A Young Woman's Journey with Kidney Disease and Blood Clots: Understanding Membranous Nephropathy

Table of Contents

• Case Presentation: The Patient's Story
• Symptoms and Initial Findings
• Physical Examination Results
• Laboratory Test Results
• Imaging Findings
• Differential Diagnosis
• Diagnostic Testing
• Disease Management
• Clinical Implications for Patients
• Limitations of This Case
• Patient Recommendations
• Source Information

Case Presentation: The Patient's Story

A 32-year-old woman arrived at the hospital with severe left flank pain, fever, and low blood oxygen levels. Her symptoms began two weeks earlier with sharp, intermittent left flank pain that worsened significantly two days before admission, becoming constant and accompanied by nausea. The day before hospitalization, she experienced multiple vomiting episodes.

On the morning of admission, she developed a dry cough and felt feverish without checking her temperature. She first visited an urgent care clinic where her temperature measured 38.1°C (100.6°F), heart rate was 113 beats per minute, and oxygen saturation was 95% on room air. The clinic noted abdominal tenderness in her left lower quadrant but no kidney area tenderness.

Symptoms and Initial Findings

Her initial laboratory results revealed several abnormalities that raised concern. The white blood cell count was markedly elevated at 19,000 per microliter (normal range: 3,800-10,800), indicating a significant immune response or infection. Her blood albumin level was low at 2.8 g/dL (normal: 3.3-5.5 g/dL), suggesting protein loss.

The urinalysis showed concerning findings with 3+ blood and 3+ protein (both should normally be negative). Her oxygen saturation dropped to 89% at the urgent care clinic, requiring oxygen supplementation at 3 liters per minute via nasal cannula to maintain 94% saturation. These findings prompted her transfer to the hospital emergency department.

Physical Examination Results

In the emergency department, her condition appeared more serious. Her temperature spiked to 39.6°C (103.3°F), blood pressure measured 102/58 mm Hg, heart rate increased to 122 beats per minute, and breathing rate accelerated to 28 breaths per minute. She required continued oxygen support.

The physical examination revealed she appeared uncomfortable and had abnormal lung sounds with inspiratory and expiratory crackles in both lungs. She had tenderness when her left lower abdomen was pressed. Notably, she had no swelling in her extremities, no oral ulcers, hair loss, or skin rash, which helped exclude some autoimmune conditions.

Laboratory Test Results

Comprehensive laboratory testing provided crucial diagnostic information. Her repeat white blood cell count remained elevated at 16,020 per microliter with neutrophil predominance (14,210 cells). The urinalysis showed persistent 3+ blood and 3+ protein with more than 100 red blood cells per high-power field (normal: 0-2) and 10-20 white blood cells per high-power field (normal: less than 10).

The protein-to-creatinine ratio in urine was dramatically elevated at 3.5 (normal: less than 0.15), indicating approximately 3.5 grams of protein loss per day through urine - a defining characteristic of nephrotic syndrome. Additional significant findings included:

• C-reactive protein (inflammatory marker): 199.9 mg/L (normal: 0-8.0)
• Erythrocyte sedimentation rate (inflammatory marker): 40 mm/hr (normal: 0-19)
• Lactate dehydrogenase: 278 U/L (normal: 110-210)
• Lactic acid: 2.2 mmol/L (normal: 0.5-2.0)
• Glycated hemoglobin (A1c): 6.2% (normal: 4.3-5.6%)

Her kidney function tests showed creatinine at 0.93 mg/dL (within normal range) but without a baseline measurement, acute kidney injury could not be ruled out.

Imaging Findings

Imaging studies revealed critical findings that explained her symptoms. Chest X-ray showed patchy opacities at the lung bases and a small left pleural effusion. Computed tomography (CT) scan of the chest with contrast revealed:

• A partial filling defect in the right lower lobar pulmonary artery suggesting pulmonary embolism
• Bronchial wall thickening and multifocal consolidative opacities with ground-glass appearance
• Small left and trace right pleural effusions
• Areas of interlobular septal thickening with ground-glass opacities

CT scan of the abdomen and pelvis showed even more significant findings:

• A nearly complete blockage (occlusive thrombus) in the left renal vein
• A partial blockage (nonocclusive thrombus) in the right renal vein
• Early heterogeneous enhancement of the kidneys with perinephric stranding
• No evidence of cancer in chest, abdomen, or pelvis

These imaging findings explained her flank pain (renal vein thromboses) and breathing difficulties (pulmonary embolism and lung abnormalities).

Differential Diagnosis

The medical team considered several possible conditions that could explain this combination of kidney and lung findings. The initial concern was pulmonary-renal syndrome, which involves both lung hemorrhage and kidney inflammation, typically caused by autoimmune conditions like:

• ANCA-associated vasculitis (autoimmune inflammation of small blood vessels)
• Anti-glomerular basement membrane disease (Goodpasture's syndrome)
• Systemic lupus erythematosus (SLE) with kidney involvement
• Antiphospholipid syndrome (abnormal blood clotting disorder)
• Cryoglobulinemic vasculitis (abnormal proteins that clump in cold temperatures)

However, the absence of certain features made these less likely. The team then focused on nephrotic syndrome, characterized by heavy proteinuria (>3.5 g/day), low blood albumin, and swelling. The presence of renal vein thrombosis pointed strongly toward specific causes of nephrotic syndrome, particularly membranous nephropathy, which has the highest association with blood clots among kidney diseases.

