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Abstract
Introduction There are fewer reports about whether the presence of hematuria affects the progression of chronic kidney disease in patients with diabetic nephropathy. We analyzed whether microscopic hematuria in diabetic nephropathy is a risk factor for end-stage kidney disease (ESKD).
Research design and methods The present study was a retrospective cohort study of patients with biopsy-proven diabetic nephropathy. We recruited 397 patients with diabetic nephropathy, which was confirmed by renal biopsy between June 1981 and December 2014 and followed them until October 2018 or death. Patients with microscopic hematuria before renal biopsy were defined as the hematuria group (n=91), and the remainder as the no-hematuria group (n=306). The main outcome was the occurrence of ESKD, which was defined by the requirement of permanent renal replacement therapies.
Results The systolic and diastolic blood pressure, serum creatinine and proteinuria were significantly higher, and the estimated glomerular filtration rate was significantly lower in the hematuria group compared with the no-hematuria group. Pathological evaluations revealed that glomerular, tubulointerstitial and vascular lesions in the hematuria group were significantly more severe. During a median of 10.1 years, 44 and 52 patients developed ESKD in the hematuria group and the no-hematuria group, respectively. Survival analyses showed that the incidence of ESKD was significantly higher in the hematuria group compared with the no-hematuria group (log-rank, p<0.0001). The multivariable Cox proportional hazards models revealed a significant association between hematuria and the incidence of ESKD after adjusting for clinically relevant factors, including proteinuria and renal pathology (adjusted HR 1.64, 95% CI 1.03 to 2.60). The subgroups of men, proteinuria ≥0.5 g/day, and systolic blood pressure ≥132 mm Hg showed a stronger association between hematuria and ESKD than their opposing subgroups.
Conclusions Microscopic hematuria is a risk factor for ESKD in diabetic nephropathy, independent of proteinuria and renal pathology.
- diabetes mellitus
- type 2
- kidney failure
- chronic
- observational study
- biopsy
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Footnotes
SO and K-iS contributed equally.
Contributors SO designed the study, researched data and wrote the manuscript. K-iS contributed to constructing the study cohort, researched data and reviewed/edited the manuscript. SO and K-iS contributed equally to this work. MM, KM, RF and KTa contributed to constructing the study cohort and the discussion, and reviewed the manuscript. ME contributed to constructing the study cohort, researched data and reviewed/edited the manuscript. YA and YS contributed to constructing the study cohort and the discussion and reviewed the manuscript. KTs contributed to constructing the study cohort and reviewed/edited the manuscript. K-iS is the guarantor of this work, who takes full responsibility for this work.
Funding This work was supported in part by JSPS KAKENHI Grant Number 15K19462.
Competing interests SO, K-iS, MM, KM, RF, KTa and ME have nothing to disclose. YA reports grants and personal fees from Sumitomo Dainippon Pharma; grants from Japanese Red Cross Society Nara Red Cross Blood Center and Kissei Pharma; personal fees from Nippon Boehringer Ingelheim, outside the submitted work. YS reports grants and personal fees from Daiichi Sankyo, Mitsubishi Tanabe Pharma, Novartis Pharma and Otsuka Pharma; grants from Ono Pharma, Takeda Pharma, Bristol-Myers Squibb, Astellas Pharma, Shionogi, Teijin, Bayer, Actelion Pharma, Kirin, Kowa, Sumitomo Dainippon Pharma, Amgen Astellas BioPharma, EP-CRSU, Roche Diagnostics and Terumo, outside the submitted work. KTs reports grants and personal fees from Baxter, Bayer and Kirin; grants from Terumo; personal fees from Chugai Pharma, Asteras Pharma, Mitsubishi Tanabe Pharma, Kissei Pharma, Sumitomo Dainippon Pharma and JCR Pharma, outside the submitted work.
Patient consent for publication Not required.
Ethics approval The study protocol was approved by the Nara Medical University Ethics Committee (2005–18) and registered in the University Hospital Medical Information Network (UMIN) clinical trial registry (UMIN000031121). Informed consent was obtained from each patient.
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement Data are available on reasonable request. Please contact the corresponding author.