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Nephrotic syndrome in adults

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36 Acute Medicine 2018; 17(1): 36-43

Review Article

Nephrotic syndrome in adults

V Mahalingasivam, J Booth, M Sheaff & M Yaqoob

Abstract
Nephrotic syndrome is an important presentation of glomerular disease characterised by heavy proteinuria,
hypoalbuminaemia and oedema. The differential diagnosis of the underlying condition is wide including primary renal
disorders and secondary diseases such as malignancy, infection, diabetes and amyloid. Presentations to acute medicine
may be with hypervolaemia, complications of the nephrotic state (such as venous thromboembolism), or complications
of therapy (such as infection).
Early recognition of nephrotic syndrome is possible through simple urinalysis for protein and testing serum albumin,
although a high index of suspicion is sometimes required in patients with comorbidities including potentially distracting
cardiac or hepatic diseases.

Keywords
Nephrotic syndrome, glomerular disease, minimal change nephropathy, focal segmental glomerulosclerosis,
membranous nephropathy

Introduction abnormal leakage of plasma proteins into the urine,

Nephrotic syndrome is defined by the triad of heavy culminating in nephrotic syndrome.
proteinuria (≥3g/24 hours), hypoalbuminaemia
(≤25g/L) and oedema. It may affect children and Oedema
adults of all ages, occurring either as a primary renal The mechanism of oedema formation in nephrotic
disorder, or as a manifestation of systemic disease, syndrome is contentious. Conventionally, oedema is
Viyaasan Mahalingasivam malignancy or the unintended consequence of explained by reduction in plasma oncotic pressure,
BMedSci MRCP medication. Patients may present with oedema, leading to fluid shift from the intravascular space
Renal Unit, Royal London
Hospital, Barts Health NHS typically peri-orbital or at dependent sites; other into the interstitium and consequent conservation
Trust, London, UK manifestations of hypervolaemia (e.g. ascites); or of filtered sodium. Recent studies, however, have
with complications of their nephrotic state, such as suggested that primary tubular defects leading to
John Booth venous thromboembolism. While an uncommon enhanced sodium uptake driving volume expansion
PhD MRCP presentation to acute medical services, early may also contribute.2
Renal Unit, Royal London
Hospital, Barts Health NHS recognition will facilitate expedient diagnosis, Oedema is often initially noticed in loose
Trust, London, UK specialist management and potentially prevent connective tissues, such as periorbital or genital
complications. regions. Untreated, this will progress to generalised
Michael Sheaff oedema collecting at dependent sites, and ultimately
MD(Res) FRCPath Pathogenesis and clinical anasarca, pleural effusions and ascites. Intestinal
Department of
Histopathology, Royal manifestations oedema may occur, potentially resulting in
London Hospital, Barts In the healthy kidney, blood passes through malabsorption, and current guidelines emphasise
Health NHS Trust, networks of capillaries forming the glomerular tuft, adequate protein intake with sufficient carbohydrate
London, UK with formation of urinary filtrate driven by Starling to mitigate potential malnutrition.3
forces. The glomerular filtration barrier consists
Magdi Yaqoob
MD FRCP of three layers: fenestrated capillary endothelial Dyslipidaemia
Renal Unit, Royal London cells, the glomerular basement membrane (GBM) Dyslipidaemia is apparent in most patients with
Hospital, Barts Health NHS and visceral epithelial cells (podocytes) (Figure 1). nephrotic syndrome and manifests with elevated
Trust London, UK Podocyte foot processes inter-digitate to form ‘slit cholesterol and triglycerides.4 Mechanisms include
diaphragms’, a vital part of the glomerular filter; increased hepatic synthesis of lipoproteins, such as
Correspondence
Viyaasan Mahalingasivam genetic mutations which disrupt the function of apolipoprotein B (ApoB), and impaired metabolism
Renal Unit integral slit diaphragm proteins (e.g. nephrin) of triglycerides through inhibition of lipoprotein
Royal London Hospital frequently lead to nephrotic disorders.1 Glomerular lipase mediated by elevated levels of sialyated
Barts Health NHS Trust filtration is dictated by size and electrical charge; angiopoietin like 4 (Angptl4).5
Whitechapel Road when the barrier is intact, the majority of large Dyslipidaemia is presumed to contribute to the
London
E1 1BB plasma proteins, including albumin, are retained increased cardiovascular risk observed in patients
Email: viyaasan@hotmail. within the circulation. Injury to any part of with nephrotic syndrome, although lipids typically
com the glomerular filtration barrier may result in normalise promptly with remission.6

