperfusion injury. Kidney Int 84:703–712
Zeisberg EM, Potenta SE, Sugimoto H, Zeisberg M, Kalluri R (2008) Fibroblasts in kidney fibrosis emerge via endothelial-to-mesenchymal transition. J Am Soc Nephrol 19:2282–2287
Zhou XJ, Rakheja D, Yu X, Saxena R, Vaziri ND, Silva FG (2008) The aging kidney. Kidney Int 74:710–720
Zhou D, Li Y, Lin L, Zhou L, Igarashi P, Liu Y (2012) Tubule-specific ablation of endogenous beta-catenin aggravates acute kidney injury in mice. Kidney Int 82:537–547
Zhou X, Fukuda N, Matsuda H, Endo M, Wang X et al (2013a) Complement 3 activates the renal renin-angiotensin system by induction of epithelial-to-mesenchymal transition of the nephrotubulus in mice. Am J Physiol Renal Physiol 305:F957–F967
Zhou Y, Xiong M, Fang L, Jiang L, Wen P et al (2013b) miR-21-containing microvesicles from injured tubular epithelial cells promote tubular phenotype transition by targeting PTEN protein. Am J Pathol 183:1183–1196
Zhou D, Li Y, Zhou L, Tan RJ, Xiao L et al (2014) Sonic hedgehog is a novel tubule-derived growth factor for interstitial fibroblasts after kidney injury. J Am Soc Nephrol 25:2187–2200
Zhou L, Li Y, Hao S, Zhou D, Tan RJ et al (2015) Multiple genes of the renin-angiotensin system are novel targets of Wnt/beta-catenin signaling. J Am Soc Nephrol 26:107–120
Zhou D, Tan RJ, Fu H, Liu Y (2016) Wnt/beta-catenin signaling in kidney injury and repair: a double-edged sword. Lab Invest 96:156–167
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Yang, L. (2019). How Acute Kidney Injury Contributes to Renal Fibrosis. In: Liu, BC., Lan, HY., Lv, LL. (eds) Renal Fibrosis: Mechanisms and Therapies. Advances in Experimental Medicine and Biology, vol 1165. Springer, Singapore. https://doi.org/10.1007/978-981-13-8871-2_7
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DOI: https://doi.org/10.1007/978-981-13-8871-2_7
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Publisher Name: Springer, Singapore
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