Clinical and pathological predictors of estimated GFR decline in patients with type 2 diabetes and overt proteinuric diabetic nephropathy

Mise, Kazuyuki; Hoshino, Junichi; Ueno, Toshiharu; Hazue, Ryo; Sumida, Keiichi; Hiramatsu, Rikako; Hasegawa, Eiko; Yamanouchi, Masayuki; Hayami, Noriko; Suwabe, Tatsuya; Sawa, Naoki; Fujii, Takeshi; Hara, Shigeko; Ohashi, Kenichi; Takaichi, Kenmei; Ubara, Yoshifumi

doi:10.1002/dmrr.2633

Cited by 53 publications

(45 citation statements)

References 24 publications

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“…Recently, it has been suggested that tubulointerstitial lesions are more important for predicting the renal prognosis than other types of lesions, such as glomerular and vascular lesions, in not only patients with DN but also, those with other renal diseases (12,27,28). Therefore, more accurate biomarkers of tubulointerstitial injury and inflammation are needed.…”

Section: Discussionmentioning

confidence: 99%

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Prognostic Value of Tubulointerstitial Lesions, Urinary N-Acetyl-β-D-Glucosaminidase, and Urinary β2-Microglobulin in Patients with Type 2 Diabetes and Biopsy–Proven Diabetic Nephropathy

Mise

Hoshino²,

Ueno³

et al. 2016

Clinical Journal of the American Society of Nephrology

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102

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Background and objectives Some biomarkers of renal tubular injury are reported to be useful for predicting renal prognosis in the early stage of diabetic nephropathy (DN). Our study compared predictions of the renal prognosis by such biomarkers and by histologic tubulointerstitial damage.Design, setting, participants, & measurements Among 210 patients with type 2 diabetes and biopsy-proven DN managed from 1985 to 2011, 149 patients with urinary N-acetyl-b-D-glucosaminidase (NAG) and urinary b2-microglobulin (b2-MG) data at the time of renal biopsy were enrolled. The primary outcome was a decline in eGFR of $50% from baseline or commencement of dialysis for ESRD.Results The median follow-up period was 2.3 years (interquartile range, 1.1-5.3), and the primary outcome was noted in 94 patients. Mean eGFR was 46.3623.2 ml/min per 1.73 m 2 , and 132 patients (89%) had overt proteinuria at baseline. Cox proportional hazards analysis revealed that the association of urinary NAG and b2-MG with the outcome was attenuated after adjustment for known promoters of progression (+1 SD for log NAG: hazard ratio [HR], 1.14; 95% confidence interval [95% CI], 0.84 to 1.55; +1 SD for log b2-MG: HR, 1.23; 95% CI, 0.94 to 1.62). In contrast, the interstitial fibrosis and tubular atrophy (IFTA) score was still significantly correlated with the outcome after adjustment for the same covariates (+1 for IFTA score: HR, 2.31; 95% CI, 1.56 to 3.43). Moreover, adding the IFTA score to a model containing known progression indicators improved prediction of the outcome (increase of concordance index by 0.02; 95% CI, 0.00 to 0.05; category-free net reclassification improvement by 0.54; 95% CI, 0.03 to 1.05; and relative integrated discrimination improvement by 0.07; 95% CI, 20.08 to 0.22).Conclusions Adding urinary NAG and b2-MG excretion to known promoters of progression did not improve prognostication, whereas adding the IFTA score did. The IFTA score may be superior to these tubulointerstitial markers for predicting the renal prognosis in advanced DN.

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Section: Discussionmentioning

confidence: 99%

“…We recently reported that the extent of interstitial fibrosis and tubular atrophy (IFTA) was a significant predictor of the renal prognosis, even after adjustment for urinary protein excretion (UP) (12,13). There have also been some other recent reports that stressed the influence of IFTA on the renal prognosis (14,15).…”

Section: Introductionmentioning

confidence: 99%

Prognostic Value of Tubulointerstitial Lesions, Urinary N-Acetyl-β-D-Glucosaminidase, and Urinary β2-Microglobulin in Patients with Type 2 Diabetes and Biopsy–Proven Diabetic Nephropathy

Mise

Hoshino²,

Ueno³

et al. 2016

Clinical Journal of the American Society of Nephrology

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102

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“…52 Another study 53 including 396 patients with DKD showed that the glomerular classes and scores of interstitial fibrosis and tubular atrophy predict the risk for ESRD or doubling of Scr. 52 Caramori et al 54 measured the renal structures in biopsies obtained from 94 type 1 diabetics without albuminuria. Greater width of the GBM and higher levels of glycated hemoglobin were independently associated with development of diabetic nephropathy.…”

Section: Histological Damagementioning

confidence: 99%

Clinical and pathological factors associated with progression of diabetic nephropathy

2017

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ABSTRACT:As an important complication of diabetic mellitus, diabetic kidney disease (DKD) is becoming a major cause of morbidity and mortality worldwide. Given the diminished quality of life and the economic cost, identification of the risk factors for DKD and initiation of in-time therapies are of great importance. The initiators of DKD include hyperglycemia and predisposing genes, while the promotors of DKD include hyperglycemia, albuminuria, hypertension, dyslipdemia, insulin resistance, anemia, long duration of diabetes, smoking, ethnicity, westernization, sex, age, and so on. This article summarizes the values and limitations of some factors in the development and progression of DKD. Further study is needed to establish whether modulating these factors can improve the outcomes of DKD.

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“…Categorical data were analyzed using the chi-squared test across the FZQZ and placebo groups. Since the majority of the patients had primary glomerular disease (PGD), and patients with diabetic nephropathy (DN) with overt proteinuria experience rapid declines in GFR, [12] a subgroup analysis according to CKD-cause (PGD, DN, and others) was performed. Kaplan–Meier methods were used to assess the secondary outcome of time to composite end-point events and their significance was assessed using the log-rank test.…”

Section: Methodsmentioning

confidence: 99%

Beneficial effects of Fu-Zheng-Qu-Zhuo oral liquid combined with standard integrated therapy in patients with chronic kidney disease (stage 3–4)

et al. 2017

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Clinical and pathological predictors of estimated GFR decline in patients with type 2 diabetes and overt proteinuric diabetic nephropathy

Abstract: Our results suggest that not only proteinuria but also tubulointerstitial lesions should be assessed to predict rapid eGFR decline in patients with type 2 diabetes who have overt proteinuria and biopsy-proven diabetic nephropathy.

Cited by 53 publications

References 24 publications

Prognostic Value of Tubulointerstitial Lesions, Urinary N-Acetyl-β-D-Glucosaminidase, and Urinary β2-Microglobulin in Patients with Type 2 Diabetes and Biopsy–Proven Diabetic Nephropathy

Prognostic Value of Tubulointerstitial Lesions, Urinary N-Acetyl-β-D-Glucosaminidase, and Urinary β2-Microglobulin in Patients with Type 2 Diabetes and Biopsy–Proven Diabetic Nephropathy

Clinical and pathological factors associated with progression of diabetic nephropathy

Beneficial effects of Fu-Zheng-Qu-Zhuo oral liquid combined with standard integrated therapy in patients with chronic kidney disease (stage 3–4)

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