MO217: Proteinuria/BMI Ratio in Primary Membranous Nephropathy as a Possible Predictive Factor of Therapeutic Efficacy
Authors: Siligato Rossella , Gembillo Guido , Calabrese Vincenzo , Cernaro Valeria , Santoro Domenico 
Published: May 2022

Abstract

BACKGROUND AND AIMS
The attempt to identify the most suitable therapies and their appropriate dose is at the base of tailored medicine approach. We decided to analyze the renal outcomes of patients affected by primary membranous nephropathy (MN) referring to our unit from January 2005 to December 2020, treated with conservative or immunosuppressive therapy, searching for any predictive factor of therapeutic response.

METHOD
We performed a retrospective analysis of 31 MN patients (M 20, F 11), checking anti-PLA2R status, kidney biopsy and comorbidities. All patients underwent a quarterly control for 1 year, evaluating blood pressure, body mass index (BMI), biochemistry, urinalysis and 24-h proteinuria. Variable distribution was evaluated with Kolgomorov–Smirnov test and data expressed as median [interquartile range (IQR) range] or mean ± SD. Basal features were analyzed with student's t- test for independent variables, Mann–Whitney test for continuous variables and Pearson's chi-squared analysis for dummy variables. Trend analysis was computed with a linear mixed model for repeated analysis.

RESULTS
We performed 186 repeated measurements, with median age at diagnosis of 52 years old (43.7–68) and eGFR of 72.8 ± 31.6 mL/min. Median reduction of proteinuria was 3.732 g/24 h (7.63–1.77). We first found a direct association of proteinuria/BMI ratio at diagnosis with proteinuria remission at last follow-up (r −.7506; P &lt; .0001), irrespective of the specific therapy.
We divided the patients according to their basal proteinuria/BMI ratio being lower or higher than the whole cohort median value. Significant differences between the two groups were found in serum albumin (3.5 ± 0.68 versus 2.52 ± 0.62 g/dL, P = .001) and LDL (132 ± 17 versus 179 ± 66 mg/dL, P = .034), but the latter was rather an effect of proteinuria, as proved by the adjusted model. Also hypertension prevalence in the higher proteinuria/BMI ratio group lacked any statistical significance.
The adjusted model proved an association in longitudinal follow-up between eGFR and both proteinuria/BMI ratio (β: 29.28, P = .037, 95% CI 1.75–56.80) and age [β = −1.27, P = .001, 95% CI −1.75–(−0.79)].
At biopsy time, almost half of the patients were anti-PLA2R positive (15), while the other were screened for secondary causes of MN (16). Irrespective of their anti-PLA2R status or the administration of Ponticelli regimen or Rituximab, complete remission was achieved in 31% of patients, while 34.5% experienced a partial remission and 34.5% did not respond to at least a therapeutic protocol.

CONCLUSION
As previously reported by Yonekura in a cross-sectional registry study, larger physical constitution defined by both BMI &gt;25 kg/m2 and body surface area (BSA) &gt;1.73 m2 was associated with higher proteinuria in glomerulonephritis such as MN and minimal change disease (MCD) [1], compared with other primary glomerulopathies. Their hypothesis was based mainly in the different distribution of lesions in podocytes, capillary walls and glomerular basement membrane, whose permeability may be worsened by both hyperfiltration associated with obesity and the overfilling of nephrotic syndrome.
In our patients, BMI was also a surrogate marker to quantify the edema amount and to attempt a clinical evaluation of therapy efficacy, along with biochemistry. Patients with higher proteinuria/BMI ratio were typically affected by nephrotic syndrome and less responsive to at least a line of RAAS inhibitors and/or immunosuppressants such as Ponticelli regimen or Rituximab treatment as demonstrated by serum albumin variations.
Albeit remission is not directly correlated with basal BMI, our results appear to confirm that patients’ body mass and extracellular fluid volume may result in more effective individualized therapies in MN but this recorded association must be confirmed by larger scale clinical trials.