eMedicine Specialties > Nephrology > Glomerular Diseases
Glomerulonephritis, Diffuse Proliferative: Differential Diagnoses & Workup
Updated: May 11, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Differential Diagnoses
Glomerulonephritis, Crescentic
Glomerulonephritis,
Membranoproliferative
Glomerulonephritis, Membranous
Glomerulonephritis, Nonstreptococcal Associated
With Infection
Glomerulonephritis, Poststreptococcal
Glomerulonephritis, Rapidly Progressive
Other Problems to Be Considered
Goodpasture syndrome is not the only cause of the pulmonary-renal syndrome (ie, renal failure, lung hemorrhage). Other important causes of pulmonary-renal symptoms include the following:
Severe cardiac failure complicated by pulmonary edema (often blood-tinged sputum) and prerenal azotemia
Renal failure from any cause complicated by hypervolemia and pulmonary edema
Immune complex–mediated vasculitides, including SLE, Henoch-Schönlein purpura, and cryoglobulinemia
Pauci-immune vasculitides, including Wegener granulomatosis and microscopic polyangiitis
Infections, such as Legionnaire disease
Renal vein thrombosis with pulmonary embolism
Workup
Laboratory Studies
- Urinalysis
- No specific urinary finding can be used to accurately predict the presence of DPGN.
- However, the finding of red blood cells and red blood cell casts strongly suggests glomerulonephritis. Proteinuria, white blood cells, and white blood cell casts may be present or absent. Renal biopsy should be obtained for histologic diagnosis and, in lupus, for classification.
- In patients with lupus who already have a histologic classification, an increase in urinary sediment abnormality should raise the suspicion of histologic transformation. A repeat biopsy may be indicated if reclassification will guide management.
- A 24-hour urine collection is used for determination of protein and creatinine excretion. Creatinine in a 24-hour urine collection is used to determine completeness of the collection as well as to calculate creatinine clearance. On average, in adults younger than 50 years, creatinine excretion less than 15-20 mg/kg (lean body mass) for women or less than 20-25 mg/kg (lean body mass) for men suggests undercollection of the urine specimen. Values greater than these suggest overcollection. Overcollection and undercollection lead to inaccurate estimation of creatinine clearance and, therefore, of glomerular filtration rate (GFR). A 24-hour urinary protein excretion in excess of 3.5 g is in the nephrotic range. A finding below 3.5 g indicates nonnephrotic proteinuria. A specific pattern for DPGN is not identified, but nephrotic range proteinuria is more common.
- Complete blood count (CBC) findings
- Anemia
- Leukopenia, lymphopenia, and thrombocytopenia are often observed in SLE.
- Serum chemistry
- Serum creatinine and urea nitrogen often are elevated.
- Serum albumin may be low if the patient is nephrotic.
- Serologic tests
- Positive antinuclear antibodies (ANAs) indicate lupus nephritis. Ninety-five percent of patients with SLE have positive ANA; however, it is not specific.
- Positive tests for anti–double-stranded DNA (anti-dsDNA) and anti-Smith (anti-Sm) antibodies are more specific for lupus (rising titers may indicate active or chronic disease).
- Depressed complement levels of C3, C4, and CH50 may suggest SLE, infectious glomerulonephritis, poststreptococcal glomerulonephritis, or cryoglobulinemia.
- ANCAs are positive (>1:40) in almost all cases of Wegener granulomatosis. Eighty to 95% are cytoplasmic ANCA (C-ANCA), while 5-20% are perinuclear ANCA (P-ANCA). In one study, a positive result for C-ANCA was used to identify Wegener granulomatosis, with a sensitivity and specificity of 65% and 88%, respectively, while a positive result for P-ANCA was used to identify Wegener granulomatosis with a sensitivity and specificity of 75% and 98%, respectively.
- Tests results that are positive for anti-GBM antibodies indicate consideration of anti-GMB disease (ie, idiopathic) and Goodpasture syndrome. Circulating anti-GBM antibodies are present in over 90% of patients, although the antibody titer does not correlate well with the manifestations or course of either the pulmonary or renal disease.
- A high titer of antistreptolysin O (ASO) shows recent streptococcal infection, indicating the possibility of poststreptococcal glomerulonephritis. Healthy children of school age (eg, 6-12 y) commonly have titers of 200-300 Todd units per mL. After streptococcal pharyngitis, the antibody response peaks at about 4-5 weeks. Antibody titers decline rapidly in the next several months and reach a slower decline after 6 months. Because 20% of patients with documented infection do not show a rise in the titer of antistreptolysin, other antistreptococcal antibodies such as anti-deoxyribonuclease (DNAse) B, anti-DNAse, and antihyaluronidase should be tested if ASO findings are negative.
