Diffuse Proliferative Glomerulonephritis Workup
- Author: Moro O Salifu, MD, MPH, FACP; Chief Editor: Vecihi Batuman, MD, FACP, FASN more...
On urinalysis, no specific finding can be used to accurately predict the presence of diffuse proliferative glomerulonephritis (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 are as follows:
Leukopenia, lymphopenia, and thrombocytopenia are often observed in SLE.
On serum chemistry studies, serum creatinine and blood urea nitrogen often are elevated. Serum albumin may be low if the patient is nephrotic.
Serologic test results may include the following:
Positive antinuclear antibodies (ANAs) indicate lupus nephritis; 95% of patients with SLE have positive ANA, but this finding 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.
Antineutrophil cytoplasmic antibody (ANCA) assays are positive (>1:40) in almost all cases of granulomatosis with polyangiitis (Wegener granulomatosis): 80-95% 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 granulomatosis with polyangiitis, with a sensitivity and specificity of 65% and 88%, respectively, while a positive result for P-ANCA was used to identify granulomatosis with polyangiitis with a sensitivity and specificity of 75% and 98%, respectively.
Tests results that are positive for anti – glomerular basement membrane (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.
See the list below:
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.
See the list below:
- 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.
Light microscopy (as seen in the image below) 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.
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 (as seen in the image below). 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.
Using electron microscopy (as seen in the image below), 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.
Xie Q, Liu Y, Liu G, Yang N, Yin G. Diffuse proliferative glomerulonephritis associated with dermatomyositis with nephrotic syndrome. Rheumatol Int. 2010 Apr. 30(6):821-5. [Medline].
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. 2009 Apr 25. [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. 2008 Aug. 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].
Opastirakul S, Chartapisak W. Pulse cyclophosphamide induction treatment in Thai children with diffuse proliferative lupus nephritis. Nephrology (Carlton). 2011 Dec 19. [Medline].
Tani C, Mosca M, d'Ascanio A, Neri R, Tavoni A, Carli L, et al. [Long term outcome of treatment of diffuse proliferative glomerulonephritis with pulse steroids and short course pulse cyclophosphamide]. Reumatismo. 2010 Jul-Sep. 62(3):215-20. [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). 2005 Oct. 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. 2000 Oct 19. 343(16):1156-62. [Medline].
Kamijo Y, Hashimoto K, Takahashi K, Ehara T, Shigematsu H, Higuchi M. Treatment with cyclosporine A improves SLE disease activity of Japanese patients with diffuse proliferative lupus nephritis. Clin Nephrol. 2011 Aug. 76(2):136-43. [Medline].
Bao H, Liu ZH, Xie HL, et al. Successful treatment of class V+IV lupus nephritis with multitarget therapy. J Am Soc Nephrol. 2008 Oct. 19(10):2001-10. [Medline].
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). 2008 May. 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. 2000 May. 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. 1990 Oct. 24(4):284-8. [Medline].
Austin HA, Balow JE. Natural history and treatment of lupus nephritis. Semin Nephrol. 1999 Jan. 19(1):2-11. [Medline].
Bosch X, Mirapeix E, Font J. [Neutrophil anticytoplasmic antibodies: their diagnostic utility in vasculitis and glomerulonephritis]. Med Clin (Barc). 1994 Mar 26. 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. 2005 Apr. 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. 1998 Feb. 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. 2000 Aug. 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. 2004 Feb. 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. 2005 Oct. 20(10):2139-45.
Garrett PJ, Dewhurst AG, Morgan LS. Renal disease associated with circulating antineutrophil cytoplasm activity. Q J Med. 1992 Oct. 85(306):731-49. [Medline].
Golbus J, McCune WJ. Lupus nephritis. Classification, prognosis, immunopathogenesis, and treatment. Rheum Dis Clin North Am. 1994 Feb. 20(1):213-42. [Medline].
Grotz W, Wanner C, Keller E. Crescentic glomerulonephritis in Wegener''s granulomatosis: morphology, therapy, outcome. Clin Nephrol. 1991 Jun. 35(6):243-51. [Medline].
Haas M. Histologic subclassification of IgA nephropathy: a clinicopathologic study of 244 cases. Am J Kidney Dis. 1997 Jun. 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). 1999 May. 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. 2000 Jan. 57(1):258-64. [Medline].
Jindal KK. Management of idiopathic crescentic and diffuse proliferative glomerulonephritis: evidence-based recommendations. Kidney Int Suppl. 1999 Jun. 70:S33-40. [Medline].
Kasinath BS, Neilson EG, Hebert L. Short-term prognosis of severe proliferative lupus nephritis. Am J Kidney Dis. 1986 Oct. 8(4):239-43. [Medline].
Lim CS, Chin HJ, Jung YC. Prognostic factors of diffuse proliferative lupus nephritis. Clin Nephrol. 1999 Sep. 52(3):139-47. [Medline].
Little MA, Pusey CD. Rapidly progressive glomerulonephritis: current and evolving treatment strategies. J Nephrol. 2004 Nov-Dec. 17 Suppl 8:S10-9.
McCarty DJ, Manzi S, Medsger TA Jr. Incidence of systemic lupus erythematosus. Race and gender differences. Arthritis Rheum. 1995 Sep. 38(9):1260-70. [Medline].
Mekhail TM, Hoffman GS. Longterm outcome of Wegener''s granulomatosis in patients with renal disease requiring dialysis. J Rheumatol. 2000 May. 27(5):1237-40. [Medline].
Nolin L, Courteau M. Management of IgA nephropathy: evidence-based recommendations. Kidney Int Suppl. 1999 Jun. 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. 2000 Feb. 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. 1998 May. 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. 1998 May-Jun. 11(3):148-50. [Medline].
Plantinga LC, Patzer RE, Drenkard C, Kramer MR, Klein M, Lim SS, et al. Association of time to kidney transplantation with graft failure among U.S. patients with end-stage renal disease due to lupus nephritis. Arthritis Care Res (Hoboken). 2014 Sep 23. [Medline].