Podocyte stress and detachment measured in urine are related to mean arterial pressure in healthy humans.
Kidney Int
; 98(3): 699-707, 2020 09.
Article
in En
| MEDLINE
| ID: mdl-32739208
ABSTRACT
Hypertension-associated progressive glomerulosclerosis is a significant driver of both de novo and all-cause chronic kidney disease leading to end-stage kidney failure. The progression of glomerular disease proceeds via continuing depletion of podocytes from the glomeruli into the ultrafiltrate. To non-invasively assess injury patterns associated with mean arterial pressure (MAP), we conducted an observational study of 87 healthy normotensive individuals who were cleared for living kidney donation. Urine pellet podocin and aquaporin2 mRNAs normalized to the urine creatinine concentration (UPodCreat ratio and UAqp2Creat ratio) were used as markers of podocyte detachment and tubular injury, respectively. The ratio of two podocyte mRNA markers, podocin to nephrin (UPodNeph) as well as the ratio of podocin to the tubular marker aquaporin2 (UPodAqp2) estimated the relative rates of podocyte stress and glomerular vs. tubular injury. The MAP was positively correlated with the UPodNeph and UPodAqp2, thereby confirming the relationship of MAP with podocyte stress and the preferential targeting of the glomerulus by higher MAP. In multivariable linear regression analysis, both UPodNeph and UPodCreat, but not UAqp2Creat or proteinuria, were both significantly related to a range of normal MAP (70 to 110 mm Hg). Systolic, as opposed to diastolic or pulse pressure was associated with UPodCreat. Thus, higher podocyte stress and detachment into the urine are associated with MAP even in a relatively "normal" range of MAP. Hence, urine pellet mRNA monitoring can potentially identify progression risk before the onset of overt hypertension, proteinuria or chronic kidney disease.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Podocytes
Type of study:
Observational_studies
Limits:
Humans
Language:
En
Journal:
Kidney Int
Year:
2020
Document type:
Article