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QUIZ PAGEMAY 2013
A Case of Postpartum Acute Kidney Injury
arteries with reactive endothelium. Red blood cells are presentbetween the hyperplastic intimal layers (trichrome stain).
illaries without inflammation (Jones silver methenamine stain).
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CLINICAL PRESENTATIONA 30-year-old Asian woman presented with oligu-ria, edema, and breathlessness for the previous 10days and was found to have severe acute kidneyinjury. She was gravida 2, para 2 and had under-gone lower segment caesarean section at term 1month earlier. Her pregnancy was uncomplicated:she had normal kidney function and no pre-eclampsia. Her previous pregnancy also was un-eventful and delivered by lower segment caesar-ean section by choice. On evaluation, blood pressurewas high at 150/90 mm Hg and urinalysis showedproteinuria and hematuria. She had no evidenceof hypertensive retinopathy. Blood work showeda creatinine level of 13.2 mg/dL (corresponding toan estimated glomerular filtration rate of 3 mL/min/1.73 m2 using the 4-variable Modification of Dietin Renal Disease [MDRD] Study equation), a hemo-globin level of 6.4 g/dL, and a platelet count of2,700,000/�L. Peripheral smear showed normo-cytic normochromic anemia with occasional sphero-cytes, teardrop cells, target cells, acanthocytes, andno evidence of significant red blood cell fragmenta-tion. Liver function and coagulation profile resultswere normal, and lactate dehydrogenase level wasmildly elevated at 730 U/L (reference range, 240-480 U/L). Results of C3, antinuclear antibody,proteinase 3 and myeloperoxidase antinuclear cyto-plasmic antibody, and antiphospholipid antibodyscreens were negative.Akidney ultrasound showednormal-sized kidneys with increased echogenicityin the renal cortex. She was oligoanuric, and hemo-dialysis treatment was initiated. A kidney biopsywas performed (Figs 1-3).
� What does the biopsy show?
� What diseases cause thesepathologic findings?
� How should this patient be treated?
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Am J Kidney Dis. 2013;61(5):xxv-xxvii
Figure 1. Moderate degree of multilayering of the intima of small
Figure 2. Preglomerular arterioles show hyperplasia of the intima withswollen endothelium. The glomerulus shows congestion of the cap-
Figure 3. The glomerulus shows focal wrinkling of the capillary
asement membranes with occasional double contours (Jonesilver methenamine stain).ZPA
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ANSWERS
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DISCUSSION
f What does the biopsyshow?
Figure 1 shows a moderate degreeof multilayering of the intima ofsmall arteries with reactive endothe-lium. Red blood cells are presentbetween the hyperplastic intimallayers. Figure 2 shows preglomeru-lar arterioles with hyperplasia ofthe intima with swollen endothe-lium. The glomerulus shows con-gestion of the capillaries withoutinflammation. Figure 3 shows aglomerulus with focal wrinkling ofthe capillary basement membranesand occasional double contours.
Thrombotic microangiopathy(TMA) is the pathologic lesioncharacterized by occluded mi-crovessels due to swollen endothe-lial cells and subendothelial aggre-gation of platelets, proteins, anddebris. All diseases associated withTMA are characterized by kidneybiopsy findings of endothelial in-jury and thrombus formation.1 Thepathologic findings primarily in-volve glomeruli and vessels, can bedivided into acute and chronic le-sions, and do not distinguish be-tween the multiple disease entitiesassociated with TMA.
f What diseases causethese pathologicfindings?
The way TMA disorders are clas-sified has fluctuated over time,and even now the term TMA isinappropriately treated as if it weresynonymous with thromboticthrombocytopenic purpura-hemo-
lytic uremic syndrome (TTP-(q
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Table 1. Features and Treatments of Various Causes of TMA
Causes ofTMA Features Treatment
� HUS Cause of childhood HUS in 90% ofcases; caused by verocytotoxin-producing Escherichia coli
Treatment is supportive, butplasma exchange may be usedin patients with significantneurologic symptoms;eculizumab may be helpful
� HUSa Cause of childhood HUS in 10% ofcases; disease of alternatecomplement pathway, may befamilial
Plasma exchange is the first-linetherapy; eculizumab may behelpful
TTP Severe deficiency of ADAMTS13(genetic or acquired) commonly isobserved, no other obvious causehas been found
Plasma exchange is the treatmentof choice; in resistant cases,glucocorticoids, rituximab, orcyclosporine may be helpful
Pregnancy orpostpartumHUS
Risk of recurrence with subsequentpregnancies; can be difficult todifferentiate clinically andhistologically from HELLPsyndrome; progression past 3 dpostpartum can help differentiatefrom HELLP syndrome
Treatment is the same as adultTTP-HUS; during pregnancy, ifdistinction from HELLPsyndrome is difficult, delivery isindicated
Drugsb Quinine is the most common causeand the only drug with documenteddrug-dependent antibodies; oftenpresents with slowly progressivekidney failure, new/acceleratedhypertension, and bland urinarysediment
Often reversible withdiscontinuation of the offendingdrug; plasma exchangeineffective; may respond torituximab
Disseminatedmalignancy
Normal or slightly reduced ADAMTS13levels; high LDH; often occurs withmucin-producing adenocarcinoma
Plasma exchange ineffective
Transplant-associatedTMA
Schistocytes �4% of RBCs; de novoprolonged or progressivethrombocytopenia; high serum LDHand low haptoglobin
No role for plasma exchange; mayrespond to rituximab
APS Kidney involvement in 25% of primaryAPS patients; clinical spectrumvaries from mild proteinuria to acute/subacute kidney failure and oftenmarked hypertension
May respond to eitherplasmapheresis orcorticosteroids andmaintenance anticoagulation
Sclerodermakidney
Abrupt onset of severe hypertension;bland urine sediment withprogressive kidney failure
ACE inhibitors are the drugs ofchoice; may progress to ESRDin 20%-50% despite treatment
Note: Apart from the causes listed here, TMA also can be caused by malignant nephroscle-rosis, radiation nephritis, and human immunodeficiency virus infection.
