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

Fangrui Ding,Jiali Mo,Qi Gao,Xiuying Tian,Jun Zheng

doi:10.1038/s41598-021-00130-y

Fangrui Ding, Jiali Mo + Show 3 more

Open Access

https://doi.org/10.1038/s41598-021-00130-y

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Abstract

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.

Highlights

Chronic kidney disease (CKD) is a recognized public health issue and an important contributor to the global disease burden[1,2,3]
The rate of podocyte mRNA excretion was estimated by detection of podocyte-specific podocin mRNA extracted from urine cell pellets
Urine podocin mRNA to creatinine was adjusted by weight of infants and 4.44-fold increase of urine podocin mRNA level was found in preterm infants compared with full-term infants depletion (P < 0.001) (Fig. 1C)

Summary

Introduction

Chronic kidney disease (CKD) is a recognized public health issue and an important contributor to the global disease burden[1,2,3]. Before published studies that indicated that prematurity is a risk factor for CKD, Brenner et al have already proposed that a low nephron number could increase the risk of CKD by reducing kidney adaptive capacity[11]. This mechanism was the first to be proposed to explain this phenomenon and is currently believed to be the most likely mechanism for long-term kidney disease. Whether the reduction in the number of nephrons caused by preterm birth drives long-term kidney disease or increases the risk for kidney diseases has not been well examined. Examination of podocyte density and podocyte area in kidney biopsy samples has been employed to examine the changes in podocyte loss in preterm rats

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Conclusion