- Throat culture findings for group A beta-hemolytic streptococci usually are negative at the time of glomerulonephritis, while ASO titers peak.
- Serum IgA levels are elevated in as many as half of patients with IgA nephropathy.
Imaging Studies
- Renal ultrasonogram: This test is used to determine renal size, confirm the presence of 2 kidneys, and rule out structural lesions that may be responsible for azotemia.
Procedures
- Kidney biopsy
- Indications, contraindications, and complications of percutaneous renal biopsy are discussed in the article Azotemia.
- Renal biopsy is the criterion standard for diagnosis of anti-GBM nephritis. Obtain a renal biopsy for histologic diagnosis and, in lupus, for classification.
- In patients with lupus who already have a histologic classification, an increase in urinary sediment abnormality should raise the suspicion of histologic transformation. A repeat biopsy may be indicated if reclassification will influence management.
Histologic Findings
Light microscopy
Light microscopy (see image below and Image 1) shows a marked hypercellularity of endothelial (ie, endocapillary) and mesangial cells, capillary loop thickening (ie, wire loops) or obliteration, and inflammatory cell infiltration. In severe forms, epithelial cell proliferation with crescent formation, necrosis, and sclerosis may be present. Inflammatory infiltration and fibrosis also may present in the interstitium. Endocapillary proliferation is typical of poststreptococcal glomerulonephritis.
Light microscopy (trichrome stain) shows globally increased cellularity, numerous polymorphonuclear cells, cellular crescent (at left of photomicrograph) and fibrinoid necrosis (brick red staining at right of photomicrograph). These findings are characteristic of diffuse proliferative glomerulonephritis.
Immunofluorescent microscopy
This technique shows (except for anti-GBM disease) a granular deposition of immunoglobulins, complement, and fibrin along the GBM, tubular basement membranes, and peritubular capillaries (see image below and Image 2). Linear deposition occurs in the GBM in anti-GBM disease. Findings on immunofluorescence are negative in ANCA-associated glomerulonephritis. If radioimmunoassay is not available, indirect immunofluorescence can be used to detect circulating anti-GBM antibodies in 60-80% of patients by incubating the patient's serum with stored sections of healthy human kidneys.
Diffuse proliferative glomerulonephritis (DPGN). Immunofluorescent microscopy shows (except for anti–glomerular basement membrane [GBM] disease) a granular deposition of immunoglobulins, complement, and fibrin along the GBM, tubular basement membranes, and peritubular capillaries (image 2a). Linear deposition occurs in the GBM in anti-GBM disease (image 2b).
Electron microscopy
Using electron microscopy (see image below and Image 3), electron dense deposits are visible in the mesangial, subendothelial, intramembranous, and subepithelial locations. In SLE, the mesangial and subendothelial deposits produce the typical wire loop lesions observed using light microscopy. Tuboreticular inclusions may be observed within endothelial cells but are not pathognomonic. Tuboreticular inclusions also may be observed in HIV nephropathy. In anti-GBM disease, the deposits are linear and intramembranous. In poststreptococcal glomerulonephritis, the deposits are subepithelial and appear as humps. Few or no deposits are visible in ANCA-associated glomerulonephritis.
Diffuse proliferative glomerulonephritis (DPGN). Using electron microscopy, electron-dense deposits are visible in the mesangial, subendothelial, intramembranous, and subepithelial locations.
More on Glomerulonephritis, Diffuse Proliferative |
| Overview: Glomerulonephritis, Diffuse Proliferative |
 Differential Diagnoses & Workup: Glomerulonephritis, Diffuse Proliferative |
| Treatment & Medication: Glomerulonephritis, Diffuse Proliferative |
| Follow-up: Glomerulonephritis, Diffuse Proliferative |
| Multimedia: Glomerulonephritis, Diffuse Proliferative |
| References |
| Further Reading |
| « Previous Page | Next Page » |
References
Vachvanichsanong P, Dissaneewate P, McNeil E. Diffuse proliferative glomerulonephritis does not determine the worst outcome in childhood onset lupus nephritis: a 23-year experience in a single centre. Nephrol Dial Transplant. Apr 25 2009;[Medline].
Demircin G, Oner A, Erdogan O, et al. Long-term efficacy and safety of quadruple therapy in childhood diffuse proliferative lupus nephritis. Ren Fail. 2008;30(6):603-9. [Medline].
Haas M, Rahman MH, Cohn RA, et al. IgA nephropathy in children and adults: comparison of histologic features and clinical outcomes. Nephrol Dial Transplant. Aug 2008;23(8):2537-45. [Medline].
Sahin GM, Sahin S, Kantarci G, Ergin H. Mycophenolate mofetil treatment for therapy-resistant glomerulopathies. Nephrology (Carlton). 2007;Jun;12(3):285-8. [Medline].
