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Saudi J Kidney Dis Transpl 2015;26(4):773-777

© 2015 Saudi Center for Organ Transplantation Saudi Journal
of Kidney Diseases
and Transplantation

Case Report

Nephrogenic Ascites – Still an Intractable Problem?

Shobhana Nayak-Rao

Department of Nephrology, St. Martha’s Hospital, Bengaluru, Karnataka, India

ABSTRACT. Nephrogenic ascites or ascites associated with renal failure is seen in end-stage
renal disease in-patients on hemodialysis but has been described occasionally in earlier stages of
renal failure. The cause can be multifactorial and a combination of inadequate dialysis and
ultrafiltration, poor nutrition and increased peritoneal membrane permeability in uremia.
Generally, the onset of nephrogenic ascites is insidious and portends a grim long-term prognosis.
We describe herein three patients who presented with refractory ascites of nephrogenic origin and
review this entity.

Introduction Case Reports

Nephrogenic ascites or ascites associated Case 1

with renal failure was first reported in the early
1970s in patients with end-stage renal disease
(ESRD).1 It is most often seen in patients on
hemodialysis, but has been described earlier in
the course of renal failure occasionally. The
putative causes for the occurrence of nephro-
genic acites include inadequate dialysis and
ultrafiltration, poor nutrition and increased
peritoneal membrane permeability in combina-
tion with impaired peritoneal lymphatic re-
absorption.2-8 We describe herein three pa-
tients who presented with refractory ascites of
nephrogenic origin and review this entity.
Correspondence to:
Dr. Shobhana Nayak-Rao,
Department of Nephrology,
St. Martha’s Hospital,
Bengaluru - 560 001, Karnataka, India
E-mail: nayak_shobhana@rediffmail.com
A 47-year-old lady, ESRD secondary to chro-
nic interstitial nephritis on twice-weekly main-
tenance hemodialysis (HD) since three years,
presented with progressively worsening abdo-
minal distension of six months duration. On
examination, she was a thin-built lady weighing
50 kg with pallor; no icterus or lymphade-
nopathy was noted. Abdominal examination
revealed massive ascites, peripheral edema 3+
till mid calf with small reducible umbilical
hernia and no palpable organomegaly. Her
cardiac and respiratory systems were normal.
Her laboratory investigations revealed hemo-
globin (Hb) of 9.2 g/dL, blood urea of 97 mg/
dL, serum creatinine of 9.7 mg/dL with normal
serum electrolytes, serum calcium of 9.7 mg/
dL and serum phosphorus of 4.9 mg/dL.
Ascitic fluid analysis revealed protein of 4.2
mg/dL, albumin of 2.1 g/dL, sugar of 94 mg/
dL and lactate dehydrogenase (LDH) of 77
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774
U/L and serum-ascites albumin gradient or gap
(SAAG) was 1.4, with serum albumin being
3.5 g/dL. The ascitic fluid white cell count was
150 cells/mm3, with 60% cells being lympho-
cytes. Cultures of fluid were negative for bac-
terial and fungal elements and the acid fast
bacilli (AFB) smear as well as smear for
malignant cells were negative. Work-up for
liver disease by ultrasound Doppler of the
hepatic and portal veins was normal and car-
diac function by 2D-ECHO revealed ejection
fraction of 55%. Markers for hepatitis B and C
virus were negative. Her urea reduction rate
(URR) on dialysis was low at 52%. She was
diagnosed to have nephrogenic ascites and
underwent aggressive 5 h sessions of thrice-
weekly dialysis with gradual reduction in
target dry weight from 50 kg to 47 kg over
four weeks. This was accompanied by dietary
salt restriction and oral nutritional protein sup-
plementation. Therapeutic large volume para-
centesis was also performed twice in a month
with intravenous albumin infusions to relieve
her of abdominal discomfort. A gradual reduc-
tion in ascites was noted in three months and
her abdominal girth had reduced by about 50%
