Masayuki Yamanouchi1,2,3,4, Junichi Hoshino2,4, Yoshifumi Ubara3,4, Kenmei Takaichi2,4, Keiichi Kinowaki5, Takeshi Fujii5, Kenichi Ohashi5,6, Koki Mise7, Tadashi Toyama8, Akinori Hara8, Miho Shimizu8, Kengo Furuichi8, Takashi Wada1,8. 1. Department of Nephrology and Laboratory Medicine, Faculty of Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan. 2. Nephrology Center, Toranomon Hospital, Tokyo, Japan. 3. Nephrology Center, Toranomon Hospital Kajigaya, Kanagawa, Japan. 4. Okinaka Memorial Institute for Medical Research, Tokyo, Japan. 5. Department of Pathology, Toranomon Hospital, Tokyo, Japan. 6. Department of Pathology, Yokohama City University Graduate School of Medicine, Kanagawa, Japan. 7. Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan. 8. Division of Nephrology, Kanazawa University Hospital, Kanazawa, Japan.
Abstract
BACKGROUND: Biopsy-based studies on nephrosclerosis are lacking and the clinicopathological predictors for progression of chronic kidney disease (CKD) are not well established. METHODS: We retrospectively assessed 401 patients with biopsy-proven nephrosclerosis in Japan. Progression of CKD was defined as new-onset end-stage renal disease, decrease of estimated glomerular filtration rate (eGFR) by ≥50% or doubling of serum creatinine, and the sub-distribution hazard ratio (SHR) with 95% confidence interval (CI) for CKD progression was determined for various clinical and histological characteristics in competing risks analysis. The incremental value of pathological information for predicting CKD progression was assessed by calculating Harrell's C-statistics, the Akaike information criterion (AIC), net reclassification improvement and integrated discrimination improvement. RESULTS: During a median follow-up period of 5.3 years, 117 patients showed progression of CKD and 10 patients died before the defined kidney event. Multivariable sub-distribution hazards model identified serum albumin (SHR 0.48; 95% CI 0.35-0.67), hemoglobin A1c (SHR 0.71; 95% CI 0.54-0.94), eGFR (SHR 0.98; 95% CI 0.97-0.99), urinary albumin/creatinine ratio (UACR) (SHR 1.18; 95% CI 1.08-1.29), percentage of segmental/global glomerulosclerosis (%GS) (SHR 1.01; 95% CI 1.00-1.02) and interstitial fibrosis and tubular atrophy (IFTA) (SHR 1.52; 95% CI 1.20-1.92) as risk factors for CKD progression. The C-statistic of a model with only clinical variables was improved by adding %GS (0.790 versus 0.796, P < 0.01) and IFTA (0.790 versus 0.811, P < 0.01). The reclassification statistic was also improved after adding the biopsy data to the clinical data. The model including IFTA was superior, with the lowest AIC. CONCLUSIONS: The study implies that in addition to the traditional markers of eGFR and UACR, we may explore the markers of serum albumin and hemoglobin A1c, which are widely available but not routinely measured in patients with nephrosclerosis, and the biopsy data, especially the data on the severity of interstitial damage, for the better prediction of CKD progression in patients with nephrosclerosis.
BACKGROUND: Biopsy-based studies on nephrosclerosis are lacking and the clinicopathological predictors for progression of chronic kidney disease (CKD) are not well established. METHODS: We retrospectively assessed 401 patients with biopsy-proven nephrosclerosis in Japan. Progression of CKD was defined as new-onset end-stage renal disease, decrease of estimated glomerular filtration rate (eGFR) by ≥50% or doubling of serum creatinine, and the sub-distribution hazard ratio (SHR) with 95% confidence interval (CI) for CKD progression was determined for various clinical and histological characteristics in competing risks analysis. The incremental value of pathological information for predicting CKD progression was assessed by calculating Harrell's C-statistics, the Akaike information criterion (AIC), net reclassification improvement and integrated discrimination improvement. RESULTS: During a median follow-up period of 5.3 years, 117 patients showed progression of CKD and 10 patients died before the defined kidney event. Multivariable sub-distribution hazards model identified serum albumin (SHR 0.48; 95% CI 0.35-0.67), hemoglobin A1c (SHR 0.71; 95% CI 0.54-0.94), eGFR (SHR 0.98; 95% CI 0.97-0.99), urinary albumin/creatinine ratio (UACR) (SHR 1.18; 95% CI 1.08-1.29), percentage of segmental/global glomerulosclerosis (%GS) (SHR 1.01; 95% CI 1.00-1.02) and interstitial fibrosis and tubular atrophy (IFTA) (SHR 1.52; 95% CI 1.20-1.92) as risk factors for CKD progression. The C-statistic of a model with only clinical variables was improved by adding %GS (0.790 versus 0.796, P < 0.01) and IFTA (0.790 versus 0.811, P < 0.01). The reclassification statistic was also improved after adding the biopsy data to the clinical data. The model including IFTA was superior, with the lowest AIC. CONCLUSIONS: The study implies that in addition to the traditional markers of eGFR and UACR, we may explore the markers of serum albumin and hemoglobin A1c, which are widely available but not routinely measured in patients with nephrosclerosis, and the biopsy data, especially the data on the severity of interstitial damage, for the better prediction of CKD progression in patients with nephrosclerosis.
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Authors: Dominik Steubl; Markus P Schneider; Heike Meiselbach; Jennifer Nadal; Matthias C Schmid; Turgay Saritas; Vera Krane; Claudia Sommerer; Seema Baid-Agrawal; Jakob Voelkl; Fruzsina Kotsis; Anna Köttgen; Kai-Uwe Eckardt; Jürgen E Scherberich Journal: Clin J Am Soc Nephrol Date: 2020-04-14 Impact factor: 8.237
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Authors: Marius A Øvrehus; Tine S Oldereid; Aydin Dadfar; Rune Bjørneklett; Knut I Aasarød; Agnes B Fogo; Joachim H Ix; Stein I Hallan Journal: Kidney Int Rep Date: 2019-12-27