Familial hematuria; clinico-pathological correlations

Area of Science:

• Nephrology
• Genetics
• Pathology

Background:

• Familial hematuria presents a diagnostic challenge, often requiring detailed family history and clinical evaluation.
• Alport's syndrome is a hereditary condition characterized by kidney disease, sensorineural deafness, and sometimes eye abnormalities.

Purpose of the Study:

• To investigate the diagnostic utility of electron microscopy (EM) in differentiating Alport's syndrome from benign familial hematuria.
• To correlate clinical findings and family history with renal biopsy findings in patients with familial hematuria.

Main Methods:

• Analysis of renal biopsy specimens from 38 patients with familial hematuria using light microscopy (LM) and electron microscopy (EM).
• Detailed clinical evaluation and family history collection, including assessment for deafness, proteinuria, and renal failure.
• Classification of families into groups based on clinical presentation (deafness, proteinuria, renal failure).

Main Results:

• EM revealed a characteristic "basket weave" pattern of lamina densa replication in 27/31 biopsies, indicative of Alport's syndrome.
• Patients with deafness, heavy proteinuria, or family history of renal failure showed progressive disease and characteristic EM changes.
• Patients without these features (Group 3) had non-progressive disease and minimal glomerular changes on EM, with lamina densa attenuation.
• The "basket weave" alteration was present even in young children (<5 years), while other features like deafness and proteinuria appeared later.

Conclusions:

• Electron microscopy is essential for the definitive diagnosis of Alport's syndrome, particularly in differentiating it from benign familial hematuria.
• The presence of deafness and heavy proteinuria indicates a poorer prognosis in Alport's syndrome.
• The "basket weave" pattern on EM is an early and consistent finding in Alport's syndrome.