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Barbara Toffoli, Federica Gilardi, Carine Winkler, Magnus Soderberg, Laura Kowalczuk, Yvan Arsenijevic, Krister Bamberg, Olivier Bonny, Béatrice Desvergne
Nephropathy in Pparg-null mice highlights PPARγ systemic activities in metabolism and in the immune system
www.plosone.org
www.plosone.org
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5.4085 0 Td
(whilst)Tj
2.6022 0 Td
(preserving)Tj
4.4277 0 Td
(PPAR)Tj
/F14 1 Tf
(\r)Tj
/F10 1 Tf
3.0954 0 Td
(expression)Tj
4.4673 0 Td
(in)Tj
1.0374 0 Td
(the)Tj
1.4684 0 Td
(trophoblast)Tj
4.7962 0 Td
([)Tj
0.83 0.64 0.02 0 k
(5)Tj
0 g
(].)Tj
1.5987 0 Td
(Normal)Tj
3.3335 0 Td
(placenta)Tj
-32.2353 -1.3039 Td
(development)Tj
5.4085 0 Td
(allows)Tj
2.6986 0 Td
(SOX2CRE)Tj
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 323.1496 607.8614 cm
BT
/F10 1 Tf
1 TL
-0.0053 Tc
0 0 Td
(tg/+)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 335.622 603.3826 cm
BT
/F15 1 Tf
1 TL
-0.004 Tc
0 0 Td
[()4()16()6()]TJ
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 358.4692 607.8614 cm
BT
/F15 1 Tf
1 TL
-0.0053 Tc
0 0 Td
[(\n)2()]TJ
/F16 1 Tf
( )Tj
/F15 1 Tf
[( )]TJ
/F16 1 Tf
( )Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 380.5795 603.3826 cm
BT
/F10 1 Tf
1 TL
-0.004 Tc
0 0 Td
(\(hereafter)Tj
4.1215 0 Td
(called)Tj
/F15 1 Tf
2.5228 0 Td
[()4()16()6()]TJ
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 469.8708 607.8614 cm
BT
/F16 1 Tf
1 TL
-0.0053 Tc
0 0 Td
( )Tj
/F15 1 Tf
[( )]TJ
/F16 1 Tf
( )Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 480.9826 603.3826 cm
BT
/F10 1 Tf
1 TL
-0.004 Tc
0 0 Td
(\))Tj
0.5612 0 Td
(pups)Tj
2.143 0 Td
(to)Tj
1.0261 0 Td
(be)Tj
1.1509 0 Td
(born.)Tj
/F15 1 Tf
-32.978 -1.2982 Td
[()4()16()6()]TJ
/F10 1 Tf
2.5058 0 Td
(expression)Tj
4.4617 0 Td
(is)Tj
0.8504 0 Td
(totally)Tj
2.7043 0 Td
(undetectable)Tj
5.3007 0 Td
(in)Tj
/F15 1 Tf
1.0375 0 Td
[()4()16()6()]TJ
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 391.4645 594.822 cm
BT
/F16 1 Tf
1 TL
-0.0053 Tc
0 0 Td
( )Tj
/F15 1 Tf
[( )]TJ
/F16 1 Tf
( )Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 404.7874 590.4 cm
BT
/F10 1 Tf
1 TL
-0.004 Tc
0 0 Td
(embryos)Tj
3.6623 0 Td
(as)Tj
1.0148 0 Td
(well)Tj
1.8198 0 Td
(as)Tj
1.0148 0 Td
(in)Tj
1.0375 0 Td
(various)Tj
3.1408 0 Td
(adult)Tj
2.2563 0 Td
(tissues)Tj
-34.4236 -1.2982 Td
(\(including)Tj
4.3823 0 Td
(liver,)Tj
2.2054 0 Td
(kidney,)Tj
3.1634 0 Td
(and)Tj
1.7291 0 Td
(bones;)Tj
2.795 0 Td
(data)Tj
1.9162 0 Td
(not)Tj
1.5704 0 Td
(shown\).)Tj
3.4128 0 Td
(The)Tj
1.7858 0 Td
(control)Tj
3.1181 0 Td
(littermates)Tj
4.4617 0 Td
(\(CTL\))Tj
2.7156 0 Td
(have)Tj
2.0579 0 Td
(no)Tj
-35.3137 -1.3039 Td
(SOX2CRE)Tj
4.422 0 Td
(transgene)Tj
4.0932 0 Td
(and)Tj
1.7348 0 Td
(two)Tj
1.7065 0 Td
(functional)Tj
/F15 1 Tf
4.3086 0 Td
[()4()16()6()]TJ
/F10 1 Tf
2.5058 0 Td
(alleles)Tj
2.6021 0 Td
(\()Tj
/F15 1 Tf
[()4()16()6()]TJ
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 439.9937 568.8566 cm
BT
/F15 1 Tf
1 TL
-0.0053 Tc
0 0 Td
[()-36( )]TJ
ET
Q
q
1 j
1 J
0 w
10 0 0 10 450.4251 564.3779 cm
BT
/F10 1 Tf
1 TL
-0.004 Tc
0 0 Td
(\).)Tj
0.788 0 Td
(Both)Tj
2.1316 0 Td
(male)Tj
2.143 0 Td
(and)Tj
1.7291 0 Td
(female)Tj
2.8573 0 Td
(have)Tj
-34.6901 -1.2982 Td
(been)Tj
2.1203 0 Td
(used)Tj
2.0637 0 Td
(throughout)Tj
4.7735 0 Td
(the)Tj
1.474 0 Td
(study,)Tj
2.6135 0 Td
(except)Tj
2.7723 0 Td
(for)Tj
1.3833 0 Td
(the)Tj
1.4683 0 Td
(52)Tj
1.1735 0 Td
(week-old)Tj
3.8778 0 Td
(time)Tj
2.0295 0 Td
(point,)Tj
2.5852 0 Td
(for)Tj
1.3833 0 Td
(which)Tj
2.6532 0 Td
(only)Tj
1.9729 0 Td
(female)Tj
-34.3443 -1.2983 Td
(were)Tj
2.1203 0 Td
(available)Tj
3.6681 0 Td
(due)Tj
1.7007 0 Td
(to)Tj
1.0205 0 Td
(a)Tj
0.6576 0 Td
(relative)Tj
3.1351 0 Td
(earlier)Tj
2.761 0 Td
(death)Tj
2.4321 0 Td
(of)Tj
1.0148 0 Td
(male)Tj
2.1429 0 Td
(mice.)Tj
-19.4568 -1.3039 Td
(Functional)Tj
4.5524 0 Td
(parameters)Tj
4.6714 0 Td
(were)Tj
2.126 0 Td
(evaluated)Tj
3.9855 0 Td
(at)Tj
0.9524 0 Td
(the)Tj
1.474 0 Td
(Mouse)Tj
2.931 0 Td
(Metabolic)Tj
4.2179 0 Td
(Evaluation)Tj
4.507 0 Td
(Facility)Tj
3.1408 0 Td
(\(MEF\))Tj
2.8856 0 Td
(of)Tj
-36.6403 -1.2983 Td
(the)Tj
1.4684 0 Td
(University)Tj
