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Diagnosis:
Membranoproliferative Glomerulonephritis Type I

In our case the glomeruli appear enlarged and hypercellular, with an increase in mesangial cellularity and matrix; the mesangial matrix increase causes an exaggeration of lobular aspect, best seen in Figure 2; this feature has given rise to the alternative name of "lobular glomerulonephritis". The capillary basement membranes are thickened by "interposition" of mesangial cells and matrix into the capillary wall. This gives rise to the tram-track or double-contoured appearance of the capillary wall, best appreciated with methenamine silver stain (Figures 5 and 6).

Membranoproliferative glomerulonephritis (MPGN) is more common in children and young adults. This entity refers to a pattern of glomerular injury with characteristic findings: proliferation of mesangial and endothelial cells, mesangial matrix expansion; thickening of the capillary walls by subendothelial immune deposits; and mesangial interposition into the capillary wall, giving rise to a double-contour or tram-track appearance on light microscopy. Crescents may be visible in approximately 10% of patient, as seen in the present case (Figure 4); this feature has been related with worse prognosis.

Although MPGN has been divided in type I, II, and III, MPGN type II is really a disease etiopathogenically diverse from type I and III and the adequate name is dense deposit disease (Walker PD, et al. Dense deposit disease is not a membranoproliferative glomerulonephritis. Mod Pathol. 2007 Mar 30; [Epub ahead of print] [PubMed link])

Hypocomplementemia is a characteristic finding in MPGN; low C3 levels are present in most of patients. Hypocomplementemia may play a role in initiating glomerular inflammation and injury. Three nephritic antibodies are described in MPGN that play a role in the development of hypocomplementemia, (1) nephritic factor of the classic pathway (NFc or C4NeF), (2) nephritic factor of the amplification loop (NFa or C3NEF), and (3) nephritic factor of the terminal pathway (NFt) (Kathuria P, Senitko M. Glomerulonephritis, Membranoproliferative. E-medicine, link). These autoantibodies are not specific for MPGN and are also seen in poststreptococcal and lupus glomerulonephritis. NFc stabilizes the classic pathway C3 convertase C4b,2a. The binding of NFa to C3b,Bb stabilizes the complex, preventing degradation by its normal inactivators, resulting in complement activation and chronic consumption of C3.

Patients with MPGN may present asymptomatic proteinuria and hematuria detected on routine urinalysis (23-30%), nephrotic syndrome (42-67%), acute nephritic syndrome (16-30%), recurrent episodes of gross hematuria (10-20%), or azotemia (Kathuria P, Senitko M. Glomerulonephritis, Membranoproliferative. E-medicine, link).

The main predictors of an adverse outcome are nephrotic syndrome and hypertension at presentation, low GFR at 1 year, and older age. Histologic characteristics: crescents, interstitial fibrosis, tubular atrophy, and multiple sclerotic glomeruli indicate a poor prognosis. Hypocomplementemia is not a predictor of disease severity or prognosis. MPGN type I with nephrotic syndrome is a progressive disease, with 50% of patients developing ESRD after 10 years and 90% of patients developing ESRD after 20 years. MPGN type I without nephrotic proteinuria has a 10-year renal survival rate of 85%.

In pregnancy, MPGN, increase the risk of fetal loss, intrauterine growth retardation, and prematurity. Patients with hypertension, renal insufficiency, and nephrotic syndrome have increased risks for a more unfavorable fetal outcome. Preeclampsia develops in 20-40% of patients with underlying renal disease. Patients with MPGN are more likely than those with most other glomerular diseases to develop deterioration of renal function, increasing proteinuria, or worsening of hypertension during pregnancy. The risk for adverse outcomes depends on the patient's severity of hypertension, 24-hour proteinuria, and the level of renal function prior to pregnancy (Jungers P, et al. Am J Kidney Dis. 1991;17:116-22. [PubMed link])

In our patient follow-up is still short (2 months) and nephrotic proteinuria and renal function alteration continue.

See the chapter Proliferative endocapillary glomerulonephritis (English version).

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Bibliography

• Kathuria P, Senitko M. Glomerulonephritis, Membranoproliferative. In: E-medicine, link. Consulted April 14th, 2007.
• Walker PD, Ferrario F, Joh K, Bonsib SM. Dense deposit disease is not a membranoproliferative glomerulonephritis. Mod Pathol. 2007 Mar 30; [Epub ahead of print] [PubMed link]
• Smith KD, Alpers CE. Pathogenic mechanisms in membranoproliferative glomerulonephritis. Curr Opin Nephrol Hypertens. 2005;14:396-403. [PubMed link]
• Cansick JC, Lennon R, Cummins CL, Howie AJ, McGraw ME, Saleem MA, Tizard EJ, Hulton SA, Milford DV, Taylor CM. Prognosis, treatment and outcome of childhood mesangiocapillary (membranoproliferative) glomerulonephritis. Nephrol Dial Transplant. 2004;19:2769-77. [PubMed link] [Full text link]
• Yanagihara T, Hayakawa M, Yoshida J, Tsuchiya M, Morita T, Murakami M, Fukunaga Y. Long-term follow-up of diffuse membranoproliferative glomerulonephritis type I. Pediatr Nephrol. 2005;20:585-90. [PubMed link]
• Antonovych TT, Sabnis SG, Broumand BB. A study of membranoproliferative glomerulonephritis in Iran. Ann Saudi Med. 1999;19:505-10. [PubMed link]
• Jungers P, Houillier P, Forget D, Henry-Amar M. Specific controversies concerning the natural history of renal disease in pregnancy. Am J Kidney Dis. 1991;17:116-22. [PubMed link]
• Abe S. An overview of pregnancy in women with underlying renal disease. Am J Kidney Dis. 1991;17:112-5. [PubMed link]

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