IgA Nephropathy Complicating Diabetic Glomerulosclerosis

Dear Sir, We read with interest the original paper by Orfila et al. [1] concerning IgA nephropathy complicating diabetic glomerulosclerosis (DGS), and we agree with the authors that IgA glomerulopathy is the most common glomerular disease superimposed upon DGS [2]. In the literature, membranous nephropathy is reported to be the most common glomerular lesion superimposed upon DGS, whereas IgA glomerulopathy is rarely reported; this situation, however, reflects bias related to the different criteria used in the past in reserving renal biopsy in insulin-dependent and non-insulin-dependent diabetes mellitus (NIDDM) patients affected with heavy proteinuria without diabetic retinopathy and diabetic neuropathy. At the present time, the prevalence of superimposed glomerulonephritis upon DGS has been reported in American [3], European [4, 5], and Asian [6, 7] patients, with a really wide spectrum of glomerulopathies. However, the prevalence of glomerular lesions other than DGS in insulin-dependent and NIDDM patients is not known, and the presence of diabetic retinopathy does not exclude the possibility of superimposed glomerulonephritis, and, conversely, the absence of diabetic retinopathy does not indicate that persistent albuminuria is due to isolated glomerulonephritis other than DGS. Undoubtedly, nephrotic syndrome associated with diabetic retinopathy is a poor predictor of glomerulonephritis superimposed upon DGS, but predictive of glomerular lesions different from DGS are acute renal failure (with no prerenal or obstructive nature), frank hematuria or macrohematuria, and proteinuria of nonnephrotic range in recent-onset diabetes, without diabetic retinopathy. From June 1973 to June 1998, we performed 67 renal biopsies in NIDDM patients, 38 males and 29 females, of a total of 1,153 renal biopsies performed in our renal unit. The clinical indications for renal biopsy were: acute renal failure in 9 patients, frank hematuria in 12, proteinuria in the absence of retinopathy in 18, mild chronic renal failure in 7, nephrotic syndrome in 20, and severe hypokalemia in 1 patient. In our retrospective study, 7 of 67 NIDDM patients (12%) showed IgA nephropathy, but 7 of 12 NIDDM patients (58.5%) biopsied because of frank hematuria had IgA nephropathy. We agree with Gans et al. [8] that the number of diabetic patients affected with Berger disease might be underestimated because only a few diabetic patients with microscopic hematuria do undergo renal biopsy. About the problem of whether the occurrence of IgA glomerulonephritis in NIDDM patients may be fortuitous or, on the contrary, may raise the possibility that functional and/or biochemical alterations in the mesangial component of diabetic patients might play a critical role in the localization of IgA immunoreactants, the debate remains open. Obviously, one may speculate that functional and structural glomerular changes induced by diabetic disease may favor the development of immunopathological glomerular disease superimposed upon DGS. Moreover, the histological features observed in our patients were in all cases indicative of two distinct glomerular pathologic processes, suggesting the existence of another disease inducing glomerulonephritis, superimposed on diabetic nephropathy. The wide spectrum of glomerulonephritis reported in NIDDM is not surprising, if we consider that diabetic patients represent a consistent proportion of the normal population. The high frequency of IgA nephropathy in NIDDM patients is not surprising too, if we consider that Berger disease is the most frequently occurring type of glomerulopathy. We do not have clinical evidence that in our NIDDM patients a superimposed IgA glomerulonephritis plays a role in a rapid progression to chronic renal failure; surely, a rapid loss of renal function (without prerenal or obstructive disorders) and the evidence of frank hematuria must be considered as features of superimposed glomerular disease which could worsen the prognosis of diabetic nephropathy.