Res J Med Allied Health Sci | July-Dec. 2019 | Volume 2 | Issue 2

Original Article

Lupus nephritis: clinico-biochemical profile of cases

from a tertiary care renal referral centre

1 2Mythri KM , Kowsalya R

1Associate Professor, Department of Microbiology

2Associate Professor, Department of BiochemistryInstiute of Nephro Urology, Victoria Hospital campus, Bangalore-560002.

Address for Correspondence:Dr. Kowsalya R, MD, BiochemistryAssociate professor of BiochemistryInstiute of Nephro Urology, Victoria Hospital campusBangalore-560002. E-m ail: r.kowsalya@gmail.com

Abstract

Introduction: Systemic lupus erythematosis is a multi-systemic disorder where renal impairemnet is seen and

remains the most dangerous life threatening complication. Renal manifestations are highly pleomorphic and

patients present with varied symptoms from asymptomatic proteinuria to renal insufficiency warranting dialysis.

Material and Methods: We describe spectrum of 50 biopsy proven cases of lupus nephritis patients at our exclusive

tertiary care renal referral centre. Results: The study consisted of 50 patients, 43 females and 7 males with mean age

30.6 ± 11.6 years at time of presentation. Clinically the frequent presenting symptoms was of nephrotic syndrome

followed by renal insufficiency. Five cases were adolescents aged between 12 and 17 years and one patient

succumbed highlighting that lupus nephritis is severe in childhood. Conclusion: Lupus nephritis is one of the

important causes of morbidity and mortality in patients with SLE. Thus with all the clinical and therapeutic

constraints the lupus nephritis management still remains a challenge.

Keywords: Lupus, nephritis, renal

IntroductionSystemic Lupus Erythematosis (SLE) is an autoimmune

disorder in which auto- antibodies are directed against

nuclear antigen. It is a disorder in which different organs

are affected including kidney. Amongst the various

organs affected the renal impairment is quite often and [1]

carries a poor prognosis. About 60% of the SLE

patients have renal involvement by the end of 5 years

and among those patients 10-20% will progress to end

stage renal disease.

The occurrence and severity of nephritis differs with

age, sex and ethnicity with a higher prevalence in

women of childbearing age. SLE is likely to be affected

among Women in childbearing age. In addition, African

and Hispanic ethnicity have been associated with [2]

greater occurrence and severity of disease. The clinical

spectrum can range from benign sub-proliferative lesion

to diffuse proliferative nephritis presenting with full

blown progressive renal failure.

1

In addition, the disease process can transform

spontaneously from one morphologic pattern to another,

hence the clinical course and outcome is highly [3]variable. Inspite of cytotoxic therapy some patients are

respond poorly; Organ damage and impairment of renal

functions are expected. Therefore, conventional

immunosuppressive treatment refractory patients are of

major concern and requires early identification and [4]development of alternative treatment modalities.

The current and new therapeutic approach are guide

mainly by histological histologic findings of the disease.

Hence renal biopsy plays a very important role in the

treatment of SLE. Although renal survival rates have

improved over the past decade, it should be stressed that

ELISA method.

Assays: Serum creatinine assay was based on Jaffe's

alkaline picrate method.

The reference range is:

Serum/Plasma: Child --0.3 to 0.7(mg/dL)

Adult Male --0.7 to 1.3 (mg/dL)

Adult Female --0.6 to 1.1(mg/dL).

The Complement C3/C4 assay was based on immuno

turbidimetric method. In this procedure the insoluble

immune complexes causing the increase in turbidity of

the sample is measured. The buffer and the sample

containing C3/C4 is incubated and a sample blank

determination is performed prior to the addition of

C3/C4 antibody. In the presence of an appropriate

antibody in excess, the C3/C4 concentration is

measured as a function of turbidity.

Reference Range:

Serum/Plasma (mg/dL) Male Female

C3 1 to 14 years 80 to 170 82 to 173

> 14 to 80 years 82 to 185 83 to 193

C4 1 to 14 years 14 to 44 13 to 46

> 14 to 80 years 15 to 53 15 to 57

ANA/dsDNA estimated by ELISA method. The antigen

binds to ANA/dsDNA specific antibody and other

unbound materials are washed. Then the enzyme

conjugate is added which binds to the antibody-antigen

complex. The substrate is added after washing an

excess of enzyme conjugate. The plate is incubated to

allow the hydrolysis of the substrate by the enzyme. The

amount of specific antibody in the sample is directly

proportional to the intensity of the color developed .

Antibody Index Interpretation

<0.9 : No Detectable ANA IgG/dsDNA by

ELISA.

0.9 to 1.1: Borderline positive. Follow-up testing is

recommended if clinically indicated.

> 1.1 Detectable ANA IgG/dsDNA by ELISA.

All statistical analyses were performed using Microsoft

excel. Descriptive and nonparametric statistics were

adopted.

ResultsWe retrospectively evaluated the clinical features and

laboratory data of 50 biopsy proven cases of lupus

current immunosuppressant regimes still achieve

suboptimal results with an additional burden of drug [5,6]induced toxicity.

