CONTINUING EDUCATION

Identification and Management

of Lupus Nephritis: An Overview
Myriam Jean Cadet, PhD, FNP-C

ABSTRACT
Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder characterized by inflammation of
organs systems in the body. Active SLE can put a patient at risk for life-threatening complications such as
lupus nephritis (LN), an inflammation of the kidneys that can cause permanent, irreversible organ damage.
LN can mimic other illnesses, and medical management may be challenging. The purpose of this article is to
aid nurse practitioners in identifying and managing LN as a complication of SLE to provide safe and quality
care to patients.

Keywords: autoimmune diseases, lupus nephritis treatments, management of lupus nephritis

Ó 2017 Elsevier Inc. All rights reserved.

Myriam Jean Cadet, PhD, FNP-C, is an adjunct professor at Lehman College School of Nursing, Bronx, NY, and can be reached at
myriam.cadet@lehman.cuny.edu. In compliance with national ethical guidelines, the author reports no relationships with business or
industry that would pose a conflict of interest.

S ystemic lupus erythematosus (SLE) is a chronic

autoimmune disease that can damage the
body’s tissues. SLE may cause diverse, irre-
versible multiple organ damage. One complication
associated with this condition is lupus nephritis (LN),
an inflammation of the kidneys. According to recent
estimates, approximately 1.5 million Americans and
at least 5 million people worldwide are affected by
lupus.1 The onset of lupus usually occurs between the
ages of 15 to 44 years. The incidence of lupus in the
United States is estimated to be about 16 000 new
cases annually.1 Data reveal that women of color (eg,
African Americans) are 2 to 3 times more likely to
develop lupus compared with other races (eg,
European Americans), and it is also more likely to
affect women of childbearing age.1 Research
estimates that 1 in every 537 young African American
women have lupus. Approximately 10% to 15% of
people with this affliction will not have a full
expected life span due to lupus complications such as
renal involvement.2
As a complication of SLE, LN develops within the
first 5 years of the illness.1 More than 40% of patients
with SLE may develop LN later in their lives.1 Two-
thirds of children affected with lupus may be at risk for
developing renal complications that will ultimately need
medical treatment, and data indicate that most people
affected with LN are between the ages of 20 to 40.1
ETIOLOGY AND PATHOGENESIS
The exact pathogenesis of SLE is not fully un-
derstood. It is caused by the production of autoan-
tibodies and immune complexes that trigger
inflammation and destruction of healthy tissues.3

This CE learning activity is designed to augment the knowledge, skills, and attitudes of nurse practitioners and assist in their understanding of how to identify and manage
patients with systemic lupus erythematosus (SLE) and lupus nephritis (LN):
A. Identify the pathogenesis and signs/symptoms/findings of SLE and LN
B. Understand the clinical evaluation and diagnosis of LN
C. Describe implementation of treatment and management with LN
The author, reviewers, editors, and nurse planners all report no financial relationships that would pose a conflict of interest.
The author does not present any off-label or non-FDA-approved recommendations for treatment.
This activity has been awarded 1.0 Contact Hours of which 0.5 credits are in the area of Pharmacology. The activity is valid for CE credit until February 1, 2020.

