The Authors Reply

We thank Dr. Delafosse and colleagues for their letter in response to our article1Lee T. Chung Y. Poulton C.J. et al.Serum albumin at partial remission predicts outcomes in membranous nephropathy.Kidney Int Rep. 2020; 5: 706-717Abstract Full Text Full Text PDF PubMed Scopus (2) Google Scholar 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.2Gupta K. Iskandar S.S. Daeihagh P. et al.Distribution of pathologic findings in individuals with nephrotic proteinuria according to serum albumin.Nephrol Dial Transplant. 2008; 23: 1595-1599Crossref PubMed Scopus (14) Google Scholar The mechanisms of hypoalbuminemia are multiple, but are significantly influenced by reduced albumin synthesis in response to systemic inflammation.3Kaysen G.A. Biological basis of hypoalbuminemia in ESRD.J Am Soc Nephrol. 1998; 9: 2368-2376PubMed Google Scholar In turn, hypoalbuminemia affects the physiologic response to inflammatory states, as highlighted by its independent association with complications of nephrotic syndrome, such as venous thromboembolism4Gyamlani G. Molnar M.Z. Lu J.L. et al.Association of serum albumin level and venous thromboembolic events in a large cohort of patients with nephrotic syndrome.Nephrol Dial Transplant. 2017; 32: 157-164Crossref PubMed Scopus (22) Google Scholar 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. Serum Albumin at Partial Remission Predicts Outcomes in Membranous NephropathyKidney International ReportsVol. 5Issue 5PreviewIn primary membranous nephropathy (MN), partial remission (PR) (≥50% reduction of proteinuria to <3.5 g/d) is associated with a greater risk of relapse and end-stage kidney disease (ESKD) compared with complete remission (CR). We aimed to determine factors associated with relapse or renal failure in patients who attain the standard definition of PR. Full-Text PDF Open AccessSerum Albumin Still of Interest to Predict Outcomes in Membranous Nephropathy in the Era of Phospholipase A2 ReceptorKidney International ReportsVol. 5Issue 9PreviewIn a recent retrospective study, Lee et al.1 demonstrated the interest of serum albumin (sAlb) as a prognostic marker of outcome in primary membranous nephropathy. The most significant limitation of their study was the absence of information about patients’ phospholipase A2 receptor (PLA2R) status. Indeed, during the past decade, accumulating evidence suggested that clinical remission is preceded by immunological remission2,3 and PLA2R serology has become an essential tool for primary membranous nephropathy monitoring. Full-Text PDF Open Access

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