Immune Complex Glomerulonephritis: A Rare Presentation in Systemic Sclerosis

Abstract

Systemic sclerosis (SSc) and renal involvement most frequently present as scleroderma renal crisis (SRC). Immune complex-mediated glomerulonephritis (GN) is an exceptionally rare renal manifestation in SSc and may complicate timely diagnosis and management. We report the case of a 40-year-old woman with a history of hypertension and Raynaud’s phenomenon who presented with progressive dyspnea, bilateral lower limb edema, and oliguria. Laboratory investigations demonstrated rapidly deteriorating renal function (serum urea/creatinine – 71/6.44 mg/dL rising to 82/7.35 mg/dL within 24 h), nephrotic-range proteinuria (urine protein–creatinine ratio ≈ 11.6), hematuria (25–30 red blood cells/high-power field), and borderline low complement C3 (80.3 mg/dL). Autoimmune analysis revealed a speckled antinuclear antibody pattern (1:100) with Scl-70 positivity. Ultrasound showed enlarged kidneys with increased cortical echogenicity, and two-dimensional echocardiography confirmed moderate pulmonary arterial hypertension. Renal biopsy demonstrated diffuse proliferative GN with neutrophilic exudation, immunoglobulin G (IgG) and C3 immune complex deposition on immunofluorescence, and acute tubular injury, without thrombotic microangiopathy, thereby excluding SRC. The patient underwent hemodialysis and was initiated on low-dose corticosteroids. She was lost to follow-up after discharge. This case underscores an atypical and rare renal presentation of SSc, emphasizing the necessity of considering alternative diagnoses when renal dysfunction occurs without features of SRC. Early renal biopsy is essential to guide appropriate and individualized therapy in such cases.

INTRODUCTION

Systemic sclerosis (SSc) is a chronic autoimmune disorder that can involve multiple organs, comprising the skin, lungs, heart, digestive system, kidneys, and musculoskeletal tissues.[1] Renal involvement is well-recognized in SSc, with scleroderma renal crisis (SRC) occurring in approximately 10% of patients. SRC usually presents with severe hypertension, sudden decline in kidney function, microangiopathic hemolytic anemia, and low platelet counts. SRC typically results from microvascular injury and ischemia, leading to a thrombotic microangiopathic process within the kidneys.[2]

Although SRC represents the most common form of renal disease in SSc, other types of glomerular involvement are rare. Immune complex-mediated glomerulonephritis (GN), including immune complex-mediated membranoproliferative GN and C3 glomerulopathy, has been reported only infrequently in SSc and is usually associated with coexisting autoimmune disorders.[3,4] These conditions are characterized by abnormal complement activation and deposition of immunoglobulins and complement components within the glomerular basement membrane.[5] These exceptionally uncommon presentations often elude early recognition, making a kidney biopsy essential for accurate characterization. Here, we report a rare case of immune complex GN in a 40-year-old female with SSc, highlighting the importance of considering alternative renal pathologies beyond SRC.

CASE REPORT

A 40-year-old woman with a known history of hypertension for 3 years on regular medication and Raynaud’s phenomenon presented with progressive breathlessness on exertion for 1 month, bilateral lower limb edema for 15 days, and reduced urine output for 3 days. She reported no history of fever, cough, sore throat, or other infectious symptoms.

Clinical and systemic examination

On admission, the patient was conscious and oriented. Her vital signs showed a blood pressure of 140/90 mmHg, a heart rate of 86 beats per minute, and an oxygen saturation of 99% on room air. Systemic evaluation demonstrated normal heart sounds (S1 and S2) on cardiovascular examination and bilaterally normal vesicular breath sounds on respiratory auscultation. The abdomen was soft and nontender, and neurological status was intact (E4V5M6). Electrocardiography demonstrated a normal sinus rhythm, and chest radiography revealed no abnormality. Dermatological examination revealed tightening of the skin over both the hands and face, consistent with features of SSc.

Laboratory investigations

Initial blood tests revealed hemoglobin – 7.3 g/dL, white blood cell count – 9700/µL, and platelets – 325,000/µL. Serum urea/creatinine levels were markedly elevated at 71/6.44 mg/dL, increasing to 82/7.35 mg/dL within 24 h. Serum sodium was 128 mEq/L, potassium – 3.85 mEq/L, calcium – 7.7 mg/dL, phosphate – 6.2 mg/dL, uric acid – 9.1 mg/dL, and intact parathyroid hormone – 143.10 pg/mL.

Urine analysis showed 3 + protein and 25–30 red blood cells per high-power field, with a urine protein–creatinine ratio of approximately 11.6. Arterial blood gas demonstrated metabolic acidosis (pH: 7.26, HCO_3: 16.6 mmol/L, and PCO_2: 38 mmHg). Blood and urine cultures showed no growth, and procalcitonin was negative.

Autoimmune and serological studies

Antinuclear antibody (ANA) testing by immunofluorescence demonstrated a weak positive reaction (1+) with a nuclear speckled pattern at a titer of 1:100, along with weak cytoplasmic granular staining. ANA blot confirmed Scl-70 positivity. Cytoplasmic antineutrophil cytoplasmic antibody (ANCA), perinuclear ANCA, and antistreptolysin O titer were negative. Complement testing showed C3 level of 80.30 mg/dL (mildly decreased) and C4 level of 22.40 mg/dL (within the normal range).

Radiological assessment

Ultrasound abdomen showed borderline enlarged kidneys with increased cortical echogenicity and loss of corticomedullary differentiation. Two-dimensional echocardiography revealed preserved left ventricular ejection fraction (60%), moderate tricuspid regurgitation, and moderate pulmonary arterial hypertension (right ventricular systolic pressure: 56 mmHg), with no other valvular abnormalities.