www.npjournal.org The Journal for Nurse Practitioners - JNP 1

These autoantibodies can directly attack healthy cells
and tissues to form tissue-damaging immune com-
plexes. In LN, for example, these autoantibodies
attack the kidneys, rendering them unable to perform
functions such as filtering blood, controlling fluids in
the body, and removing waste products. Identified
autoantibodies in SLE include anti-double-stranded
DNA (anti-dsDNA), anti-Smith (Sm), and antinu-
clear antibody (ANA).
The development of autoantibodies can result from
various factors, and evidence points to environmental
factors such as car fumes, cigarette smoking, and
alcohol consumption as causative in SLE.4 Other
factors such as Epstein-Barr virus and hydralazine drug
therapy have been implicated as triggers for SLE, as
have hormones such as estrogen or prolactin.4 The
increased incidence of SLE among African Americans,
Asian Americans, and people of Hispanic/Latino
ethnicity, compared with whites and people
of European American descent, suggests genetic
factors.5-7 An estimated 20% of people who have been
affected by lupus have had a parent or sibling that
either has lupus or is prone to developing the illness.1
CLINICAL PRESENTATION
A thorough physical assessment of a patient’s clinical
presentation is critical before establishing a diagnosis
of SLE and LN, and then determining management
and treatment plans. SLE can affect various body
systems, including the kidneys, central nervous sys-
tem, lungs, skin, and the cardiovascular and muscu-
loskeletal systems. The clinical features that an NP,
especially in primary care, will see are the signs and
symptoms of fever, fatigue, and joint pain or swelling.
A malar rash (butterfly rash) over the nasolabial folds,
bridge of the nose, or cheeks is also symptom of SLE.
Some patients may experience photosensitivity rash
after sun exposure and describe the rash site as pruritic
or painful. Alopecia is another manifestation of SLE
in which the autoimmune disease targets the hair
follicles. Chronic diseaseeassociated anemia also
tends to occur because of reduced red blood cell
(RBC) production.1 SLE can be a constant struggle
during flare-ups and times of increased disease
activity, and signs and symptoms of SLE can last from
weeks to months in most patients during these
periods. It is critical for nurse practitioners (NPs) to
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assess the clinical presentations of patients with SLE
to prevent serious organ damage and LN.
A patient with LN presents with the same clinical
manifestations of SLE as other patients. However, there
are several other presentations that NPs need to look
for in the context of LN. Among these is the nephrotic
syndrome, in which the kidneys excrete excessive
amounts of protein. This is an indication of glomerular
lesions, which can damage kidney function. Another
presentation is peripheral edema due to hypo-
albuminemia, caused by the inflammatory response.
Hypertension is also prevalent and an important feature
of LN; patients may present with dizziness, headache,
or visual disturbances.1 Early identification of these
clinical presentations is crucial to improve kidney
outcomes and prevent further renal failure.
DIAGNOSTIC EVALUATION
No single laboratory test can rule out a diagnosis of
SLE or LN. Initial laboratory tests include a complete
blood count (CBC), comprehensive metabolic pro-
file, and a urinalysis. A CBC result may indicate
anemia of chronic disease, such as normocytic nor-
mochromic anemia, which is commonly found in
