1 Department of Medicine and Western Australian Heart Research Institute, University of Western Australia 2 Department of Nephrology, Royal Perth Hospital, Perth, Western Australia
Sir,
We read with interest that Arnadottir et al. [1] demonstrated significantly lower total plasma homocysteine levels in nephrotic patients compared with non-nephrotic patients matched for renal function. A positive correlation between serum creatinine, glomerular filtration rate, and homocysteine was seen and this has been previously documented [2,3]. The study also demonstrated that total plasma homocysteine was negatively correlated with serum albumin and positively correlated with urinary albumin excretion [1]. We would like to communicate the significance of total plasma homocysteine in a larger number of nephrotic patients and its contribution to cardiovascular risk in these patients.
We measured total plasma homocysteine in 21 patients with primary idiopathic nephrotic syndrome and 20 non-nephrotic patients matched for age and body mass index (BMI) and with similar serum creatinine and glomerular filtration rate (GFR), calculated using the Cockcroft and Gault equation. Homocysteine was measured by a fluorescence polarization immunoassay (Axis Biochemicals ASA, Oslo, Norway) (intra-assay CV 1.4%, inter-assay CV 3.7%). We also measured brachial artery flow-mediated dilatation (FMD %), which reflects endothelial function, an early cardiovascular risk marker [4]. Unlike Arnadottir et al., we found no difference in total plasma homocysteine between groups despite a statistically significant difference between groups in urinary protein to creatinine ratio and serum albumin (both P<0.001) (Table 1). Within the nephrotic group, homocysteine was significantly correlated with serum creatinine (r=0.58, P<0.01) and calculated GFR (r=-0.45, P<0.05), but not with urinary protein or serum albumin. This is not consistent with the findings of Arnadottir et al., and we would question the validity of employing correlational analyses using data pooled from non-homogeneous populations. We would be interested in whether these associations persisted within the nephrotic group alone. Finally, consistent with epidemiological data [5], we found impaired brachial FMD in the nephrotic group. However, homocysteine was not correlated with FMD (r=-0.18, P=0.43).
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1 Department of Medicine, Landspitali University Hospital Hringbraut, Reykjavik, Iceland 2 Department of Clinical Chemistry 3 Department of Nephrology, University Hospital in Lund, Lund, Sweden
Sir,
Very little is known about the effect of proteinuric renal disease on homocysteine metabolism. Therefore, the study presented in the letter by Dogra et al. constitutes a significant contribution to the field. However, like our study, it is small. The part of the study comparing nephrotic to non-nephrotic patients is larger (21 vs 11 patients) while the part of the study comparing nephrotic patients before and after improvement of their disease is smaller (5 vs 11 patients) than in our study. The small size of both studies is their main drawback and, at least in the case of our study, this precluded adjustment of plasma homocysteine concentrations to renal function. The study of Dogra et al. would have been well served by such adjustment especially since the nephrotic and the non-nephrotic patients do not seem to have been glomerular filtration rate matched in a pair-wise fashion.
We agree with Dogra et al. that correlational analyses of data pooled from non-homogeneous populations is questionable. The correlations between the plasma homocysteine concentrations and the serum albumin concentrations as well as the urinary protein excretion did not reach statistical significance in the nephrotic group of our study, again probably due to the small size of the group.
The nephrotic syndrome is associated with increased cardiovascular risk. Therefore, it is noteworthy that neither we nor Dogra et al. found any signs of increased plasma homocysteine concentration in nephrotic patients. However, larger studies, empowered for multivariate analyses, are needed to clarify this issue.