European Journal of Obstetrics & Gynecology and

Reproductive Biology 108 (2003) 99102

Case report
Pathogenesis of acute renal failure associated with the HELLP
syndrome: a case report and review of the literature
Kottarathil A. Abrahama, Mairead Kennellyb,
Anthony M. Dormanc, J. Joseph Walshea,*
a
Department of Nephrology, Beaumont & Rotunda Hospitals, Dublin 9, Ireland
b
Department of Obstetrics, Rotunda Hospital, Dublin, Ireland
c
Department of Renal Pathology, Beaumont Hospital, Dublin, Ireland
Received 13 March 2002; received in revised form 13 August 2002; accepted 16 August 2002

Abstract

Acute renal failure is a rare but serious complication of pregnancy. We describe a 31-year-old woman with haemolytic anemia, elevated
liver enzymes, low platelets (HELLP syndrome) who developed acute peripartum renal failure. Renal biopsy performed 2 weeks later because
of persistent oliguria revealed thrombotic microangiopathy and acute tubular necrosis. This case highlights the probable pathogenesis of acute
renal failure in HELLP patients and explains why it resolves in the majority of cases. A review of the literature that describes renal histology in
HELLP patients is presented.
# 2002 Elsevier Science Ireland Ltd. All rights reserved.

Keywords: Acute renal failure; HELLP syndrome; Histopathology

1. Introduction pathophysiology of ARF in the HELLP syndrome and its

The hypertensive complications of pregnancy continue to
adversely impact on obstetric practice worldwide [1]. Some
of these women go on to develop pre-eclampsia, fatty liver of
pregnancy or haemolytic anemia, elevated liver enzymes
and low platelets (HELLP syndrome). The HELLP syn-
drome was first defined by Weinstein in 1982 in describing a
case of severe pre-eclampsia complicated by haemolytic
anemia, elevated liver enzymes and low platelets [2] and is
associated with increased risks of morbidity and mortality
[3]. Presentation can be varied [4] but this syndrome has
been noted to be a major cause of ARF that is severe enough
to require dialysis [5]. However, in our experience and
that of others, the majority of patients with HELLP who
develop ARF recover function [3,5,6]. This observation
and the potential risk of invasive procedures in pregnancy
have precluded renal biopsies in most patients. As a result,
there is a lack of information on renal histology from
individuals with the HELLP syndrome and the pathological
processes involved remain controversial [79]. We believe
that our patients renal biopsy findings can best explain the
*
Corresponding author. Tel.: 353-1-8092567; fax: 353-1-8092899.
E-mail address: joseph.walshe@beaumont.ie (J.J. Walshe).
varied outcome.
2. Case report
A 31-year-old primigravida was admitted at 26 weeks
gestation because of pre-eclampsia (PET), with recent-onset
hypertension (190/105 mm Hg) and 3 proteinuria. Labora-
tory investigations on admission revealed normal liver and
renal function with a serum creatinine of 80 mmol/l, elevated
serum uric acid at 539 mmol/l, haemoglobin 9.3 g/dl and a
platelet count of 324  109 l1. She was treated with labe-
tolol and a-methyldopa but despite improved BP control she
developed an abruption followed by intrauterine death 3
days later. After a failed trial of induction, the foetus was
delivered by cesarean section because of worsening hepatic
(serum aspartate transaminase 343 IU/l, alanine transami-
nase 77 IU/l) and renal (serum creatinine of 230 mmol/l)
function.
The patient remained oliguric after surgery with a serum
creatinine of 381 mmol/l, potassium of 5.4 mmol/l and uric
acid of 670 mmol/l. The platelet count had dropped to
81  109 l1, though the coagulation profile remained nor-
mal. The peripheral blood smear showed schistocytes and

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100 K.A. Abraham et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 108 (2003) 99102

Fig. 1. Light microscopy showing granular casts (C) with tubular necrosis (N), double contour formation in glomerular peripheral capillary loops associated
with segmental endocapillary inflammation (E) and an arteriole with an organising thrombotic lesion (T). (Periodic Acid Schiff, Methenamine silver
impregnation with haematoxylin and eosin counterstain, original magnification 400.)