© 2018 Rila Publications Ltd.

Acute Medicine 2018; 17(1): 36-43
Figure 1. Electron micrograph of a normal glomerular filtration barrier
Hypercoagulability
Nephrotic syndrome confers an increased risk
for both venous and arterial thromboembolism
with approximately 25% of patients experiencing
a thrombotic event.7 Hypercoagulability results
from increased urinary loss of anticoagulant factors
(e.g. antithrombin III) and increased synthesis of
pro-coagulant factors, particularly fibrinogen.8,9
Membranous nephropathy (MN) is associated with the
highest risk of thrombosis among the nephrotic states.10
The renal vein is a common site of thrombosis
in nephrotic syndrome, possibly due to stimulation
of thrombin production in the glomerular efferent
vessels as a result of glomerular injury.11 This
may present acutely with flank pain and visible
haematuria, but more commonly leads to silent
deterioration in renal function, particularly in older
patients.10 Radiological investigation should be
according to local expertise.
Infection
Patients with nephrotic syndrome are predisposed
to infection due to the loss of immune proteins
including immunoglobulin G (IgG) and alternative
pathway complement components.12 Sepsis,
particularly with encapsulated bacterial organisms
such as Streptococcus pneumoniae, remains a significant
cause of morbidity and mortality.
© 2018 Rila Publications Ltd.
37
Nephrotic syndrome in adults
Causes and classification
Nephrotic syndrome may occur due to primary
glomerular disorders, or as a consequence of systemic
disease involving the kidney (Table 1).12 The majority
of causes require renal biopsy for diagnosis, and are
classified according to light microscopic patterns of
injury (Figure 2).
Minimal change nephropathy (MCN)
MCN is characterised by global podocyte foot-process
effacement (flattening and simplification) on electron
microscopy (EM) (Figure 2B) with near-normal
appearances on light microscopy (LM). It occurs
most frequently in children, but also accounts for
approximately 15% of nephrotic syndrome in adults.13
Excretory renal function is typically preserved.
MCN is usually idiopathic and the underlying
disease process remains unclear; circumstantial
evidence exists both for T cell-mediated podocyte
injury and for activity of a ‘circulating permeability
factor’.14, 15 It is not infrequently seen in individuals
with manifestations of atopy (e.g. asthma).16
Initial management is with prednisolone 1mg/
kg/day (maximum 80mg/day) for 4-16 weeks,
tapered slowly over six months once remission has
been achieved. Up to 20% of adults may be steroid
resistant and time to remission is often prolonged.17
Most adults will experience at least one relapse,
38 Acute Medicine 2018; 17(1): 36-43

Nephrotic syndrome in adults

Table 1. Primary and secondary aetiologies of nephrotic syndrome by histological lesion