autoimmune disorders; this is caused by a decrease in
RBC production. The most common laboratory test
results in SLE are decreased hemoglobin, increased
ferritin, and decreased or normal iron and total iron
binding capacity. The first line of testing that NPs
need to perform in patients with SLE is a periodic
screening of renal parameters to evaluate renal
function and outcomes, such as blood urea nitrogen
and creatinine. A comprehensive metabolic panel
such as blood urea nitrogen and creatinine can be
ordered for this purpose. Creatinine measures the
amount of waste product in the blood. An increase in
the creatinine level of 2 mg/dL indicates a 50%
reduction in the estimated glomerular filtration rate,
which results in a decrease of renal function.1
Urinalysis
A urinalysis is required to establish a diagnosis for SLE
and also to test for renal function or damage leading
to a diagnosis of LN. Increased values of laboratory
tests such as sediment rate, RBCs, and cellular casts
are signs of poor renal function. Proteinuria is a
urinary biomarker that can be found in the urine
Volume 14, Issue 1, January 2018
analysis because of the inability of the kidneys to filter
waste products, which can cause renal damage. Pro-
teinuria may also cause a false-negative result due to
patients’ intake of a vitamin C supplement.8
Biomarkers
Second-level testing that supports the diagnosis of
SLE or LN disease activity and that NPs need to
understand includes anti-dsDNA, ANA, complement
test (C3 or C4), C-reactive protein (CRP), and
erythrocyte sedimentation rate (ESR). Generally it is
the rheumatologist or nephrologist who will order
these biomarkers; however, NPs need to understand
their usefulness in diagnosing a patient with SLE and
LN. The anti-dsDNA biomarker is used to analyze
autoantibodies, and a normal result is negative; a
positive test result is associated with lupus. Anti-
dsDNA is not specific to lupus, however, and may be
detected in other conditions.
ANA also helps establish a diagnosis of lupus by
detecting the presence of autoantibodies. Thus, a
positive result correlates with active SLE and LN. Up
to 97% of patients with SLE test positive for ANA.1
This test has a low specificity and a high sensitivity;
thus, it may not detect the antibodies in patients with
SLE. A low C3 or C4 indicates active SLE.1 As
already noted, CRP and ESR are two additional
biomarkers that indicate disease activity of SLE and
LN.1 High levels of CRP and ESR in the blood
indicate chronic inflammation.
Although these initial laboratory tests are used to
rule out the disease process, they cannot confirm the
histopathology classifications of LN. Also, they
cannot predict histological changes, confirm LN
diagnosis, or aid in treatment management and
response or prognosis. Therefore, a renal biopsy may
be necessary in patients with suspicious laboratory
evidence and a clinical presentation of nephritis.
Renal Biopsy
A renal biopsy is an invasive procedure that provides
useful information on the histological classes of
LN.9,10 Diagnosis of LN relies on a renal biopsy to
stage the disease.3 Although the NP does not perform
a renal biopsy, it is important to understand the
histopathological classifications for LN, particularly
for patients with recurrent episodes of nephritis. The
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American College of Rheumatology (ACR)
recommends a renal biopsy for any patient with
suspected active LN. According to the ACR,
persistent proteinuria
0.5 g/24 h plus hematuria or

