Urine RAS components in mice and people with type 1 diabetes and chronic kidney disease

American Journal of Physiology - Renal Physiology

Volumn 313, Issue 2, 2017, Pages F487-F494

  Wysocki, Jan ^a   Goodling, Anne ^b   Burgaya, Mar ^a   Whitlock, Kathryn ^c   Ruzinski, John ^b   Batlle, Daniel ^a   Afkarian, Maryam ^d  

^a NORTHWESTERN UNIVERSITY   (United States)

^b UNIVERSITY OF WASHINGTON SCHOOL OF MEDICINE   (United States)

^c Seattle Children's Hospital Research Institute   (United States)

^d UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

Aminopeptidase A; Angiotensin converting enzyme; Angiotensin converting enzyme 2; Angiotensinogen; Cathepsin D; Diabetic kidney disease; Renin angiotensin system

Indexed keywords

ANGIOTENSIN CONVERTING ENZYME 2; ANGIOTENSIN II; ANGIOTENSINOGEN; CATHEPSIN D; CREATININE; DIPEPTIDYL CARBOXYPEPTIDASE; DIPEPTIDYL CARBOXYPEPTIDASE INHIBITOR; GLUTAMYL AMINOPEPTIDASE; RAS PROTEIN; BIOLOGICAL MARKER; ENZYME;

ADULT; ALBUMIN CREATININE RATIO; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CHRONIC KIDNEY FAILURE; CONTROLLED STUDY; CREATININE URINE LEVEL; DIABETIC NEPHROPATHY; DIABETIC RETINOPATHY; ENZYME ACTIVITY; FEMALE; HUMAN; HYPERTENSION; INSULIN DEPENDENT DIABETES MELLITUS; MALE; MOUSE; NONHUMAN; PRIORITY JOURNAL; RENAL SYSTEM PARAMETERS; RENIN ANGIOTENSIN ALDOSTERONE SYSTEM; STREPTOZOTOCIN-INDUCED DIABETES MELLITUS; URINE LEVEL; ANIMAL; CHEMICALLY INDUCED; COMPLICATION; DIABETES MELLITUS, EXPERIMENTAL; DIABETES MELLITUS, TYPE 1; DIABETIC NEPHROPATHIES; DRUG EFFECTS; MIDDLE AGED; PREDICTIVE VALUE; RENAL INSUFFICIENCY, CHRONIC; UPREGULATION; URINALYSIS; URINE;

ADULT; ANGIOTENSIN-CONVERTING ENZYME INHIBITORS; ANIMALS; BIOMARKERS; DIABETES MELLITUS, EXPERIMENTAL; DIABETES MELLITUS, TYPE 1; DIABETIC NEPHROPATHIES; ENZYMES; FEMALE; HUMANS; MALE; MICE; MIDDLE AGED; PREDICTIVE VALUE OF TESTS; RENAL INSUFFICIENCY, CHRONIC; RENIN-ANGIOTENSIN SYSTEM; UP-REGULATION; URINALYSIS;

EID: 85026846888     PISSN: 1931857X     EISSN: 15221466     Source Type: Journal    
DOI: 10.1152/ajprenal.00074.2017     Document Type: Article

References (69)