4.405 0 Td
(of)Tj
1.0148 0 Td
(Lausanne.)Tj
4.2576 0 Td
(Urinary)Tj
3.4016 0 Td
(measurements)Tj
6.032 0 Td
(were)Tj
2.126 0 Td
(done)Tj
2.228 0 Td
(using)Tj
2.3867 0 Td
(spot)Tj
1.9049 0 Td
(urines)Tj
2.7155 0 Td
(or)Tj
1.0999 0 Td
(24h)Tj
1.7007 0 Td
(urine)Tj
-34.7411 -1.2982 Td
(collection)Tj
4.1103 0 Td
(from)Tj
2.2053 0 Td
(metabolic)Tj
4.1442 0 Td
(cages.)Tj
2.5569 0 Td
(Urinary)Tj
3.4015 0 Td
(albumin)Tj
3.5716 0 Td
(and)Tj
1.7292 0 Td
(glucose)Tj
3.1747 0 Td
(were)Tj
2.1203 0 Td
(evaluated)Tj
3.9911 0 Td
(with)Tj
1.9956 0 Td
(Albuwell)Tj
-33.0007 -1.2983 Td
(M)Tj
1.1112 0 Td
(ELISA)Tj
2.829 0 Td
(kit)Tj
1.2812 0 Td
(\(Exocell,)Tj
3.668 0 Td
(USA\))Tj
2.4548 0 Td
(and)Tj
1.7292 0 Td
(QuantiChrom)Tj
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 387.8362 490.8472 cm
BT
/F10 1 Tf
1 TL
-0.0053 Tc
0 0 Td
(TM)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 401.3291 486.4251 cm
BT
/F10 1 Tf
1 TL
-0.004 Tc
0 0 Td
(Glucose)Tj
3.4242 0 Td
(Assay)Tj
2.5115 0 Td
(Kit)Tj
1.4626 0 Td
(\(BioAssay)Tj
4.2066 0 Td
(System,)Tj
3.2768 0 Td
(USA\),)Tj
-35.0132 -1.3039 Td
(respectively.)Tj
5.108 0 Td
(At)Tj
1.2019 0 Td
(sacrifice,)Tj
3.7077 0 Td
(kidneys)Tj
3.2995 0 Td
(were)Tj
2.1203 0 Td
(rapidly)Tj
3.0387 0 Td
(snap-frozen)Tj
4.9832 0 Td
(or)Tj
1.0998 0 Td
(put)Tj
1.5591 0 Td
(in)Tj
1.0375 0 Td
(PFA)Tj
1.9899 0 Td
(4%)Tj
1.4513 0 Td
(for)Tj
1.389 0 Td
(the)Tj
1.4683 0 Td
(subse-)Tj
-33.4542 -1.2982 Td
(quent)Tj
2.5228 0 Td
(embedding)Tj
4.7282 0 Td
(in)Tj
1.0375 0 Td
(paraffin.)Tj
ET
Q
q
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 433.9275 cm
BT
/F0 1 Tf
1 TL
-0.0033 Tc
0 0 Td
(Detection)Tj
4.3937 0 Td
(of)Tj
1.0441 0 Td
(autoantibodies)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 416.9196 cm
BT
/F10 1 Tf
1 TL
-0.004 Tc
0 0 Td
(Plasma)Tj
3.0727 0 Td
(levels)Tj
2.3754 0 Td
(of)Tj
1.0148 0 Td
(anti-nuclear)Tj
5.091 0 Td
(antibodies)Tj
4.3653 0 Td
(\(ANAs\))Tj
3.3619 0 Td
(and)Tj
1.7291 0 Td
(anti-dsDNA)Tj
5.1647 0 Td
(IgGs)Tj
2.1033 0 Td
(were)Tj
2.1203 0 Td
(measured)Tj
4.1102 0 Td
(by)Tj
-34.5087 -1.2982 Td
(commercially)Tj
5.6579 0 Td
(available)Tj
3.6623 0 Td
(ELISAs)Tj
3.1918 0 Td
(\(Alpha)Tj
2.965 0 Td
(Diagnostic)Tj
4.5298 0 Td
(International,)Tj
5.7089 0 Td
(USA\).)Tj
2.6816 0 Td
(Antibodies)Tj
4.6147 0 Td
(anti)Tj
/F14 1 Tf
1.7688 0 Td
()Tj
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 552.6425 402.2929 cm
BT
/F10 1 Tf
1 TL
-0.0053 Tc
0 0 Td
(2)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 556.2141 403.937 cm
BT
/F10 1 Tf
1 TL
-0.004 Tc
0 0 Td
(-gly-)Tj
-35.6199 -1.2982 Td
(coprotein1)Tj
4.5581 0 Td
(were)Tj
2.1203 0 Td
(determined)Tj
4.8529 0 Td
(by)Tj
1.1792 0 Td
(ELISA,)Tj
3.0557 0 Td
(coating)Tj
3.1635 0 Td
(a)Tj
0.6519 0 Td
(96)Tj
1.1736 0 Td
(well-plate)Tj
4.0875 0 Td
(with)Tj
2.0012 0 Td
(1)Tj
/F18 1 Tf
[()]TJ
/F10 1 Tf
(g/well)Tj
3.5944 0 Td
(of)Tj
1.0147 0 Td
(recombinant)Tj
-31.453 -1.3039 Td
(mouse)Tj
/F14 1 Tf
2.8573 0 Td
()Tj
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 233.4614 376.2708 cm
BT
/F10 1 Tf
1 TL
-0.0053 Tc
0 0 Td
(2)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 237.033 377.9149 cm
BT
/F10 1 Tf
1 TL
-0.004 Tc
0 0 Td
(-glycoprotein1)Tj
6.0717 0 Td
(\(6575-AH-050,)Tj
6.2702 0 Td
(R&D)Tj
2.2791 0 Td
(Systems\))Tj
3.7587 0 Td
(overnight)Tj
4.0818 0 Td
(at)Tj
0.9525 0 Td
(4C.)Tj
1.9729 0 Td
(After)Tj
2.2904 0 Td
(blocking,)Tj
-31.3793 -1.2982 Td
(mouse)Tj
2.8573 0 Td
(plasma)Tj
3.033 0 Td
(samples)Tj
3.3789 0 Td
(\(dil)Tj
1.6044 0 Td
(1:100\))Tj
2.6872 0 Td
(were)Tj
2.1203 0 Td
(loaded)Tj
2.8913 0 Td
(and)Tj
1.7291 0 Td
(incubated)Tj
4.1783 0 Td
(at)Tj
0.9524 0 Td
(37C)Tj
2.2224 0 Td
(for)Tj
1.3889 0 Td
(1h.)Tj
1.4457 0 Td
(The)Tj
1.7858 0 Td
(detection)Tj
-32.275 -1.2983 Td
(was)Tj
1.6951 0 Td
(done)Tj
2.228 0 Td
(with)Tj
2.0012 0 Td
(HRP-conjugated)Tj
6.9278 0 Td
(anti)Tj
1.7688 0 Td
(mouse)Tj
2.8573 0 Td
(IgG-Fc)Tj
3.0444 0 Td
(antibody)Tj
3.7644 0 Td
(and)Tj
1.7291 0 Td
(TMB)Tj
2.3018 0 Td
(as)Tj
1.0148 0 Td
(substrate)Tj
3.804 0 Td
(\(Bethyl)Tj
-33.1367 -1.3039 Td
(Laboratoires,)Tj
5.4651 0 Td
(USA\).)Tj
ET
Q
q
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 312.4913 cm
BT
/F0 1 Tf
1 TL
-0.0033 Tc
0 0 Td
(Angiography)Tj
