A survey on manifestations, laboratory findings and pathological renal biopsy based classification of patients with lupus nephritis

Lupus nephritis comprises a spectrum of glomerular, vascular, and tubulointerstitial lesions, which has significant racial variations in severity and manifestations. The current International Society of Nephrology/Renal Pathology Society classification (2003) has been successfully improved for the categorization of lupus glomerulonephritis.

A SURVEY ON MANIFESTATIONS, LABORATORY FINDINGS

AND PATHOLOGICAL RENAL BIOPSY-BASED

CLASSIFICATION OF PATIENTS WITH LUPUS NEPHRITIS

Bui Van Khanh 1 ; Nguyen Van Doan 1 ; Nguyen Dang Dung 2

SUMMARY

Introduction: Lupus nephritis comprises a spectrum of glomerular, vascular, and tubulointerstitial lesions, which has significant racial variations in severity and manifestations The current International Society of Nephrology/Renal Pathology Society classification (2003) has been successfully improved for the categorization of lupus glomerulonephritis Methods: This study is a retrospective analysis on clinical manifestations and the pathological features of lupus nephritis Clinical manifestations and laboratory test were collected and analysed by SPSS 20.0 program Results: Among the 38 patients with lupus nephritis, 92.1% was female, with the major manifestations being hypertension (47.4%), edema (44.7%), skin malar rash (36.9%), arthritis (57.9%), anemia (81.1%), oral ulcer (21.1%) The mean SLEDAI was 20.58 ± 6.46, and mean serum level of creatinine was 152.86 ± 125.96 µmol/L Percentage of patients with hypoalbuminemia was 75% Of the patients involved, 94.4% showed with decrease of C3 complement, 69.4% of C4 complement The mean 24-hour urine protein was 5.03 ± 4.88 g 94.4% of the patients had ANA test positive, among which 69.4% positive with anti-dsDNA, and 14.3% positive with anti-Sm autoantibodies On the basis of this classification, 38 patients with lupus nephritis revealed the following distribution: Class I: 0%; class II: 5.3%; class III: 50%; class IV: 28.9%; class V: 10.5%; combined classes III & IV: 2.6%; and class VI: 2.6% Conclusions: In patients with lupus nephritis, manifestations and laboratory findings by renal biopsy were clinically valuable in identifying different renal classifications of lupus pathology, which was helpful for diagnosis and treatment guide

* Keywords: Lupus nephritis; Clinical Manifestation; Laboratory finding

INTRODUCTION

Renal involvement is one of the most

severe complications of systemic lupus

erythematosus (SLE) and the clinical

presentation of lupus nephritis (LN) is

highly variable, ranging from mild

asymptomatic proteinuria to rapidly

progressive glomerulonephritis [1, 2] The renal morphological expression can vary considerably among patients or within an individual over time [3, 4] Performing renal biopsies to accurately determine the prognosis and to guide treatment in

LN patients is greatly needed Recently,

1 Bachmai Hospital

2 Vietnam Military Medical University

Corresponding author: Nguyen Dang Dung (dzungmd@yahoo.com)

Date received: 30/08/2018

Date accepted: 16/11/2018

the International Society of

Nephrology/Renal Pathology Society

(ISN/RPS) 2003 classification of LN was

proposed [5] However, very few

publications are currently available

concerning the demographic, clinical, and

pathological features of LN in Vietnam [8]

Therefore, this study aimed to: Assess

the clinical and basic laboratory features

according to ISN/RPS 2003 classification,

renal pathological activity, and chronicity

index of the patients

SUBJECTS AND METHODS

1 Subjects

Patients with LN who underwent renal

biopsy between 2015 and 2017 in the

Center of Allergy and Clinical Immunology,

Bachmai Hospital, were included in this

study All patients met the American College

of Rheumatology (ACR) revised criteria

for the classification of SLE [3] For

inclusion, patients had to have adequate

renal biopsy samples for histological

diagnosis, including > 10 glomeruli

Consequently, data of 38 patients were

available in the study

2 Methods

* Study design:

This is a retrospective analysis on

clinical manifestations and the pathological

features of renal biopsy of LN patients

* Data collection:

For included patients, clinical records

and laboratory parameters at the time of

biopsy were collected Renal

biopsy-confirmed LN cases were classified

according to the 2003 ISN/RPS classification [3] Data regarding

available for 100% of the patients Activity indices (AIs) and chronicity indices (CIs) were calculated accordingly In addition, the following parameters were collected: Demographic data (sex, age), extrarenal SLE manifestations, SLEDAI, anti-dsDNA antibody, anti-nuclear antibodies, anti-Sm antibody, and hematological and biochemical parameters (including CBC, hemoglobin, serum levels of urea, creatinine, albumin, and complement) Nephrotic syndrome was defined as a simultaneous existence of generalized edema, an increase in the proteinuria of

