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

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.

The nephroprotective action of Passiflora edulis in streptozotocin-induced diabetes

“…Studies have shown that glomerular and tubular changes are strongly associated with the pathogenesis of DKD 24,25 . In line with this finding, podocyte and tubule biomarkers may predict the onset or progression of DKD [18][19][20] . Furthermore, accumulated evidence has demonstrated that urinary podocytes and tubular proteins can be positively correlated with hyperglycemia 26,27 , and interestingly, these levels are elevated even in normoalbuminuric patients with diabetes 25,28 .…”

“…Herein, we revealed the nephroprotective action of AFA extract adjuvant to insulin, as indicated by the maintenance of baseline expression levels of mRNA (Nphs1, Nphs2, Wt1, and Lrp2) and protein (nephrin, podocin, WT1, and megalin) in the kidney tissue. Interestingly, nephroprotection was also evidenced through the www.nature.com/scientificreports/ reduction of urinary loss of nephrin, podocin, WT1, and megalin, given that these proteins are markers of kidney glomerular and tubular integrity, and their loss is typically associated with the onset of kidney dysfunction [18][19][20] . Nephrin and podocin are slit diaphragm-associated proteins involved in the maintenance of the glomerular filtration barrier.…”

Urine podocyte mRNA loss in preterm infants and related perinatal risk factors

“…In addition to the hypothesis of lower nephron numbers, our recent study [ 19 ] also put forward the involvement of the podocyte depletion hypothesis [ 20 – 23 ]. In that study, a preterm rat model was established by delivery 2 days early.…”

“…Although that study identified the role of podocyte loss caused by preterm birth in long-term CKD in animal studies, there are many differences between preterm rats and preterm infants because preterm infants experience a much more complex disease process, such as asphyxia, infection, oxygen therapy, drug exposure, and various maternal factors. Podocyte loss in preterm infants has rarely been reported [ 19 , 24 ]. In addition, it is also unclear which perinatal factors affect podocyte loss.…”

The acute toxicity of ethyl acetate extract from soursop leaf endophytic fungi in rats

“…Creatinine (reiged diagnostic kit) [14] Creatinine level measurements were done using Reiged Diagnostic Kit. The kit included R1, R2, and creatinine 2 mg/dL standard solutions.…”