Duplex Kidney

Abstract: The murine genes, Foxc1 and Foxc2 (previously, Mf1 and Mfh1), encode forkhead/winged helix transcription factors with virtually identical DNA-binding domains and overlapping expression patterns in various embryonic tissues. Foxc1/Mf1 is disrupted in the mutant, congenital hydrocephalus (Foxc1/Mf1(ch)), which has multiple developmental defects. We show here that, depending on the genetic background, most Foxc1 homozygous mutants are born with abnormalities of the metanephric kidney, including duplex kidneys and double ureters, one of which is a hydroureter. Analysis of embryos reveals that Foxc1 homozygotes have ectopic mesonephric tubules and ectopic anterior ureteric buds. Moreover, expression in the intermediate mesoderm of Glial cell-derived neurotrophic factor (Gdnf), a primary inducer of the ureteric bud, is expanded more anteriorly in Foxc1 homozygous mutants compared with wild type. These findings support the hypothesis of Mackie and Stephens concerning the etiology of duplex kidney and hydroureter in human infants with congenital kidney abnormalities (Mackie, G. G. and Stephens, F. G. (1975) J. Urol. 114, 274–280). Previous studies established that most Foxc1(lacZ)Foxc2(tm1) compound heterozygotes have the same spectrum of cardiovascular defects as single homozygous null mutants, demonstrating interaction between the two genes in the cardiovascular system. Here, we show that most compound heterozygotes have hypoplastic kidneys and a single hydroureter, while all heterozygotes are normal. This provides evidence that the two genes interact in kidney as well as heart development.

Abstract: The dimercaptosuccinic acid (DMSA) renal scan is a method for assessing kidney function. Indications for DMSA scanning in children with urinary tract infection (UTI), as well as timing, have changed. Pitfalls in interpreting DMSA scans include: (1) acute pyelonephritis (APN), (2) tubular dysfunction, (3) hypertension, (4) use of captopril in patients with renovascular hypertension and (5) duplex kidneys. Interpretation of DMSA scans in children with UTI vary according to timing and clinical setting. During the course of a febrile UTI a DMSA scan may reveal a normal kidney, APN or a non-functioning, small and/or ectopic kidney. In the absence of UTI (up to 6 months) in children with vesicoureteric reflux a DMSA scan may indicate a normal kidney, renal scarring (reflux nephropathy), occult duplex kidney and allows the progression of scarring and hypertrophy of normal areas of the kidney to be followed anatomically. The DMSA renal scan in now the most reliable test for the diagnosis of APN. The transient abnormalities due to APN can occur in normal or scarred kidneys. Lesions due to reflux nephropathy (defined as a defect in the renal outline or contraction of the whole kidney) are permanent. Intravenous urography reveals renal abnormalities later than the DMSA scan. If abnormalities are seen on a DMSA scan performed during the course of APN it is impossible to predict the outcome: they can progress to permanent scarring or heal completely. An abnormal DMSA scan during a febrile UTI allows the identification of children at risk of developing renal scars. These children should be carefully investigated, maintained on long-term quimioprophylaxis and followed.