with management.
Case 2
A 50-year-old lady, ESRD secondary to dia-
betic nephropathy on maintenance HD twice-
weekly since one year, presented with pro-
gressively increasing ascites of four months
duration. She had recently attained menopause
and the patient attributed her abdominal dis-
tension to this. Examination revealed a cachexic
lady with severe ascites. Her dry weight was
between 45 and 49 kg. Her investigations re-
vealed Hb of 8.9 g/dL, blood urea of 102
mg/dL, serum creatinine of 7.9 mg/dL, normal
serum electrolytes, serum calcium of 8.9 mg/
dL and serum phosphorus of 5.2 mg/dL. Se-
rum albumin was low at 2.9 and ascitic fluid
albumin was 2.1 with a SAAG of 0.8 g/dL.
Ascitic fluid analysis revealed an exudate with
lymphocytic predominance. A complete work-
up for hepatic, cardiac and malignant causes
was negative. Her URR on dialysis was 54%.
Hepatitis B and C markers were negative.
Nayak-Rao S
Abdominal tuberculosis was initially suspec-
ted; however, ascitic fluid adenosine deami-
nase was low and mycobacterial polymerase
chain reaction of the fluid was also negative.
She received thrice-weekly 5 h dialysis ses-
sions with fluid removal of 3–4 L per session;
however, this was poorly tolerated by the pa-
tient due to frequent hypotensive episodes
occurring during dialysis. She also underwent
therapeutic large volume paracentensis to
relieve her abdominal discomfort. Nutritional
supplementation was given with a high-protein
diet. Despite adequacy of HD improving to
URR of 71% and target dry weight reducing to
44 kg from her previous weight of 49 kg, there
had been only minimal improvement in her
general condition in the last five months.
Case 3
A 53-year-old male, ESRD secondary to type-
2 Diabetes mellitus on maintenance HD for
two years, presented with ascites of six months
duration. He was on twice-weekly HD with
target weight of 68–70 kg, which had been
progressively reduced since the last two
months. On examination, his blood pressure
was 130/80 mm Hg, he had moderate to mas-
sive ascites and no palpable abdominal orga-
nomegaly was noted. His investigations re-
vealed Hb of 8.6 g/dL, blood urea of 84 mg/
dL, serum creatinine of 7.4 mg/dL, serum
calcium of 8.7 mg/dL and serum phosphorus
of 3.9 mg/dL. His URR on dialysis was 56%.
Ascitic fluid analysis revealed an exudate with
protein of 5.4 g/dL, albumin of 2.3 g/dL, LDH
of 145 U/L and cell count of 250, 95% of
which were lymphocytes. Serum albumin was
low at 2.7 g/dL, with SAAG of <1.0. Culture
of fluid was negative and AFB and malignant
cells were negative. A complete evaluation to
look for cardiac and hepatic causes was
negative. He was diagnosed to have dialysis-
related ascites. His dialysis treatments were
intensified and his dry weight was gradually
reduced by 1.0 kg/week till 66 kg. At the last
follow-up of four months, there has been a
minimal reduction in ascites.
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Nephrogenic ascites: an intractable problem 775

Table 1. Recommended evaluation for nephrogenic ascites.

1. History and physical examination: History of massive ascites with minimal peripheral edema in
dialysis patient, cachexia, dialysis-related hypotension, anorexia
2. General blood chemistries including BUN, serum creatinine, liver function tests
3. Paracentesis and ascitic fluid analysis for low SAAG (<1.0 g/dL), WBC count 25–150 cells/mm3),
negative culture and cytology
4. Thyroid function tests, estimation of iron studies, hepatitis viral markers, parathyroid hormone level,
ultrasound abdomen with portal venous Doppler, echocardiogram with right and left atrial pressure
estimation, abdominal CT, peritoneoscopy with peritoneal biopsy (when relevant) - to rule out liver
disease with portal hypertension, peritoneal infection/malignancy, pancreatic causes, cardiac causes such
as cardiomyopathy and pericardial effusions