1. Afkarian M, Hirsch IB, Tuttle KR, Greenbaum C, Himmelfarb J, de Boer IH. Urinary excretion of RAS, BMP, and WNT pathway components in diabetic kidney disease. Physiol Rep 2: e12010, 2014. doi:10. 14814/phy2.12010.
2. Afkarian M, Zelnick LR, Hall YN, Heagerty PJ, Tuttle K, Weiss NS, de Boer IH. Clinical manifestations of kidney disease among us adults with diabetes, 1988-2014. JAMA 316: 602-610, 2016. doi:10.1001/jama. 2016.10924.
3. Brenner BM, Cooper ME, de Zeeuw D, Keane WF, Mitch WE, Parving HH, Remuzzi G, Snapinn SM, Zhang Z, Shahinfar S. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med 345: 861-869, 2001. doi:10. 1056/NEJMoa011161.
4. Breyer MD, Böttinger E, Brosius FC III, Coffman TM, Harris RC, Heilig CW, Sharma K. Mouse models of diabetic nephropathy. J Am Soc Nephrol 16: 27-45, 2004. doi:10.1681/ASN.2004080648.
5. Brosius FC III, Alpers CE, Bottinger EP, Breyer MD, Coffman TM, Gurley SB, Harris RC, Kakoki M, Kretzler M, Leiter EH, Levi M, McIndoe RA, Sharma K, Smithies O, Susztak K, Takahashi N, Takahashi T. Mouse models of diabetic nephropathy. J Am Soc Nephrol 20: 2503-2512, 2009. doi:10.1681/ASN.2009070721.
6. Burns KD, Lytvyn Y, Mahmud FH, Daneman D, Deda L, Dunger DB, Deanfield JE, Dalton RN, Elia Y, Har R, Van JA, Bradley TJ, Slorach C, Hui W, Xiao F, Zimpelmann J, Mertens L, Moineddin R, Reich HN, Sochett EB, Scholey JW, Cherney DZ. The relationship between urinary renin angiotensin system markers, renal and vascular function in adolescents with type 1 diabetes. Am J Physiol Renal Physiol 312: F335-F342, 2016. doi:10.1152/ajprenal.00438.2016.
7. Cao Z, Bonnet F, Davis B, Allen TJ, Cooper ME. Additive hypotensive and anti-albuminuric effects of angiotensin-converting enzyme inhibition and angiotensin receptor antagonism in diabetic spontaneously hypertensive rats. Clin Sci (Lond) 100: 591-599, 2001. doi:10.1042/cs1000591.
8. Chodavarapu H, Grobe N, Somineni HK, Salem ES, Madhu M, Elased KM. Rosiglitazone treatment of type 2 diabetic db/db mice attenuates urinary albumin and angiotensin converting enzyme 2 excretion. PLoS One 8: e62833, 2013. doi:10.1371/journal.pone.0062833.
9. Fox C, Cocchiaro P, Oakley F, Howarth R, Callaghan K, Leslie J, Luli S, Wood KM, Genovese F, Sheerin NS, Moles A. Inhibition of lysosomal protease cathepsin D reduces renal fibrosis in murine chronic kidney disease. Sci Rep 6: 20101, 2016. doi:10.1038/srep20101.
10. Fox J, Guan S, Hymel AA, Navar LG. Dietary Na and ACE inhibition effects on renal tissue angiotensin I and II and ACE activity in rats. Am J Physiol Renal Physiol 262: F902-F909, 1992.
11. Graciano ML, Cavaglieri RC, Dellê H, Dominguez WV, Casarini DE, Malheiros DM, Noronha IL. Intrarenal Renin-Angiotensin system is upregulated in experimental model of progressive renal disease induced by chronic inhibition of nitric oxide synthesis. J Am Soc Nephrol 15: 1805-1815, 2004. doi:10.1097/01.ASN.0000131528.00773.A9.
12. Haber PK, Ye M, Wysocki J, Maier C, Haque SK, Batlle D. Angiotensin-converting enzyme 2-independent action of presumed angiotensinconverting enzyme 2 activators: novelty and significance. Hypertension 63: 774-782, 2014. doi:10.1161/HYPERTENSIONAHA.113.02856.
13. He W, Tan RJ, Li Y, Wang D, Nie J, Hou FF, Liu Y. Matrix metalloproteinase-7 as a surrogate marker predicts renal Wnt/β-catenin activity in CKD. J Am Soc Nephrol 23: 294-304, 2012. doi:10.1681/ASN. 2011050490.
