UNRAVELING THE URINARY TGF-β1 SIGNATURE: A DEEP DIVE INTO DIABETIC NEPHROPATHY

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UNRAVELING THE URINARY TGF-β1 SIGNATURE: A DEEP DIVE INTO DIABETIC NEPHROPATHY
Akshay
Kulkarni
Atul Sajgure atul.sajgure@dpu.edu.in Dr. D. Y. Patil Medical College, Hospital & Research Centre, Pune Nephrology Pune
Charan Bale charan.bale@dpu.edu.in Dr. D. Y. Patil Medical College, Hospital & Research Centre, Pune Nephrology Pune
Pavan Wakhare pavan.wakhare@dpu.edu.in Dr. D. Y. Patil Medical College, Hospital & Research Centre, Pune Nephrology Pune
Nilesh Shinde nilesh.shinde@dpu.edu.in Dr. D. Y. Patil Medical College, Hospital & Research Centre, Pune Nephrology Pune
Abhijit Chavan abhijit9621@gmail.com Dr. D. Y. Patil Medical College, Hospital & Research Centre, Pune Nephrology Pune
Urmila Anandh uanandh@gmail.com Amrita Hospital Nephrology Faridabad
Tushar Dighe tushar.dighe@dpu.edu.in Dr. D. Y. Patil Medical College, Hospital & Research Centre, Pune Nephrology Pune
 
 
 
 
 
 
 
 

This abstract is part of my collaboration with my mentor in the ISN mentorship program.

Diabetic nephropathy represents a significant contributor to end-stage kidney disease (ESKD). Among the numerous cytokines implicated in the development of diabetic nephropathy, one of paramount importance is transforming growth factor beta-1 (TGF-β1). Its primary function lies in facilitating the deposition of extracellular matrix. Diabetic nephropathy typically presents with elevated renal levels of TGF-β1, and the measurement of its urinary excretion can serve as a valuable indicator for predicting outcomes.

We conducted a prospective observational study in India, comprising two groups: group A, consisting of 10 cases of diabetic nephropathy in individuals aged ≥ 18 years with a urinary protein creatinine ratio (UPCR) exceeding 0.5 mg/mg, and group B, which consisted of 10 healthy controls. The study excluded individuals with active urinary tract infections, those in chronic kidney disease (CKD) stage Vd requiring maintenance hemodialysis, and recipients of renal transplants. Our assessments included the estimation of urinary TGF-β1 levels using a 24-hours urine sample, measurement of 24-hours urine protein, and baseline laboratory investigations. Urinary TGF-β1 levs were estimated using multicolor flow cytometry, the MACSQuant® Analyzer 10 Flow Cytometer (Miltenyi Biotec, Bergisch Gladbach, Germany).

The mean age in group A was 51.30 ± 10.60 years and 48.90 ± 10.82 years in group B. The mean value of 24 hours urine protein was 5763.10 ± 2801.43 mg/24 hours in group A and 133.60 ± 21.01 mg/24 hours in group B (p<0.001).  There was a significant difference between the serum creatinine levels in group A and B(2.72± 1.87 vs 0.86± 0.18 mg/dl, p=0.006).  The estimated glomerular filtration rate(eGFR) was  41.90 ± 30.49 ml/min/1.73 m2  in group A and 104.80 ± 21.99 ml/min/1.73 m2 in group B (p<0.001). In diabetic nephropathy cases (group A), the mean value of urinary TGF-β1 level was 88.33 ± 12.44 ng/24 hours, whereas in the control group (group B), it was 29.03 ± 3.23 ng/24 hours. Notably, group A exhibited a significant elevation in urinary TGF-β1 levels compared to group B (p < 0.001). However, there was no significant correlation between urinary TGF-β1 levels and estimated glomerular filtration rate (eGFR) (r = 0.376, p = 0.285) or 24-hours urinary protein levels (p = 0.334, r = 0.341) in diabetic nephropathy cases. Furthermore, glycosylated haemoglobin (HbA1c) levels did not demonstrate a significant correlation with urinary TGF-β1 levels (r = -0.265, p = 0.46).

Comparison of mean urinary TGF-β1 levels of groups A and B

Significantly elevated urinary TGF-β1 levels were observed in diabetic nephropathy patients when compared to the healthy controls. No significant correlations were found between urinary TGF-β1 levels and proteinuria, estimated glomerular filtration rate (eGFR), or HbA1c levels in diabetic nephropathy patients. 

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