How they begin and how they end: classic and new theories for the development and deterioration of congenital anomalies of the kidney and urinary tract, CAKUT.
CAKUT are problems that often require surgical intervention or, in the worst case, lead to renal failure and the need for dialysis and/or renal transplantation. It is believed that these anomalies share a common genetic cause and to date there has been no good animal model with which to study these abnormalities. Although the abnormal interaction between the ureteral bud and metanephric blastema leads to renal hypodysplasia, vesicoureteral reflux, and ectopic ureters to name a few, the genetic and biochemical modulation of urinary tract development is not understood. Studies using the mouse strain mutant for angiotensin type 2 (AT2) receptors have given new insight into this mystery. The animals show defective apoptosis of undifferentiated mesenchymal cells in the area surrounding the developing kidney and urinary tract. This abnormal apoptosis may well interfere with the normal interaction between the ureteral bud and metanephric blastema resulting in CAKUT. This abnormal interaction would theoretically lead to preexisting intrinsic abnormalities of the kidney, which are programmed and take effect early in embryonic development. In the worst cases, the renal abnormalities would lead to progressive deterioration of renal function. Undoubtedly, there are more genes and biochemical modulators involved in this process other than the RAS and AT2 receptors. Our current animal model gives new and unique possibilities with which to study development of the kidney and urinary tract and ultimately seek ways of preventing an often debilitating disease process.
Pope
J C
JC
Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Brock
J W
JW
Adams
M C
MC
Stephens
F D
FD
Ichikawa
I
I
D000818:Animals; D006801:Humans; D007668:Kidney / Q000002:abnormalities* / Q000196:embryology; D007676:Kidney Failure, Chronic / Q000196:embryology; D051379:Mice; D008954:Models, Biological; D051381:Rats; D014513:Ureter / Q000002:abnormalities / Q000196:embryology; D014517:Ureteral Obstruction / Q000196:embryology; D014551:Urinary Tract / Q000002:abnormalities* / Q000196:embryology