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      Fractional excretion of total protein predicts renal prognosis in Japanese patients with primary membranous nephropathy

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          ABSTRACT

          Background

          Primary membranous nephropathy (pMN) is one of the most common types of glomerulonephritis, with a third of patients progressing to renal insufficiency. Various prognostic factors have been reported, of which urinary protein and renal function are the most critical parameters. Fractional excretion of total protein (FETP) indicates protein leakage that accounts for creatinine kinetics and serum protein levels. In this study, we investigated the association between FETP and renal prognosis in pMN.

          Methods

          We retrospectively identified 150 patients with pMN. FETP was calculated as follows: (serum creatinine × urine protein)/(serum protein × urine creatinine) %. We divided the patients into three groups according to FETP values and compared the clinicopathological findings. The primary outcome was an estimated glomerular filtration rate (eGFR) decrease of ≥30% from the baseline level.

          Results

          FETP was associated with urinary protein and renal function, Ehrenreich and Churg stage, and global glomerulosclerosis. The primary outcome was observed in 38 patients (25.3%), and the frequency of the primary outcome was higher in the high FETP group ( P = .001). FETP is higher than protein–creatinine ratio (PCR) in the area under the curve. In the multivariate analysis adjusted for age, eGFR, PCR and treatment, FETP was significantly associated with primary outcome (adjusted hazard ratio, 8.19; P = .019).

          Conclusions

          FETP is a valuable indicator that can reflect the pathophysiology and is more useful than PCR as a predictor of renal prognosis in patients with Japanese pMN.

          Graphical Abstract

          Graphical Abstract

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          Most cited references41

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          Revised equations for estimated GFR from serum creatinine in Japan.

          Estimation of glomerular filtration rate (GFR) is limited by differences in creatinine generation among ethnicities. Our previously reported GFR-estimating equations for Japanese had limitations because all participants had a GFR less than 90 mL/min/1.73 m2 and serum creatinine was assayed in different laboratories. Diagnostic test study using a prospective cross-sectional design. New equations were developed in 413 participants and validated in 350 participants. All samples were assayed in a central laboratory. Hospitalized Japanese patients in 80 medical centers. Patients had not participated in the previous study. Measured GFR (mGFR) computed from inulin clearance. Estimated GFR (eGFR) by using the modified isotope dilution mass spectrometry (IDMS)-traceable 4-variable Modification of Diet in Renal Disease (MDRD) Study equation using the previous Japanese Society of Nephrology Chronic Kidney Disease Initiative (JSN-CKDI) coefficient of 0.741 (equation 1), the previous JSN-CKDI equation (equation 2), and new equations derived in the development data set: modified MDRD Study using a new Japanese coefficient (equation 3), and a 3-variable Japanese equation (equation 4). Performance of equations was assessed by means of bias (eGFR - mGFR), accuracy (percentage of estimates within 15% or 30% of mGFR), root mean squared error, and correlation coefficient. In the development data set, the new Japanese coefficient was 0.808 (95% confidence interval, 0.728 to 0.829) for the IDMS-MDRD Study equation (equation 3), and the 3-variable Japanese equation (equation 4) was eGFR (mL/min/1.73 m2) = 194 x Serum creatinine(-1.094) x Age(-0.287) x 0.739 (if female). In the validation data set, bias was -1.3 +/- 19.4 versus -5.9 +/- 19.0 mL/min/1.73 m2 (P = 0.002), and accuracy within 30% of mGFR was 73% versus 72% (P = 0.6) for equation 3 versus equation 1 and -2.1 +/- 19.0 versus -7.9 +/- 18.7 mL/min/1.73 m(2) (P < 0.001) and 75% versus 73% (P = 0.06) for equation 4 versus equation 2 (P = 0.06), respectively. Most study participants had chronic kidney disease, and some may have had changing GFRs. The new Japanese coefficient for the modified IDMS-MDRD Study equation and the new Japanese equation are more accurate for the Japanese population than the previously reported equations.
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            KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases

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              Membranous nephropathy

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                Author and article information

                Contributors
                Journal
                Clin Kidney J
                Clin Kidney J
                ckj
                Clinical Kidney Journal
                Oxford University Press
                2048-8505
                2048-8513
                May 2024
                20 March 2024
                20 March 2024
                : 17
                : 5
                : sfae071
                Affiliations
                Division of Nephrology and Hypertension, The Jikei University School of Medicine , Tokyo, Japan
                Division of Nephrology and Hypertension, The Jikei University School of Medicine , Tokyo, Japan
                Division of Nephrology and Hypertension, The Jikei University School of Medicine , Tokyo, Japan
                Division of Nephrology and Hypertension, The Jikei University School of Medicine , Tokyo, Japan
                Division of Nephrology and Hypertension, The Jikei University School of Medicine , Tokyo, Japan
                Division of Nephrology and Hypertension, The Jikei University School of Medicine , Tokyo, Japan
                Division of Nephrology and Hypertension, The Jikei University School of Medicine , Tokyo, Japan
                Division of Nephrology and Hypertension, The Jikei University School of Medicine , Tokyo, Japan
                Division of Nephrology and Hypertension, The Jikei University School of Medicine , Tokyo, Japan
                Division of Nephrology and Hypertension, The Jikei University School of Medicine , Tokyo, Japan
                Author notes
                Correspondence to: Go Kanzaki; E-mail: g-kanzaki@ 123456jikei.ac.jp
                Author information
                https://orcid.org/0000-0001-6030-2746
                https://orcid.org/0000-0002-7795-369X
                https://orcid.org/0000-0001-9525-2638
                https://orcid.org/0000-0001-7150-6947
                https://orcid.org/0000-0003-1918-0390
                https://orcid.org/0000-0002-5407-5265
                Article
                sfae071
                10.1093/ckj/sfae071
                11063954
                38699483
                5a79b3ba-ad46-40e2-8ec6-7778d7a548e3
                © The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 15 September 2023
                : 02 May 2024
                Page count
                Pages: 11
                Categories
                Original Article
                AcademicSubjects/MED00340

                Nephrology
                clearance,fractional excretion of total protein,nephrotic syndrome,primary membranous nephropathy,renal prognosis

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