INTRODUCTION:

Lupus nephritis (LN) is known to occur in up to 60% of patients suffering from systemic lupus erythematosus (SLE) [1]. The clinical presentation of lupus nephritis as well as the histopathological pattern of kidney involvement is highly variable in patients of SLE. The focal and diffuse forms of LN (class III and IV, respectively) usually manifest as nephritic urinary sediments and are known to culminate into renal failure. However, membranous nephritis (class V) usually presents with nephrotic-range proteinuria. Previous studieshave demonstrated that clinical features alonecannot be relied upon for ruling out renal involvement in SLE [2,3]. It is largely accepted that renal biopsy is an important method todocument and diagnose early, the involvement of kidneys in patients of SLE. It is also necessary to make a definitive diagnosis of Lupus Nephritis and to grade the histopathological subtype as well as to decide the line of proper treatment.

However, the timing of performing biopsyis crucial and sometimes this decision to perform a renal biopsy may  be controversial. In some previous studies, renal biopsy was recommended in patients with proteinuria > 500 mg/24 h in the absence of acute renal failure [4]. However, other studies have recommended biopsy only in patients with levels of proteinuria > 1000 mg/24 h and abnormal urinary sediment [5]. Also, many important case studies have suggested that significant kidney damage may occur in the setting of active proliferative LN without clinical signs of renal involvementor even in the absence of significant proteinuria[6, 7]. An early intervention is crucial to prevent poor outcome in patients of lupus nephritis, therefore it is opined that kidney biopsies be performed early so that diagnoses can be made at anappropriate  point and definitive treatment can be initiated well in time[8].

We present here a rare case of lupus nephritis where there was no dipstick proteinuria yet the patient had stage 4 lupus nephritis.

CASE REPORT:

A 22 year old female patient presented to us with complaints of fever on and off for the last one and a half years, associated with generalized weakness and loss of hair for six months. There was also a history of distension of abdomen for the last 20 days. On taking a detailed history, the patient revealed that she also had recurrent oral ulcers and had swelling over feet off and on. There was also a history of intake of anti-tuberculous medication for 6 months.

On examination, her vitals were stable. Pallor was present, alopecia was noted and there was rash associated with dark pigmentation of the skin over the malar area. Oral ulcers and pedal edema were also present. On doing a per abdomen examination, moderate ascites was appreciated along with splenomegaly.  The Central nervous System, Cardiovascular System and Respiratory System were normal on examination.

Routine investigations were ordered which revealed a hemoglobin of 6.7 gm%, Total Leukocyte Count of 2400 per mm³.  Differential Leukocyte Count was P₈₀L₂₆ and the platelet count was 37000 per mm³. Mean Corpuscular Volume (MCV) was 92.6 fl, Erythrocyte Sedimentation Rate (ESR) was 58 mm in the first hour. General Blood Picture (GBP) revealed a normocytic, normochromic smear with a reticulocyte count of 0.8%. Blood Urea was 22 mg% and serum creatinine was 0.6 mg%. Liver function test, blood glucose, serum proteins and iron studies were normal. Urine examination was normal with no evidence of proteinuria. Serum TSH was 5.002. Coomb’s test was negative.

Keeping in view the clinical presentation and the initial laboratory investigations, anti-nuclear antibodies (ANA) and double stranded DNA (ds-DNA) were ordered which came out to be positive. In view of  the clinical and laboratory findings a diagnosis of Systemic Lupus Erythematosus (SLE) was made as the patient had 5 out of 11 criteria of SLE (Malar Rash; Oral Ulcers;alopecia; hematological findings in the form of normocytic anemia and thrombocytopenia; and immunological findings in the form of positive ANA and ds-DNA).

Since the patient had ascites and palpable spleen, an ultrasound of the abdomen was ordered which revealed a coarse echotextureof  liver, with a portal vein diameter of 5 mm along with splenomegaly and ascites. The kidney size was normal bilaterally with a maintained corticomedullary differentiation. As the patient had florid signs of SLE without any direct evidence of renal involvement, it was planned to aggressively investigate the involvement of the kidneys, because incipient nephropathy is known to exist in patients having active and florid manifestations of SLE, even in the absence of proteinuria. Keeping in view the above fact, a urinary Albumin:Creatinine ratio was ordered, which came out to be 151.12 mg/g. In the light of microalbuminuria and florid features of SLE, it was decided to go for a kidney biopsy, which revealed mesangial and endocapillary cell proliferation with neutrophil infiltration in capillary tufts. All the viable glomeruli revealed segmental subendothelialfuchsinophilic deposits (wire loop lesions). Tubules showed focally prominent cytoplasmic vacuolar change (Fig 1). Few inspissated hyaline casts were seen in tubular lamina. Focal and mild chronic interstitial inflammation was noted. Arteries showed medial thickening and sub-intimal sclerosis while the arterioles exhibited focal hyalinosis and vacuolization in smooth muscle cells of media.

