ORIGINAL ARTICLE
Year : 2019  |  Volume : 2 |  Issue : 2 |  Page : 1-5 |  DOI : https://doi.org/10.46319/RJMAHS.2019.v02i02.001

Lupus nephritis: clinico-biochemical profile of cases from a tertiary care renal referral centre.

Mythri KM¹, Kowsalya R^2*
1Associate Professor, Department of Microbiology, ² Associate Professor, Department of Biochemistry, Instiute of Nephro Urology, Victoria Hospital campus, Bangalore-560002.

*Corresponding author:
Dr. Kowsalya R, MD, Biochemistry Associate professor of Biochemistry Instiute of Nephro Urology, Victoria Hospital campus Bangalore-560002.
E-mail: 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
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Introduction
            Systemic 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 carries a poor prognosis.[1] 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 greater occurrence and severity of disease.[2] 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 variable.[3] 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 development of alternative treatment modalities.[4]
            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 current immunosuppressant regimes still achieve suboptimal results with an additional burden of drug induced toxicity.[5,6]
            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 Methods
We 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 (MDRD) formula.[7]

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 levels persistently above 1.5mg/dL. [8, 9]
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 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.

Results
We retrospectively evaluated the clinical features and laboratory data of 50 biopsy proven cases of lupus 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 three-fourths of the patients (84%) had positive antinuclear antibodies and 71% had positive antidsDNA 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.

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

	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 %
*MAP = mean arterial pressure

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

Discussion
Study showed highest number of patients had presbycusis (37.14%) followed by ISSNHL(34.2%). CVI, Head injury, Meniere's disease, infection, post-traumatic were other etiologies identified which was similar to Kumar et al study.[13] considering the patients age, ISSNHL was the most common etiology in younger age group and presbycusis will remain as the most common cause in older age group. Mean hearing loss of ISSNHL at the time of presentation was 62.2dB; The maximum number (48.6%) were in the moderate hearing loss group. A study conducted by Kyu Ho Lee et al. in 2015 on 122 patients also observed mean PTA of 62.84dB in one of the groups studied.[14] Symptoms wise 31 patients had reduced hearing, 27 along with tinnitus, 6 patients along with both tinnitus and giddiness, 4 presented with only tinnitus. Our study out of 17 sudden sensorineural hearing loss, 14 showed good recovery(72%) similar to a study conducted by Zadeh et al on 51 patients showed improvement in 37 patients (73%).[15] Our data showed that there was a statistically significant difference in the average PTA measured between one month and 3-month post-treatment( p <0.001), which indicates that there is a need for long term treatment.

Conclusion
ISSNHL is the most common etiology of SNHL in the younger and presbycusis among aged. There is a significant difference in improvement between one and 3 months. Hence, long term treatment given for better outcome. Gender, vertigo, tinnitus and laterality does not play a significant role in recovery. The treatment outcome is better for younger patients and ISSNHL than for elderly patients and Presbycusis.
           

Limitations of the study: There are no control group, small sample size, and short follow up; therefore there is a need for study with a large group.

Acknowledgements:Nil
Financial support and sponsorship:Nil
Conflict of interest: Nil

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