Postpartum Atypical Hemolytic Uremic Syndrome: an Unusual and Severe Complication Associated with IgA Nephropathy

Chin Med Sci J September 2015

Vol. 30, No. 3 P. 189-192

CHINESE MEDICAL SCIENCES JOURNAL CASE REPORT

Postpartum Atypical Hemolytic Uremic Syndrome: an Unusual and Severe Complication Associated with IgA Nephropathy Li-xian Sun1, Wen-ling Ye2*, Yu-bing Wen2, and Xue-mei Li2 1

Department of Cardiology, 2Department of Nephrology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China

Key words: acute kidney injury; hemolytic uremic syndrome; IgA nephropathy; pregnancy Chin Med Sci J 2015; 30(3):189-192

I

GA nephropathy (IgAN) is one of the most common

medical history was negative before gestation.

types of primary glomerulonephritis, which occurs

Five days after cesarean section in the 40th gestational

more frequently in patients of reproductive age.

week, her urine volume started to decline, her blood

Atypical

pressure

hemolytic

uremic

syndrome

(aHUS)

increased

with

maximum

measurement at

without diarrhea is rare and has a poor prognosis. In the

180/110 mm Hg, and she developed progressive AKI. She

absence of appropriate therapy, pregnancy-related aHUS

had no fever, nor abnormality on neurological examinations.

is associated with high morbidity and mortality. This report

Her platelet count dropped to a minimum of 48×109/L, and

described a successfully treated case of postpartum aHUS

hemoglobin to 80 g/L with red blood cell fragmentation in

associated with IgAN. Repeated renal biopsy was per-

peripheral blood smears. Her urinary protein excretion was

formed to demonstrate serial renal pathologic changes

6.24 g/day. Serum biochemical parameters revealed low

after successful treatment.

albumin (18 g/L) and total protein (32 g/L) and elevated lactate dehydrogenase (1324 U/L). Her alanine amino-

CASE DESCRIPTION A 26-year-old female (gravida 1, para 1) presented with acute kidney injury (AKI), nephrotic syndrome,

transferase, aspartate aminotransferase, immunoglobulin and serum complement concentrations were normal. The detection for antinuclear antibodies (ANA), lupus anticoagulant and anticardiolipin antibody was negative.

thrombocytopenia and hemolytic anemia 5 days after

The diagnosis of HUS was made and she was treated

delivery. Routine urinalysis showed protein (1-2+) and

with intravenous methylprednisolone (60 mg/day) and

blood (2-3+) at the 22nd gestational week. Her blood

fresh frozen plasma infusion (400-600 ml/day) for 1 week,

pressure remained normal during the pregnancy, and her

followed by oral methylprednisolone [0.8 mg/(kg·d)]. Hemodialysis three times per week was initiated when her

Received for publication July 3, 2014.

serum creatinine was measured at 521 μmol/L one week

*Corresponding author Tel: 86-10-69155058, E-mail: wenlyepumch@

after delivery. Her platelet count gradually increased to

163.com

(80-100)×109/L and her blood pressure was controlled at

190

CHINESE MEDICAL SCIENCES JOURNAL

September 2015

lower than 140/90 mm Hg by angiotensin-converting enzyme

scribed with prednisone [1 mg/(kg⋅d)], which was decre-

inhibitors and angiotensin receptor blocker. A percutaneous

mented gradually after 6 weeks and maintained with the

renal biopsy was performed 2 weeks after delivery. Immuno-

dose of 5 mg/day for 1 year. She was also administered

fluorescence showed intense (3+) staining for IgA and C3

oral cyclophosphamide (100 mg/d) with cumulative dosage

in the mesangial area (Fig. 1A). Light microscopy displayed

of 9 grams. Her serum creatinine concentration decreased

severe mesangial proliferation and typical lesions of

to 110-120 μmol/L, and her 24-hour urinary protein was

thrombotic microangiopathy (TMA), including subendo-

less than 1 g in the follow-up visits after one year.

thelial mucosal edema, fibro-necrosis and marked thickening of the artery walls in the majority of afferent arterioles and

DISCUSSION

interlobular arteries (Fig. 1 B, C). The lumen of most arterioles was nearly completely occluded.

HUS, a form of TMA characterized by thrombocy-

Her renal function partially improved after 6 weeks of

topenia, hemolytic anemia and AKI, is a life-threatening

treatment, when hemodialysis and methylprednisolone

disorder presenting in 2.3%-9.1% of obstetric women with

were discontinued. She was referred to our hospital 7

AKI.1,2 In contrast to typical HUS, which is associated with

months after delivery because of sustained nephrotic-

diarrhea, aHUS, which occurs without diarrhea, is rare and

range proteinuria and renal dysfunction. Laboratory tests

has a poorer prognosis. It is usually secondary to autoim-

showed blood (3+) in urine, proteinuria of 3.21 g/24 h,

mune disease, malignant hypertension or medication.3

hemoglobin of 104 g/L, platelet count of 239×109/L, and

Pregnancy is also a risk factor for aHUS, with the highest

serum creatinine concentration of 143 μmol/L. Repeated

incidence near term and during the postpartum period.

