A Case Study
By James A. Tumlin, M.D.
Southeast Renal Research Institute, Charlotte, NC
A 37-year-old African American female with a four-year history of systemic lupus erythematosus (SLE) presented to her rheumatologist with diffuse arthralgias, myalgias, malar rash and alopecia. In addition, the patient reported a four-month history of “foamy” urine, associated with lower extremity edema, which prevented her from wearing her shoes and left her unable to work due to reduced mobility.
- Vital Signs: blood pressure–140/110, temperature–97.8 F, pulse–80, weight–187 pounds (previous weight 135 pounds).
- Head, Eyes, Ear, Nose, and Throat: diffuse alopecia of scalp and malar rash across face; pupils equal, round and reactive to light; mouth and throat normal with no tonsillar enlargement, thrush or ulcers.
- Neck: supple with full range of motion, no membranous inflammation, no involvement of lymph nodes or thyroid.
- Lungs: decreased air exchange in the right lower lobe and mild abnormal voice quality in left lower lobe but no friction rub.
- Cardiovascular: normal S1 and S2.
- Abdomen: bulging flanks and shifting dullness with mild right upper quadrant point tenderness.
- Extremities: +4 pitting edema up to the hips bilaterally, with seepage of serosanguinous fluid at the ankles.
- Neurological: nonfocal.
- Skin: no discoid lesions noted.
Laboratory Test Results
- CBC: White count 5.9, hemoglobin 8.8, hematocrit 25.4, MCV 85, platelets 102,000. Chemistries: sodium is 141, potassium 3.3, chloride 29, bicarbonate 29, creatinine 1.3, total protein 3.0, albumin less than 1, SGOT 25, SGPT 12 and LDH 123. Cholesterol 550 mg/dl.
- Serologies: Anti-dsDNA 104; anti-SM positive; C3-49 and C4 < 10; anti-SSA positive; anti-SSB negative; antiphospholipid antibody panel negative; Coomb’s antibody test negative. Urinalysis: Specific gravity 6.0, pH 1.015, blood +3, protein +4; red blood cells crenated with 15–18 per high-powered field, two red cell casts noted, no white cells seen. Urinary protein 3,030 mg protein in 24 hrs.
- Renal Ultrasound: kidneys edematous and echogenic (right 13.1 cm and left 12.9 cm). Upper and Lower Extremity Doppler Ultrasound: abnormal blood flow consistent with thrombi in left femoral and right subclavian veins.
History, physical findings and lab results were consistent with nephritis and nephrotic syndrome, plus secondary deep venous thrombosis.
Patient was admitted to a local hospital where a renal consult was obtained. Kidney biopsy revealed diffuse proliferative glomerulonephritis with extensive sub-epithelial and sub-endothelial dense deposits in more than 75 percent of glomeruli sampled. Endothelial cell swelling was associated with interstitial edema; a cellular crescent and focal cellular necrosis were observed. Biopsy findings satisfied criteria for WHO (World Health Organization) Class IV lupus nephritis. The patient was stabilized with intravenous steroids and started on a monthly regimen of cyclophosphamide. Anti-coagulation therapy was also utilized.
This patient’s severe lower extremity edema and massive ascites are secondary to markedly low serum protein, itself secondary to large protein losses in the urine. Patients with nephrotic range proteinuria (>3,000 mg/day) are also at increased risk of deep venous thrombosis because three of the commonly wasted proteins serve anti-clotting functions (Protein C, Protein S, and Antithrombin III).
The Nephrologist’s View
- The patient completed six months of cyclophosphamide therapy but continued to report debilitating lower extremity edema, and ascites requiring large volume paracentesis. At this point several clinical options were entertained: 1) symptomatic control using diuretics, steroids and azathioprine, anticipating eventual dialysis; 2) oral daily mycophenolate; or 3) repeat kidney biopsy and re-induction therapy with steroids and cyclophosphamide.
- The third alternative was selected and the patient admitted to a tertiary center hospital. Biopsy showed endocapillary proliferation and karyorrhexis in 32 percent of glomeruli observed. Cortical tissue demonstrated patchy mild interstitial fibrosis; no cellular crescents were seen. Following six months of re-induction treatment (Gourley protocol) both extremity edema and ascites had resolved, with associated improvement in renal function (creatinine 1.3, <500 mg protein in 24-hr urine). Remission was maintained using oral mycophenolate and low-dose prednisone.
A growing body of data indicates that as many as 30 percent of patients with proliferative forms of lupus nephritis will have residual lesions following treatment with standard National Institutes of Health induction protocol. Patients with persistent clinical features of nephrotic syndrome, plus associated renal function laboratory abnormalities, may have residual disease. A repeat kidney biopsy allows the clinician to identify patients who may benefit from re-induction therapy.
alopecia - hair loss.
ascites - abnormal accumulation of fluid in the abdominal cavity.
biopsy - (to obtain) a sample of tissue for examination.
cellular crescent - areas of intense inflammation that have been associated with a greater likelihood of kidney failure.
crenated red blood cell - a type of RBC abnormality, as seen under the microscope; sign of kidney inflammation.
discoid lesion - skin rash characteristic of some types of lupus. echogenic—indicating abnormal tissue, as seen by ultrasound examination.
edema - tissue swelling from fluid accumulation.
glomerulus - a microscopic structural component of the kidney, critical to kidney function.
induction protocol - method of treatment for a particular acute illness designed to put the patient into remission.
karyorrhexis - fragmentation of a cell nucleus, indicating cellular damage from a disease process.
paracentesis - the removal of accumulated fluid from the abdominal cavity.
proteinuria - protein in the urine (always abnormal).
S1 and S2: first and second heart sounds. SGOT/SGPT/LDH - enzymes that reflect liver function. thrombi - blood clots.
thrush - a common fungal infection caused by Candida albicans.