L LSUHSC-S Renal Pathology Consultative Services

Interesting Case

Case Study #: 4

08/17/09

Answers

By: Stephen M. Bonsib, M.D.

Xin Gu, M.D.

Ami Bhalodia, M.D.

318-675-4557 phone

318-675-4541 fax

sbonsi@lsuhsc.edu

Clinical History: 37 year old white male with presents with hematuria, proteinuria, and swelling of hands and feet.

Case courtesy of Dr. Maximo Lamarche, MD

Figure 1: PAS stain of a glomerulus showing minimal segmental mesangial expansion

Figure 2: IF for IgA reveals distinct granular mesangial staining

Figure 3: EM showing mesangial deposits

Figure 4: EM of the mesangial deposits

Question:

1.
What is your diagnosis based on the light microscopy, IF and EM findings?
2.
What geographical distribution is characteristic of this disease?
3.
What percentage of patients with this disease progress to end-stage renal disease?
4.
What conditions is the secondary form of this disease associated with?

Answer:

1. The biopsy reveals mild hypercellularity in the mesangial areas, and strong IgA deposition in the mesangium on IF. The EM shows elongated paramesangial (“mesangial waist”) deposits. Based on these findings the diagnosis is - mesangial IgA nephropathy

2. IgA nephropathy is the most common primary glomerulopathy in the world. It has a high incidence in Asia, with a majority of patients being young males. It appears to be much less common in North America and Europe. IgA nephropathy is more common in whites and Asians and is rare in blacks.

3. Acute renal failure is seen in up to 10% of patients with IgA nephropathy and up to 30% of patients progress to end-stage renal disease.

4. Secondary forms of IgA nephropathy can be associated with chronic liver disease, cirrhosis, lung, breast, and GI carcinomas, hematopoietic diseases and autoimmune diseases.

Discussion:

The pathogenesis of IgA nephropathy remains complex. The characteristic biopsy findings by IF are granular deposits of IgA and C3 in the glomerular mesangium, at times accompanied by deposits of IgG and IgM. However, the presentation of the disease can be variable, both clinically and pathologically.

Clinical features range from asymptomatic hematuria to RPGN with microscopic hematuria, recurrent macroscopic hematuria, spontaneously resolving acute renal failure, or proteinuria that can be nephrotic range.

A vast number of glomerular lesions can be seen, but mesangial proliferation with prominent IgA deposition is observed in almost all biopsies. The recent international consensus classification, The Oxford Classification of IgA Nephropathy, incorporates the various histological lesions of IgA nephropathy to aid in prediction of clinical outcome.

References:

Roberts I et al. The oxford classification of IgA nephropathy: pathology definitions, correlations, and reproducibility. Kidney Inter 2009; 76: 546-556

Barratt J, Feehally J. IgA nephropathy. J Am Soc Nephrol 2005; 16: 2088-2097

Haas M. Histologic subclassification of IgA nephropathy: a clinicopathologic study of 244 cases. Am J Kidney Dis 1997; 29: 829–842

Daniel L, Saingra Y, Giorgi R, Bouvier C, Pellissier J-F, Berland Y. Tubular lesions determine prognosis of IgA nephropathy. Am J Kidney Dis 2000; 35: 13–20

To KF, Choi PCL, Szeto CC et al. Outcome of IgA nephropathy in adults graded by chronic histological lesions. Am J Kidney Dis 2000; 35: 392–400

Freese P, Norden G, Nyberg G. Morphologic high-risk factors in IgA nephropathy. Nephron 1998; 79: 420–425

Lee SMK, Rao VM, Franklin WA et al. IgA nephropathy: morphologic predictors of progressive renal disease. Hum Pathol 1982; 13: 314–322

Heptinstall’s Pathology of the Kidney. 6th edition.