renal biopsy showed moderate mesangial hypercellularity

This is also the time of greatest risk for thrombotic events

with segmental sclerosis and ischemic glomerular lesions

and for

(Fig. 1 D-F). Immunofluorescence findings were comparable

syndromes: preeclampsia, eclampsia, and hemolysis, elevated

with those observed during the first biopsy. She was pre-

liver enzymes, and low platelets (HELLP) syndrome.4

the

occurrence

of

other pregnancy-related

Figure 1. Serial renal pathologic changes 2 weeks and 7 months after delivery. A. Immunofluorescence showing diffuse and massive deposits of IgA in the mesangial area, confirming the diagnosis of IgA nephrology (×400). B. First renal biopsy performed 2 weeks postpartum, showing fibrinoid necrosis in the afferent arterioles. The glomerulus display severe mesangial proliferation and intracapillary thrombi (periodic acid-schiff stain, ×200). C. Renal biopsy at 2 weeks postpartum, showing severe mucosal edema with almost entirely occluded lumen in the interlobular (periodic acid-schiff stain, ×200). D-F. Renal biopsy taken 7 months after delivery, revealing moderate mesangial hypercellularity with mesangial expansion and segmental sclerosis (D, HE, ×200) and enlargement of the Bowman capsule (E, PASM, ×200). The vascular lumen of the interlobular arteries being re-canalized with mild intimal elastic membrane thickening (E&F, PASM, ×200).

Vol. 30, No.3

CHINESE MEDICAL SCIENCES JOURNAL

191

Although IgAN is one of the most common primary

this patient, may result in further injury of endothelial cells

glomerulonephritis, its diagnosis can only be confirmed by

of glomerular capillaries by the deposition of IgA immune

the immunolocalization of mesangial IgA deposition.

complexes at subendothelium, expansion of the mesangial

Pregnancy-related aHUS is quite rare in the setting of IgAN.

matrix, and mesangial cells proliferating into the subendo-

A search in Medline using the keywords “pregnancy”,

thelium.

“hemolytic uremic syndrome” and “IgAN” yielded no

Recently, genetic abnormalities of complement regulatory

articles published between 1966 and 2013. The incidence

genes are regarded as one of pathogenic mechanisms of

of aHUS associated with IgAN may be underestimated

aHUS.9,10 A review of 21 pregnant French women with

because some pregnant women with aHUS have no

aHUS found that 18 of them had complement abnormalities

opportunity to renal biopsy with the contraindication of severe

and 17 had dysregulation of alternative complement

illness or continuous thrombocytopenia. The strong depos-

regulatory proteins.10 However, the involvement of the

ition of IgA in mesangial areas and pathological findings

complement pathway in HUS development in this case is

typical of mesangial proliferation confirmed the diagnosis

uncertain, since her complement level was normal at the

of IgAN in this case. Routine examination during the

time of HUS diagnosis. Several mechanisms may contribute

pregnancy showed microhematuria and proteinuria without

to the association between aHUS and IgAN in this patient,

hypertension, which is the most common manifestation of

including hypercoagulable state and oxidative stress caused

IgAN, indicating that this patient had developed IgAN

by nephrotic syndrome, severe hypertension, mutations of

before aHUS.

genes encoding regulators of the alternative complement

Pregnancy-related HUS has a very poor prognosis, with a maternal mortality rate of 44% and a perinatal mortality 5

rate of 80%. Although the standard treatment of aHUS

pathway, and high coagulation activity related to pregnancy. However,

further

investigations

and

researches

are

requisite to explore the exact mechanisms of aHUS. In conclusion, although aHUS is rarely associated with

associated with IgAN is uncertain, early plasma exchange, are considered

IgAN, it should be considered in pregnant women with

effective and have been associated with a favorable

underlying glomerulonephritis when AKI occurs. Renal

outcome.6 Fortunately, the hemolytic anemia, thrombocy-

biopsies should be performed to exclude concomitant

topenia, and renal dysfunction in this case were rapidly

glomerulonephritis and titrate the appropriate therapy

ameliorated after plasma infusion, glucocorticoid therapy,

strategies for aHUS patients, especially in those with a

and hemodialysis. Sustained nephrotic-range proteinuria

history of microhematuria and proteinuria.

plasma

infusion, and glucocorticoids

and hypoalbuminemia, confirmed by repeated renal biopsy, was further improved after prescription of prednisone and

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NOTICE OF RETRACTION The Editor retracts the following article from Chinese Medical Sciences Journal: Liu K, Hao J, Shi J, Dai C, Guo X. Blood Lead Levels During Pregnancy and Its Influencing Factors in Nanjing, China. Chin Med Sci J 2013; 28(2): 95-101. The first author, Kang-sheng Liu, admitted to the editors to flaws in data collection and analysis that affect the authenticity and accuracy of this article. Dr Liu takes full responsibility for this.