5.7591 0 Td
(for)Tj
1.3795 0 Td
(retinal)Tj
2.9008 0 Td
(vessels)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 295.4834 cm
BT
/F15 1 Tf
1 TL
-0.004 Tc
0 0 Td
[()4()16()6()]TJ
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 222.8598 299.9055 cm
BT
/F16 1 Tf
1 TL
-0.0053 Tc
0 0 Td
( )Tj
/F15 1 Tf
[( )]TJ
/F16 1 Tf
( )Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 236.1826 295.4834 cm
BT
/F10 1 Tf
1 TL
-0.004 Tc
0 0 Td
(mice)Tj
2.1543 0 Td
(often)Tj
2.2847 0 Td
(showed)Tj
3.2485 0 Td
(corneal)Tj
3.1747 0 Td
(problems)Tj
3.9742 0 Td
(such)Tj
2.0579 0 Td
(as)Tj
1.0148 0 Td
(opacity)Tj
3.1238 0 Td
(due)Tj
1.7008 0 Td
(to)Tj
1.0261 0 Td
(the)Tj
1.4683 0 Td
(lack)Tj
1.8199 0 Td
(of)Tj
1.0148 0 Td
(Meibomian)Tj
-31.6797 -1.3039 Td
(glands)Tj
2.8006 0 Td
(\(data)Tj
2.2562 0 Td
(not)Tj
1.5704 0 Td
(shown\).)Tj
3.4129 0 Td
(Thus,)Tj
2.4775 0 Td
(to)Tj
1.0261 0 Td
(attempt)Tj
3.3052 0 Td
(to)Tj
1.0261 0 Td
(maintain)Tj
3.8381 0 Td
(a)Tj
0.652 0 Td
(transparency)Tj
5.4084 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.4684 0 Td
(cornea,)Tj
3.1521 0 Td
(the)Tj
1.474 0 Td
(ani-)Tj
-34.8828 -1.2982 Td
(mals)Tj
2.0749 0 Td
(were)Tj
2.1202 0 Td
(treated)Tj
2.9991 0 Td
(with)Tj
1.9955 0 Td
(Vismed)Tj
3.3109 0 Td
(for)Tj
1.3833 0 Td
(7)Tj
0.6916 0 Td
(days)Tj
1.9956 0 Td
(before)Tj
2.7382 0 Td
(investigating)Tj
5.3178 0 Td
(the)Tj
1.4683 0 Td
(eye)Tj
1.5194 0 Td
(fundus.)Tj
3.2201 0 Td
(Before)Tj
2.812 0 Td
(each)Tj
2.0296 0 Td
(fluo-)Tj
-35.6765 -1.2983 Td
(rescein)Tj
3.0387 0 Td
(angiography)Tj
5.2099 0 Td
(\(FA\),)Tj
2.3358 0 Td
(2832)Tj
2.6418 0 Td
(week)Tj
2.2451 0 Td
(old)Tj
1.5023 0 Td
(mice)Tj
2.1543 0 Td
(were)Tj
2.1203 0 Td
(anesthetized)Tj
5.1704 0 Td
(by)Tj
1.1792 0 Td
(intraperitoneal)Tj
6.1795 0 Td
(injection)Tj
-33.7773 -1.3039 Td
(of)Tj
1.0148 0 Td
(a)Tj
0.6519 0 Td
(solution)Tj
3.4808 0 Td
(of)Tj
1.0148 0 Td
(ketamine/xylazine)Tj
7.5175 0 Td
(\(66.7)Tj
2.211 0 Td
(mg/kg)Tj
2.7949 0 Td
(/)Tj
0.5499 0 Td
(9.88)Tj
1.8709 0 Td
(mg/kg\).)Tj
3.3619 0 Td
(Upon)Tj
2.5285 0 Td
(full)Tj
1.5307 0 Td
(dilation)Tj
3.3165 0 Td
(after)Tj
2.0352 0 Td
(instilla-)Tj
-33.8793 -1.2983 Td
(tion)Tj
1.8425 0 Td
(of)Tj
1.0148 0 Td
(Tropicamide)Tj
5.3857 0 Td
(\(0.5%,)Tj
2.7212 0 Td
(SDU)Tj
2.1657 0 Td
(Faure/The)Tj
0 Tc
3.7757 0.051 Td
()Tj
-0.004 Tc
0.4025 -0.051 Td
(a\))Tj
0.9921 0 Td
(and)Tj
1.7291 0 Td
(Phenylephrine)Tj
6.0605 0 Td
(hypochloride)Tj
5.5218 0 Td
(\(2.5%,)Tj
2.7213 0 Td
(Bausch)Tj
-34.3329 -1.2982 Td
(Lomb)Tj
2.5908 0 Td
(Minims\),)Tj
3.94 0 Td
(animals)Tj
3.3336 0 Td
(were)Tj
2.1203 0 Td
(placed)Tj
2.7949 0 Td
(onto)Tj
2.0806 0 Td
(the)Tj
1.4684 0 Td
(positioning)Tj
4.7735 0 Td
(table.)Tj
2.3527 0 Td
(Then)Tj
2.3301 0 Td
(an)Tj
1.2019 0 Td
(ophthalmic)Tj
4.7905 0 Td
(gel)Tj
-33.7773 -1.2983 Td
(\(Goniovisc)Tj
4.609 0 Td
(2.5%,)Tj
2.3811 0 Td
(HUB)Tj
2.3017 0 Td
(Pharmaceuticals\))Tj
7.1092 0 Td
(was)Tj
1.7008 0 Td
(applied)Tj
3.1521 0 Td
(on)Tj
1.2756 0 Td
(the)Tj
1.4683 0 Td
(eye)Tj
1.5251 0 Td
(and)Tj
1.7291 0 Td
(the)Tj
1.4683 0 Td
(objective)Tj
3.7814 0 Td
(was)Tj
1.7008 0 Td
(oriented)Tj
-34.2025 -1.3039 Td
(for)Tj
1.3833 0 Td
(imaging.)Tj
3.7132 0 Td
(Just)Tj
1.7348 0 Td
(after)Tj
2.0353 0 Td
(intraperitoneal)Tj
6.1795 0 Td
(injection)Tj
3.7587 0 Td
(of)Tj
1.0148 0 Td
(a)Tj
0.6519 0 Td
(solution)Tj
3.4866 0 Td
(of)Tj
1.0148 0 Td
(fluorescein)Tj
4.6035 0 Td
(\(10)Tj
/F18 1 Tf
1.5137 0 Td
[()]TJ
/F10 1 Tf
(L)Tj
1.2642 0 Td
(of)Tj
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4.7791 0 Td
(compared)Tj
4.1953 0 Td
(to)Tj
1.0148 0 Td
(control)Tj
-34.1572 -1.2982 Td
(mice.)Tj
2.3471 0 Td
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(may)Tj
1.9105 0 Td
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(partly)Tj
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(the)Tj
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(hyperphagia)Tj
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(showed)Tj
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(circulating)Tj
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(leptin.)Tj
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(remained)Tj
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(important)Tj