14. Hollenberg NK, Osei SY, Lansang MC, Price DA, Fisher ND. Salt intake and non-ACE pathways for intrarenal angiotensin II generation in man. J Renin Angiotensin Aldosterone Syst 2: 14-18, 2001. doi:10.3317/ jraas.2001.002.
15. Hosojima H, Miyauchi E, Morimoto S. Urinary excretion of angiotensin-converting enzyme in NIDDM patients with nephropathy. Diabetes Care 12: 580-582, 1989. doi:10.2337/diacare.12.8.580.
16. Hsu CY, Ballard S, Batlle D, Bonventre JV, Böttinger EP, Feldman HI, Klein JB, Coresh J, Eckfeldt JH, Inker LA, Kimmel PL, Kusek JW, Liu KD, Mauer M, Mifflin TE, Molitch ME, Nelsestuen GL, Rebholz CM, Rovin BH, Sabbisetti VS, Van Eyk JE, Vasan RS, Waikar SS, Whitehead KM, Nelson RG. Cross-Disciplinary Biomarkers Research: Lessons Learned by the CKD Biomarkers Consortium. Clin J Am Soc Nephrol 10: 894-902, 2015. doi:10.2215/CJN.11541114.
17. Huang XR, Chen WY, Truong LD, Lan HY. Chymase is upregulated in diabetic nephropathy: implications for an alternative pathway of angiotensin II-mediated diabetic renal and vascular disease. J Am Soc Nephrol 14: 1738-1747, 2003. doi:10.1097/01.ASN.0000071512.93927.4E.
18. Ju W, Nair V, Smith S, Zhu L, Shedden K, Song PX, Mariani LH, Eichinger FH, Berthier CC, Randolph A, Lai JY, Zhou Y, Hawkins JJ, Bitzer M, Sampson MG, Thier M, Solier C, Duran-Pacheco GC, Duchateau-Nguyen G, Essioux L, Schott B, Formentini I, Magnone MC, Bobadilla M, Cohen CD, Bagnasco SM, Barisoni L, Lv J, Zhang H, Wang HY, Brosius FC, Gadegbeku CA, Kretzler M. Tissue transcriptome-driven identification of epidermal growth factor as a chronic kidney disease biomarker. Sci Transl Med 7: 316ra193, 2015. doi:10.1126/ scitranslmed.aac7071.
19. Kalender B, Oztürk M, Tunçdemir M, Uysal O, Dagistanli FK, Yegenaga I, Erek E. Renoprotective effects of valsartan and enalapril in STZ-induced diabetes in rats. Acta Histochem 104: 123-130, 2002. doi: 10.1078/0065-1281-00643.
20. Kim SS, Song SH, Kim IJ, Yang JY, Lee JG, Kwak IS, Kim YK. Clinical implication of urinary tubular markers in the early stage of nephropathy with type 2 diabetic patients. Diabetes Res Clin Pract 97: 251-257, 2012. doi:10.1016/j.diabres.2012.02.019.
21. Kobori H, Harrison-Bernard LM, Navar LG. Urinary excretion of angiotensinogen reflects intrarenal angiotensinogen production. Kidney Int 61: 579-585, 2002. doi:10.1046/j.1523-1755.2002.00155.x.
22. Kobori H, Ohashi N, Katsurada A, Miyata K, Satou R, Saito T, Yamamoto T. Urinary angiotensinogen as a potential biomarker of severity of chronic kidney diseases. J Am Soc Hypertens 2: 349-354, 2008. doi:10.1016/j.jash.2008.04.008.
23. Lai KN, Leung JC, Lai KB, To WY, Yeung VT, Lai FM. Gene expression of the renin-angiotensin system in human kidney. J Hypertens 16: 91-102, 1998. doi:10.1097/00004872-199816010-00014.
24. Lavrentyev EN, Estes AM, Malik KU. Mechanism of high glucose induced angiotensin II production in rat vascular smooth muscle cells. Circ Res 101: 455-464, 2007. doi:10.1161/CIRCRESAHA.107.151852.
25. Leehey DJ, Singh AK, Bast JP, Sethupathi P, Singh R. Glomerular renin angiotensin system in streptozotocin diabetic and Zucker diabetic fatty rats. Transl Res 151: 208-216, 2008. doi:10.1016/j.trsl.2008.01.003.
26. Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF III, Feldman HI, Kusek JW, Eggers P, Van Lente F, Greene T, Coresh J. A new equation to estimate glomerular filtration rate. Ann Intern Med 150: 604-612, 2009. doi:10.7326/0003-4819-150-9-200905050-00006.
27. Lewis EJ, Hunsicker LG, Clarke WR, Berl T, Pohl MA, Lewis JB, Ritz E, Atkins RC, Rohde R, Raz I. Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med 345: 851-860, 2001. doi:10.1056/ NEJMoa011303.