≥ 3.5 g/24 hours and a decrease in serum albumin to ≤ 30 g/L

* Statistical analysis:

Data with normal distribution and non-normal distribution were presented as mean ± SD and median and range, respectively Categorical variables were presented as percentage All statistical evaluations were performed using the SPSS Program, version 20.0

RESULTS AND DISCUSSION

1 Baseline demographic, clinical and laboratory features of the patients

at the time of renal biopsy

Renal involvement is a frequent and serious organ manifestation of SLE and is also a major cause of mortality and morbidity, especially when it occurs as proliferative LN Our study was conducted

on 38 patients

Table 1: The characteristics of patients

(n = 38)

[mean ± SD, or n (%)]

Table 2: Baseline laboratory features

of the patients

Variable

Value [mean ± SD,

or n (%)]

Leukopenia (WBC < 4 G/L)

(n = 37)

8 (21.6)

Thrombocytopenia (PLT < 100 G/l)

(n = 37)

6 (16.2)

< 30 g/L) (n = 36)

27 (75.0)

125.96

Urine protein 24 hours (g/24 hrs)

Most of the patients with lupus glomerulonephritis were female, accounting for 92.1%, which is similar to those of other authors [6, 7, 8, 9] The mean age

of patients with lupus glomerulonephritis

at the time of biopsy was 31.24 ± 12.41 years, the most common age group was

20 - 40 years, which was similar to that reported by Hamid Nasri et al with mean age of their patients being 32.7 ± 12 years Hypertension, edema, malar rash, arthritis and oral ulcer were the most manifestation at the time of renal biopsy

It was implied that LN does not only have manifestation of renal damage, but also other organs It was further demonstrated

by high SLEDAI being 20.58 ± 6.46 In patients with SLE and renal disease, the presence of haematuria, proteinuria, hypoalbuminemia, low C3, C4, and positive anti-dsDNA may positively predict proliferative LN Although renal biopsies remain the best way of diagnosis of LN, clinicians in ereas where renal biopsies are not available may use these clinical findings and other laboratory tests as alternatives for diagnosis of LN This may help guiding proper therapy

2 Histopathological features of biopsies

* The classification of renal biopsy of lupus nephritis by ISN/RPS:

Class I: 0 patient; class II: 2 patients (5.3%); class III: 15 patients (50.0%); class IV: 12 patients (28.9%); class V:

4 patients (10.5%); class VI: 1 patient (2.6%); mix class III + IV, IV + V: 1 patient (2.6%)

The ISN/RPS lupus nephritis class III and IV occurred more frequently than other classes of LN

Renal biopsy plays an important role in

the diagnosis and management of LN,

which provides information about kidney

damage, activity levels, as well as chronic

kidney disease of injury Our study results

were mainly attributable to class III and

class IV, similar to those in other studies

[8], where class III was higher, which was

not consistent with studies rescues in

the area [8] This difference may be

explained by the choice of biopsy

patients, primarily in patients with severe

clinical manifestations such as edema,

elevated 24-hour proteinuria Another factor contributing to this explanation is that most of patients in our study went to hospital when it was relatively late for diagnosis and treatment, leading to more severe renal damage Classes I and II were low which is also explained by our selection of patients with a renal biopsy, focusing only on those with severe clinical and urinalysis, according to the medical literature Abnormalities in clinical and urinalysis were less common in LN classes I and II [1]

Table 3: The characteristics of subclasses III and IV

Class

IV

The characteristics of LN subclasses

III and IV have shown that the majority of

subclasses were active

Classes III and IV of LN are often

associated with subclasses A or A/C, and

are less common in subclass C alone,

suggesting that the glomerular injury is

continuous, resulting in a pathological

glomerulosclerosis

Percentage of class V of LN (10.5%)

was followed by kidney damage in class III

and IV, which was lower than that

reported by other groups, such as the

Japanese authors 15.6%, USA 29.4%,

UK 18.9% [8] This may possibly be due

to our small number of patients

In our study, only 1 patient (2.6%) was

of class VI of LN, which was relatively low

in percentage, possibly be due to the choice of patients Class VI kidney damage is end-stage renal disease, with complete fibrosis of more than 90% of glomerular, which leads to clinical end-stage renal disease such as chronic renal failure, anuria In these patients, we do not indicate a kidney biopsy Other authors have also reported that the prevalence of kidney damage in class VI

is very low, being 1% by Japan authors, 3.3% in the United States and 0.6% in the United Kingdom [8]