Abbreviations: ACE, angiotensin-converting enzyme; APS, antiphospholipid syndrome; D�HUS, diarrhea-positive hemolytic uremic syndrome; D� HUS, diarrhea-negative hemolytic uremicsyndrome; ESRD, end-stage renal disease; HELLP, hemolysis, elevated liver enzymes, lowplatelet count; HUS, hemolytic uremic syndrome; LDH, lactate dehydrogenase; RBC, red bloodcell; TMA, thrombotic microangiopathy; TTP, thrombotic thrombocytopenic purpura.
aAlso known as atypical HUS.bDrugs include mitomycin C, cisplatin, gemcitabine, vascular endothelial growth factors
bevasizumab), immunosuppressives (cyclosporine, tacrolimus), and other drugs such asuinine and ticlopidine.
Am J Kidney Dis. 2013;61(5):xxv-xxvii
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HUS).2 Although one can be confi-ent of the diagnosis of postpartumUS in the clinical setting de-
cribed, the morphologic findingsre not specific to this conditionnd many diseases centeredround the endothelium-plateletnteraction will manifest the sametructural lesions. These includeiarrhea-positive HUS, which ac-ounts for 90% of HUS in chil-ren, and diarrhea-negative HUS,r atypical HUS, which is a dis-ase of the alternative comple-ent pathway. TTP, which should
e reserved for genetic or ac-uired deficit of the enzymaticctivity ofADAMTS13, will showhe same histologic features. Whenther precise causes or mecha-isms of the process are known, its called secondary TMA. Pro-esses that can induce these changesnclude malignant hypertension, an-iphospholipid syndrome, radiationxposure, bone marrow transplanta-ion, scleroderma, medication (cal-ineurin inhibitors, clopidogrel, mi-omycin C, gemcitabine, cisplatin,nti–vascular endothelial growthactor agents, etc), and neoplasias.able 1 lists the diseases respon-ible for TMA, their key features,nd the appropriate treatment forach condition.
How should this patientbe treated?
aternal mortality was as high as
5% in cases of postpartum HUS 2Am J Kidney Dis. 2013;61(5):xxv-xxvii
n the pre–plasma exchange era,s reported in a series by Weiner.3
Since the introduction of plasmaexchange, the outcome has im-proved significantly, as shown ina more recent series of 11 patientsin which 9 survived.4 Althoughhere was no evidence of signifi-ant red blood cell fragmentationn the peripheral smear, whichften is considered the hallmarkf the disease, this patient wasreated successfully with 6 ses-ions of plasma exchange usingresh frozen plasma as the replace-ent fluid. There was gradual im-
rovement in kidney function overhe next 4 months, with serumreatinine level decreasing to 1.9g/dL (estimated glomerular fil-
ration rate, 31 mL/min/1.73 m2).his case emphasizes the impor-
ance of initiating plasma ex-hange in patients with postpar-um HUS even if there is somencertainty about the diagnosis.
FINAL DIAGNOSISPostpartum HUS.
REFERENCES1. Halevy D, Radhakrishnan J,
Glen Markowitz G, Appel G. Throm-botic microangiopathies. Crit Care
lin. 2002;18:309-320.2. De Serres S, Isenring P. Renal
hrombotic microangiopathy revisited:hen a lesion is not a clinical finding.audi J Kidney Dis Transplant. 2010;
1:411-416.3. Weiner CP. Thrombotic mi-croangiopathy in pregnancy and thepostpartum period. Semin Hematol.1987;24:119-129.
4. Egerman RS, Witlin AG, Fried-man SA, Sibai BM. Thromboticthrombocytopenic purpura and hemo-lytic uremic syndrome in pregnancy:review of 11 cases. Am J Obstet Gyne-col. 1996;175:950-956.
CASE PROVIDED AND AUTHORED BY
Shashidhar Baikunje, MD,FRCP(UK),1 Mahesha Vank-alakunti, MD,2 and RamaPrakasha Saya, MD,3 1Depart-ment of Nephrology, K.S. HegdeMedical Academy, Deralakatte,Mangalore; 2Department of Ne-phropathology, Manipal Hospital,Bengaluru; and 3Department ofMedicine, K.S. Hegde MedicalAcademy, Deralakatte, Manga-lore, Karnataka, India.
ddress correspondence to ShashidharBaikunje, MD, FRCP(UK), De-partment of Nephrology, K.S.Hegde Medical Academy, De-ralakatte, Mangalore, Karnataka,India. E mail: [email protected] by the National KidneyFoundation, Inc.
ttp://dx.doi.org/10.1053/j.ajkd.012.12.032UPPORT: None.
FINANCIAL DISCLOSURE: The authorsdeclare that they have no relevantfinancial interests.
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