Other causes of nephrotic syndrome were considered but deemed less likely:

• Minimal change disease and focal segmental glomerulosclerosis: Usually present with dramatic swelling, less associated with thrombosis
• Diabetic kidney disease: Her A1c of 6.2% made this unlikely
• Lupus nephritis: No history of joint pain, rash, or other autoimmune symptoms
• Secondary causes from infections, cancer, or medications: No evidence in history

Diagnostic Testing

The diagnostic team performed specific blood tests to identify the cause of her nephrotic syndrome. They tested for anti-PLA2R (phospholipase A2 receptor) antibodies, which are associated with primary membranous nephropathy. Two different testing methods were used:

1. Indirect immunofluorescence testing: This method uses fluorescent tags to detect antibodies binding to PLA2R receptors. Her test was positive.
2. ELISA (enzyme-linked immunosorbent assay): This quantitative test measured her antibody level at 400.3 RU/mL (normal: <14 RU/mL).

The combination of positive results on both tests, along with her clinical presentation, confirmed the diagnosis of phospholipase A2 receptor-associated membranous nephropathy. This serologic testing has 99% specificity for this condition, meaning almost all people with positive tests truly have the disease.

Disease Management

The management of membranous nephropathy depends on several factors. For patients with preserved kidney function, doctors often recommend a 6-month observation period since approximately 30% of patients may experience spontaneous improvement without immunosuppressive treatment. However, this patient required immediate intervention due to several high-risk features:

• Severe hypoalbuminemia (blood albumin <2.5 g/dL)
• Multiple thromboembolic events (renal vein thromboses and pulmonary embolism)
• High level of anti-PLA2R antibodies (400.3 RU/mL)

Treatment typically involves immunosuppressive therapy. The historical gold standard is the modified Ponticelli regimen, which involves alternating months of corticosteroids and alkylating agents (like cyclophosphamide) over 6 months. Newer treatment approaches consider the trajectory of anti-PLA2R antibody levels - if levels decrease spontaneously, immunosuppression might be deferred, but rising levels would indicate need for treatment.

Additionally, she required immediate treatment for her thromboembolic complications with anticoagulant medications to prevent further clotting.

Clinical Implications for Patients

This case illustrates several important points for patients with similar symptoms. First, flank pain with fever and breathing difficulties should never be ignored, especially when accompanied by decreased oxygen levels. The combination of significant protein in urine and blood clots, particularly in unusual locations like renal veins, should raise suspicion for membranous nephropathy.

Patients should know that membranous nephropathy is an autoimmune condition where the body attacks its own kidney cells, specifically targeting the PLA2R receptors on podocytes (specialized kidney cells that maintain the filtration barrier). This attack causes leaks in the kidney's filtering system, allowing massive protein loss into urine.

The blood clotting risk is particularly high in this condition because protein loss leads to decreased levels of natural anticoagulants while the liver compensates by producing more clotting factors. The risk is highest when blood albumin falls below 2.5 g/dL, as seen in this patient.

Limitations of This Case

While this case provides valuable insights, it has several limitations. As a single case report, it cannot establish general patterns or treatment responses for all patients with membranous nephropathy. The patient's family history (sister with end-stage kidney disease who died at age 18) suggests possible genetic factors, but these weren't fully explored.

Without a kidney biopsy, we cannot definitively rule out other concurrent kidney conditions, though the highly specific anti-PLA2R antibody testing makes this unlikely. The case also doesn't provide long-term follow-up information about her response to treatment or eventual outcome.

Patient Recommendations

Based on this case, patients should consider the following recommendations:

1. Seek immediate medical attention for persistent flank pain accompanied by fever, breathing difficulties, or decreased oxygen saturation
2. Request thorough urinalysis if you have unexplained swelling, especially if accompanied by flank pain or respiratory symptoms
3. Ask about specific testing for anti-PLA2R antibodies if you're diagnosed with nephrotic syndrome, as this can provide a non-invasive diagnosis
4. Discuss thrombosis prevention with your nephrologist if you have nephrotic syndrome with low albumin levels (<2.5 g/dL)
5. Maintain regular follow-up with both nephrology and hematology specialists if diagnosed with membranous nephropathy, given the dual risks of kidney progression and clotting complications

Patients should also be aware that new treatments are constantly emerging for autoimmune kidney diseases, and consultation with a specialized nephrologist is essential for optimal management.

Source Information

Original Article Title: Case 10-2025: A 32-Year-Old Woman with Flank Pain, Fever, and Hypoxemia

Authors: Anushya Jeyabalan, MD; Cynthia L. Czawlytko, MD; Laurence H. Beck, Jr., MD, PhD; Claire Trivin-Avillach, MD; Dennis C. Sgroi, MD; Eric S. Rosenberg, MD

Publication: The New England Journal of Medicine, April 10, 2025; 392:1428-1437

DOI: 10.1056/NEJMcpc2412517

This patient-friendly article is based on peer-reviewed research from the Case Records of the Massachusetts General Hospital.