0.5 g/24 h plus cellular casts warrants performance
of a renal biopsy.11
Histopathology findings of the renal biopsy will
identify the location of the lesions in the glomeruli.12
The International Society of Nephrology and the
Renal Pathology Society described 6 classifications
(Table 1) to guide patient treatment and prognosis in
LN.13 The biopsy results from class I to VI may
indicate active disease or chronic disease. Active disease
may be reversible with treatment, whereas chronic
disease may be an indication of scarring and fibrosis of
the kidneys that may not respond to drug therapy.
MANAGING LN
The goal of treatment of SLE and LN is to manage
the acute and chronic symptoms of the disease.
Treatments of these conditions focus on the preser-
vation of renal function or loss. The treatment
paradigm of LN includes two phases when treating
class I to class VI LN, the induction and the main-
tenance phases, which comprise different therapies
based on the pathology result. A rheumatologist and
nephrologist usually manage the first, or induction,
phase. The maintenance phase is managed by an NP
or other health care provider in collaboration with
the rheumatologist and nephrologist.
Induction Phase
The induction phase treatment goal is to decrease
inflammation of the kidneys and to relieve LN
symptoms. Medication therapy for LN usually
involves a corticosteroid (CS), particularly for patients
who have significant renal disease. A CS (eg, pred-
nisone) is an anti-inflammatory drug therapy that
decreases the inflammation process. These medica-
tions may cause many side effects with long-term use,
including osteoporosis, weight gain, elevated blood
pressure, diabetes mellitus, high cholesterol, cataract,
glaucoma, peptic ulcer disease, and dyspepsia.
Intravenous cyclophosphamide (CYC) or oral
mycophenolate mofetil (MMF) immunosuppressive
agents may be used for aggressive proliferative lesions
of the kidneys.11 CYC is an immune modulator that
The Journal for Nurse Practitioners - JNP 3
Table 1. International Society of Nephrology/Renal Pathology Society 2003 Classifications of Lupus Nephritis (LN)
Class I. Minimal mesangial LN
Class II. Mesangial proliferative LN
Class III. Focal LNa
Class IV. Diffuse LNa
Class V. Membranous LNb
Class VI. Advanced sclerosing LN
EM ¼ electron microscopy; GN ¼ glomerulonephritis; IF ¼ immunofluorescence; LM ¼ light microscopy.
a
Indicate the proportion of glomeruli with active and with sclerotic lesions. Indicate the proportion of glomeruli with fibrinoid necrosis and with cellular crescents. Indicate
and grade (mild, moderate, severe) tubular atrophy, interstitial inflammation and fibrosis, severity of arteriosclerosis or other vascular lesions.
b
May occur in combination with class III or IV, in which case both will be diagnosed; may show advanced sclerosis.
decreases inflammation of the kidneys. Its side effects
include anemia, sterility, bladder problems, and renal
impairment. MMF drug therapy inhibits B- and
T-cell lymphocyte proliferation. This medication is
teratogenic, and therefore a pregnancy test is
recommended before starting therapy. Other side
effects of MMF agents include acute renal failure and
anemia. Because these immunosuppressive drugs
have a plethora of undesirable side effects, the NP
needs to monitor patients with LN closely to ensure
safe and effective care.14
Maintenance Phase
The goal of the maintenance phase of therapy is to
prolong life and to induce remission,9 or, more
generally, to manage patients’ health and prevent
renal flares. This treatment phase includes a CS and
4 The Journal for Nurse Practitioners - JNP
 Normal glomeruli by LM, but mesangial immune deposits by IF
 Purely mesangial hypercellularity of any degree or mesangial matrix
expansion by LM, with mesangial immune deposits
 There may be a few isolated subepithelial or subendothelial deposits
visible by IF or EM, but not by LM
 Active or inactive focal, segmental and/or global endo- and/or extracapillary
GN involving <50% of all glomeruli, typically with focal subendothelial
immune deposits, with or without mesangial alterations
 III (A): purely active lesions: focal proliferative LN
 III (A/C): active and chronic lesions: focal proliferative and sclerosing LN
 III (C): chronic inactive with glomerular scars: focal sclerosing LN
 Active or inactive focal, segmental, and/or global endo- and/or extracapillary
GN involving >50% of all glomeruli, typically with diffuse subendothelial
immune deposits, with or without mesangial alterations
 This class is divided into diffuse segmental (IV-S) when >50% of the involved
glomeruli have segmental lesions and diffuse global (IV-G) when >50% of the
involved glomeruli have global lesions
 Segmental is defined as a glomerular lesion that involves less than half of
the glomerular tuft
 IV-S(A) or IV-G(G): Purely active lesions: diffuse segmental or global
proliferative LN
 IV-S(A/C) or IV-G (A/C): Active and chronic lesions: diffuse segmental or
global proliferative and sclerosing LN
 IV-S(C) or IV-G(C): Inactive with glomerular scars: diffuse segmental or
global sclerosing LN
 Global or segmental subepithelial immune deposits or their morphologic
sequelae by LM and by IF or EM, with or without mesangial alterations