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(a)Tj
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(decrease)Tj
3.5603 0 Td
(in)Tj
1.0261 0 Td
(tubular)Tj
3.0898 0 Td
(reabsorption)Tj
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(\()Tj
0.83 0.64 0.02 0 k
(S2)Tj
1.4911 0 Td
(Fig)Tj
0 g
(\).)Tj
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-23.38 -1.304 Td
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1.6101 0 Td
(next)Tj
1.9559 0 Td
(performed)Tj
4.4729 0 Td
(systematic)Tj
4.3597 0 Td
(histopathology)Tj
6.1398 0 Td
(analyses)Tj
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(of)Tj
1.0148 0 Td
(the)Tj
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1.0148 0 Td
[()4()16()6()]TJ
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 522.9921 307.5023 cm
BT
/F16 1 Tf
1 TL
-0.0053 Tc
0 0 Td
( )Tj
/F15 1 Tf
[( )]TJ
/F16 1 Tf
( )Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 536.3149 303.0236 cm
BT
/F10 1 Tf
1 TL
-0.004 Tc
0 0 Td
(mice)Tj
2.1543 0 Td
(at)Tj
-35.7843 -1.2982 Td
(different)Tj
3.6567 0 Td
(time-points.)Tj
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(analyses)Tj
3.4866 0 Td
(of)Tj
1.0148 0 Td
(kidney)Tj
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(sections)Tj
3.4072 0 Td
(at)Tj
0.9525 0 Td
(3,)Tj
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(7,)Tj
0.9184 0 Td
(and)Tj
1.7348 0 Td
(1520)Tj
2.6362 0 Td
(weeks)Tj
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(of)Tj
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(age)Tj
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(revealed)Tj
3.5206 0 Td
(an)Tj
1.2076 0 Td
(age-associated)Tj
5.93 0 Td
(increase)Tj
3.4696 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.4683 0 Td
(glomerular)Tj
4.6318 0 Td
(cross-sectional)Tj
6.1058 0 Td
(area)Tj
1.8822 0 Td
(in)Tj
/F15 1 Tf
1.0375 0 Td
[()4()16()6()]TJ
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 525.5433 281.4803 cm
BT
/F16 1 Tf
1 TL
-0.0053 Tc
0 0 Td
( )Tj
/F15 1 Tf
[( )]TJ
/F16 1 Tf
( )Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 538.8661 277.0582 cm
BT
/F10 1 Tf
1 TL
-0.004 Tc
0 0 Td
(mice.)Tj
2.381 0 Td
(At)Tj
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(7)Tj
0.6917 0 Td
(weeks)Tj
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(of)Tj
1.0148 0 Td
(age,)Tj
1.7631 0 Td
(this)Tj
1.6781 0 Td
(area)Tj
1.8822 0 Td
(was)Tj
1.7008 0 Td
(already)Tj
3.1067 0 Td
(significantly)Tj
5.091 0 Td
(higher)Tj
2.8006 0 Td
(compared)Tj
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(to)Tj
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(control)Tj
3.1237 0 Td
(littermates)Tj
4.4559 0 Td
(\()Tj
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(Fig)Tj
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(1A)Tj
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(and)Tj
1.7292 0 Td
(1B)Tj
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(\).)Tj
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(1520)Tj
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1.0148 0 Td
(age,)Tj
1.7688 0 Td
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2.5058 0 Td
(showed)Tj
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(glomerular)Tj
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(lesions)Tj
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(with)Tj
1.9956 0 Td
(moderate-to-severe)Tj
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(of)Tj
1.0148 0 Td
(the)Tj
1.4683 0 Td
(mesangial)Tj
4.2179 0 Td
(areas,)Tj
2.4718 0 Td
(together)Tj
3.532 0 Td
(with)Tj
2.0012 0 Td
(moderate)Tj
4.0252 0 Td
(mesangial)Tj
4.2179 0 Td
(cell)Tj
1.5591 0 Td
(proliferation.)Tj
5.4934 0 Td
(Females)Tj
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3.2485 0 Td
(similar)Tj
2.9877 0 Td
(glomerular)Tj
4.6318 0 Td
(lesions)Tj
2.9366 0 Td
(at)Tj
0.9525 0 Td
(this)Tj
1.6724 0 Td
(age,)Tj
1.7688 0 Td
(although)Tj
3.7531 0 Td
(the)Tj
1.4683 0 Td
(changes)Tj
3.4016 0 Td
(were)Tj
2.1259 0 Td
(generally)Tj
3.8324 0 Td
(less)Tj
1.61 0 Td
(severe)Tj
-34.3896 -1.2983 Td
(\()Tj
0.83 0.64 0.02 0 k
(Fig)Tj
1.8198 0 Td
(1C)Tj
0 g
(\).)Tj
1.9219 0 Td
(At)Tj
1.2019 0 Td
(this)Tj
1.6781 0 Td
(time-point,)Tj