Ong LM, Hooi LS, Lim TO, et al. Randomized controlled trial of pulse intravenous cyclophosphamide versus mycophenolate mofetil in the induction therapy of proliferative lupus nephritis. Nephrology (Carlton). Oct 2005;10(5):504-10. [Medline].
Jayne D. Current management of lupus nephritis: popular misconceptions. Lupus. 2007;16(3):217-20. [Medline].
Chan TM, Li FK, Tang CS. Efficacy of mycophenolate mofetil in patients with diffuse proliferative lupus nephritis. Hong Kong-Guangzhou Nephrology Study Group. N Engl J Med. Oct 19 2000;343(16):1156-62. [Medline].
Ginzler EM, Dooley MA, Aranow C, et al. Mycophenolate mofetil or intravenous cyclophosphamide for lupus nephritis. N Engl J Med. Nov 24 2005;353(21):2219-28. [Medline]. [Full Text].
[Best Evidence] Bao H, Liu ZH, Xie HL, et al. Successful treatment of class V+IV lupus nephritis with multitarget therapy. J Am Soc Nephrol. Oct 2008;19(10):2001-10. [Medline].
Glassock RJ. IgA nephropathy: challenges and opportunities. Cleve Clin J Med. 2008;Aug;75(8):569-76. [Medline]. [Full Text].
Hiramatsu N, Kuroiwa T, Ikeuchi H, et al. Revised classification of lupus nephritis is valuable in predicting renal outcome with an indication of the proportion of glomeruli affected by chronic lesions. Rheumatology (Oxford). May 2008;47(5):702-7. [Medline].
Aasarod K, Iversen BM, Hammerstrom J. Wegener''s granulomatosis: clinical course in 108 patients with renal involvement. Nephrol Dial Transplant. May 2000;15(5):611-8. [Medline].
Andrews M, Edmunds M, Campbell A. Systemic vasculitis in the 1980s--is there an increasing incidence of Wegener''s granulomatosis and microscopic polyarteritis?. J R Coll Physicians Lond. Oct 1990;24(4):284-8. [Medline].
Austin HA, Balow JE. Natural history and treatment of lupus nephritis. Semin Nephrol. Jan 1999;19(1):2-11. [Medline].
Bosch X, Mirapeix E, Font J. [Neutrophil anticytoplasmic antibodies: their diagnostic utility in vasculitis and glomerulonephritis]. Med Clin (Barc). Mar 26 1994;102(11):412-7. [Medline].
Chan TM, Tse KC, Tang CS, et al. Long-term study of mycophenolate mofetil as continuous induction and maintenance treatment for diffuse proliferative lupus nephritis. J Am Soc Nephrol. Apr 2005;16(4):1076-84. [Medline].
Clark WF, Moist LM. Management of chronic renal insufficiency in lupus nephritis: role of proteinuria, hypertension and dyslipidemia in the progression of renal disease. Lupus. 1998;7(9):649-53. [Medline].
Coppo R, Gianoglio B, Porcellini MG. Frequency of renal diseases and clinical indications for renal biopsy in children (report of the Italian National Registry of Renal Biopsies in Children). Group of Renal Immunopathology of the Italian Society of Pediatric Nephrology and Group of Renal. Nephrol Dial Transplant. Feb 1998;13(2):293-7. [Medline].
D''Amico G. Natural history of idiopathic IgA nephropathy: role of clinical and histological prognostic factors. Am J Kidney Dis. Aug 2000;36(2):227-37. [Medline].
Flanc RS, Roberts MA, Strippoli GF. Treatment of diffuse proliferative lupus nephritis: a meta-analysis of randomized controlled trials. Am J Kidney Dis. Feb 2004;43(2):197-208. [Medline].
Frisch G, Lin J, Rosenstock J. Mycophenolate mofetil (MMF) vs placebo in patients with moderately advanced IgA nephropathy: a double-blind randomized controlled trial. Nephrol Dial Transplant. Oct 2005;20(10):2139-45.
Garrett PJ, Dewhurst AG, Morgan LS. Renal disease associated with circulating antineutrophil cytoplasm activity. Q J Med. Oct 1992;85(306):731-49. [Medline].
Golbus J, McCune WJ. Lupus nephritis. Classification, prognosis, immunopathogenesis, and treatment. Rheum Dis Clin North Am. Feb 1994;20(1):213-42. [Medline].
Grotz W, Wanner C, Keller E. Crescentic glomerulonephritis in Wegener''s granulomatosis: morphology, therapy, outcome. Clin Nephrol. Jun 1991;35(6):243-51. [Medline].
