Serum hemoglobin concentration and risk of renal function decline in early stages of diabetic kidney disease: a nationwide, biopsy-based cohort study

Yamanouchi, Masayuki; Furuichi, Kengo; Shimizu, Miho; Toyama, Tadashi; Yamamura, Yuta; Oda, Megumi; Kitajima, Shinji; Hara, Akinori; Iwata, Yasunori; Sakai, Norihiko; Oba, Yuki; Matsuoka, Shusaku; Ikuma, Daisuke; Mizuno, Hiroki; Suwabe, Tatsuya; Hoshino, Junichi; Sawa, Naoki; Kitamura, Hiroshi; Suzuki, Yuichi; Sato, Hiroshi; Uesugi, Noriko; Ueda, Yoshihiko; Nishi, Shinichi; Yokoyama, Hitoshi; Nishino, Tomoya; Samejima, Ken-ichi; Kohagura, Kentaro; Shibagaki, Yugo; Makino, Hírofumi; Matsuo, Seiichi; Ubara, Yoshifumi; Wada, Takashi

doi:10.1093/ndt/gfab185

Cited by 16 publications

(11 citation statements)

References 29 publications

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“…These findings showed anemia was indeed an independent risk factor for rapid eGFR decline in type 2 diabetic patients. A recent multicenter cohort study in Japan revealed that circulating Hb concentration, associated with tubulointerstitial injury, could be a predictor for DKD progression ( 37 ), which was consistent with our results.…”

Section: Discussionsupporting

confidence: 93%

Anemia is a risk factor for rapid eGFR decline in type 2 diabetes

Xie

Shao

et al. 2023

Front. Endocrinol.

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ObjectiveTo investigate the association between anemia and progression of diabetic kidney disease (DKD) in type 2 diabetes.MethodsThis was a retrospective study. A total of 2570 in-patients with type 2 diabetes hospitalized in Jinan branch of Huashan hospital from January 2013 to October 2017 were included, among whom 526 patients were hospitalized ≥ 2 times with a median follow-up period of 2.75 years. Annual rate of eGFR decline was calculated in patients with multiple admissions. A rate of eGFR decline exceeding -5 ml/min per 1.73 m2 per year was defined as rapid eGFR decline. The prevalence of DKD and clinical characteristics were compared between anemia and non-anemia patients. Correlation analysis was conducted between anemia and clinical parameters. Comparison of clinical features were carried out between rapid eGFR decline and slow eGFR decline groups. The risk factors for rapid DKD progression were analyzed using logistic regression analysis.ResultsThe prevalence of anemia was 28.2% among the 2570 diabetic patients, while in patients with DKD, the incidence of anemia was 37.8%. Patients with anemia had greater prevalence of DKD, higher levels of urinary albumin-to-creatinine ratio (UACR), serum creatinine, BUN, urine α1-MG, urine β2-MG, urine NAG/Cr, hsCRP, Cystatin C, homocysteine and lower eGFR, as compared to the patients without anemia. Anemia was correlated with age, UACR, eGFR, urinary NAG/Cr, hsCRP and diabetic retinopathy (DR). Logistic regression analysis of 526 patients with type 2 diabetes during the follow-up period showed that anemia was an independent risk factor for rapid eGFR decline.ConclusionAnemia is associated with worse renal function and is an independent risk factor for rapid eGFR decline in type 2 diabetes.

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Section: Discussionsupporting

confidence: 93%

Anemia is a risk factor for rapid eGFR decline in type 2 diabetes

Xie

Shao

et al. 2023

Front. Endocrinol.

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“…Numerous studies have shown the greater risks of cardiovascular disease and kidney disease progression associated with low Hb levels. [24][25][26][27][28] Taken together, these findings underscore the importance of stable Hb control within the target Hb range. The increased risks of adverse clinical events even in the group whose Hb level was fluctuating around the lower limit of target Hb range suggest the importance of maintaining Hb level within the target range of Hb 11-13 g/dl.…”

Section: Discussionmentioning

confidence: 62%

Anemia Treatment, Hemoglobin Variability, and Clinical Events in Patients With Nondialysis-Dependent CKD in Japan

