Urinary podocyte mRNAs precede microalbuminuria as a progression risk marker in human type 2 diabetic nephropathy

Fukuda, Akira; Minakawa, Akihiro; Kikuchi, Masao; Sato, Yuji; Nagatomo, Masanao; Nakamura, Shuji; Mizoguchi, Tetsu; Fukunaga, Naoya; Shibata, Hirotaka; Naik, Abhijit S.; Wiggins, Roger C.; Fujimoto, Shouichi

doi:10.1038/s41598-020-75320-1

Cited by 21 publications

(36 citation statements)

References 51 publications

(84 reference statements)

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“…T2DM causes the aggregation and release of inflammatory factors that damage the kidneys and lead to TN formation. In this process, MAU is an early predictor of diabetic nephropathy, which reflects the balance between glomerular filtration and renal tubular reabsorption of albumin [28,29]. erefore, we infer that the underlying mechanism of positive correlation between MAU and TNs might be attributed to inflammation.…”

Section: Discussionmentioning

confidence: 81%

The Correlation between Microalbuminuria and Thyroid Nodules in Type 2 Diabetic Mellitus

Cao

Cui

Miao

et al. 2022

International Journal of Endocrinology

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Objective. To investigate the correlation between thyroid nodules and microalbuminuria in type 2 diabetic mellitus. Methods. A total of 270 patients with type 2 diabetes at Tongzhou Branch of Dongzhimen Hospital were enrolled in this retrospective study. Data were collected from the inpatient electronic files between January 2018 and January 2020. The laboratory indexes of the two groups (thyroid nodule group with 172 cases and control group including 98 cases without thyroid nodules) were statistically analyzed by binomial logistic regression analysis and Spearman correlation analysis. Results. The proportion of microalbuminuria (MAU) in the thyroid nodule group was larger than that in the control group. Age, serum TT4, and FT4 in the thyroid nodule group were significantly higher compared with the control group. The binary logistic regression analysis indicated that age, sex, FT4, and MAU were the risk factors for thyroid nodule in T2DM patients. Spearman correlation analysis showed that the thyroid nodule was significantly positively correlated with MAU, age, FT4, and TT4. Conclusions. MAU might be an independent risk factor for thyroid nodule in type 2 diabetic mellitus.

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Section: Discussionmentioning

confidence: 81%

The Correlation between Microalbuminuria and Thyroid Nodules in Type 2 Diabetic Mellitus

Cao

Cui

Miao

et al. 2022

International Journal of Endocrinology

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“…Previous studies have confirmed that the detection of podocyte mRNA excretion is a more sensitive marker than proteinuria and creatinine. A significant increase in podocyte mRNA loss can be detected in kidney diseases negative for albuminuria or proteinuria 17,42,43 . However, in this study, at age of 3 weeks, a higher level of proteinuria in premature rats was detected, while the change in the podocyte mRNA excretion level was mild, even though there was no significant difference between preterm and full-term 24-h podocyte mRNA excretion.…”

Section: Discussionmentioning

confidence: 99%

Increasing urinary podocyte mRNA excretion and progressive podocyte loss in kidney contribute to the high risk of long-term renal disease caused by preterm birth

Ding

Gao

Tian

et al. 2021

Sci Rep

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Podocyte abnormalities are common mechanism driving the progression of glomerular diseases, which account for most chronic kidney diseases (CKDs). However, the role of podocyte in the mechanism of high-risk long-term CKD caused by prematurity has not been well clarified. In present study, urine samples of 86 preterm infants and 32 full-term infants were collected, and podocyte-specific podocin mRNA levels in urine pellet were applied to indicate urinary podocyte mRNA excretion. In addition, in a preterm animal rat model, preterm rats were identified by delivery 2 days early. From the age of 3 weeks–12 months, urine samples were collected to examine podocyte mRNA excretion by measuring podocyte-specific podocin mRNA levels. Kidney samples at the age of 3 weeks, 2 months, and 12 months were collected from 8, 5 and 6 preterm rats and 9, 6 and 8 full-term rats, respectively, to examine podocyte density and podocyte area by measuring the podocyte specific nuclear marker WT-1 and the podocyte specific marker synaptopodin. As results, a more than threefold increase of urinary podocyte-specific podocin mRNA excretion rate was found in preterm infants compared with full-term infants. In addition, there was negative correlation between gestational age at birth and urinary podocin mRNA excretion. In preterm rats, a reduction in the total number of differentiated podocytes in glomeruli and an increased podocyte podocin mRNA excretion rate in urine were detected at the end of kidney differentiation. Moreover, long-term follow-up data in preterm rats showed there was an increased the risk of renal disease indicated by persistent podocyte mRNA loss, proteinuria, and enlarged glomeruli. In conclusion, increasing podocyte mRNA excretion in urine and podocyte loss in kidney led by prematurity drive the progression of long-term abnormal kidney function and could potentially explain the high risk of long-term CKD in preterm infants.

