History and Physical Examination
Patients with membranoproliferative glomerulonephritis (MPGN) may present in 1 of 5 ways, as follows:
-
Asymptomatic proteinuria and hematuria detected on routine urinalysis (23-30%), prompting further investigations
-
Nephrotic syndrome (42-67%): Periorbital or dependent edema may develop in patients with nephritic or nephrotic presentations; anasarca is present in a few patients
-
Acute nephritic syndrome (16-30%): Patients with an acute nephritic presentation may develop a decrease in urine output (oliguria)
-
Recurrent episodes of gross hematuria (10-20%): Patients may have episodes of gross hematuria similar to those observed with IgA nephropathy—these episodes are usually associated with upper respiratory infections
-
Azotemia: Patients may develop acute kidney injury with the acute nephritic syndrome, which usually correlates with crescentic transformation on histology; other patients may present with advanced chronic renal insufficiency
Fatigue may also occur and is secondary to anemia or azotemia. The anemia is often disproportional to the degree of renal insufficiency and relates to complement-mediated lysis of red cells. Conjunctival pallor is also indicative of anemia.
Hypertension is present in approximately 80% of patients at initial presentation. It is typically mild, although an occasional patient with dense deposit disease (MPGN type II) may present with severe hypertension.
A strong association is present between partial lipodystrophy (PLD) and dense deposit disease; Fat atrophy usually affects the upper limbs, trunk, and face.
The finding of a drusen on fundus examination of a patient with glomerulonephritis suggests the diagnosis of dense deposit disease. Drusen are yellowish deposits of extracellular material that are found between the basement membrane of the retinal pigment epithelium and the inner collagenous zone of the Bruch membrane. Choroidal neovascularization, macular degeneration, and visual loss may also develop in dense deposit disease.
Complications
Progressive decline in kidney function and end-stage renal disease (ESRD) are among the complications seen in patients with membranoproliferative glomerulonephritis (MPGN) (see Prognosis).
Recurrent disease after transplantation
Recurrent disease is a risk among those patients who receive a renal transplant. [2] Of patients with type I disease, 30-70% develop recurrent MPGN, and 30-40% of the recurrences lead to graft failure. The rate of recurrence of MPGN type II ranges from 50% to 100%; although recurrences may be mild, eventually 50% of the grafts fail. Recurrence rates of MPGN type III are not known.
Recurrent MPGN needs to be differentiated from transplant glomerulopathy, which has a similar histology but lacks immune deposits.
Secondary hypertension, edema, and infections
Hypertension is present in 80% of patients at presentation; patients generally develop worsening of hypertension with the progression of renal insufficiency.
Periorbital or dependent edema may occur in patients with a nephritic or nephrotic presentation, and anasarca is present in a few patients.
The propensity for infections with encapsulated bacteria, including Streptococcus, Haemophilus, and Klebsiella species, is increased. Prophylactic antibiotics and hyperimmune globulins may be useful in some patients. Administer the pneumococcal vaccine and yearly influenza vaccination to all patients.
Thromboembolism tendency
Loss of anticoagulant antithrombin III, proteins C and S, increased procoagulants, defective fibrinolysis, increased platelet aggregability, hyperlipidemia, endothelial cell injury, and steroids may lead to thrombosis. The renal vein is a common site of thrombosis because of hemoconcentration and loss of the anticoagulants through glomerular filtration.
Hyperlipidemia
Hyperlipidemia is a significant adverse event in patients with nephrotic syndrome. Very low-density lipoprotein (VLDL), low-density lipoprotein (LDL), and intermediate density lipoprotein (IDL) levels are increased early in the disease. High-density lipoprotein (HDL) levels may be variable, but levels of the cardioprotective fraction HDL2 usually are decreased. Lipoprotein-a levels are increased.
Hyperlipidemia in patients with nephrotic syndrome may cause accelerated atherosclerosis and increased coronary events. Also, hyperlipidemia may accelerate the progression of renal disease.
Other complications of MPGN include the following:
-
Protein calorie malnutrition
-
Growth retardation
-
Anemia is often multifactorial; urinary losses of transferrin cause iron deficiency, decreased production of erythropoietin, and complement-mediated red blood cell lysis
-
Hypocalcemia and secondary hyperparathyroidism may result from vitamin D deficiency due to urinary losses of cholecalciferol-binding globulin and failure to form activated vitamin D
-
Depressed total thyroxine levels may be caused by loss of the thyroxine-binding globulin; however, thyroid stimulating hormone (TSH) and free thyroxine levels are usually normal
-
Membranoproliferative glomerulonephritis (MPGN) type I. Glomerulus with lobular accentuation from increased mesangial cellularity. A segmental increase occurs in the mesangial matrix, and the peripheral capillary walls are thickened (hematoxylin and eosin stained section; original magnification × 250). Courtesy of John A. Minielly, MD.
-
Membranoproliferative glomerulonephritis (MPGN) type I. Electron microscopy of prominent, glomerular, subendothelial, immune-type electron deposits (original magnification × 11,400). Courtesy of John A. Minielly, MD.
-
Membranoproliferative glomerulonephritis (MPGN) type I. Glomerulus with mesangial interposition producing a double contouring of basement membranes, which, in areas, appear to surround subendothelial deposits (Jones silver methenamine–stained section; original magnification × 400). Courtesy of John A. Minielly, MD.
-
Membranoproliferative glomerulonephritis (MPGN) type II. Electron microscopy of glomerular basement membrane, intramembranous, somewhat linear, electron dense deposit (ie, dense deposit disease; original magnification × 11,400). Courtesy of John A. Minielly, MD.
-
Membranoproliferative glomerulonephritis (MPGN) type I. Immunofluorescent stained section. Intense, peripheral, glomerular, capillary loop deposition of immunoglobulin G (IgG) in an interrupted linear pattern corresponding to extensive subendothelial immune deposits (original magnification × 400). Courtesy of John A. Minielly, MD.