Histological lesion Primary disorders Secondary causes
Minimal change nephropathy Atopy (e.g. asthma)
(MCN) Hodgkin’s disease
Minimal change
Drugs (e.g. NSAIDs, lithium)
SLE
Primary FSGS ‘Secondary FSGS’ – hyperfiltration injury
•• Reduced nephron mass
◊ Renal agenesis
◊ Scarring secondary to reflux
◊ Unilateral nephrectomy
◊ Prematurity
Focal segmental ◊ Low birthweight
glomerulosclerosis •• Vascular damage
(FSGS) ◊ Sickle cell disease
◊ Diabetes
◊ Hypertension
•• Increased glomerular load
◊ Obesity
HIVAN (collapsing glomerulopathy)
Genetic (e.g. NPHS1, NPHS2)
Idiopathic membranous See Table 2
Membranous
nephropathy (MN)
C3 glomerulopathy Infection
•• Hepatitis C (usually with cryoglobulins)
•• Bacterial endocarditis
Mesangio-capillary
•• Mycoplasma
glomerulonephritis
Other infections
(MCGN)
Autoimmune
•• SLE
•• Sjogren’s syndrome
Diabetes
Plasma cell disorders
•• AL amyloidosis
Others •• Light chain deposition disease (LCDD)
Other paraprotein material deposition
AA amyloidosis
Pre-eclampsia
NSAID (non-steroidal anti-inflammatory drug), HIVAN (HIV-associated nephropathy), SLE (systemic lupus erythematosus)

and many become steroid dependent. Second line
therapies include cyclophosphamide or a calcineurin
inhibitor (CNI) (i.e. ciclosporin or tacrolimus).18
Focal segmental glomerulosclerosis (FSGS)
FSGS accounts for approximately 35% of cases of
adult nephrotic syndrome.13 In primary FSGS, EM
resembles MCN but there are also scarred segments
of the glomerular tuft on LM (Figure 2C). As with
MCN, a ‘circulating permeability factor’ causing
podocyte injury seems integral to pathogenesis,
although its identity remains elusive.19, 20 The term
‘secondary’ FSGS usually describes hyperfiltration
injury in the presence of reduced nephron mass
(e.g. renal agenesis) or vascular damage (e.g. sickle
cell disease).21 In addition, there are genetic causes
resulting from mutations in genes encoding podocyte
slit diaphragm proteins leading to disease in childhood
or early adulthood.22 An association between FSGS
with progressive chronic kidney disease (CKD) and
variants in the apolipoprotein L1 (APOL1) gene has
been demonstrated in African-American patients.23
Without treatment, FSGS can result in end-stage
kidney disease (ESKD).24 Current guidelines advise
reserving treatment for patients with overt nephrotic
syndrome, in a manner analogous to MCN.25
Membranous nephropathy (MN)
MN remains the commonest cause of adult-onset
nephrotic syndrome in the UK.26, 27 Typified by heavy
proteinuria, the majority of patients are nephrotic
at presentation, and persistent disease is associated

© 2018 Rila Publications Ltd.

Acute Medicine 2018; 17(1): 36-43 39

Nephrotic syndrome in adults

A. Normal glomerulus
Note the normal capillary
wall thickness and lack of
mesangial alterations, H&E
x400.
B. Minimal change
nephropathy (MCN)
Electron micrograph
demonstrating
generalised effacement
of the podocyte foot
processes. Compare
with Figure 1.
C. Primary focal segmental
glomerulosclerosis (FSGS)
This tuft has a discrete
segmental area of sclerosis
adjacent to the hilum, H&E x400.
D. Membranous nephropathy (MN)
Two adjacent glomeruli show conspicuous
spike formation on silver stain, Hexamine
silver x250.

E. Mesangio-capillary F. Diabetic nephropathy G. HIV-associated H. Amyloidosis

glomerulonephritis (MCGN) A typical nodular nephropathy (HIVAN) There is deposition of amyloid
This glomerulus shows several glomerulosclerosis that is There is a collapsed tuft within the glomerulus and nearby
thick capillary loops with classical, but not specific for, lying between a segmentally peritubular areas, Congo red x400.
obvious double contours, diabetic glomerulopathy, H&E sclerosed glomerulus and
Hexamine silver x640. x400. a dilated tubule filled with
proteinaceous material, PAS
x200.
Figure 2. Histological examples of glomerular injury leading to nephrotic syndrome H&E (haematoxylin and eosin), PAS (periodic acid-Schiff)