* Activity index (n = 32):

Type 1 (0 - 8): 26 patients (81.25%); type 2 (9 - 16): 6 patients (18.75%); type 3: (17 - 24): 0 patient Mean activity index (AI) value: 5.91 ± 3.21

The AI of the study was mainly found

in mild (81.3%) and moderately active

(18.8%) groups, with an average activity

index of 5.91 ± 3,21, which is the same to

that of Pham Hoang Ngoc Hoa (6.53 ±

4.66) [1], suggesting that the majority of

patients having been evaluated for renal

biopsy were flare disease, and consistent

with clinical manifestations such as

elevated urinary proteinuria or clinical

edema

* Chronicity index (n =32):

Type 1 (≤ 1): 14 patients (43.8%); type 2

(2 - 3): 13 patients (40.6%): type 3 (≥ 4):

5 patients (15.6%) Mean chronic index

(CI) value: 1.94 ± 1.46

The most common CI was the mild CI

(43.8%), with an average CI of 1.94 ± 1.46,

which was lower than that of Pham

Hoang Ngoc Hoa (2.21 ± 2.57) [1]

Table 4: Results of immunofluorescence

staining of renal biopsies in LN (n = 38)

Immunofluorescence

immunofluorescence stained markers

were high with IgG and C1q, C3, and IgA,

IgM, C4 Of 38 patients undergoing renal

biopsy, 10.5% showed all 6 markers

(IgG, IgM, IgA, C3, C4, C1q deposition

at gromeruli) positive by

immuno-fluorescense staining

Characteristics of fluorescent immuno-staining are important for the differential diagnosis of lupus glomerulonephritis versus other nephropathy Our study found that 100% of patients were positive for at least one immunological marker, and 10.5% of patients were positive for all immunological markers, of which IgG and C1q showed very high positive rates of 94.7% and 92.1%, respectively The results of this study are similar to that of Pham Hoang Ngoc Hoa et al [1]

CONCLUSION

This study indicates that clinical and laboratory fundings at renal biopsy are clinically valuable in identifying different renal classifications of lupus pathology, activity, and chronicity index Our results suggest that patients with class III and IV had signicantly higher proportions of microscopic hematuria, proteinuria, impaired renal function, anemia, hypoalbuminemia, and positive anti-DNA antibody All of these findings correlated well with high activity index and chronicity index of lupus pathology

REFERENCES

1 Phạm Hoàng Ngọc Hoa, Nguyễn Văn Hưng Apply the classification of International

Society of Nephrology/Renal Pathology Society (ISN/RPS) 2003 in diagnosis of LNitis Hochiminh Medicine 2015, Vol 19, No 5

2 Adeel Zubair, Marianne Frieri Lupus

nephritis: Review of the literature Curr Allergy Asthma Rep 2013, 13, pp.580-586

3 Bevra H Hahn, Maureen A McMahon, Alan Wilkinson et al American College of

Rheumotology Guidelines for screening, treatment, and management of LN Arthritis Care and Research 2012, 64, pp.797-808

4 Jan J Weening, Vivette D D’Agati,

Melvin M Schwartz et al The Classification of

Glomerulonephritis in Systemic Lupus

Erythematosus Revisited JASN 2004,

February 1, 2, Vol 15, No 2, pp.241-250

5 George K Bertsias, Maria Tektonidou,

ZahirAmoura et al Joint European League

Against Rheumatism and European Renal

Association-European Dialysis and

Transplant Association (EULAR/ERA-EDTA)

recommendations for the management of

adult and paediatric lupus nephritis Ann

Rheum Dis 2012, 71, pp.1771-1782

6 Hamid Nasri, Ali Ahmadi,

AzarBaradaran et al Clinicopathological

correlations in lupus nephritis; a single center experience J Nephropathol 2014, 3 (3), pp.115-120

7 Hitoshi Yokoyama, Hiroshi Okuyama,

Hideki Yamaya Clinicopathological insights

into lupus glomerulonephritis in Japanese and

Asians Clin Exp Nephrol 2011, 15,

pp.321-330

8 IG Okpechi et al Clinicopathological

insights into lupus nephritis in South Africans:

A study of 251 patients Lupus 2012, 21, pp.1017-1024

9 Z Wang et al Clinicopathological

characteristics of familial SLE patients with

LN Lupus 2009, 18, pp.243-248