As lupus has no cure, the ultimate management goal is to

stop progression of the disease. There is a lack of data

from this part of the country both in terms of disease

management and outcome. This retrospective study was

undertaken to review the clinic-pathological profile of

SLE patients from an exclusive tertiary care renal

referral institute.

Materials and methodsWe included 50 biopsy proven lupus nephritis patients

presenting to our tertiary care renal referral centre for

this retrospective study.

Patients demographic data, clinical history and

laboratory biochemical parameters were included.

Glomerular filtration rate (GFR) was estimated in all the

patients by Modification of Diet in Renal Disease [7](MDRD) formula.

Clinical definitions: Normal renal function was

defined as GFR - 90ml/mm/1.73m2 estimated using the

MDRD formula, hematuria -5 RBCs per high power

field in the urinary sediment, nephrotic syndrome -

proteinuria more than 3.5g/day with hypoalbuminemia,

oedema and hyperlipidemia. Nephritic syndrome -

hematuria (usually with dysmorphic RBCs/ RBCs

casts) with proteinuria less than 3.0g/day, hypertension

and elevated serum creatinine, chronic renal failure -

severe irreversible kidney damage and serum creatinine [8, 9]

levels persistently above 1.5mg/dL.

eGFR [Estimated glomerular filtration rate]:

calculated using online calculator.

Stage I [GFR ³ 90] : Kidney damage with normal kidney

function

Stage II [GFR =89 to 60]: Kidney damage with mild loss

of kidney function

Stage III [GFR =59 to 30]: Kidney damage with

moderate loss of kidney function

Stage IV [GFR =29 to 15 ]: Kidney damage with severe

loss of kidney function

Stage V [GFR < 15] : Kidney failure

The Biochemical parameters were analyzed in the

Abbott Architect integrated analyzer, while the

connective tissue disorder markers -Anti-nuclear

antibody and ds-DNA antibody were estimated by

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Mythri KM, et al.: Lupus nephritis

three-fourths of the patients (84%) had positive

antinuclear antibodies and 71% had positive anti-

dsDNA antibodies while the C3 and C4 complement

fractions were low in 37 patients. Table-1 shows

demographics and laboratory parameters across Lupus

nephritis patients based on egfr. The extra-renal

manifestations at the presentation of lupus nephritis

were as follows: arthritis in patients, skin involvement,

fever, lymphoadenopathy and CNS involvement. Class

IV was the most common histopathology followed by

class III and II. The percentage distribution of patients'

characteristics at presentation is shown in the Figure-1.

nephritis. The mean age of the patients was 30.6±11.6

years. Seven patients were male and 43 patients were

female. 15 patients (30 %) had arterial hypertension. At

presentation, all the patients fulfilled the diagnostic

criteria laid by American College of Rheumatology. All

the patients had renal insufficiency (median serum

creatinine 1.9 mg/dl), while 55% of patients with

nephrotic syndrome (median proteinuria 2.88g/24

hours), renal manifestations ranged from decreased

renal output to hematuria and nephrotic syndrome.

More than 90% patients had microscopic haematuria

(median number of erythrocytes 10/hpf). More than

Res J Med Allied Health Sci | July-Dec. 2019 | Volume 2 | Issue 2 3

Table-1 shows demographics and laboratory parameters across Lupus nephritis patients based on egfr.

*MAP = mean arterial pressure

Mythri KM, et al.: Lupus nephritis

Figure-1: Pie- chart showing percentage distribution of patients characteristics at presentation

GROUP I GROUP II GROUP III GROUP IV

eGFR (mL/min/1.73 m2) 103.6 96.77 54.12 28.4

Number of cases 8 9 31 2

Male/female 1/7 2/7 4/27 0/2

Age (years) 28.22 ± 6.6 29.43 ± 14.64 28.28 ± 8.91 38.33 ± 16.26

MAP (mmHg)* 102.4 98.4 104.1 95.6

Serum creatinine (mg/dL) 1.35 ± 1.22 1.51 ± 1.1 1.9 ± 0.49 2.77 ± 1.38

Hemoglobin (g/dL) 9.42 ± 1.36 8.4 ± 0.56 8.6 ± 1.7 8.2 ± 0.4

24-hour proteinuria (g/day) 2.16 ± 1.9 2.69 ± 1.59 4.2 ± 2.8 3.25 ± 1.2

C3 (mg/dL) 56.9 ± 30.5 37.8 ± 18.1 17.5 ± 7.78 29.98 ± 23.53

C4 (mg/dL) 16.5 ± 3.09 17 ± 4.65 17 ± 7.07 16.55 ± 12.38

ANA 78.80% 82.60% 89.6 % 100 %

ds DNA 67.80% 76.00% 71.90% 100 %

is to stop progression of the disease.

The histopathologic classification continue to guide the

therapy as the current biomarkers including serum

creatinine, urinalysis and level of proteinuria are not

sufficient for knowing the severity of the disease

process. The treatment regime consists of an induction

phase followed by a maintenance phase. The treatment

for lupus nephritis has changed significantly based on

large part of data from well conducted randomized [19, 20, 21]

clinical trials. The current biomarkers including

serum creatinine, urinalysis and level of proteinuria are

not sufficient for knowing the degree and severity of an

individual patient's illness.