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4.7395 0 Td
[()4()16()6()]TJ
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 336.4724 216.4535 cm
BT
/F16 1 Tf
1 TL
-0.0053 Tc
0 0 Td
( )Tj
/F15 1 Tf
[( )]TJ
/F16 1 Tf
( )Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 349.7952 212.0314 cm
BT
/F10 1 Tf
1 TL
-0.004 Tc
0 0 Td
(mice)Tj
2.1543 0 Td
(did)Tj
1.542 0 Td
(not)Tj
1.5761 0 Td
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(nodular)Tj
3.3846 0 Td
(glomerulosclerosis)Tj
7.6535 0 Td
(and)Tj
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(were)Tj
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(no)Tj
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(findings)Tj
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(in)Tj
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(the)Tj
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(tubulointerstitial)Tj
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(compartment.)Tj
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(the)Tj
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(context)Tj
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(of)Tj
1.0148 0 Td
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(type)Tj
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(2)Tj
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(diabetes,)Tj
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(the)Tj
1.4683 0 Td
(renal)Tj
2.2451 0 Td
(functional)Tj
4.3086 0 Td
(alterations)Tj
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(and)Tj
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(histological)Tj
4.7678 0 Td
(modifications)Tj
5.7373 0 Td
(in)Tj
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1.0375 0 Td
[()4()16()6()]TJ
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 338.2866 177.5055 cm
BT
/F16 1 Tf
1 TL
-0.0053 Tc
0 0 Td
( )Tj
/F15 1 Tf
[( )]TJ
/F16 1 Tf
( )Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 351.6094 173.0267 cm
BT
/F10 1 Tf
1 TL
-0.004 Tc
0 0 Td
(mice)Tj
2.1543 0 Td
(were)Tj
2.1203 0 Td
(consistent)Tj
4.2576 0 Td
(with)Tj
1.9956 0 Td
(an)Tj
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(early)Tj
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(stage)Tj
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(of)Tj
1.0148 0 Td
(diabetic)Tj
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(nephropathy.)Tj
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Q
q
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 126.9921 cm
BT
/F0 1 Tf
1 TL
-0.0033 Tc
0 0 Td
(Chronic)Tj
3.6189 0 Td
(kidney)Tj
3.0756 0 Td
(damages)Tj
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(in)Tj
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0.9826 0 Td
(Pparg)Tj
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Q
q
1 j
1 J
0 w
8.9997 0 0 7.999 375.1937 132.3212 cm
BT
/F7 1 Tf
1 TL
-0.0044 Tc
0 0 Td
[()]TJ
/F0 1 Tf
(/)Tj
/F7 1 Tf
[()]TJ
ET
Q
q
1 j
1 J
0 w
11.9999 0 0 11.9999 392.2582 126.9921 cm
BT
/F0 1 Tf
1 TL
-0.0033 Tc
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(ageing)Tj
3.1748 0 Td
(mice)Tj
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(associate)Tj
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(diabetic)Tj
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(antiphospholipid)Tj
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(syndrome)Tj
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Q
q
1 j
1 J
0 w
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BT
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1 TL
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(Searching)Tj
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(for)Tj
1.3833 0 Td
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3.1918 0 Td
(signs)Tj
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(nephropathy,)Tj
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(we)Tj
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(evaluated)Tj
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(the)Tj
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(evolution)Tj
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(of)Tj
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(the)Tj