with progressive renal impairment.28, 29 Kidney
biopsy shows thickened capillary loops on LM, and
pathognomonic basement membrane ‘spikes’ on
silver staining (Figure 2D), with IgG and complement
C3 deposits in the capillary wall corresponding to
subepithelial electron-dense deposits.29
Primary MN presents at a mean age of 55 with 2:1
male predominance.29 The majority of patients harbour
antibodies to the phospholipase A2 receptor (PLA2R)
expressed on podocytes.30 While the pathogenicity of
these antibodies has not been conclusively determined,
levels correlate with disease severity and disappearance
usually heralds remission.30, 31 Anti-PLA2R testing
is now available routinely, although histological
confirmation is still recommended.30
Secondary MN accounts for approximately 20%
of cases (Table 2). Occult malignancy should always
be considered; where anti-PLA2R is negative and
no alternative secondary cause has been identified,
extensive investigation such as cross-sectional
imaging and endoscopy may be pursued at the
discretion of the responsible nephrologist.28
All patients with primary MN should receive
renin-angiotensin system inhibition (RASi)
therapy (i.e. angiotensin converting enzyme
(ACE) inhibitor or angiotensin-2 receptor
blocker (ARB)) for control of proteinuria unless
contraindicated (e.g. hyperkalaemia), although
discussion with a nephrologist is recommended
in advanced renal impairment. Approximately
a third of patients will remit spontaneously
without further treatment.32 Individuals with
persistent nephrotic syndrome after six months of
conservative therapy, or severe complications (e.g.
thromboembolism), or progressive decline in eGFR,
warrant immunosuppression. Options include
oral cyclophosphamide administered in blocks,
alternating with corticosteroids - the ‘Ponticelli
regimen’-, or a CNI.33
Mesangio-capillary glomerulonephritis (MCGN)
MCGN may present either with nephrotic syndrome,
or as a ‘nephritic’ process with active urinary sediment
(i.e. red cell casts or dysmorphic red cells), renal
impairment and hypertension. Biopsy demonstrates
mesangial cell proliferation and characteristic ‘tram-
track’ double contours of capillary loops on silver
staining (Figure 2E).

© 2018 Rila Publications Ltd.