Lupus nephritis is considered as a serious medical

problem as it affects commonly younger age group. [21]

They end with ESRD without any specific treatment.

With kidney diseases emerging as a major health

problem globally and ESRD showing an alarming

growth rate, efforts are needed for early diagnosis and

proper management of these patients. More studies are

needed to explore the possible modes of disease

progression and treatment, especially in India which is a

developing country for favorable patient outcome.

Clinical significance

India as a developing country, financial constraints are

enormous, renal disorders are neglected due to lack of

awareness in patients because of the low socio-

economic and educational background. As a

consequence patients present late with advanced disease

process. This may also be partially attributed to

disparities in the biopsy policies and requirement of

immune-fluorescence facilities to confirm the

diagnosis. A definite plan of action should be

implemented in countries like India with an estimated [22]

ESRD of 150-200 pmp and limited resources.

Conclusion Lupus nephritis is one of the most severe manifestations

of systemic lupus erythematosus, which is associated

with significant morbidity and mortality of SLE

patients. It is a situation of concern as our patients

approach medical help only after they develop overt

manifestations of renal disease due to unawareness

which need to be addressed.

Financial support and sponsorship: Nil

Conflicts of interest: Nil

Discussion In our study a peak incidence of lupus nephritis was

found in second / third decade with female

preponderance as reported by Malavia et al. In our study,

the age of patients at diagnosis ranged from 10 to 47 [10]

years. The mean age of subjects in our study (30.6 ±

11.6) was similar to the subjects who participated in the

study by Chakrabarti etal. A younger age at diagnosis is [11]

considered to be a poor prognostic marker.

When compared to Caucasians, Asians exhibit more

severe clinical manifestations in lupus. The incidence of

lupus nephritis presenting as nephrotic syndrome and

renal failure reported varies in different regions of the

world. Many studies have reported that renal failure is [12]

the main feature at presentation. In India also a similar

reports of higher incidence of renal failure among lupus [13]patients has been reported. Renal insufficiency was

seen in all of our patients as our institute is a tertiary care

referral centre and patients are referred after noting the

deranged renal function.

The other common modes of clinical symptoms

described are hematuria, proteinuria and hypertension.

Patients of lupus nephritis are known to develop

proteinuria more frequently and according to Bono et al [14]45% of the patients present with nephrotic syndrome.

Our study showed nephrotic range proteinuria in 55% of

cases, akin to the studies reporting nephrotic range [15]proteinuria ranging from 20 to 50%.

These differences in SLE prevalence and/or severity

among different ethnic groups may be due to the

complex interplay of factors such as genetic

predisposition, environmental, and socioeconomic [16]

factors. The disease course depends on a number of

factors. The spectrum may be a potentially severe

course, negative prognostic baseline measurements

would greatly assist treatment decisions and ensure [17]closer monitoring to prevent renal decline.

Our study was small but lupus nephritis is a rare

condition and the majority of published studies do not

contain larger numbers, and so we believe this study is a

valid enrichment of the literature. Short term prognosis

was good in our patients but, most of the cases were lost

to follow up. The survival rate is low compared to

western countries; patients are gradually lost to follow-

up within 3 months, primarily due to economic [18]reasons. As there is no cure for lupus, the ultimate goal

Res J Med Allied Health Sci | July-Dec. 2019 | Volume 2 | Issue 24

Mythri KM, et al.: Lupus nephritis

12. Thumboo, J . and Wee H.L. Sys temic lupus

erythematosus in Asia: is it more common and more

severe? APLAR Jourl of Rheum.2006; 9: 320–6.

13. Siddappa S, Kowsalya R, Mythri KM. A pathological

spectrum of lupus nephritis: A view of 62 cases from a

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14. Bono L, Cameron JS, Hicks JA. The very long-term

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15. Singh S, Devidayal, Minz R, Nada R, Joshi K. Childhood

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Rhematol Int. 2006; 26:604-7.

16. Murali R, Jeyaseelan L, Rajaratnam S, John L, Ganesh A.

Systemic lupus erythematosus in Indian patients:

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17. Minoru Satoh, Monica Vázquez-Del Mercado and

Edward K. L. Chan. Clinical interpretation of antinuclear

antibody tests in systemic rheumatic diseases. Mod

Rheumatol. 2009; 19(3): 219–28.

18. Tak Mao Chan. Determinants of patient survival in

systemic lupus erythematosus-focusing on lupus

nephritis. Ethn Dis. 2006;16[2]:S2-66–S2-69.

19. Andrew S. Bomback and Gerald B. Appel. Updates on

the Treatment of Lupus Nephritis. J Am Soc Nephrol:

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20. Gourley MF, Austin HA 3rd, Scott D et al. Methyl

prednisolone and cyclophosphamide, alone or in

combination, in patients with lupus nephritis. A

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125:549–57.

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