polychromasia with further confirmation of ongoing hae-
molysis being provided by a reticulocyte count of 2.2%
(range 0.22%), serum haptoglobins 0.32 g/l (range 0.45
2.43), d-dimers 11.6 mg/ml (range 0.10.5) and serum lactate
dehydrogenase 3874 IU/l (range 220450). The patients
Coombs test and autoantibody screen were negative and
her serum complement levels were within normal limits.
All cultures including high vaginal swab were negative and
retained products of pregnancy were excluded by pelvic
ultrasound. Renal imaging confirmed normal sized kidneys
with adequate perfusion, impaired function and no urinary
obstruction. At no stage was the woman hypotensive, nor did
she receive any recognized tubular nephrotoxin.
A diagnosis of HELLP syndrome and acute renal failure
was made. Haemodialysis was commenced because of per-
sistent oliguria. The patients BP was effectively controlled
with labetolol, amlodipine and dialysis ultrafiltration. Persis-
tent renal failure despite the normalisation of her HELLP
parameters by the 6th post-partum day prompted a renal
biopsy 2.5 weeks after admission. Renal histopathology
revealed severe, diffuse tubular necrosis (Fig. 1). In addition,
organizing thrombi and lumen stenosis (Fig. 1) were noted in
two small arterioles; these endovascular thrombi being the
diagnostic features of thrombotic microangiopathy (TMA)
[10]. Vasculitis was excluded by the lack of inflammation in
the arteriolar walls. Segmental endocapillary proliferation
was noted in the glomeruli (Fig. 1) and electron microscopy
demonstrated subendothelial fluffy material.
Haemodialysis was continued until recovery of renal
function began. The patient was weaned off all anti-hyper-
tensives over the 2 months following renal recovery and has
remained normotensive off of all medication. Four months
after cessation of haemodialysis, her serum creatinine had
returned to 107 mmol/l and has remained at that level for the
subsequent 8 months.
3. Discussion
Acute renal failure remains a serious, though uncommon,
medical complication of pregnancy. It has historically been
described in association with haemorrhagic or septic shock,
but is also known to occur in severe pre-eclampsia [11]. The
HELLP syndrome, a condition thought to be closely linked
to PET, has more recently been identified as a significant risk
factor in the development of severe renal dysfunction [5].
We believe that this case is the first to clearly illustrate the
probable pathogenic processes that give rise to acute renal
failure in patients with this syndrome.
Our patient developed PET followed by the HELLP
syndrome. The presence of microangiopathic haemolytic
anemia and renal failure suggested thrombotic microangio-
pathy involving the kidney that was later confirmed on
histology. Since the other recognized clinical conditions
that are associated with renal TMA, such as the vasculitides,
malignant hypertension, scleroderma, transplant rejection
and the haemolytic-uraemic syndrome due to autoimmune
diseases, infections, malignancy or drug toxicity [12] were
excluded, we believe that the HELLP syndrome is the only
likely explanation in this patient.
It is known from renal studies that the primary event in the
development of TMA is endothelial damage [13], which was
identified histologically in our patient and has been reported
previously in patients with HELLP [7,8]. Similar glomerular
subendothelial deposits and endothelial cell swelling have
also been reported by Kincaid-Smith and co-workers [14] as
 K.A. Abraham et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 108 (2003) 99102 101

Fig. 2. Probable sequence of events leading to ARF in the HELLP syndrome.

the most consistent features in renal biopsy specimens from
patients with pre-eclampsia, thereby suggesting that the
initial pathology is similar. However, patients with HELLP
evidence a subsequent progression to endovascular throm-
bosis, lumen occlusion, hypoperfusion with reduction in
glomerular filtration and renal failure [12]. The resulting
tissue ischaemia may also give rise to ATN [15]. Thrombotic
microangiopathy can, therefore, cause renal failure by
directly reducing glomerular filtration and indirectly, as a
result of ischaemia induced tubular necrosis and/or infarc-
tion (Fig. 2).
The finding of ATN as the dominant lesion accounts for
the resolution of renal failure in this woman and also
explains why severe renal failure is frequently reversible
in patients who survive the other complications associated
with the HELLP syndrome [3]. While previous authors have
focused on the glomerular lesions, tubular necrosis has been
identified in these cases also [7,9]. As the tubular epithelium
has the capacity for regeneration, renal recovery is to be
expected in such situations. The disproportion between the
extent of tubular necrosis and the degree of thrombotic
microangiopathy noted here, may well result from the
known vulnerability of renal tubular cells in pregnant
women with liver dysfunction to vasomotor insults [16].
The consequent potential for recovery may help explain our
success in transplanting cadaveric kidneys from HELLP
donors who had biopsy proven renal involvement [17].
However, we know from the other renal conditions giving
rise to TMA that recovery does not always occur [18,19], as
indeed can be the case with the HELLP syndrome [3]. In
these circumstances, ongoing thrombotic microangiopathy
is one possible explanation, while thrombosis of such a
degree as to result in renal infarction [20] is another.
TMA is recorded in only two of the 21 HELLP patients
whose renal biopsy findings have been published previously
(Table 1). The histological evidence for renal TMA is known
not to be uniform and endovascular thrombi are conse-
quently often missed on biopsy because of sampling bias
[21]. This observation, together with the paucity of literature
describing renal pathology in patients with HELLP may
explain why the linkage between TMA, acute tubular
necrosis and renal failure has not been previously reported.
Even in the solitary case report documenting conjoint TMA
and ATN, Kahra et al. [7] attribute their findings to the

Table 1
Summary of papers with descriptions of renal histology in HELLP patients

First Ref. no. No. pt. No. HELLP/no. No. Glom. TMA ATN Renal dx in HELLP patients
author PET bx ds

Kahra et al. [7] 1 1/1 1 0 1 1 HUS

Beller et al. [8] 130 12/130 11 9 1 0 GN-3, endotheliosis-4, nephrosclerosis-2,
HUS-1, normal-1
Fang et al. [9] 1 1/1 1 1 0 1 GN
Pourrat et al. [22] 6 4/4 6 3 0 3 Glom. endotheliosis and ATN
Ghosh et al. [23] 1 1/1 1 0 0 1 ATN
Mohaupt [24] 1 1/1 1 Acute cortical necrosis
Key: bx, biopsy; ds, disease; dx, diagnosis; GN, glomerulonephritis; Glom., glomerular; HUS, haemolytic-uraemic syndrome.
102 K.A. Abraham et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 108 (2003) 99102
coincidental development of haemolytic-uraemic syndrome
in a patient who was affected by the HELLP syndrome.
In contrast, we believe that endothelial damage with the
subsequent development of thrombotic microangiopathy
resulting in tubular necrosis are the likely pathogenic pro-
cesses giving rise to acute renal failure in patients with the
HELLP syndrome. Obviously, further studies to confirm
these findings are warranted.
Acknowledgements
The authors gratefully acknowledge the assistance pro-
vided by Drs. Catherine Wall and Aisling ORiordan in the
care of this patient and retrieval of her records.
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