Discussion covered by the state or insurance policies

These three cases bring to light the condition
termed as dialysis-related ascites, a problem
that has been most often described in ESRD
patients on HD. The entity of nephrogenic
ascites or ascites associated with renal failure
was initially reported by Mahoney et al in
1970.1 Since then, this issue has been ad-
dressed in few reviews and some case re-
ports.2-8 Nephrogenic ascites has been known
by several names such as nephrogenous ascites,
dialysis ascites, HD-associated ascites and
idiopathic ascites. The term nephrogenic ascites
is preferred as the onset of ascites may occur
earlier in the course of renal failure and well
before the initiation of dialysis. The exact
incidence of nephrogenic ascites is not known;
however, the incidence may be slightly higher
in developing countries like India. To the best
of our knowledge, no data exist on the preva-
lence of this diagnosis at presentation or at
patient follow-up.
Nephrogenic ascites could be possibly due to
a combination of factors such as poor nutri-
tion, late presentation leading to delay in ini-
tiation of appropriate renal replacement the-
rapy and inadequate dialysis. Dialysis not being
Table 2. Possible pathogenetic mechanisms for nephrogenic ascites.
1. Elevated hepatic venous hydrostatic pressure
2. Volume overload
3. Increased peritoneal membrane permeability
a. Secondary to uremic toxins
b. Prior exposure to dialysis solutions
c. Circulating immune complexes
d. Renin–angiotensin activation
e. Hemosiderosis
4. Impaired peritoneal lymphatic drainage
necessitates patients to fund their own treat-
ments, and this leads to poor compliance with
the dialysis schedule. Marked center to center
variability in incidence of nephrogenic ascites
of 0.7–20%, wide age of onset of 11–71 years
(mean 42 years) and male preponderance
(male:female = 2:1) has been reported.9 The
largest case series of nephrogenic ascites in
138 patients was reported by Gluck et al.5 The
diagnosis of nephrogenic ascites is one of ex-
clusion and needs a thorough work–up to rule
out hepatic, cardiac, infective and malignant
causes of ascites. In about 15% of cases, an
extensive evaluation may reveal secondary
causes for ascites (Table 1).
The pathogenesis of ascites remains incon-
clusive. Several pathogenetic factors including
hepatic vein hydrostatic pressure, fluid reten-
tion, increased peritoneal membrane permea-
bility and impaired peritoneal lymphatic drai-
nage have been considered (Table 2). Fluid
retention has been observed in ⅔ of the re-
ported patients in some reviews.2,5 However,
the role of fluid retention and ascites formation
is not clearly defined because dialysis patients
display signs of fluid overload frequently with-
out demonstrable ascites. Changes in peritoneal
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776
Table 3. Therapeutic options for nephrogenic ascites.
Modality Benefit
1. Fluid and salt restriction with Decreases ascites
intensified hemodialysis and
ultrafiltration
2. Hyperalimentation therapy Improves nutrition
3. Repeated paracentesis Reduces symptoms
4. CAPD Reduces ascites/improves nutrition
5. Peritoneovenous shunt Reduces ascites, dialysis
6. Kidney transplant Definitive therapy
membrane permeability due to uremic toxins,2,5
exposure to dialysis solutions,5 renin–angiotensin
activation, circulating immune complexes10 and
iron deposition11 have all been implicated in
ascites formation. Histologically, the perito-
neum is grossly normal; microscopy can been
normal,12 but more often shows chronic inflam-
mation and mesothelial cell proliferation with
variable degree of submesothelial fibrosis.13
The rate of ascites removal in nephrogenic
ascites has been seen to be much slower than
in patients with ascites and normal renal func-
tion.2 This was demonstrated by Morgan et al,6
wherein radiolabeled albumin was used to esti-
mate the rate of reasorption and transfer across
the peritoneal membrane. Impaired peritoneal
fluid drainage was demonstrated in patients
with nephrogenic ascites. Rate of clearance of
albumin was lower at a median value of 14