90% of glomeruli globally sclerosed without residual activity
MMF or azathioprine (AZA). AZA is an
immunosuppressive agent that inhibits T
lymphocytes and blocks the lupus autoimmune
inflammation process.11 AZA may cause pancreatitis
and autoimmune hepatitis. Therefore, liver function
tests should be monitored when patients are taking
this medication.
ACR Treatment Guidelines for Class I to VI LN
Class I/II. The ACR guidelines do not recommend
any specific treatments such as immunosuppressive
therapy for class I and II LN unless patients’ proteinuria
laboratory result is more than 1000 mg/d,11 in which
case patients can be treated with an immunosuppressive
agent to decrease inflammation to the kidneys. The
goal of treatment for class I/II LN is to optimize a
therapeutic approach to prevent further renal injury.
Volume 14, Issue 1, January 2018
 Class III/IV. The ACR recommends aggressive
drug therapy to manage class III/IV LN.11 The
recommended immunosuppressive agents (MMF, AZA,
or CYC) and glucocorticoids.11 Therapeutic monitoring
of these drugs and side effects are crucial to prevent the
progression of end-stage renal disease (ESRD).
Class V/VI. Class V/VI LN should be treated
with immunosuppressive treatments or renal
replacement.11 For example, MMF combined with
glucocorticoids can be used as initial treatment for
class V.15 The ACR’s guidelines recommend starting
renal replacement therapy such as dialysis for class VI
patients, which may be more beneficial than
immunosuppressive drug treatments for patients who
progress toward ESRD.11
ADJUNCTIVE TREATMENTS
Adjunctive treatments are beneficial in the manage-
ment of SLE and LN to control inflammation and
prevent long-term kidney damage. When patients
with SLE are undergoing adjunctive treatments, the
NP will need to monitor their progress, however.
The following conditions are crucial to monitor
during these treatments.
Hypertension
The ACR guidelines recommend close monitoring
of patients’ blood pressure and the use of angiotensin-
converting enzyme (ACE) inhibitors or angiotensin
receptor blockers (ARB). These drugs produce
renoprotective effects and help decrease protein-
uria.9,11 Both ACE and ARB drug therapy are
contraindicated in pregnancy because they are
teratogenic, and thus caution is recommended when
treating patients who may become pregnant.11,16 The
ACR guidelines recommend a target blood pressure
goal of <130/80 mm Hg to slow the progression of
kidney disease.11
Hyperlipidemia
The ACR recommends treating hyperlipidemia in
patients with LN using statin drug therapy. For
example, atorvastatin is an 3-hydroxy-3-methyl-
glutaryl coenzyme A reductase inhibitor agent pre-
scribed to prevent cardiovascular disease.11 Heart
disease is a risk factor implicated in LN morbidity and
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mortality rates. Therefore, aggressive treatment with
statin therapy is needed to prevent further heart
complications. NPs need to remember not only to
have a baseline for liver function and creatinine but
also to monitor patients’ laboratory results
periodically.
Renal Function
Hydroxychloroquine (HCQ; Plaquenil) is a drug
used to treat rheumatic and inflammatory skin
diseases and is also an antimalarial agent. It has been
shown to improve renal function and decrease
autoantibody production when treating patients with
LN.16 HCQ causes ocular conditions such as
retinopathy. A referral to an ophthalmologist is
strongly recommended, as is an annual retinal
examination to monitor retinopathy.
Osteoporosis
Patients taking high doses of CS during long-term
therapy may need prophylaxis treatments to prevent
osteoporosis, a serious complication associated with
this drug regimen. Patients should be routinely
treated with calcium and vitamin D (1000 IU/d)
supplements or bisphosphonates (eg, alendronate
[Fosamax]) to manage this condition.16 Alendronate
inhibits osteoclast activity. NPs should have a baseline
of calcium and creatinine levels (avoid use if
creatinine clearance is <35) before this drug is
commenced. A serious reaction of alendronate is
femur fractures, osteonecrosis of the jaw,
hypocalcemia, and esophagitis. Regular bone mineral
density scans should be performed annually to
monitor the progression of osteoporosis.16
Vascular Complications
The vascular complications related to LN are
antiphospholipid syndromeeassociated nephropa-
thy (APSN) or thrombotic microangiopathy
(TMA), both of which cause alterations in blood
coagulation, such as arterial or venous throm-
