The nature of glomerular dysfunction in preeclampsia

The nature of glomerular dysfunction in preeclampsia. Justine Norman Introduction N orm al pregn an cy w a s com p ared to p reec la m p tic (P E ) p reg n a n cy w ith resp ect to g lo m eru lar ultrafiltration nitric o x id e (N O ) a c tiv ity , d er iv ed from the m eta b o lism o f L -arg in in e (L -arg) to c itru llin e . T w o b iom athem atica l m o d e ls , the “iso p o r o u s p lu s sh u n t” (m ean pore s iz e r„ ,shunt co m p o n en t o \,) and “lo g n o rm a l” (m ean pore s iz e U , standard d ev ia tio n S ), to g eth er w ith fractional dextran c lea ra n ce (0„) en ab led estim ation o f g lom eru lar u ltrafiltration param eters (K r u ltrafiltration c o e ff ic ie n t , APtransglom erular pressu re). N O a ctiv ity w a s a sse s se d from p lasm a and 24h r urinary N O x (nitrate and nitrite), seco n d m essen g er c y c lic G M P (cG M P ) and N O sy n th a se in h ib itor a sy m m etr ic -D -m eth y l-a r g in in e (A D M A ). Late pregnant (L P ) and postpartum (P P ) data are presen ted . A s N O m ig h t m ed iate g esta tio n a l renal v a sod ila ta tion , the e ffe c ts o f in fu sed L -argin in e (N O precursor) com p ared to g ly c in e , on ultrafiltration w ere ex a m in ed , testin g the h y p o th e sis that N O d e f ic ie n c y is im portant in renal v a so co n str ic tio n and hyp o filtration o f PE. Methodology 16 h ea lth y w o m en (controls: C N T L ) stu d ied in LP and > 4 m o n th s PP. 12 untreated p reec la m p tic (PE ) p rim igrav id as stu d ied LP and PP. h o llo w in g a 4 8 hour lo w nitrate/n itrite d iet, basal m ea su rem en ts w ere undertaken: p lasm a N O x , cG M P , L -arg and A D M A , 2 4 hour urinary N O x and cG M P . E ach then u n derw en t a 4 -h ou r neutral dextran, paraam inohippurate and in u lin in fu sio n . A fter lh there w ere 3 x 2 0 m in c lea ra n ces to m easure g lom erular filtration rate (G F R ), e f fe c t iv e renal p la sm a flow (E R P F ) and to obta in 0 n data. A fter 2h , each rece iv ed an a m in o a c id (aa) in fu s io n , e ith er L -argin in e or g ly c in e (1 m l/m in ). 3 x 2 0 m in c o lle c tio n p eriod s w ere again repeated after lh . Results S tu d y group G FR ml/min G FR during aa E R PF ml/min E R P F du rin g aa Kr r o C0o U S LP CNTL 8 . 6 6 0 . 4 0 . 0 0 5 51 1.18 G ly c 1 3 2 + /-9 144 + /-1 4 6 6 5 + /-7 3 7 1 3 + /-7 9 L-arg 1 5 1 + /-7 1 4 7+ /-9 7 0 8 + /-2 2 7 2 0 + /-3 3 PP CNTL 9.5 6 2 . 6 0 . 0 0 3 56 1.14 G ly c 1 0 0 + /-1 0 1 0 9 + /-1 6 5 2 1 + /-6 0 5 7 4 + /-7 0 L-arg 9 4 + /-6 . 9 1 + /-5 5 0 7 + /-3 9 5 0 5 + /-3 4 LP PE 6 . 4 6 2 . 4 0.01 52 1.22 G ly c 113 + /-9 1 0 8 + /-7 . 8 6 5 0 + /-6 0 6 1 7 + /-4 9 L-arg 1 1 4 + /-1 9 10 7 + /-1 5 . 3 5 4 1 +/-71 5 4 2 + /-7 4 PP PE 8 . 9 64 0 . 0 0 5 5 9 1.14 G lyc 8 3 + /-1 0 8 5 + /9 . 3 4 2 1 + /-5 8 41 7+7-53 L-arg 8 7 + /-8 8 9 + /-7 4 2 5 + /-3 7 4 6 7 + 7 -3 9 S tu d y group P lasm a N o x (m icroM ) 2 4 h rU N O x (m icroM ) P lasm a cG M P (p m o l/m l) 2 4 h rU cG M P (n m o le s) A D M A (uM ) LP C N T L 14.1 + /2 . 2 1096 + /103 6 . 3 + /0 . 4 17 2 8 + /183 0 . 4 7 + /0 . 0 7 PP C N T L 2 2 . 6 + 12.1 862 + /1 16 7 . 4 + /0 . 7 8 2 9 + /96 0 . 5 5 + / 0 . 0 6 LP PE 2 7 + / 5 . 3 1168 +72 6 5 7 . 3 + /0 . 7 1255 + /99 0 . 5 8 + / 0 . 1 PP PE 2 5 . 6 + /-5 . 1 9 0 8 + /9 8 8 + /0 . 9 7 7 2 + /95 0 . 5 3 + /0 . 0 7 Conclusions N orm al p regn an cy is a sso c ia ted w ith in creased G FR , E R P F , 0)o and S (p < 0 .0 5 ) . PE p reg n a n cy is a sso c ia te d w ith red uced K tbut increased rt) , G\„ U and S. PL v a lu e s PP approach con tro ls . From the in d ic e s that w ere u tilised , there w as no e v id e n c e o f sig n ifica n t N O d e f ic ie n c y in P reec lam p sia and e v en i f there w a s a relative d e fic ie n c y the in fu sio n o f the N O precu rsor L -a rg in in e fa iled to augm ent the d ecrea sed renal h a em o d y n a m ics o f p reec la m p sia . In PE the h y p o filtra tio n therefore h a s both a h a em o d y n a m ic and a structural b a sis , it r eco v ers PP and L -arg has no a m elio ra tin g e ffe c t in LP, or PP.