Saudi Journal of Kidney Diseases and Transplantation

ORIGINAL ARTICLE
Year
: 2008  |  Volume : 19  |  Issue : 1  |  Page : 32--40

Correlation of Clinical and Pathological Findings in Patients with Lupus Nephritis: A Five-Year Experience in Iran


Simin Torabi Nezhad, Roushank Sepaskhah 
 Shiraz Nephrology Center, Shiraz Medical School, Shiraz, Iran

Correspondence Address:
Simin Torabi Nezhad
Full Professor of Pathology, Shiraz Nephrology Center, Shiraz University of Medical Sciences, Shiraz Medical School, Shiraz
Iran

Abstract

Lupus nephritis (LN) is the most common and serious manifestation of systemic lupus erythematousus (SLE). The World Health Organization (WHO) and International Society of Nephrology/Renal Pathology Society (ISN/RPS 2003) classifications tend to correlate with the clinical syndrome and provide valuable information regarding prognosis and guideline for treatment. We retrospectively studied patients with biopsy proven lupus nephritis at our center from 1999 - 2003 to find whether clinical and laboratory parameters used to evaluate how close the diagnosis correlated with WHO and/ or ISN/RPS 2003 classification. There were 144 patients of whom 84.7 % were females with a mean age of 25.6 ± 10.3 years at the time of renal biopsy. The most frequent SLE presenting features were arthralgia, edema and hypertension. WHO class IV and ISN/RPS class IV were compatible with these most frequent SLE presenting features in 56% and 54.9% of the cases, respectively. Edema, hypertension, increased BUN and Creatinine, increased 24 hours urine protein excretion and decreased serum albumin level were related with a worse class of lupus nephritis. We conclude that there is a correlation between some clinical and laboratory findings, and histopathological lupus classification on renal biopsy ,which remains indispensable in the management of lupus nephritis.



How to cite this article:
Nezhad ST, Sepaskhah R. Correlation of Clinical and Pathological Findings in Patients with Lupus Nephritis: A Five-Year Experience in Iran.Saudi J Kidney Dis Transpl 2008;19:32-40


How to cite this URL:
Nezhad ST, Sepaskhah R. Correlation of Clinical and Pathological Findings in Patients with Lupus Nephritis: A Five-Year Experience in Iran. Saudi J Kidney Dis Transpl [serial online] 2008 [cited 2019 Sep 20 ];19:32-40
Available from: http://www.sjkdt.org/text.asp?2008/19/1/32/37430


Full Text

 Introduction



Systemic Lupus Erythematosus (SLE) is an autoimmune disease characterized by chronic immune complex formation and variable manifestations that include multiple organ involvement, accompanied by multiple labo­ratory abnormalities, and frequent exacerbate­ions.[1] Survival of patients with SLE has improved remarkably over the past decades. Earlier diagnosis, awareness of the vascular risk factors such as hypertension, nephrotic syndrome and antiphospholipids syndrome, and better approaches to treatment have undoubtley contributed to the improved prognosis of patients with SLE.[2],[3],[4]

Renal involvement is common in SLE and often determines the course of the disease. [1] Nearly 70-80% of all cases of SLE have some clinical manifestation of lupus nephritis, mostly glomerulonephritis. The vast majority of these patients present with class IV of the World Health Organization (WHO) and the International Society of Nephrology/ Renal Pathology Society (ISN/RPS 2003) classifications of lupus nephritis; up to 40% of the patients with diffuse proliferative glomerulonephritis die or lose their renal function within five years after diagnosis. [1]

We aim in this study to compare the demographic, clinical and laboratory, and histopathological findings in our patients with lupus nephritis and different classes of lupus nephritis according to the WHO and the ISN/ RPS 2003 classifications.

 Patients and Methods



We retrospectively studied all the patients with lupus nephritis had at least one repre­senttative renal biopsy and evaluated in our referral center from 1999 - 2003. All the biopsies with at least 10 glomeruli were reviewed by a single nephropathologist. Each biopsy was classified according to WHO classification (class I normal, class II pure mesangial alteration, class III focal segmental glomerulonephritis, class IV diffuse glomeru­lonephritis, class V diffuse membranous glomerulonephritis, and class VI advanced sclerosing glomerulonephritis) and ISN/RPS 2003 classification system (class I minimal mesangial lupus nephritis (LN), class II mesangioproliferative LN, class III focal LN, class IV diffuse segmental (IV-S) or global (IV- G) LN, class V membranous LN, class VI advanced sclerosing LN). [5] The activity and chronicity indices were also calculated.

Available medical charts of the patients were reviewed. Clinical findings including abdominal pain, alopecia, arthralgia, arthritis, ascitis, chest pain, convolution, diarrhea, dyspnea, dysuria, edema, fever, flank pain, hematuria, hypertension, malaise, myalgia, skin rash, and weight loss were evaluated.

