Weinan Wu1,2,3,4,5, Yiming Jin1,2,3,4,5,6, Lisha Teng1,2,3,4,5, Xue Shao1,2,3,4,5, Yucheng Wang1,2,3,4,5, Shi Feng1,2,3,4,5, Cuili Wang1,2,3,4,5, Hong Jiang1,2,3,4,5, Jianyong Wu1,2,3,4,5. 1. Kidney Disease Center, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China. 2. Key Laboratory of Nephropathy, Zhejiang Province, Hangzhou 310003, China. 3. Kidney Disease Immunology Laboratory, the Third-Grade Laboratory, State Administration of Traditional Chinese Medicine of China, Hangzhou 310000, China. 4. Key Laboratory of Multiple Organ Transplantation, Ministry of Health of China, Hangzhou 310000, China. 5. Institute of Nephropathy, Zhejiang University, Hangzhou 310003, China. 6. Department of Nephropathy, Shaoxing Second Hospital, Shaoxing 312000, China.
Abstract
BACKGROUND: Renal diabetic changes are frequent in kidney transplantation (KTx) donors. Whether these diabetic changes are reversible remains a topic of debate. This study aimed to test the hypothesized reversibility of diabetic changes after KTx. METHODS: C57BL/6J mice were randomly divided into three groups: the control group, early-stage group (ESG), and advanced-stage group (ASG). Diabetes mellitus (DM) was induced in mice by intraperitoneal injection of streptozotocin (STZ) at 50 mg/kg body weight for five consecutive days. Blood glucose levels ≥16.7 mmol/L were indicative of diabetic mice. The kidneys from ESG and ASG were transplanted to control mice 12 or 32 weeks after STZ injection. Kidney tissue, blood, and 24-hour urine specimens of donor and recipient mice were collected before KTx and 28 days after KTx, respectively. We measured the body weight, blood glucose, histological changes, reactive oxygen species (ROS), apoptosis. Electron microscopy was also performed to evaluate the mitochondrial morphology. The expression of NADPH oxidases (NOXs) was assessed by qRT-PCR. RESULTS: Kidneys from early-stage diabetic mice showed evidence of lesion reversal four weeks after KTx, including decreased urinary albumin and reversal of histological changes. Besides, mitochondrial swelling, oxidative stress, apoptosis, and overexpression of NOXs in the kidneys were also suppressed. Conversely, no changes were observed in kidneys from advanced-stage diabetic mice after KTx. CONCLUSIONS: We confirmed that early-stage but not advanced-stage diabetic nephropathy (DN) is reversible, which is related to reduced NOX expression and improvement in mitochondrial function. These results indicated that kidneys with early-stage DN could be used for KTx in clinical practice, as the disease may be reversed following KTx. 2019 Annals of Translational Medicine. All rights reserved.
BACKGROUND: Renal diabetic changes are frequent in kidney transplantation (KTx) donors. Whether these diabetic changes are reversible remains a topic of debate. This study aimed to test the hypothesized reversibility of diabetic changes after KTx. METHODS: C57BL/6J mice were randomly divided into three groups: the control group, early-stage group (ESG), and advanced-stage group (ASG). Diabetes mellitus (DM) was induced in mice by intraperitoneal injection of streptozotocin (STZ) at 50 mg/kg body weight for five consecutive days. Blood glucose levels ≥16.7 mmol/L were indicative of diabetic mice. The kidneys from ESG and ASG were transplanted to control mice 12 or 32 weeks after STZ injection. Kidney tissue, blood, and 24-hour urine specimens of donor and recipient mice were collected before KTx and 28 days after KTx, respectively. We measured the body weight, blood glucose, histological changes, reactive oxygen species (ROS), apoptosis. Electron microscopy was also performed to evaluate the mitochondrial morphology. The expression of NADPH oxidases (NOXs) was assessed by qRT-PCR. RESULTS: Kidneys from early-stage diabetic mice showed evidence of lesion reversal four weeks after KTx, including decreased urinary albumin and reversal of histological changes. Besides, mitochondrial swelling, oxidative stress, apoptosis, and overexpression of NOXs in the kidneys were also suppressed. Conversely, no changes were observed in kidneys from advanced-stage diabetic mice after KTx. CONCLUSIONS: We confirmed that early-stage but not advanced-stage diabetic nephropathy (DN) is reversible, which is related to reduced NOX expression and improvement in mitochondrial function. These results indicated that kidneys with early-stage DN could be used for KTx in clinical practice, as the disease may be reversed following KTx. 2019 Annals of Translational Medicine. All rights reserved.
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