Serum Hemoglobin Concentration and Risk of Renal Function Decline in Early Stages of Diabetic Kidney Disease

A Nationwide, Biopsy-Based Cohort Study

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

Disclosures

Nephrol Dial Transplant. 2022;37(3):489-497. 

In This Article

Results

Baseline Clinical and Pathological Characteristics of the Patients, Overall and Stratified by Quartiles of Serum Hb Concentration

Among 895 patients in the overall cohort, 246 patients who had a eGFR≥60 mL/min/1.73 m2 at kidney biopsy were included in this analyses. The study flow and selection of study population were summarized in Supplementary data, Figure S1.

Table 1 shows the baseline characteristics of the patients, overall and stratified by the quartile of serum Hb concentration. The characteristics of overall cohort were as follows: median (interquartile range) age of 56 (45–63) years old, men 62.6%, known duration of diabetes 10 (5–17) years, BMI 22.9 (20.9–25.6), systolic BP 136 (124–150) mmHg, diastolic BP 78 (70–87) mmHg, HbA1c 7.9% (6.6–9.6), total cholesterol 210 (177–238) mg/dL, eGFR 76.2 (66.6–86.6) mL/min/1.73 m2 and UACR 534 (100–1480) mg/g Crea. There were no patients who had been received erythropoiesis-stimulating agents or iron supplementation before and at the time of kidney biopsy. Percentage of males, BMI and eGFR increased by increasing serum Hb concentration quartiles, whereas age and UACR decreased by increasing serum Hb concentration quartiles.

Associations of Quartiles of Serum Hb Concentration With Clinical and Pathological Characteristics

Table 2 shows the results of matrix correlation of serum Hb concentration quartiles and clinical and pathological characteristics. Serum Hb concentration quartiles were significantly correlated with eGFR, UACR and with all scores of renal lesions including interstitial lesions, especially with scores of interstitial fibrosis and tubular atrophy (IFTA) (ρ = −0.52, P < 0.001).

Quartiles of Serum Hb Concentration and Rate of DKD Progression

During the median follow-up duration of 4.1 years after the date of kidney biopsy, 95 (38.6%) developed DKD progression. The cumulative incidence of DKD progression according to the quartiles of serum Hb concentration is shown in Figure 1. The cumulative incidence of DKD progression increased significantly with decreasing serum Hb concentration (P for trend <0.01).

Figure 1.

Cumulative incidence of DKD progression according to quartiles of serum Hb concentration. DKD progression was defined as a composite of new onset ESKD (dialysis, kidney transplantation or death from renal cause), a doubling of serum creatinine or a decrease of eGFR by ≥50%.

In the subgroup analysis of male (n = 154) and female (n = 92) patients, the cumulative incidence of DKD progression was similar to that in the overall cohort (Supplementary data, Figure S2A and B). In the subgroup analysis of patients with normo- and microalbuminuria (n = 93; n = 39 in normoalbuminuria, n = 54 in microalbuminuria), the cumulative incidence of DKD progression was also similar to that in the overall cohort, although there was a marginal significant trend across serum Hb groups (Supplementary data, Figure S3).

Table 3 presents HRs and 95% CI for the association between the quartiles of serum Hb concentration and incident DKD progression. Compared with the fourth quartile, the unadjusted HRs (95% CI) of DKD progression were 1.48 (0.78–2.80) for the third quartile, 2.34 (1.29–4.24) for the second quartile and 3.81 (2.14–6.80) for the first quartile, respectively. After adjusting for known risk factors of DKD progression at baseline, the HRs of DKD progression remain unchanged [the HRs in the third, second and first quartile were 1.46 (0.71–3.64), 2.33 (1.07–5.75) and 2.74 (1.26–5.97), respectively].

Incremental Prognostic Value of Serum Hb Concentration Over Known Risk Factors of DKD Progression

Figure 2 shows the statistics showing the incremental prognostic value of serum Hb concentration over standard established clinical risk factors of DKD progression. The global Chi-squared likelihood ratio increased from 55.1 to 60.8 (P < 0.001) with addition of serum Hb concentration to the clinical model alone, which showed an equivalent value of adding IFTA scores to the clinical model alone (global Chi-squared likelihood ratio increased from 55.1 to 62.4; P < 0.001). Likewise, addition of serum Hb concentration to the clinical model alone improved the AIC and BIC values, which is also an improvement equivalent to the clinical model alone.

Figure 2.

Incremental prognostic value of DKD. Incremental value of serum Hb concentration and IFTA over standard clinical assessment of established risk factors of DKD progression were shown with global Chi-squared likelihood ratio, AIC and BIC. Model 1: standard clinical assessment of established risk factors of DKD progression (age, gender, BMI, known duration of diabetes, systolic BP, Hb A1c, eGFR, UACR and RAS blocker use). Model 2: Model 1 + serum Hb concentration. Model 3: Model 1 + IFTA.

processing....