The laboratory values were recorded for each patient included hemoglobin level, white blood cell count, platelet count, total protein, albumin level, blood urea nitrogen (BUN), creatinine, triglyceride, cholesterol, comple­ments C3 and C4, anti-double stranded DNA, anti-nuclear antibody, erythrocyte sediment­tation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), lupus nephritis (LE) cells, urinalysis, 24-hour urine protein excre­tion, and glomerular filtration rate (GFR).

 Statistical Analysis



We used the statistical package for social sciences (SPSS) computer program to deter­mine whether there was an association bet­ween the WHO and ISN/RPS 2003 classi­fications and the clinical and laboratory para­meters at the time of biopsy. P values were calculated by the chi square test, Student "t" test, and analysis of variance. P values less than 0.05 was considered statistically significant.

 Results



There were 144 patients with SLE with a representative renal biopsy included in the study; 122 (84.7%) were female with a mean age at presentation of 25.6±10.3 years (range 2 to 63 years). The age distribution of patients at time of kidney biopsy was as follow: 2.1% before 10 years of age, 27.8% from 10 to 19 years, 36.1% from 20 - 29 years, 23.6% from 30 - 39 years, 8.35 from 40 - 49 years and 2.1% > 50 years; 16.2% of patients were in pediatric age group 1.5 mg/dl (P= 0.001 and P= 0.0000), respectively. The mean GFR was 72.63 ± 43.62 ml/min with 41.8% of patients having GFR less than 60 ml/min and 4.1 % less than 15 ml/min. The highest mean GFR was detected in WHO and ISN/RPS class II and the lowest mean value in WHO and ISN/RPS 2003 class IV lupus nephritis. Significant correlation between GFR and ISN/RPS 2003 was found (P= 0.003). The mean 24 hours urine protein excretion was 4.45±7.40 gm ranging between zero and 57 gm per day, while 38.5% of patients excreted more than 3.5 gm protein per day. There was a signi­ficant correlation between proteinuria and ISN/RPS 2003 classification (P= 0.023), [Table 3],[Table 4].

No significant correlation of urinalysis findings was found with the WHO and ISN/ RPS 2003 classifications [Table 5],[Table 6].

 Discussion



Renal involvement is common in Systemic Lupus Erythematosus (SLE) and often deter­mines the course of the disease.[6] The glome­rular lesions that frequently accompany SLE have been the subject of intense investigation by clinicians and pathologists for nearly a half of century. These efforts have generated numerous attempts to classify and categorize the pathological features of lupus nephritis. After several revisions of WHO classification of lupus nephritis, the recent ISN/RPS 2003 classification aims to enhance the quality of communication among renal pathologists and clinical nephrologists regarding patho­logic findings in lupus nephritis. [5],[7]

In our study, the mean age and sex distribution was similar to most of the studies.[8],[9],[10],[11]

The frequency of different renal pathology classes of lupus nephritis vary in the different series. In our study compared class IV lupus nephritis, outnumbers other classes as found in most of the other studies.[8],[12],[13],[14],[15] Nevertheless, in two studies the class II & III were more frequent than other classes. [16],[17]

The most frequent clinical manifestations in our study were arthralgia, edema (61.1%), and hypertension; similar to the Leaker et al, report whose patients leading presenting features were arthralgia, renal involvement and skin rash. [10]

Anemia was more common finding in our patients than other cohorts; [18],[19] 18.1% had hematocrit levels [20] In our study, the mean BUN level similar to that reported by Seedat et al. [21] Most studies reported mean serum creatinine of 1.5 mg/dl.[9],[22],[23],[24]

Our patients' mean serum creatinine level was > 1.5 mg/dl and mean GFR was 72.63±43.62 ml/min. In our study, the serum creatinine level and GFR had a significant correlation with WHO and ISN/RPS 2003 classes, the lowest level detected in class IV, similar to a study from China, where there was a signi­ficant correlation of the WHO classification and renal function. [6] Austin et al, demonstrated that an elevated serum creatinine level at the time of renal biopsy was associated with an increased rate of development of renal failure and was a very strong clinical prognostic indicator. [9],[20]

In our study, the highest protein excretion was found in class V (WHO and ISN/RPS 2003) comparable to was reported elsewhere. [9],[22],[23],[24],[25],[26] Proteinuria > 3.5 gm/day was detected in 38.5 % of our patients, similar to other studies. [19],[26] In our patients correlation between 24 hours urine protein excretion and ISN/RPS 2003 classes was statistically signi­ficant, different from another study that did not find a significant correlation with the WHO classes. [6]

In our study, 16% of the patients had gross and 75.2% had microscopic hematuria, which is similar to those reported by some authors, [18],[27] but more than the 38% reported from Peru. [28] Granular casts, hyaline casts and RBC casts were present in 35%, 20%, and 20.5% of our patients, respectively, in comparison with 52% 50%, and 3%, respectively, in another report. [18]