40
Nephrotic syndrome in adults
Table 2. Causes of secondary membranous nephropathy29, 54
Cause Examples
Cancer Lung cancer, prostate cancer, stomach cancer, thyroid cancer
Infection Hepatitis B, hepatitis C, HIV, syphilis, malaria, schistosomiasis
SLE (class V), rheumatoid arthritis, sarcoidosis, Sjogren’s syndrome, ankylosing spondylitis,
Inflammatory
IgG4 disease
Haematological Graft-versus-host disease, chronic lymphocytic leukaemia
Drugs NSAIDs, gold, penicillamine, captopril, lithium
Primary MCGN is rare; frequently such
patients have isolated C3 deposition on
immunohistochemistry, and harbour a genetic or
acquired abnormality in the alternative complement
pathway (so-called C3 glomerulopathy).34
Secondary MCGN is considerably more
common with causes including systemic lupus
erythematosus (SLE), hepatitis C (often with
circulating cryoglobulins), chronic infections (e.g.
bacterial endocarditis) or haematological malignancy.
Treatment is generally of the underlying cause,
although hepatitis C-associated cryoglobulinaemic
MCGN often responds well to rituximab.35
Diabetic nephropathy
Diabetes is the commonest cause of CKD in
both the developed world and in many emerging
economies.36 Diagnosis is made without kidney
biopsy when there is convincing evidence that a
competing diagnosis is unlikely, such as the presence
of concurrent retinopathy or neuropathy. Where a
biopsy is performed, typical findings include GBM
thickening, mesangial matrix expansion, and nodular
glomerulosclerosis (Kimmelstiel-Wilson nodules)
(Figure 2F). Clinical features include progressive
albuminuria and declining renal function. Nephrotic
syndrome is not uncommon and is predictive of poor
prognosis.
Management involves RASi therapy, careful
control of blood pressure and glycaemia, optimisation
of cardiovascular risk factors, and surveillance to
ensure timely counselling about renal replacement
therapy where ESKD is anticipated.
HIV-associated nephropathy (HIVAN)
HIVAN is a collapsing glomerulopathy, and is
classified as a subtype of FSGS although bears little
relationship either clinically or histologically to the
primary form. Seen exclusively in black African or
Caribbean patients, and characterised histologically
by ‘collapse’ of the glomerular tuft (Figure 2G) and
microcystic tubular dilatation, HIVAN often presents
with heavy proteinuria accompanied by marked
impairment of renal function, although oedema is
often surprisingly limited.37, 38 Patients are typically
Acute Medicine 2018; 17(1): 36-43
immunodeficient and viraemic at presentation,
and incidence has reduced in the era of widespread
anti-retroviral therapy.39 Renal outcomes are largely
dictated by the degree of scarring at diagnosis.40
Biopsy can distinguish other HIV-associated lesions
such as HIV-associated immune complex kidney
disease (HIVICK) and IgA nephropathy.38
Lupus nephritis (LN)
Renal involvement is very common in patients with
SLE, affecting approximately 40% of individuals
at some point in their disease course.41 LN is
categorised according to the Renal Pathology Society/
International Society of Nephrology (RPS/ISN)
classification.42 The commonest pattern of injury
is a proliferative glomerulonephritis with fibrinoid
necrosis, subendothelial deposits and positive
immunohistochemistry for IgG, C3 and complement
C1q (class III or IV), with dominant clinical features
being progressive renal impairment, moderate
proteinuria and active urinary sediment. Nephrotic
syndrome is usually caused by a membranous
lesion with subepithelial deposits (class V). It is not
uncommon for class V to accompany class III or IV;
such mixed disease portends a worse prognosis43 and
therapy should be targeted towards the latter lesions.
Most guidelines advise treatment with mycophenolate
or a CNI alongside corticosteroids for isolated class V
LN if patients have nephrotic-range proteinuria or
progressive renal impairment.44
Lupus podocytopathy is a rare presentation with
appearances of MCN or FSGS in patients otherwise
fulfilling criteria for SLE. Cases may be accompanied
by proliferation and immune deposits confined to
the mesangium (i.e. class II). It is reported typically
to be steroid responsive.45, 46
Plasma cell disorders and amyloidosis
While the most common mechanism of renal
injury in patients with myeloma is precipitation
of light chain casts within tubules (myeloma cast
nephropathy), plasma cell disorders may also
cause nephrotic syndrome through alternative
mechanisms. The most frequent glomerular disease
processes are light chain (AL) amyloidosis and light
© 2018 Rila Publications Ltd.
Acute Medicine 2018; 17(1): 36-43 41

Nephrotic syndrome in adults

Table 3. Routine workup for a patient presenting with nephrotic syndrome

Workup of nephrotic syndrome
Urine:
Urinalysis, early morning urinary ACR and PCR, urine culture, urine protein electrophoresis, examination for
casts
Bloods:
Full blood count, urea & electrolytes, bicarbonate, liver function tests, bone profile, C-reactive protein,
erythrocyte sedimentation rate, coagulation screen, group & save, HbA1C, immunoglobulins, serum protein
electrophoresis, free light chain ratio, complement, ANA, anti-dsDNA, ENA, anti-PLA2R, HIV antibody,
hepatitis B surface antigen, hepatitis C antibody, blood cultures, cryoglobulins (discuss with biochemistry
laboratory in advance)
Imaging:
Renal tract ultrasound, chest radiograph, echocardiography (if infective endocarditis suspected)
Histopathology:
Renal biopsy
Ideally a sample of ≥20 glomeruli for LM, immunostaining and EM; reviewed by a specialist renal pathologist
ACR (albumin: creatinine ratio), PCR (protein: creatinine ratio), HbA1C (haemoglobin A1C), ANA (anti-nuclear
antibody), anti-dsDNA (anti-double-stranded DNA antibody), ENA (extractable nuclear antibodies), anti-PLA2R
(anti-phospholipase A2 receptor antibody), LM (light microscopy), EM (electron microscopy)