mL/h (range 10–21 mL/ h) compared with a
median value of 45 (range 10–75 mL/h) in
those with ascites of other etiology. This is
however normalized after successful kidney
transplant, suggesting an effect of uremia.
Secondary hyperparathyroidism as a possible
cause and subsequent cure of ascites after
parathyroidectomy has been described in one
patient.7
In nephrogenic ascites, ascitic fluid analysis
reveals exudate (high protein), low ascitic
albumin gradient (SAAG <1.0) and low neu-
trophil count. Patients frequently present with
moderate to massive ascites, hypertension,
minimal lower extremity edema, cachexia and
a history of dialysis-associated hypotension.5
Nephrogenic ascites is usually associated with
a grave prognosis. The average survival ranges
Nayak-Rao S
Drawback
Limited by hypotension
Not proven
Excess protein losses
Self-limited early protein
loss
Shunt infection/blockage
Ascites may recur after
graft failure
from seven to 10.7 months, with 44% of pa-
tients dying within 15 months of diagnosis.5
Management of nephrogenic ascites is complex
(Table 3) and includes a combination of inten-
sive dialysis with good ultrafiltration, intra-
dialytic albumin infusions along with a high-
protein diet. Strict volume control has been
emphasized in the treatment of nephrogenic
acites by Gunal et al.14 Intensive dialysis is
effective in ⅓ to ¼ of patients as early as with-
in three weeks. Continuous ambulatory perit-
oneal dialysis (CAPD) and peritoneovenous
shunts (PVS) are the other treatment options.
The efficacy of PVS to treat massive refrac-
tory ascites has been reported by Holm et al.15
In their study of 14 patients on chronic main-
tenance hemodialysis (average of 20.4 ± 2.9
months) with refractory ascites of nephrogenic
origin, 12 patients obtained significant relief
after placement of a PVS. Of these patient,
nine patients (75%) survived for one year and
six patients (50%) had survived for three or
more years, thereby improving the previous
dismal prognosis of patients with nephrogenic
ascites.16 Hemodynamic improvement has been
noted after PVS in patients who did not tole-
rate excessive ultrafiltration before.16 Objec-
tive improvements were also noted in nutri-
tional status, with weight gain and subjective
improvement in appetite and physical acti-
vities. Complications of shunt placement are
seen in about half of the cases, and include
catheter tip migration, infection and occlusion.
These complications necessitate either minor/
major revisions or removal of the shunt.
CAPD is also effective in the treatment of
ascites by controlling ascites formation.17 This
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Nephrogenic ascites: an intractable problem
is by reducing the intraperitoneal fluid protein
concentration thus limiting osmotic fluid shift
into the peritoneal space. Within six months of
continued treatment, the amount of total pro-
tein excretion in the dialysis effluent decreases
over time from 26.5 to 50 g/day to 7 to 9.5
g/day, with a subsequent rise in serum protein
and albumin levels and resolution of ascites.
Therapies with less-predictable outcomes in-
clude instillation of intraperitoneal cortico-
steroids and binephrectomy. The definitive
therapy is renal transplantation and nearly all
reported patients with nephrogenic ascites
have had a complete resolution within two to
six weeks after successful transplantation. Re-
currence of ascites may occur after loss of
graft function.
Our patients were all on twice-weekly dia-
lysis with resultant low URR, reflecting that
they were underdialyzed and intensification of
the dialysis regimen resulted in some objective
improvement.
In conclusion, nephrogenic ascites is a rare
condition with grave prognosis and a multifac-
torial cause. Although no prospective studies
have been performed comparing the various
treatment modalities, on the basis of the
current data, intensive dialysis, kidney trans-
plantation, CAPD and PVS placement offer
the best hope for an improvement in quality of
life and recovery.
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