The Authors Reply

We thank Dr. Delafosse and colleagues for their letter in response to our article¹ on the prognostic value of serum albumin in patients with primary membranous nephropathy. Our retrospective analysis lacked measurements of anti-PLA2R antibody titers to assess the prognostic value of normalized albuminemia independently of immunologic remission. We are therefore delighted to see that in their data, normalization of serum albumin at the time of immunologic remission is associated with a greater likelihood of complete remission and fewer relapses. These findings highlight an important question: What does the measurement of serum albumin truly capture in membranous nephropathy and other nephrotic diseases? Albuminemia is clearly far more than a corollary measure of urinary loss of protein. The inverse correlation between albuminemia and the degree of proteinuria is rather weak (Figure 1). Data suggest that the relationship between proteinuria and hypoalbuminemia differs between different nephrotic diseases.² The mechanisms of hypoalbuminemia are multiple, but are significantly influenced by reduced albumin synthesis in response to systemic inflammation.³ In turn, hypoalbuminemia affects the physiologic response to inflammatory states, as highlighted by its independent association with complications of nephrotic syndrome, such as venous thromboembolism⁴ and infections. It stands to reason that albuminemia provides a measure of the systemic effect of nephrotic syndrome and its “disease activity” independently of proteinuria. While awaiting confirmation in other cohorts, this report by Delafosse et al. augments the recognition of hypoalbuminemia as a valuable indicator of systemic disease activity in membranous nephropathy, possibly independently of the autoimmune process.

Figure 1.

Correlation between serum albumin level (g/dl) and proteinuria (urine protein/creatinine ratio, g/g) in patients with primary membranous nephropathy (MN) from the Glomerular Disease Collaborative Network MN registry.