chain deposition disease (LCDD). Such diseases are
now often referred to as ‘monoclonal gammopathies
of renal significance (MGRS)’ when they fail to meet
criteria for myeloma on conventional grounds.47
AL amyloidosis is caused by the extracellular
deposition of amyloid fibrils formed from
monoclonal immunoglobulin light chains. Kidney
biopsy typically shows glomeruli expanded by
amorphous eosinophilic deposits in the mesangium
and capillary loops; these deposits exhibit apple
green birefringence on Congo-red staining
viewed under cross-polarised light (Figure 2H).
In most cases, deposits stain either for κ or λ light
chains only, confirming clonality. There is often
concurrent involvement of other organ systems,
and suspicious clinical features include periorbital
pupura, macroglossia, progressive sensorimotor
neuropathy and autonomic dysfunction. The
extent of cardiac involvement is the most important
determinant of prognosis. LCDD often shows
nodular glomerulosclerosis resembling diabetic
nephropathy, with Congo-red negative glomerular
deposits which typically exhibit light chain class
restriction. Treatment of both processes usually
follows established myeloma protocols.
AA amyloidosis results from deposition of serum
amyloid A protein in conditions associated with
systemic inflammation. Most cases occur secondary
to an underlying auto-inflammatory disease such
as rheumatoid arthritis or familial periodic fever,
or recurrent or persistent infection as seen in
bronchiectasis or intravenous drug use. Extrarenal
involvement is less common and occurs later in the
disease course than with AL amyloidosis. Treatment
is of the underlying disorder.48
Evaluation of nephrotic syndrome in
the acute medical unit/ambulatory care
Initial detection of proteinuria is usually made by
manual or automated qualitative dipstick urinalysis.
These point-of-care reagent strips are sensitive to
albumin but typically less so to other proteins such as
globulins or light chains. Laboratory quantification
can be performed by measuring urinary protein:
creatinine ratio (PCR) or albumin: creatinine ratio
(ACR). These tests are preferably performed on an
early morning urine sample and are considerably
less cumbersome than 24-hour collection. PCR
can quantify total protein excretion and is often
favoured in the nephrology clinic, with 100mg/
mmol conveniently approximating to a daily protein
excretion of 1g; consequently ≥300mg/mmol is
expected in patients with nephrotic syndrome. Marked
discrepancy between PCR and ACR warrants further
investigation with urinary protein electrophoresis,
particularly where a plasma cell disorder is suspected.
Investigations required as part of the initial
evaluation of a patient presenting with nephrotic
syndrome are listed in Table 3. Urgent specialist
referral should be made to the local nephrology
service. Most presentations can be managed in the
outpatient setting and many units have established
day-case biopsy services. Haemorrhage is the most
important complication of biopsy ranging from mild
visible haematuria to shock although catastrophic
outcomes such as nephrectomy or death are rare
in the modern era with the use of protocols and
improved accessibility to endovascular intervention.
Patients who are anticoagulated or on antiplatelets
require a personalised plan for these drugs based on
assessment of risk and benefit.49

© 2018 Rila Publications Ltd.