Diagnosis

Considering Raynaud’s phenomenon, skin sclerosis, and moderate pulmonary arterial hypertension, along with serological positivity for Scl-70, a diagnosis of SSc was established.

Renal biopsy

Renal biopsy demonstrated diffuse proliferative GN with prominent intraglomerular neutrophilic exudation, along with moderately severe acute tubular injury [Figure 1]. Direct immunofluorescence studies revealed immunoglobulin G- and C3-containing glomerular immune complex deposits, supporting an immune complex-mediated pathogenesis [Figure 2]. Importantly, there were no histopathological features suggestive of thrombotic microangiopathy (TMA). These findings, in conjunction with negative blood and urine cultures and normal procalcitonin levels, indicated an immune-mediated rather than infectious etiology. This is a rare presentation, as renal involvement in SSc predominantly manifests as SRC, typically associated with TMA, which was absent.

Figure 1.

Diffuse proliferative glomerulonephritis with prominent intraglomerular neutrophilic exudation (H&E, ×400)

Figure 2.

IgG- and C3-containing glomerular immune complex deposits (Immunofluorescence, ×400)

Management and follow-up

The patient underwent three sessions of hemodialysis on alternate days, after which renal parameters improved (urea – 63 mg/dL, creatinine – 5.54 mg/dL, phosphorus – 4.8 mg/dL, and sodium/potassium – 131/3.46 mEq/L). As SRC was ruled out, ACE inhibitors cannot be used alone. Low-dose corticosteroids were started cautiously due to the risk of steroid-induced renal crisis. Anti-dsDNA and anti-Sm antibody testing was recommended to rule out SSc-systemic lupus erythematosus (SLE) overlap syndrome, but could not be obtained due to the economic condition of the patient. She was discharged on oral steroids with a plan to start mycophenolate mofetil after 2 weeks, but unfortunately, she was lost to follow-up.

DISCUSSION

Scleroderma is a connective tissue disorder characterized by widespread microvascular dysfunction and fibrosis. Symptoms such as Raynaud’s phenomenon, digital ulcers, and ischemic complications arise from intimal thickening of small and medium-sized arteries without features of vasculitis.[6] The disease is more prevalent in females, with peak incidence between 30 and 50 years of age,[6] which corresponds with the age (40 years) of the present patient.

Renal involvement in SSc most commonly manifests as SRC, typically presenting with accelerated hypertension and rapidly progressive renal failure. However, not all renal pathology in SSc represents SRC, and a spectrum of non-SRC glomerular diseases is increasingly recognized, including immune complex-mediated GN, ANCA-associated vasculitis, and lupus-like nephritis.[7,8] Immune complex GN in SSc is exceptionally rare, with fewer than 20 cases documented in the literature, making early recognition and biopsy confirmation crucial for optimal management.

From an immunopathogenic perspective, many glomerulonephritides are autoimmune-mediated. In systemic autoimmune diseases such as SLE, immune complex deposition within glomeruli is a well-established mechanism driving nephritis. In contrast, immune complex GN is not a typical renal manifestation of SSc, which is primarily a vasculopathic and fibrosing disorder.[9,10] The presence of immune complex-mediated diffuse proliferative GN in this patient therefore reflects an uncommon and distinctly different pathogenic process from SRC, underscoring the need for histological confirmation when renal impairment occurs in SSc.

SSc may also overlap with SLE in approximately 7% of patients, particularly in the presence of low complement levels, and should therefore remain a key differential diagnosis.[11] In suspected SRC, evaluation for TMA, including peripheral smear, lactate dehydrogenase, and haptoglobin is essential.[12]

In the current case, the patient demonstrated seropositivity for Scl-70, supporting the diagnosis of SSc. Although testing for anti-dsDNA and anti-Sm antibodies was recommended to exclude SSc-SLE overlap, this could not be completed. Renal biopsy revealed diffuse proliferative immune complex GN without features of TMA, thereby excluding SRC. This distinction was clinically important, as ACE inhibitors, the cornerstone therapy for SRC, were contraindicated in this setting, and management instead required cautious immunosuppression.

While previous cases reported by Ramaswami et al.,[2] Nayebirad et al.,[5] and Pal[13] demonstrated favorable outcomes following early diagnosis and treatment, our patient showed improvement despite having complications. Overall, this case reinforces the importance of maintaining a broad differential diagnosis in SSc patients presenting with renal dysfunction, recognizing that immune complex GN, although rare, remains a possible manifestation. Timely renal biopsy is essential to distinguish between SRC and non-SRC pathologies, enabling appropriate, individualized management to improve outcomes.

CONCLUSION

Immune complex-mediated GN represents an exceptionally rare renal manifestation of SSc. In this case, renal impairment developed without the characteristic features of SRC, and the definitive diagnosis was established only through renal biopsy, which demonstrated diffuse proliferative GN without evidence of TMA. The borderline complement levels and seropositivity for Scl-70 supported the diagnosis of SSc-associated immune pathology. Crucially, distinguishing this entity from SRC directly influenced management, particularly the decision to avoid ACE inhibitors, which are standard in SRC but may be inappropriate in non-SRC glomerular disease. This case underscores the critical importance of early renal biopsy and careful diagnostic evaluation in atypical renal presentations of SSc to guide precise and individualized therapy.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that her name and initials will not be published and due efforts will be made to conceal her identity, but anonymity cannot be guaranteed.

Conflicts of interest

There are no conflicts of interest.

Funding Statement

Nil.