Dataset Information

Prognostic Value of Tubulointerstitial Lesions, Urinary N-Acetyl-?-d-Glucosaminidase, and Urinary ?2-Microglobulin in Patients with Type 2 Diabetes and Biopsy-Proven Diabetic Nephropathy.

ABSTRACT:

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-?-d-glucosaminidase (NAG) and urinary ?2-microglobulin (?2-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 46.3±23.2 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 ?2-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 ?2-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, -0.08 to 0.22).

Conclusions

Adding urinary NAG and ?2-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.

SUBMITTER: Mise K

PROVIDER: S-EPMC4822660 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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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.

Mise Koki K Hoshino Junichi J Ueno Toshiharu T Hazue Ryo R Hasegawa Jumpei J Sekine Akinari A Sumida Keiichi K Hiramatsu Rikako R Hasegawa Eiko E Yamanouchi Masayuki M Hayami Noriko N Suwabe Tatsuya T Sawa Naoki N Fujii Takeshi T Hara Shigeko S Ohashi Kenichi K Takaichi Kenmei K Ubara Yoshifumi Y

Clinical journal of the American Society of Nephrology : CJASN 20160122 4

<h4>Background and objectives</h4>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.<h4>Design, setting, participants, & measurements</h4>Among 210 patients with type 2 diabetes and biopsy-proven DN managed from 1985 to 2011, 149 patients with urinary N-acetyl-β-d-glucosaminidase (NAG) ...[more]

PMID: 26801478

Similar Datasets

Project description:OBJECTIVE: We evaluated the structural-functional relationships and the prognostic factors for renal events, cardiovascular events, and all-cause mortality in type 2 diabetic patients with biopsy-proven diabetic nephropathy. RESEARCH DESIGN AND METHODS: Japanese type 2 diabetic patients with biopsy-proven diabetic nephropathy (n = 260) were enrolled. Patients were stratified by albuminuria (proteinuria) and estimated glomerular filtration rate (eGFR) at the time of renal biopsy. The outcomes were the first occurrence of renal events (requirement of dialysis or a 50% decline in eGFR from baseline), cardiovascular events (cardiovascular death, nonfatal myocardial infarction, coronary interventions, or nonfatal stroke), and all-cause mortality. RESULTS: The factors associated with albuminuria (proteinuria) regardless of eGFR were hematuria, diabetic retinopathy, low hemoglobin, and glomerular lesions. The factors associated with low eGFR regardless of albuminuria (proteinuria) were age and diffuse, nodular, tubulointerstitial, and vascular lesions. The glomerular, tubulointerstitial, and vascular lesions in patients with normoalbuminuria (normal proteinuria) and low eGFR were more advanced compared to those in patients with normoalbuminuria (normal proteinuria) and maintained eGFR. In addition, compared to patients with micro-/macroalbuminuria (mild/severe proteinuria) and low eGFR, their tubulointerstitial and vascular lesions were similar or more advanced in contrast to glomerular lesions. The mean follow-up period was 8.1 years. There were 118 renal events, 62 cardiovascular events, and 45 deaths. The pathological determinants were glomerular lesions, interstitial fibrosis and tubular atrophy (IFTA), and arteriosclerosis for renal events, arteriosclerosis for cardiovascular events, and IFTA for all-cause mortality. The major clinical determinant for renal events and all-cause mortality was macroalbuminuria (severe proteinuria). CONCLUSIONS: Our study suggests that the characteristic pathological lesions as well as macroalbuminuria (severe proteinuria) were closely related to the long-term outcomes of biopsy-proven diabetic nephropathy in type 2 diabetes.