Type II is an immune complex deposition disease, such as HSP, SLE, or post-streptococcal GN, in which granular complex deposits are seen. Treatment is directed toward treating the underlying cause.
Type III is pauci-immune (no immune deposits), showing necrotizing crescentic GN on biopsy, and is associated with a positive ANCA.1,18 They are associated with systemic small-vessel vasculitis, such as granulomatosis with polyangiitis (formerly known as Wegener’s granulomatosis), microscopic polyangiitis, and Churg-Strauss syndrome, or can be limited to renal involvement.1,18 Complement levels are normal. Treatment is steroids and immunosuppressive agents, such as cyclophosphamide.
A summary of the findings found in the glomerulonephritides and how complement levels are affected are found in Table 2 and Table 3, respectively.
Secondary Causes of Nephrotic Diseases
Diabetic nephropathy. Diabetic nephropathy is the single most common cause of progressive renal failure in the United States.3 Up to 50% of patients with diabetes present with diabetic nephropathy.19 Current recommendations are to screen yearly for microalbuminuria at the time of diagnosis.3 Treatment involves use of ACE-Is or ARBs to reduce proteinuria and slow the progression of renal disease.
HIV-associated nephropathy. HIV-associated nephropathy commonly presents as the collapsing variant of FSGS. However, it can present as other forms of glomerulopathy, such as MPGN or IgA nephropathy, as well as an immune complex GN with “lupus-like” features without evidence of SLE.19,20 Therefore, HIV nephropathy has now been categorized as a separate entity.3 ACE-Is, HAART therapy, and corticosteroids are the mainstays of treatment.
Amyloidosis. Renal involvement is seen in both primary (AL) and secondary (AA) amyloidosis. Eighty percent of patients with AL have renal disease, and 25% of these patients have nephrotic syndrome.16 Diagnosis is made with Congo Red stain, which shows fibrillary amyloid deposits within the mesangium and capillary walls. Treatment is directed at the underlying process.
Systemic lupus erythematosus. SLE is divided into six classes (I-VI) based on the involvement and severity of renal disease, and steroids and immunosuppressive agents are used for treatment, also based on the severity of the disease.21
Back to the Case
Our patient presented to the hospital with abdominal pain, low-grade fever, HTN, edema, hypoalbuminemia, and new-onset renal failure with gross hematuria and proteinuria. The presence of proteinuria and hypoalbuminemia, combined with peripheral and periorbital edema, suggests glomerular loss of albumin, such as in nephrotic syndrome. His renal failure in the setting of the sudden development of gross hematuria with flank pain is concerning for a renal vein thrombosis, and an abdominal magnetic resonance venography did in fact visualize a renal vein thrombosis.
He was admitted to the hospital and was started on therapeutic intravenous heparin, and bridged to warfarin. Subsequent renal biopsy confirmed the findings of membranous nephropathy, which was suspected due to his renal vein thrombosis. Therapy was initiated with corticosteroids after the biopsy, and he responded well. Because of his risk factors for further thromboembolic events, lifelong anticoagulation therapy was recommended.
For patients with glomerular disease, differentiating between nephrotic and nephritic syndromes and understanding key clinical and laboratory differences can lead to easier identification and treatment.
Drs. Khan and Smith are assistant professors of medicine, and Dr. Ansari is associate division director, in the Division of Hospital Medicine at Loyola University Medical Center, Maywood, Ill.