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(lesions)Tj
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(increasing)Tj
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(age.)Tj
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(At)Tj
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(52)Tj
1.1679 0 Td
(weeks,)Tj
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2.8346 0 Td
[()4()16()6()]TJ
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 355.8614 87.4204 cm
BT
/F16 1 Tf
1 TL
-0.0053 Tc
0 0 Td
( )Tj
/F15 1 Tf
[( )]TJ
/F16 1 Tf
( )Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 369.1842 82.9984 cm
BT
/F10 1 Tf
1 TL
-0.004 Tc
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(mice)Tj
2.1543 0 Td
(exhibited)Tj
3.9288 0 Td
(altered)Tj
2.9423 0 Td
(renal)Tj
2.245 0 Td
(functions)Tj
3.9912 0 Td
(based)Tj
2.4718 0 Td
(on)Tj
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Q
q
0.45 0.36 0.35 0.01 k
1 j
1 J
0 w
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576 703.8893 l
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f*
208.7748 703.3893 m
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f*
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f*
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f*
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f*
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f*
486.7152 690.3893 m
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f*
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f*
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f*
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f*
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f*
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f*
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f*
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f*
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f*
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f*
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f*
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f*
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f*
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f*
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f*
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f*
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f*
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f*
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f*
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f*
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f*
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f*
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208.7748 552.89 m
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341.1408 552.89 m
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f*
341.1408 540.39 m
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f*
486.7152 552.89 m
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486.2151 540.8901 l
486.2151 552.89 l
f*
486.7152 540.39 m
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486.2151 540.8901 l
f*
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208.7748 527.8901 l
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f*
208.7748 527.8901 m
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341.1408 527.8901 m
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575.9991 456.6402 m
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575.9991 457.1402 l
f*
0 g
7.9999 0 0 7.9999 36 708.7181 cm
BT
/F4 1 Tf
1 TL
-0.005 Tc
0 0 Td
(Table)Tj
2.7992 0 Td
(1.)Tj
1.2614 0 Td
(Functional)Tj
5.23 0 Td
(renal)Tj
2.5724 0 Td
(paramete)Tj
4.3725 0 Td
(rs)Tj
1.141 0 Td
(of)Tj
1.1551 0 Td
(control)Tj
3.5717 0 Td
(and)Tj
/F21 1 Tf
1.9842 0 Td
(Pparg)Tj
ET
Q
q
1 j
1 J
0 w
5.9998 0 0 5.3325 251.0929 712.2897 cm
BT
/F22 1 Tf
1 TL
-0.0067 Tc
0 0 Td
[()]TJ
/F21 1 Tf
(/)Tj
/F22 1 Tf
[()]TJ
ET
Q
q
1 j
1 J
0 w
7.9999 0 0 7.9999 262.3748 708.7181 cm
BT
/F4 1 Tf
1 TL
-0.005 Tc
0 0 Td
(mice)Tj
2.4661 0 Td
(at)Tj
1.0914 0 Td
(3)Tj
0.7653 0 Td
(and)Tj
1.9843 0 Td
(7)Tj
0.7653 0 Td
(weeks)Tj
3.1749 0 Td
(of)Tj
1.1551 0 Td
(age.)Tj
0 Tc
-39.6994 -1.8567 Td
