PREGNANCY ASSOCIATED THROMBOTIC THROMBOCYTOPENIC PURPURA AND ACUTE KIDNEY INJURY
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1 VII, 2013, 2 33 A, PREGNANCY ASSOCIATED THROMBOTIC THROMBOCYTOPENIC PURPURA AND ACUTE KIDNEY INJURY M. Lubomirova Clinic of Nephrology, University Hospital Aleksandrovska So a : ( ), /HELLP, (AFLP) (TTP) -..,,.,, AFLP HELLP -,, -. :,, : -,,.,,,... 1, 1431, MLjubomirova@yahoo.com Summary: Acute kidney injury (AKI) is a rare but serious complication of pregnancy. Renal insuf ciency can complicate several other pregnancy-speci c conditions. In particular, severe preeclampsia/hellp syndrome, acute fatty liver of pregnancy (AFLP) and thrombotic thrombocytopenic purpura (TTP) are all frequently complicated by AKI, and share several clinical features which pose diagnostic challenges to the clinician. In this article, we discuss the clinical and laboratory features, pathophysiology and treatment of these 3 conditions, with particular attention to renal manifestations. It is imperative to distinguish these conditions to make appropriate therapeutic decisions which can be lifesaving for the mother and fetus. Typically AFLP and HELLP improve after delivery of the fetus, whereas plasma exchange is the rst-line treatment for TTP. Key words: pregnancy, acute kidney injury, thrombotic thrombocytopenic purpura Address for correspondence: Assist Prof. M. Lubomirova, MD, PhD, Clinic of Nephrology, University Hospital Aleksandrovska, 1 Sv. Georgi So yski, Bg So a, MLjubomirova@yahoo.com ( ), , -, -,.,
2 34 - [1, 2, 3, 4, 5] , 295 /1.,. 1-9% -, 40-60%., -,, , 10%. - [1, 2, 3, 4, 5]. - /., 50% -, [1, 2, 3, 4, 5]., -,. - RIFLE, -, -, [3, 4, 6]. > 1 mg/dl mg/dl ( 48 ). ( ).,, -, Cockcroft-Gault Cockcroft-Gault, Modi cations in Diet and Renal Disease MDRD [7]. -. Cockcroft-Gault, -., ,., -. Cockcroft-Gault = (140 ) * ( kg) * (0.85, ) / (72 * Scr*) (ml/min/1.73 m 2 ) = 175 (Scr) ( - ) (0.742, ) (1.212, - ) Scr* : = UV/P, U e , V,. -. RIFLE (R = risk ( ); I = injury ( ); F = failure ( ); L = loss ( ); E end stage renal disease ( ). 1,,,. - - RIFLE, -.
3 35 1. RIFLE RIFLE - Scr* / Scr* 1,5 > 25% Scr* 2 > 50% Scr* 3 > 75% Scr 354 mol/l ( 4 mg/ dl) 44 mol/l (0,5 mg/dl) = > 4 3, - ml/kg/h < 0.5 ml/kg/h 6 < 0.5 ml/kg/h 12 < 0.3 ml/kg/h RIFLE AKIN - (. 2) ,5 mol/l (0,3 mg/dl), 1.,, 3 [3, 4, 6]. 2. AKIN AKIN Scr* - / Scr* 1,5-2 Scr* 26,5 mol/l ( 0,3 mg/dl) Scr* 2-3 Scr* 3 Scr 354 mol/l ( 4 mg/ dl), 44 mol/l (0,5 mg/dl),, ml/kg/h < 0.5 ml/kg/h 6 < 0.5 ml/kg/h 12 < 0.3 ml/kg/h RIFLE AKIN, -, [3, 4, 6]. Neutrophil gelatinase associated lipocalin (NGAL)., NGAL interleukin (IL) 18 cystatin C. idney injury molecul-1 (KIM-1), [3, 4, 5, 8, 9, 10, 11]. - RIFLE AKIN,., :,,.,,, -,., - -,, / -.,
4 36,,, -, -, ( - ). de novo 20.., -,, , ,. -, [1, 2, 3, 4, 5, 11, 12]. (. 3,. 1 2) [11, 12].. 1. O,. 2.
5 37 :, Hyperemesis gravidarum Thrombothic microangyopathy thrombothic thrombocytopenic purpura (TTP) HUS hemolytic uremic syndrome Preeclampsia/HELLP syndrome* Acute fatty liver -, de novo (, ) HELLP syndrome*,, A PREGNANCY-ASSOCIATED THROMBOTIC MICROANGIOPATHIES ( -TMA), /.,, p-tma: 1. ( ) 2. - (HUS). ( ) : ( ),,, ( ) - < 1,4 mg/dl), -,,, -,,, [13]. HUS. - -, > 2.3 mg/dl, , HELLP, TTP, HUS , -. Disintegrin Metalloproteinase thrombospondin 9 (ADAMT-13), -, Von Willebrand. ADAMT-13 Von Willebrand,, -, ADAMT-13 ADAMT-13 10%. -, -. ADAMT-13, 67-85% [11, 12, 13, 14]. HUS (ahus non- Shiga-like toxin-associated HUS) -., ù, -. (factor H, factor I, membrane cofactor protein MCP, CD46, 3 B) - (.. 3 4).