28. Liu F, Brezniceanu ML, Wei CC, Chénier I, Sachetelli S, Zhang SL, Filep JG, Ingelfinger JR, Chan JS. Overexpression of angiotensinogen increases tubular apoptosis in diabetes. J Am Soc Nephrol 19: 269-280, 2008. doi:10.1681/ASN.2007010074.
29. Mann JF, Schmieder RE, McQueen M, Dyal L, Schumacher H, Pogue J, Wang X, Maggioni A, Budaj A, Chaithiraphan S, Dickstein K, Keltai M, Metsärinne K, Oto A, Parkhomenko A, Piegas LS, Svendsen TL, Teo KK, Yusuf S; ONTARGET investigators. Renal outcomes with telmisartan, ramipril, or both, in people at high vascular risk (the ONTARGET study): a multicentre, randomised, double-blind, controlled trial. Lancet 372: 547-553, 2008. doi:10.1016/S0140-6736(08)61236-2.
30. Mezzano S, Droguett A, Burgos ME, Ardiles LG, Flores CA, Aros CA, Caorsi I, Vío CP, Ruiz-Ortega M, Egido J. Renin-angiotensin system activation and interstitial inflammation in human diabetic nephropathy. Kidney Int Suppl 64: S64-S70, 2003. doi:10.1046/j.1523-1755.64.s86. 12.x.
31. Miller JJ, Changaris DG, Levy RS. Conversion of angiotensin I to angiotensin II by cathepsin A isoenzymes of porcine kidney. Biochem Biophys Res Commun 154: 1122-1129, 1988. doi:10.1016/0006-291X(88)90257-4.
32. Miyauchi E, Hosojima H, Morimoto S. Urinary angiotensin-converting enzyme activity in type 2 diabetes mellitus: its relationship to diabetic nephropathy. Acta Diabetol 32: 193-197, 1995. doi:10.1007/BF00838491.
33. Mizuiri S, Hemmi H, Arita M, Ohashi Y, Tanaka Y, Miyagi M, Sakai K, Ishikawa Y, Shibuya K, Hase H, Aikawa A. Expression of ACE and ACE2 in individuals with diabetic kidney disease and healthy controls. Am J Kidney Dis 51: 613-623, 2008. doi:10.1053/j.ajkd.2007.11.022.
34. Moon JY, Jeong KH, Lee SH, Lee TW, Ihm CG, Lim SJ. Renal ACE and ACE2 expression in early diabetic rats. Nephron, Exp Nephrol 110: e8-e16, 2008. doi:10.1159/000149586.
35. Nadarajah R, Milagres R, Dilauro M, Gutsol A, Xiao F, Zimpelmann J, Kennedy C, Wysocki J, Batlle D, Burns KD. Podocyte-specific overexpression of human angiotensin-converting enzyme 2 attenuates diabetic nephropathy in mice. Kidney Int 82: 292-303, 2012. doi:10.1038/ ki.2012.83.
36. Ninomiya T, Perkovic V, de Galan BE, Zoungas S, Pillai A, Jardine M, Patel A, Cass A, Neal B, Poulter N, Mogensen CE, Cooper M, Marre M, Williams B, Hamet P, Mancia G, Woodward M, Macmahon S, Chalmers J. Albuminuria and kidney function independently predict cardiovascular and renal outcomes in diabetes. J Am Soc Nephrol 20: 1813-1821, 2009. doi:10.1681/ASN.2008121270.
37. Nishiyama A, Konishi Y, Ohashi N, Morikawa T, Urushihara M, Maeda I, Hamada M, Kishida M, Hitomi H, Shirahashi N, Kobori H, Imanishi M. Urinary angiotensinogen reflects the activity of intrarenal renin-angiotensin system in patients with IgA nephropathy. Nephrol Dial Transplant 26: 170-177, 2011. doi:10.1093/ndt/gfq371.
38. Owen CA, Campbell EJ. Angiotensin II generation at the cell surface of activated neutrophils: novel cathepsin G-mediated catalytic activity that is resistant to inhibition. J Immunol 160: 1436-1443, 1998.
39. Parving HH, Lehnert H, Bröchner-Mortensen J, Gomis R, Andersen S, Arner P. The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes. N Engl J Med 345: 870-878, 2001. doi:10.1056/NEJMoa011489.
40. Ramaha A, Patston PA. Release and degradation of angiotensin I and angiotensin II from angiotensinogen by neutrophil serine proteinases. Arch Biochem Biophys 397: 77-83, 2002. doi:10.1006/abbi.2001.2687.