On direct immunofluorescence (DIF), following pattern was observed:

            IgA                              :           2+  Capillary wall granular and mesangial

            IgG                              :           3+  Capillary wall granular and mesangial

            IgM                             :           2+  Capillary wall granular and mesangial

            C₃                                           :           3+  Capillary wall granular and mesangial

            C₁q                              :           3+  Capillary wall granular and mesangial

Kappa light chains      :           3+  Capillary wall granular and mesangial

Lambda light chains   :            3+  Capillary wall granular and mesangial

The overall impression of the kidney biopsy was: Diffuse Lupus Nephritis with active lesions: ISN/RPS class IV G A. Indices (NIH) of disease activity 10/24 and chronicity 1/12 were reported.

Since the patient had evidence of altered liver echotexture on ultrasonography, a gastroduodenoscopy was performed which was normal.  Patient was advised a liver biopsy, however he refused the same.

DISCUSSION.

It is already known that nephritis is the most serious complication of SLE. In most of the SLE patients, nephritis is asymptomatic and hence it is generally accepted that urinalysis should be ordered in any patient suspected of having SLE. Renal biopsy should be considered in any patient of SLE who has clinical or laboratory evidence of active nephritis, especially upon the first episode of nephritis [9]. Early clinical and histologic diagnosis of lupus nephritis is pivotal in order to minimize the risk of End Stage Renal Disease (ESRD).

Our case was interesting in many ways. First, the decision to go for an early renal biopsy in the presence of normal urinalysis is indeed debatable. However, it has already been opined in previous studies that some patients with lesser amount of proteinuria may also manifest active disease and biopsy should be considered in the presence of new proteinuria/hematuria [10]. However, our case becomes much more significant and rare as our patient did not even have dipstick proteinuria. All that could suggest a very early renal involvement in our patient was microalbuminuria. However, renal biopsy revealed extensive renal involvement with severely active florid lupus nephritis. If renal involvement in our patient was missed at this stage, a few months later, the patient would have presented with ESRD or at least with massive proteinuria and advanced renal disease, and there would have been very limited therapeutic options and renal replacement therapy might have become unavoidable.

This case highlights the fact that dipstick proteinuria should not be the only screening tool for lupus nephritis and any patient presenting with SLE should be investigated thoroughly for renal involvement. This case also strengthens the paradigm shift towards performing renal biopsy even in the absence of dipstick proteinuria.

A few more interesting observations were noted in this patient which make this case even more interesting. The presence of ascites, coarse liver echotexture and splenomegaly demand an explanation in our patient. Serositis is one of the presenting features of SLE, however, pleural and pericardial involvement are more common compared to ascites [11]. In other words, serositis in SLE, presenting as ascites in the absence of pleural or pericardial involvement is rare in literature.

Splenomegaly is known to be present in most immune mediated disorders and iscommon in SLE. However, in the presence of a coarse liver echotexture,it needs to be settled whether splenomegaly was actually due to an immune mediated mechanism as part of SLE or due to an underlying cirrhosis and portal hypertension because the ultrasound of the patient had revealed an altered liver echotexture. However, upper gastrodudenoscopy was normal with no evidence of portal gastropathy or esophageal varices. However, a liver biopsy was indicated as it would have clarified the nature of liver involvement as autoimmune hepatitis could have been the cause of an altered echotexture which has a clinical association with SLE. Since the patient refused liver biopsy, the nature of liver involvement remainedobscure; however, not much difference could have been made in either case, especially if there was evidence of cirrhosis. What was more important was the early detection of renal involvement which prevented Chronic Kidney Disease and ESRD in this patient.

CONCLUSION:

Renal involvement is the most serious complication of SLE. Most of the time, it is the clinical presentation which makes a physician suspect renal involvement. However, our case has demonstrated that advanced stage renal disease may be present in a patient of SLE even in the absence of clinical features suggesting renal involvement or even in the absence of dipstick proteinuria. This case highlights the importance of an early renal biopsy in patients of SLE.

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