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“…The supernatant was removed, the pellet suspended in 1.5 mL of diethyl pyrocarbonate-treated phosphate-buffered saline, and centrifuged at 12000 × g for 5 min at 4°C. The washed pellet was resuspended in RLT/β-mercaptoethanol buffer (RNeasy Kit; Qiagen, Germantown, MD) and frozen at −80°C until RNA extraction (16,23,28). cDNA standard curves were constructed using these serially diluted standards as described previously (16,23,28).…”

Section: Extraction Of Rna From Human Urinary Sedimentmentioning

confidence: 99%

“…The washed pellet was resuspended in RLT/β-mercaptoethanol buffer (RNeasy Kit; Qiagen, Germantown, MD) and frozen at −80°C until RNA extraction (16,23,28). cDNA standard curves were constructed using these serially diluted standards as described previously (16,23,28). The concentration of urinary sediment podocin mRNA was standardized by the creatinine concentration and was expressed as M/g creatinine.…”

Section: Extraction Of Rna From Human Urinary Sedimentmentioning

confidence: 99%

Excretion Patterns of Urinary Sediment and Supernatant Podocyte Biomarkers in Patients with CKD

et al. 2022

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Background: Podocyte depletion causes glomerulosclerosis, and persistent podocyte loss drives progression to end-stage kidney disease. Urinary sediment podocyte (u-sed Pod) mRNA excretion and urinary supernatant podocyte (u-sup PCX) protein have been used to monitor disease activity in glomerular diseases. However, the differences in these markers among pathologies have not been investigated. We examined the roles of these markers in kidney diseases. Methods: From January 2013 to March 2016, early morning urine samples were collected from 12 healthy controls and 172 patients with kidney disease (minor glomerular abnormality with mild proteinuria and/or microscopic hematuria, n = 15; minimal change nephrotic syndrome [MCNS], n = 15; membranous nephropathy [MN], n = 15; IgA nephropathy [IgAN], n = 60; crescentic glomerulonephritis [Cres GN], n = 19; lupus nephritis [LN], n = 10; others, n = 38). We examined u-sed Pod mRNA excretion, u-sup PCX protein and the urinary protein:creatinine ratio (u-PCR). Results: U-sed Pod mRNA excretion was significantly correlated with u-sup PCX protein (r = 0.37, p < 0.001). Both u-sed Pod mRNA excretion and u-sup PCX protein were significantly correlated with u-PCR (r = 0.53, p < 0.001 and r = 0.35, p < 0.001, respectively). Interestingly, u-sed Pod mRNA excretion was significantly increased in proliferative-type glomerulonephritis-including IgAN with extracapillary proliferative lesions, Cres GN and LN class IV-and significantly correlated with the rate of crescent formation, whereas u-sup PCX protein was significantly increased only in MN and subepithelial dense deposit-type LN compared with controls. Conclusions: Higher u-sed Pod mRNA excretion and u-sup PCX protein were associated with proliferative-type glomerulonephritis indicating podocyte detachment and subepithelial dense deposit-type glomerulonephritis, respectively. The results suggest that u-sed Pod mRNA excretion and u-sup PCX protein have usefulness for the diagnosis and measurement of disease activity with regard to glomerular diseases.

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Urinary podocyte mRNAs precede microalbuminuria as a progression risk marker in human type 2 diabetic nephropathy

Cited by 21 publications

References 51 publications

The Correlation between Microalbuminuria and Thyroid Nodules in Type 2 Diabetic Mellitus

The Correlation between Microalbuminuria and Thyroid Nodules in Type 2 Diabetic Mellitus

Increasing urinary podocyte mRNA excretion and progressive podocyte loss in kidney contribute to the high risk of long-term renal disease caused by preterm birth

Excretion Patterns of Urinary Sediment and Supernatant Podocyte Biomarkers in Patients with CKD

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