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3.9118 0 Td
(ers)Tj
24.9592 0 Td
(CTL)Tj
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16.3206 0 Td
(Pparg)Tj
ET
Q
q
1 j
1 J
0 w
5.9998 0 0 5.3325 420.1511 697.4362 cm
BT
/F22 1 Tf
1 TL
0 0 Td
[()]TJ
/F21 1 Tf
(/)Tj
/F22 1 Tf
[()]TJ
ET
Q
q
1 j
1 J
0 w
7.9999 0 0 7.9999 517.6062 693.8645 cm
BT
/F4 1 Tf
1 TL
0 0 Td
(P)Tj
0.8929 0 Td
(value)Tj
-61.0941 -1.6228 Td
(3)Tj
0.7795 0 Td
(weeks)Tj
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-0.7795 -1.5591 Td
(Body)Tj
2.4945 0 Td
(weight)Tj
3.0969 0 Td
(\(g\))Tj
20.0552 0 Td
(12.36)Tj
/F7 1 Tf
2.7142 0 Td
[( )]TJ
/F0 1 Tf
0.7654 0 Td
(0.39\(N)Tj
3.2103 0 Td
(=)Tj
0.8149 0 Td
(7\))Tj
10.1411 0 Td
(8.30)Tj
/F7 1 Tf
2.1614 0 Td
[( )]TJ
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0.7724 0 Td
(0.44\(N)Tj
3.2103 0 Td
(=)Tj
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(5\))Tj
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[( )]TJ
/F0 1 Tf
(0.0001)Tj
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(Glycemia)Tj
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(\(mmol/L\))Tj
20.9978 0 Td
(10.05)Tj
/F7 1 Tf
2.7142 0 Td
[( )]TJ
/F0 1 Tf
0.7653 0 Td
(0.25\(N)Tj
3.2103 0 Td
(=)Tj
0.815 0 Td
(11\))Tj
9.8646 0 Td
(15.97)Tj
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2.7142 0 Td
[( )]TJ
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0.7724 0 Td
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(=)Tj
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(10\))Tj
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(0.0113)Tj
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(kidney)Tj
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(w.)Tj
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(\(x100\))Tj
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[( )]TJ
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(=)Tj
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(7\))Tj
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(1.69)Tj
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[( )]TJ
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(0.06\(N)Tj
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(=)Tj
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(5\))Tj
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[( )]TJ
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(0.0001)Tj
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(creatinine)Tj
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[()]TJ
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(mol/L\))Tj
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[( )]TJ
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(10\))Tj
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(11.2)Tj
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2.1615 0 Td
[( )]TJ
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0.7653 0 Td
(0.9\(N)Tj
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(=)Tj
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(8\))Tj
10.4386 0 Td
(0.4088)Tj
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(Glucosuria/)Tj
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(creatininuri)Tj
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(a)Tj
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[( )]TJ
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(=)Tj
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(6\))Tj
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(7.16)Tj
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[( )]TJ
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0.7724 0 Td
(1.91\(N)Tj
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(=)Tj
0.8079 0 Td
(4\))Tj
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(0.0241)Tj
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(Urine)Tj
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(albumi)Tj
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(e)Tj
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(\()Tj
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[()]TJ
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(g/mg\))Tj