42
Nephrotic syndrome in adults
Indications for hospital admission include resistant
oedema requiring intravenous diuretic therapy,
or acute complications such as sepsis or venous
thromboembolism.
General therapeutic measures
Dietary sodium restriction
Patients should ideally be provided with tailored
dietary recommendations to reduce salt intake to
help ameliorate fluid retention.
Diuretics
Loop diuretics are the cornerstone of symptomatic
treatment for oedema. Higher doses of diuretic may be
required as drug binding to albumin in urine appears
to limit bioavailability of the pharmacologically active
drug.50 Addition of diuretics working more distally in
the nephron (such as a thiazide or mineralocorticoid
receptor antagonist) may be required to achieve
successful diuresis in patients with resistant oedema
by combining to maximally reduce sodium
reabsorption.12
Patients should be encouraged to record their
weight regularly as a guide to fluid accumulation.
RASi therapy
ACE-inhibitors and ARBs have important
antiproteinuric effects mediated by reduction of both
systemic blood pressure and glomerular perfusion
pressure. RASi therapy is generally not started in
nephrotic patients where abrupt remission with
disease-modifying therapy is anticipated (e.g. MCN)
so should be discussed first with the local nephrology
service. Blood pressure, renal function and serum
potassium should be closely monitored when using
these agents and doses optimised where possible.51
These drugs are contraindicated in pregnancy.52
Hypertension
Patients should also be encouraged to monitor blood
pressure at home. The target blood pressure in patients
with persistent nephrotic syndrome is <130/80, and can
often be achieved through a combination of diuretics
and RASi therapy. Non-dihydropyridine calcium-
channel blockers (CCBs) (e.g. diltiazem) are preferred
as next-line as they may also have antiproteinuric
effects. Some data suggests that dihydropyridine
CCBs (e.g. amlodipine) may exacerbate proteinuria as
well as worsening peripheral oedema.53
Lipid lowering therapy
Statins are the preferred therapy for management
of dyslipidaemia. Initiation is generally deferred
in patients for whom abrupt response to disease-
modifying therapy is anticipated.
Acute Medicine 2018; 17(1): 36-43
Smoking cessation
Patients with nephrotic syndrome are at increased
cardiovascular risk and so smoking cessation
counselling should be provided.4
Systemic anticoagulation
The risk of thromboembolism is a significant concern,
especially in MN. Patients with serum albumin less
than 25g/L and particularly those with additional
risk factors appear to be the most susceptible.3
Systemic anticoagulation needs to be considered
on an individual basis, balancing benefits against
bleeding risks. Warfarin is generally preferred to low-
molecular-weight heparin because of potentially low
levels of antithrombin III impeding efficacy.3
Complications of treatment
Immunosuppressive drugs are associated with
their own adverse effects and so their use should
be overseen by a specialist unit with provision of
appropriate counselling. Corticosteroids should be
accompanied by prophylaxis for peptic ulceration,
osteoporotic fracture and vigilance for corticosteroid-
induced diabetes. Individual risk of infection should
be assessed and prophylaxis against Pneumocystis jirovecii
and Mycobacterium tuberculosis may be appropriate.
Family planning counselling is important
early on after diagnosis for both men and women.
Definitive contraception can be challenging given
increased risks of venous thromboembolism,
although progesterone-only methods can be used.
Cyclophosphamide is gonadotoxic so sperm or
ovum storage may be necessary. Patients (including
males) are advised not to conceive while taking
mycophenolate due to potential teratogenicity, but
CNIs and azathioprine are generally considered safe.
RASi therapy is contraindicated in pregnancy.
Summary
Nephrotic syndrome is an important presentation of
glomerular disease characterised by heavy proteinuria,
hypoalbuminaemia and oedema. The differential
diagnosis is wide including primary renal disorders
and secondary diseases such as malignancy, infection,
diabetes and amyloid. Presentations to acute
medicine may be with hypervolaemia, complications
of the nephrotic state, or complications of therapy.
Early recognition of nephrotic syndrome is
possible through simple urinalysis for protein and
testing serum albumin, although a high index of
suspicion is sometimes required in patients with
comorbidities including potentially distracting
cardiac or hepatic diseases.
Conflict of Interest
Nothing to declare.
© 2018 Rila Publications Ltd.
Acute Medicine 2018; 17(1): 36-43
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