bosis.17 APSN is an autoimmune disorder of
unknown origin. The patient may present with
stroke, pulmonary embolism (tachypnea and
dyspnea), or deep vein thrombosis (leg swelling).
The antiphospholipid antibody laboratory results
The Journal for Nurse Practitioners - JNP 5
are the hallmark test for APSN. The ACR
guidelines suggest treating TMA primarily with
plasma exchange for vascular complications.11
Heparin or warfarin anticoagulant drugs are
recommended to treat venous thrombosis. When
using a warfarin drug therapy, the international
normalized ratio should be maintained at a level of
2.0 to 3.0. These vascular complications will need
proper disease management and referrals to
improve survival rates among patients with LN.
CONCLUSION
The overall goal of treatment for LN is to preserve
renal function. Prompting recognition of the disease
presentation and effective treatments can lead to
better renal outcomes. NPs need to be well equipped
with adequate knowledge and skills to help decrease
renal injury. Their roles are to assess, diagnose,
manage, and evaluate patient’s health to prevent
irreversible renal damage, which is one of the pre-
dictors of mortality rates among lupus
nephritis patients.
References
1. Lupus Foundation of America. 2017. How lupus affects the renal (kidney) system.
http://www.resources.lupus.org/entry/how-lupus-affects-therenal-system.
2. Wallace DJ, Hahn BH. Dubois’ lupus erythematosus and related syndromes.
8th ed. Philadelphia, PA: Elsevier Saunders; 2013.
3. Schwartz N, Goilav B, Putterman C. (2014). The pathogenesis, diagnosis and
treatment of lupus nephritis. Curr Opin Rheumatol. 2014;26(5), 502e509.
https://doi.org/10.1097/BOR.0000000000000089.
6 The Journal for Nurse Practitioners - JNP
4. National Kidney Foundation. Lupus and kidney disease (lupus nephritis).
Published 2017. https://www.kidney.org/atoz/content/lupus.
5. Anders HJ, Weening JJ. Kidney disease in lupus is not always “lupus
nephritis”. Arthritis Res Ther. 2013;15(2):108.
6. Takvorian SU, Merola JF, Costenbader KH. Cigarette smoking, alcohol
consumption and risk of systemic lupus erythematosus. Lupus. 2014;23(6),
537-544. https://doi.org.10.1177/0961203313501400.
7. Wu L, Yu F, Tan Y, et al. Inclusion of renal vascular lesions in the 2003
ISN/RPS system for classifying lupus nephritis improves renal outcome
predictions. Kidney Int. 2013;83(4):715-723. https://doi.org/10.1038/ki
.2012.409.
8. Mambatta AK, Jayalakshmi Jayarajan VLR, Harini S, Menon S, Kuppusamy J.
Reliability of dipstick assay in predicting urinary tract infection. J Fam Med
Primary Care. 2015;4(2):265-268.
9. Mok CC. Understanding lupus nephritis: diagnosis, management, and
treatment options. Int J Women Health. 2012;4:213-222.
10. Wilhelmus S, Bajema IM, Bertsias GK, et al. Lupus nephritis management
guidelines compared. Nephrol Dial Transplant. 2015;31(6), 904e991. https://
doi.org/10.1093/ndt/gfv102.
11. Hahn BH, McMahon M, Wilkinson A, et al. American College of
Rheumatology Guidelines for screening, case definition, treatment and
management of lupus nephritis. Arthritis Care Res. 2012;64(6):797-808.
https://doi.org/10.1002/acr.21664.
12. Haas M, Rastaldi MP, Fervenza FC. Histologic classification of glomerular
diseases: clinicopathologic correlations, limitations exposed by validation
studies, and suggestions for modification. Kidney Int. 2014;85(4):779-793.
https://doi.org/10.1038/ki.2013.375.
13. Weening JJ, D’agati VD, Schwartz MM, et al. The classification of
glomerulonephritis in systemic lupus erythematosus revisited. Kidney Int.
2004;65(2), 521-530. https://doi.org/10.1111/j.1523-1755.2004.00443.x
14. Gavilanes LZ, Valarezo AC. Rituximab in lupus nephritis: a non-systematic
review. Reumatol Clín. 2016;12(4):210-215.
15. Bertsias GK, Tektonidou M, Amoura Z, et al. Joint European League Against
Rheumatism and European Renal AssociationeEuropean Dialysis and
Transplant Association (EULAR/ERA-EDTA) recommendations for the
management of adult and paediatric lupus nephritis. Ann Rheum Dis.
2012;71(11):1771-1782.
16. Bose B, Silverman ED, Bargman JM. Ten common mistakes in the
management of lupus nephritis. Am J Kidney Dis. 2014;63(4):667-676.
17. Mavragani CP, Fragoulis GE, Somarakis G, et al. Clinical and Laboratory
Predictors of Distinct Histopathogical Features of Lupus Nephritis. Medicine.
2015;94(21):e829. https://doi.org/10.1097/MD.0000000000000829.
1555-4155/17/$ see front matter
© 2017 Elsevier Inc. All rights reserved.
https://doi.org/10.1016/j.nurpra.2017.09.020
Volume 14, Issue 1, January 2018