In our study, no significant correlation was found between serologic findings and LN classification of either WHO or ISN/RPS. However, Mok et al, found that serum level of C3, C4 and anti-dsDNA significantly correlated with the WHO classification. [6]

At the time of renal biopsy 61.1% of our patients were hypertensive. In other studies hypertension were detected in 38%, 54.3%, 32.4%, and 46% of LN.[28],[29],[30],[31] In our series hypertension was detected at the time of renal biopsy in 34.6%, 41.6%, 71.2% and 66.6% of patients with WHO classes II, III, IV, and V respectively, while Chakrabarti et al, reported 0%, 37%, 80% and 50% respectively. [29] Another study in southern China found hypertension in 22%, 24%, 37%, and 16% of the patients in class II, III, IV, and V without a significant correlation between hypertension and WHO classi­fication, [6] while our study found a significant correlation with WHO and ISN/RPS 2003 classifications. Furthermore, Naiker et al, detected renal failure in hypertensive patients more than non hypertensive ones (47% versus 18.55) and also reported that hyper­tension was associated with higher mean creatinine value. [32] They mentioned that patients with hypertensive renal vascular lesions represented a high risk subgroup with higher incidence of renal failure impair­ment and worse renal function than non hypertensive group; severe proliferative lupus histology was more prevalent in the hyper­tensive patients. [32] Hypertension is associated with the development of end-stage renal disease (ESRD) in lupus nephritis patients with a relative risk of 1.67, [33] but there is no correlation between survival and hyper­tension at the time of diagnosis of lupus or at the time of incipient nephritic syndrome. [16],[18]

ESRD developed in 13% of our patients during their disease course and as follow: 7.6% of class II LN, 16.6% of class III, 11.4% in class IV, 0% in class V & 100% in class VI of LN. Compared to other studies, ESRD was less frequent in our patients, as Mok et al, reported ESRD in 14% of their patients with 2% class II 24.5% of class III. [6] Other studies reported ESRD in 11%, 18.1%, 26%, and 14.3% of their patients and in these reports only patients with class III, IV or V progressed to ESRD.[19],[34],[35],[36]

Nephritic syndrome was detected in 38.5% of our patients in their disease course, comparable to other studies.[6],[8],[16],[26] In our study, nephritic syndrome developed in 50% of class I LN,26.9% of class II, 16.7% of class III, 42.8% of class IV and 44.4% of patients with class V LN, in WHO classification, compared to other reported study of 22%, 48%, and 20 % in class III, IV and V of LN respectively. [6] Regarding the significance of nephritic syndrome, some have found that the presence of heavy proteinuria and or nephritic syndrome were predictive of unfavorable prognosis,[8],[18] while others suggested that the presence of nephritic syndrome at the time of initial biopsy was associated with increased probability of developing renal failure. [16] However, the patients who had remission of the nephritic syndrome had sig­nificantly lower probability of renal failure or death than did the patients without remission. [16] Another study also reported that the presence of nephritic syndrome at the onset of lulus nephritis was a poor prognostic sign. [18]

In our study during hospitalization, three patients died, all of them were in class IV WHO and ISN/RPS 2003. The causes of death included pulmonary hemorrhage, sepsis and heart failure. The mortality rate in other studies was reported as 17%, 34%, 35.7%, and 20.7%; cardiovascular diseases, sepsis, and renal failure were the leading causes of death with variable incidence in different studies.[10],[16],[18],[34] The mortality rate of the patients on hemodialysis is very high ranging from 28.6% to 53.7% and is more associated with sepsis as a cause of death. [8],[34]

The proposed new classification of lupus nephritis, ISN/RPS 2003, which was deve­loped from the earlier 1982 and 1995 WHO classifications, incorporates new information regarding behavior of specific types of lupus nephritis, standardizes definitions, and encourages uniformity and reproducibility of reported pathological findings. [7] Furthermore, it eliminates category I that includes normal glomeruli, clarifies status of class III, defines more precisely class IV, simplifies class V, and proposes strict definition for class VI. [5],[7] Several recent studies claimed better commu­nication between pathologists and nephrologists using the new classification. [15],[37],[38],[39]

We conclude that our study suggests some meaningful correlation between edema, hyper­tension, increased serum BUN and creatinine, and increased 24 hours urine protein excre­tion with lupus nephritis classes of WHO & ISN/RPS 2003 classifications. ISN/RPS 2003 is superior to WHO classification, because definitions are clearer and sub classification are more clinically relevant. It also facilitates accurate communication between patho­logists and clinicians. Renal biopsy is still beneficial for better evaluation of renal status and determination of lupus nephritis class, activity and chronicity index.

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