41. Reich HN, Oudit GY, Penninger JM, Scholey JW, Herzenberg AM. Decreased glomerular and tubular expression of ACE2 in patients with type 2 diabetes and kidney disease. Kidney Int 74: 1610-1616, 2008. doi:10.1038/ki.2008.497.
42. Reilly CF, Tewksbury DA, Schechter NM, Travis J. Rapid conversion of angiotensin I to angiotensin II by neutrophil and mast cell proteinases. J Biol Chem 257: 8619-8622, 1982.
43. Riera M, Márquez E, Clotet S, Gimeno J, Roca-Ho H, Lloreta J, Juanpere N, Batlle D, Pascual J, Soler MJ. Effect of insulin on ACE2 activity and kidney function in the non-obese diabetic mouse. PLoS One 9: e84683, 2014. doi:10.1371/journal.pone.0084683.
44. Rossing K, Jacobsen P, Pietraszek L, Parving HH. Renoprotective effects of adding angiotensin II receptor blocker to maximal recommended doses of ACE inhibitor in diabetic nephropathy: a randomized doubleblind crossover trial. Diabetes Care 26: 2268-2274, 2003. doi:10.2337/ diacare.26.8.2268.
45. Rykl J, Thiemann J, Kurzawski S, Pohl T, Gobom J, Zidek W, Schlüter H. Renal cathepsin G and angiotensin II generation. J Hypertens 24: 1797-1807, 2006. doi:10.1097/01.hjh.0000242404.91332.be.
46. Salem ES, Grobe N, Elased KM. Insulin treatment attenuates renal ADAM17 and ACE2 shedding in diabetic Akita mice. Am J Physiol Renal Physiol 306: F629-F639, 2014. doi:10.1152/ajprenal.00516.2013.
47. Schlueter W, Keilani T, Batlle DC. Tissue renin angiotensin systems: theoretical implications for the development of hyperkalemia using angiotensin-converting enzyme inhibitors. Am J Med Sci 307, Suppl 1: S81-S86, 1994.
48. Schwager SL, Carmona AK, Sturrock ED. A high-throughput fluorimetric assay for angiotensin I-converting enzyme. Nat Protoc 1: 1961-1964, 2006. doi:10.1038/nprot.2006.305.
49. Singh R, Singh AK, Leehey DJ. A novel mechanism for angiotensin II formation in streptozotocin-diabetic rat glomeruli. Am J Physiol Renal Physiol 288: F1183-F1190, 2005. doi:10.1152/ajprenal.00159.2003.
50. Soler MJ, Riera M, Batlle D. New experimental models of diabetic nephropathy in mice models of type 2 diabetes: efforts to replicate human nephropathy. Exp Diabetes Res 2012: 1, 2012. doi:10.1155/2012/616313.
51. Soler MJ, Wysocki J, Ye M, Lloveras J, Kanwar Y, Batlle D. ACE2 inhibition worsens glomerular injury in association with increased ACE expression in streptozotocin-induced diabetic mice. Kidney Int 72: 614-623, 2007. doi:10.1038/sj.ki.5002373.
52. Song L, Healy DP. Kidney aminopeptidase A and hypertension, part II: effects of angiotensin II. Hypertension 33: 746-752, 1999. doi:10.1161/ 01.HYP.33.2.746.
53. Tipnis SR, Hooper NM, Hyde R, Karran E, Christie G, Turner AJ. A human homolog of angiotensin-converting enzyme. Cloning and functional expression as a captopril-insensitive carboxypeptidase. J Biol Chem 275: 33238-33243, 2000. doi:10.1074/jbc.M002615200.
54. Tonnesen MG, Klempner MS, Austen KF, Wintroub BU. Identification of a human neutrophil angiotension II-generating protease as cathepsin G. J Clin Invest 69: 25-30, 1982. doi:10.1172/JCI110437.
55. Van Kats JP, Schalekamp MA, Verdouw PD, Duncker DJ, Danser AH. Intrarenal angiotensin II: interstitial and cellular levels and site of production. Kidney Int 60: 2311-2317, 2001. doi:10.1046/j.1523-1755. 2001.00049.x.
56. Velez JC. The importance of the intrarenal renin-angiotensin system. Nat Clin Pract Nephrol 5: 89-100, 2009. doi:10.1038/ncpneph1015.