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(53.35)Tj
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2.7142 0 Td
[( )]TJ
/F0 1 Tf
0.7654 0 Td
(7.77\(N)Tj
3.2103 0 Td
(=)Tj
0.8149 0 Td
(6\))Tj
9.3119 0 Td
(296.50)Tj
/F7 1 Tf
3.267 0 Td
[( )]TJ
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0.7653 0 Td
(87.31\(N)Tj
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(=)Tj
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(4\))Tj
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(0.0082)Tj
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(7)Tj
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(weight)Tj
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(\(g\))Tj
20.0552 0 Td
(23.68)Tj
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2.7142 0 Td
[( )]TJ
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0.7654 0 Td
(0.28\(N)Tj
3.2103 0 Td
(=)Tj
0.8149 0 Td
(7\))Tj
9.8647 0 Td
(23.02)Tj
/F7 1 Tf
2.7142 0 Td
[( )]TJ
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0.7653 0 Td
(0.82\(N)Tj
3.2103 0 Td
(=)Tj
0.815 0 Td
(6\))Tj
9.8858 0 Td
(0.4383)Tj
-60.4067 -1.5591 Td
(24h)Tj
1.878 0 Td
(water)Tj
2.6645 0 Td
(intake)Tj
2.8772 0 Td
(\(ml\))Tj
18.5033 0 Td
(5.17)Tj
/F7 1 Tf
2.1615 0 Td
[( )]TJ
/F0 1 Tf
0.7653 0 Td
(0.43\(N)Tj
3.2103 0 Td
(=)Tj
0.815 0 Td
(7\))Tj
10.141 0 Td
(30.51)Tj
/F7 1 Tf
2.7142 0 Td
[( )]TJ
/F0 1 Tf
0.7653 0 Td
(0.78\(N)Tj
3.2103 0 Td
(=)Tj
0.815 0 Td
(7\))Tj
/F7 1 Tf
9.5953 0 Td
[( )]TJ
/F0 1 Tf
(0.0001)Tj
-60.1162 -1.5661 Td
(24h)Tj
1.878 0 Td
(urinary)Tj
3.2669 0 Td
(output)Tj
2.9906 0 Td
(\(ml\))Tj
17.7875 0 Td
(1.05)Tj
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2.1615 0 Td
[( )]TJ
/F0 1 Tf
0.7653 0 Td
(0.10\(N)Tj
3.2103 0 Td
(=)Tj
0.815 0 Td
(7\))Tj
10.4174 0 Td
(26.33)Tj
/F7 1 Tf
2.7142 0 Td
[( )]TJ
/F0 1 Tf
0.7653 0 Td
(1.3\(N)Tj
2.6646 0 Td
(=)Tj
0.8079 0 Td
(6\))Tj
/F7 1 Tf
9.8717 0 Td
[( )]TJ
/F0 1 Tf
(0.0001)Tj
-60.1162 -1.5591 Td
(Plasma)Tj
3.5433 0 Td
(Urea)Tj
2.3811 0 Td
(Nitrogen)Tj
3.9757 0 Td
(\(mmol/L\))Tj
16.2993 0 Td
(8.0)Tj
/F7 1 Tf
1.6087 0 Td
[( )]TJ
/F0 1 Tf
0.7724 0 Td
(1.10\(N)Tj
3.2032 0 Td
(=)Tj
0.815 0 Td
(5\))Tj
10.4174 0 Td
(11.10)Tj
/F7 1 Tf
2.7142 0 Td
[( )]TJ
/F0 1 Tf
0.7653 0 Td
(1.10\(N)Tj
3.2103 0 Td
(=)Tj
0.815 0 Td
(4\))Tj
9.8858 0 Td
(0.0043)Tj
-60.4067 -1.5661 Td
(Plasma)Tj
3.5433 0 Td
(creatinine)Tj
4.5284 0 Td
(\()Tj
/F7 1 Tf
[()]TJ
/F0 1 Tf
(mol/L\))Tj
17.8513 0 Td
(8.77)Tj
/F7 1 Tf
2.1615 0 Td
[( )]TJ
/F0 1 Tf
0.7653 0 Td
(0.57\(N)Tj
3.2103 0 Td
(=)Tj
0.815 0 Td
(7\))Tj
10.141 0 Td
(19.61)Tj
/F7 1 Tf
2.7142 0 Td
[( )]TJ
/F0 1 Tf
0.7653 0 Td
(1.45\(N)Tj
3.2103 0 Td
(=)Tj
0.815 0 Td
(7\))Tj
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9.5953 0 Td
[( )]TJ
/F0 1 Tf
(0.0001)Tj
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(Creatinine)Tj
4.7481 0 Td
(clearan)Tj
3.2457 0 Td
(ce)Tj
1.2826 0 Td
(\(ml/min\))Tj
16.0939 0 Td
(0.498)Tj
/F7 1 Tf
2.7142 0 Td
[( )]TJ
/F0 1 Tf
0.7653 0 Td
(0.060\(N)Tj
3.763 0 Td
(=)Tj
0.8079 0 Td
(7\))Tj
9.319 0 Td
(0.189)Tj
/F7 1 Tf
2.7142 0 Td
[( )]TJ
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0.7724 0 Td
(0.025\(N)Tj
3.756 0 Td
(=)Tj
0.8149 0 Td
(6\))Tj
9.6095 0 Td
(0.0009)Tj
-60.4067 -1.5661 Td
(Urine)Tj
2.6008 0 Td
(glucose)Tj
3.6425 0 Td
(\(mg/24h\))Tj
19.6797 0 Td
(1.64)Tj
/F7 1 Tf
2.1615 0 Td
[( )]TJ
/F0 1 Tf
0.7653 0 Td
(0.15\(N)Tj
3.2103 0 Td
(=)Tj
0.815 0 Td
(7\))Tj
9.0425 0 Td
(2273.03)Tj
/F7 1 Tf
3.8127 0 Td
[( )]TJ
/F0 1 Tf
0.7653 0 Td
(144.30\(N)Tj
4.3158 0 Td
(=)Tj
0.8079 0 Td
(6\))Tj
/F7 1 Tf
8.4969 0 Td
[( )]TJ
/F0 1 Tf
(0.0001)Tj
-60.1162 -1.5591 Td
(Urine)Tj
2.6008 0 Td
(albumi)Tj
2.9126 0 Td
(n)Tj
0.7796 0 Td
(\()Tj
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[()]TJ
/F0 1 Tf
(g/24h\))Tj
19.3536 0 Td
(62.86)Tj
/F7 1 Tf
2.7142 0 Td
[( )]TJ
/F0 1 Tf
0.7654 0 Td
(8.78\(N)Tj
3.2103 0 Td
(=)Tj
0.8149 0 Td
(4\))Tj
9.0426 0 Td
(1025.28)Tj
/F7 1 Tf
3.8127 0 Td
[( )]TJ
/F0 1 Tf
0.7653 0 Td
(52.03\(N)Tj
3.763 0 Td
(=)Tj
0.8079 0 Td
(4\))Tj
/F7 1 Tf
8.7733 0 Td
[( )]TJ
/F0 1 Tf
(0.0001)Tj
-60.1162 -2.3457 Td
(Functiona)Tj
4.3583 0 Td
(l)Tj
0.4535 0 Td
(parame)Tj
3.3591 0 Td
(ters)Tj
1.8922 0 Td
(of)Tj
1.063 0 Td
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