Kuragano,

Okami,

Tanaka-Mizuno

et al. 2023

Kidney360

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Background: Anemia management in patients with non-dialysis-dependent chronic kidney disease has attracted attention with the introduction of novel therapeutic agents; however, few studies have provided comprehensive epidemiologic information. Methods: A retrospective cohort study was conducted in adult patients with stage ≥3a non-dialysis-dependent chronic kidney disease and hemoglobin <11 g/dL (January 2013–November 2021; N=26,626) to assess longitudinal treatment patterns, hemoglobin, and iron parameters (ferritin and transferrin saturation) for anemia management. Time-dependent Cox proportional hazard models were applied to assess the risk of clinical events, including death, cardiovascular events, dialysis introduction, and red-blood-cell transfusion, associated with temporal fluctuation patterns of hemoglobin levels. Results: The cumulative incidence of anemia treatment initiation within 12 months was 37.1%, including erythropoiesis-stimulating agents 26.5%, iron oral 16.8%, iron intravenous 5.1%, and hypoxia-inducible factor prolyl hydroxylase inhibitor 0.2%. The mean (±standard deviation) hemoglobin levels were improved from 9.9±1.2 g/dL to 10.9±1.6 g/dL at 12 months. Despite erythropoiesis-stimulating agents or hypoxia-inducible factor prolyl hydroxylase inhibitor therapy, 30.1% of patients remained hemoglobin <10 g/dL. The risks of premature death, cardiovascular events, dialysis introduction, and red-blood-cell transfusion were significantly higher in groups with consistently low hemoglobin or low-amplitude hemoglobin fluctuation around the lower limit of target hemoglobin range than in patients with target hemoglobin range (p <0.05). Likewise, significantly higher risks for dialysis introduction and red-blood-cell transfusion were associated with high-amplitude hemoglobin fluctuation across target hemoglobin range were observed. Conclusions: The findings underscore the importance of stable hemoglobin control within the target range to reduce the mortality and morbidity risks in patients with non-dialysis-dependent chronic kidney disease while highlighting the suboptimal and heterogeneous treatment of anemia in clinical practice.

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“…In the present study, low Hb levels were associated with an increased risk of developing DKD. Although previous studies have demonstrated the predictive value of Hb for the risk of renal function decline in the early stages of DKD [43] , the negative association between baseline Hb concentrations and the risk of follow-up DKD has often been ignored [13,44] . We speculate that patients with diabetes often have anaemia, which can lead to renal hypoxia and accelerate the progression of diabetic nephropathy [45,46] .…”

Section: Discussionmentioning

confidence: 99%

A SuperLearner approach to predicting diabetic kidney disease upon the initial diagnosis of T2DM in hospital

Lin,

Liu,

Wang

et al. 2023

Preprint

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Background Diabetic kidney disease (DKD) is a serious complication of diabetic mellitus (DM) and is asymptomatic until the advanced stage. We developed and validated a predictive model for DKD in patients with an initial diagnosis of type 2 Diabetes Mellitus (T2DM) based on real-world data. Methods Data from 3,291 patients (1740 men, 1551 women) newly diagnosed with T2DM at Ningbo Municipal Hospital of Traditional Chinese Medicine (2011–2023) were retrospectively collected. Data were randomly divided into training and validation cohorts. Forty-six readily available medical characteristics at initial diagnosis of T2DM from the electronic medical record (EMR) were used to develop prediction models based on linear, non-linear, and SuperLearner approaches. Model performance was evaluated using the area under the curve (AUC). Shapley additive explanation (SHAP) was used to interpret the best-performing models. Results Of the 3291 participants, 563 (17.1%) were diagnosed with DKD during a median follow-up of 2.53 years. The SuperLearner model had the highest AUC (0.7138, 95% CI [0.673, 0.7546]) for the holdout internal validation set in predicting any DKD stage. Top-ranked features were WBC_Cnt*, Neut_Cnt, Hct, and Hb. High WBC_Cnt, low Neut_Cnt, high Hct, and low Hb levels were associated with an increased risk of developing DKD. Conclusions We developed and validated a DKD risk prediction model for patients with newly diagnosed T2DM. Using routinely available clinical measurements, the SuperLearner model can predict DKD during hospital visits. Prediction accuracy and SHAP-based model interpretability may help improve early detection, targeted interventions, and prognosis of patients with DM.

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Serum hemoglobin concentration and risk of renal function decline in early stages of diabetic kidney disease: a nationwide, biopsy-based cohort study

Cited by 16 publications

References 29 publications

Anemia is a risk factor for rapid eGFR decline in type 2 diabetes

Anemia is a risk factor for rapid eGFR decline in type 2 diabetes

Anemia Treatment, Hemoglobin Variability, and Clinical Events in Patients With Nondialysis-Dependent CKD in Japan

A SuperLearner approach to predicting diabetic kidney disease upon the initial diagnosis of T2DM in hospital

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