57. Viau A, El Karoui K, Laouari D, Burtin M, Nguyen C, Mori K, Pillebout E, Berger T, Mak TW, Knebelmann B, Friedlander G, Barasch J, Terzi F. Lipocalin 2 is essential for chronic kidney disease progression in mice and humans. J Clin Invest 120: 4065-4076, 2010. doi:10.1172/JCI42004.
58. Volland H, Pradelles P, Ronco P, Azizi M, Simon D, Créminon C, Grassi J. A solid-phase immobilized epitope immunoassay (SPIE-IA) permitting very sensitive and specific measurement of angiotensin II in plasma. J Immunol Methods 228: 37-47, 1999. doi:10.1016/S0022-1759(99)00097-6.
59. Wada T, Furuichi K, Sakai N, Iwata Y, Yoshimoto K, Shimizu M, Takeda SI, Takasawa K, Yoshimura M, Kida H, Kobayashi KI, Mukaida N, Naito T, Matsushima K, Yokoyama H. Up-regulation of monocyte chemoattractant protein-1 in tubulointerstitial lesions of human diabetic nephropathy. Kidney Int 58: 1492-1499, 2000. doi:10.1046/j. 1523-1755.2000.00311.x.
60. Wilkinson-Berka JL, Gibbs NJ, Cooper ME, Skinner SL, Kelly DJ. Renoprotective and anti-hypertensive effects of combined valsartan and perindopril in progressive diabetic nephropathy in the transgenic (mRen-2)27 rat. Nephrol Dial Transplant 16: 1343-1349, 2001. doi:10.1093/ndt/ 16.7.1343.
61. Wintroub BU, Klickstein LB, Dzau VJ, Watt KW. Granulocyte-angiotensin system. Identification of angiotensinogen as the plasma protein substrate of leukocyte cathepsin G. Biochemistry 23: 227-232, 1984. doi:10.1021/bi00297a009.
62. Wong DW, Oudit GY, Reich H, Kassiri Z, Zhou J, Liu QC, Backx PH, Penninger JM, Herzenberg AM, Scholey JW. Loss of angiotensinconverting enzyme-2 (Ace2) accelerates diabetic kidney injury. Am J Pathol 171: 438-451, 2007. doi:10.2353/ajpath.2007.060977.
63. Wysocki J, Garcia-Halpin L, Ye M, Maier C, Sowers K, Burns KD, Batlle D. Regulation of urinary ACE2 in diabetic mice. Am J Physiol Renal Physiol 305: F600-F611, 2013. doi:10.1152/ajprenal.00600.2012.
64. Wysocki J, Ye M, Khattab AM, Fogo A, Martin A, David NV, Kanwar Y, Osborn M, Batlle D. Angiotensin-converting enzyme 2 amplification limited to the circulation does not protect mice from development of diabetic nephropathy. Kidney Int 91: 1336-1346, 2017. doi:10.1016/j.kint. 2016.09.032.
65. Wysocki J, Ye M, Soler MJ, Gurley SB, Xiao HD, Bernstein KE, Coffman TM, Chen S, Batlle D. ACE and ACE2 activity in diabetic mice. Diabetes 55: 2132-2139, 2006. doi:10.2337/db06-0033.
66. Yamamoto-Nonaka K, Koike M, Asanuma K, Takagi M, Oliva Trejo JA, Seki T, Hidaka T, Ichimura K, Sakai T, Tada N, Ueno T, Uchiyama Y, Tomino Y. Cathepsin D in Podocytes Is Important in the Pathogenesis of Proteinuria and CKD. J 2016. doi:10.1681/ASN. 2015040366.
67. Yamamoto T, Nakagawa T, Suzuki H, Ohashi N, Fukasawa H, Fujigaki Y, Kato A, Nakamura Y, Suzuki F, Hishida A. Urinary angiotensinogen as a marker of intrarenal angiotensin II activity associated with deterioration of renal function in patients with chronic kidney disease. J Am Soc Nephrol 18: 1558-1565, 2007. doi:10.1681/ASN. 2006060554.
68. Ye M, Wysocki J, Naaz P, Salabat MR, LaPointe MS, Batlle D. Increased ACE 2 and decreased ACE protein in renal tubules from diabetic mice: a renoprotective combination? Hypertension 43: 1120-1125, 2004. doi:10.1161/01.HYP.0000126192.27644.76.
69. Ye M, Wysocki J, William J, Soler MJ, Cokic I, Batlle D. Glomerular localization and expression of Angiotensin-converting enzyme 2 and Angiotensin-converting enzyme: implications for albuminuria in diabetes. J Am Soc Nephrol 17: 3067-3075, 2006. doi:10.1681/ASN.2006050423.