On the methodology for measuring thickness of glomerular basement membranes

Sir, We read with interest the multicentre Italian study by Frascà et al. [1] that confirms that a proportion of patients (6/51) with thin glomerular basement membrane disease (TBMD) have an underlying type IV collagen mutation that may not always be benign. In the ‘subjects and methods’ section they state that the measurements of glomerular basement membrane was performed by the method published by us [2]. However, our work involved a comparison between the Orthagonal Intercepts Method (OIM) and our modification of direct measurement (MDM) method, applying it on two glomeruli rather than one. Frascà et al. [1] do not state which of the two (or both) methods was used in their study. We found that although the MDM method is acceptable for diagnosing TBMD, on average the values were about 80 nm less than those obtained with OIM. As one of the patients described by Frascà was only 8 years old we would also remind readers that basement membrane thickness is age related [3]. 5/18 patients with suggestive family histories or 6/51 in the overall group had collagen IV mutations suggesting that other genes involved in the production or turnover of glomerular basement membrane are likely to be equally important in the pathogenesis of this variant/ disease. It would also be interesting to know if any of the ultrastructural lesions correlated with collagen IV mutations.