Haas M. Histologic subclassification of IgA nephropathy: a clinicopathologic study of 244 cases. Am J Kidney Dis. Jun 1997;29(6):829-42. [Medline].
Huong DL, Papo T, Beaufils H. Renal involvement in systemic lupus erythematosus. A study of 180 patients from a single center. Medicine (Baltimore). May 1999;78(3):148-66. [Medline].
Ioannidis JP, Boki KA, Katsorida ME. Remission, relapse, and re-remission of proliferative lupus nephritis treated with cyclophosphamide. Kidney Int. Jan 2000;57(1):258-64. [Medline].
Jindal KK. Management of idiopathic crescentic and diffuse proliferative glomerulonephritis: evidence-based recommendations. Kidney Int Suppl. Jun 1999;70:S33-40. [Medline].
Kasinath BS, Neilson EG, Hebert L. Short-term prognosis of severe proliferative lupus nephritis. Am J Kidney Dis. Oct 1986;8(4):239-43. [Medline].
Lim CS, Chin HJ, Jung YC. Prognostic factors of diffuse proliferative lupus nephritis. Clin Nephrol. Sep 1999;52(3):139-47. [Medline].
Little MA, Pusey CD. Rapidly progressive glomerulonephritis: current and evolving treatment strategies. J Nephrol. Nov-Dec 2004;17 Suppl 8:S10-9.
McCarty DJ, Manzi S, Medsger TA Jr. Incidence of systemic lupus erythematosus. Race and gender differences. Arthritis Rheum. Sep 1995;38(9):1260-70. [Medline].
Mekhail TM, Hoffman GS. Longterm outcome of Wegener''s granulomatosis in patients with renal disease requiring dialysis. J Rheumatol. May 2000;27(5):1237-40. [Medline].
Nolin L, Courteau M. Management of IgA nephropathy: evidence-based recommendations. Kidney Int Suppl. Jun 1999;70:S56-62. [Medline].
Polenakovic M, Grcevska L. Survival rate of patients with glomerulonephritis. Acta Med Croatica. 1992;46(1):15-20. [Medline].
Research Group on Progressive Chronic Renal Disease. Nationwide and long-term survey of primary glomerulonephritis in Japan as observed in 1,850 biopsied cases. Research Group on Progressive Chronic Renal Disease. Nephron. 1999;82(3):205-13. [Medline].
Shoji T, Nakanishi I, Suzuki A. Early treatment with corticosteroids ameliorates proteinuria, proliferative lesions, and mesangial phenotypic modulation in adult diffuse proliferative IgA nephropathy. Am J Kidney Dis. Feb 2000;35(2):194-201. [Medline].
Tomino Y. IgA nephropathy. From molecules to men. Contrib Nephrol. 1999;126:III-IX, 1-115. [Medline].
Wyatt RJ, Julian BA, Baehler RW. Epidemiology of IgA nephropathy in central and eastern Kentucky for the period 1975 through 1994. Central Kentucky Region of the Southeastern United States IgA Nephropathy DATABANK Project. J Am Soc Nephrol. May 1998;9(5):853-8. [Medline].
Yahya TM, Pingle A, Boobes Y. Analysis of 490 kidney biopsies: data from the United Arab Emirates Renal Diseases Registry. J Nephrol. May-Jun 1998;11(3):148-50. [Medline].
Further Reading
Clinical guidelines:
ACR Appropriateness Criteria® hematuria. American College of Radiology - Medical Specialty Society. 1995 (revised 2005). 6 pages. NGC:004611
Specific management of IgA nephropathy: role of triple therapy and cytotoxic therapy. Caring for Australasians with Renal Impairment - Disease Specific Society. 2005 Sep. 11 pages. NGC:006136
Clinical trials:
Calcitriol in the Treatment of Immunoglobulin A Nephropathy
Safety Study of AMG 811 in Subjects With Systemic Lupus Erythematosus With and Without Glomerulonephritis
Keywords
diffuse proliferative glomerulonephritis, lupus, nephritis, glomerular, glomerulonephritis, lupus nephritis, glomerulus, lupus nephritis class IV, DPGN, autoimmune disorders, systemic lupus erythematosus, SLE, connective tissue disease, glomeruli, vasculitis syndromes, Wegener granulomatosis, glomerular basement membrane, microscopic polyangiitis, Churg-Strauss syndrome, essential mixed cryoglobulinemia, membranoproliferative glomerulonephritis, Henoch-Schönlein purpura, connective tissue diseases, rapidly progressive glomerulonephritis, RPGN,anti–glomerular basement membrane disease, anti-GBM disease, antineutrophil cytoplasmic antibody–associated glomerulonephritis, ANCA-associated glomerulonephritis, crescentic glomerulonephritis, Goodpasture syndrome, microscopic polyarteritis nodosa