6 p-. 4. HUS (ahus non-shiga-like toxinassociated HUS) : -, factor H, factor I, membrane cofactor protein MCP, CD46 3 B. antifactor H-. ADAMT-13 ahus -,,., -, - HUS-TTP, [14]. A pregnancy-asso ciated thrombotic microangiopathies (p-tma), -,. - p-tma - 2-3, ADAMTS ahus, 6. p-tma, -, - HELLP (. 4). 4., HELLP, AFLP, TTP ahus HELLP AFLP TTP ahus % 80% 25-50% 0/+ + / / / / + 0/ / / /+ 0/ ADAMTS-13* < 10% / - : 0 ; 0/+ ; + ; ++
7 39 p-tma 2/ ,. -,,.. 70%, p-tma, -, (. 5 6). (A) ( 250). 5 -, - p-tma, HUS, ahus p-tma, HUS, ahus,,,, / I LDH 24 HBV, HCV, HIV ( NA, anti-dna, RF, ACLA, lupus anticoagulant) - ADAMTS 13 ( / / / - ),, -, -,,, SLE, RA, antiphospholipid syndrome TMA - (B) ( 400). 5. p-tma (hemolytic uremic syndrome; HUS). - Masson s trichrome p-tma, : 10-20% - - (30-80%), :, - [4, 5, 9, 10, 11, 12]. p-tma. 6.. p-tma, - (plasma exchange, PEX)., -, PEX 90 20% ADAMTS-13.,. PEX, -
8 40,.. -- PEX - a -TMA. PEX : 1. PEX 1,5 plasma volume exchange FFP fresh frozen plazma, solvent-detergent-treated (S/D) plasma. 2. PEX 2, x 10 9 /l) 3. PEX, -, -, - PEX [1, 2, 3, 4, 5, 6, 15]. p-tma, [16]. - PEX, - /. Methylprednisolon - 1 g - 1 mg/kg 30. Rituximab - -, -. Cyslosporin A [3, 4, 16, 17]. -TMA ADAMT mg -, 50 x 10 9 /l ahus, factor H I anti-factor H. ahus,. -, p-tma [3, 4, 5, 16, 17]. 1. P r i m e r of Kidney Diseases. 5th edition. National Kidney Foundation. Philadelphia, Academic Press, 2005, Textbook of Nephrology. Second edition. Williams and Wilkins, KDIGO AKI. Clinical practice guidelines for acute kidney injury. Kidney Int. Suppl., 2, 2012, KDIGO. Clinical practice guideline for acute kidney injury. KDI- GO for Acute Kidney Injury w w w.renal.org/guidelines. 6. R i c c i, Z., D. N. Cruz et Cl. Ronco. Classi cation and staging of acute kidney injury: beyond the RIFLE and AKIN criteria. Nat. Rev. Nephrol. advance online publication, 1 March Cirillo, M. Rationale, pros and cons of GFR estimation: the Cockcroft-Gault and MDRD equations. G. Ital. Nefrol., 26, 2009, 3, Machado, S. et al. Acute kidney injury in pregnancy: a clinical challenge. J. Nephrol, 25, 2012, 1, R e n a l Disease in Pregnancy. Ed. J. M. Davison, Catherine- Nelson-Piercy, Sean Kehoe and Phillip Baker. Published by RCOG Press at the Royal College of Obstetricians and Gynaecolodists, London, Bellomo, R., J. Kellum et C. Ronco. Acute kidney injury. lancet.com, published online may 21, L i s o w s k a - M y j a k, B. Serum and urinary biomarkers of acute kidney injury. Blood Purif., 29, 2010, 4, doi: / Epub 2010 Apr L a f a y e t t e, R. AKI in pregnant patient two levels at stake. Nephrol. Times, 3, 2010, 5, Ganesan, Ch. et E. Sharon. MaynardAcute kidney injury in pregnancy: the thrombotic microangiopathies. J. Nephrol., 24, 2011, 5, Lattuada, A. et al. Mild to moderate eduction of a von Willebrand factor cleaving protease (ADAMTS-13) in pregnant women with HELLP microangiopathic syndrome. Haematologica, 88, 2003, G e o r g e, J. N. Clinical practice. thrombotic thrombocytopenic purpura. N. Engl. J. Med., 354, 2006, M a r t i n, J. N. Jr. et al. Thrombotic thrombocytopenic purpura in 166 pregnancies: Am. J. Obstet. Gynecol., 199, 2008, G e o r g e, J. N. The thrombotic thrombocytopenic purpura and hemolytic uremic syndromes: evaluation, management, and long-term outcomes experience of the Oklahoma TTP- HUS registry, Kidney Int., 112, 2009, Suppl., S52-S54.
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