TERATOLOGY 44:7-10 (1991)

Compensatory Renal Growth in Human Fetuses With Unilateral Renal Agenesis NIKOLAS HARTSHORNE, THOMAS SHEPARD, AND MASON BARR, JR. Department of Pathology, University of California, San Francisco, California 94143 (N.H.);Department of Pediatrics, RD-20,University of Washington, Seattle, Washington 98195 (T.S.);Departments of Pediatrics and Pathology, Uniuersity of Michigan, A n n Arbor, Michigan 48109-0718(M.B.)

ABSTRACT To determine whether compensatory growth of the kidney occurs during fetal life we studied 20 human specimens with a unilateral kidney as a n isolated defect. The mean combined kidney weight to body weight ratio x 100 in controls was 0.76 0.14 (SD) and in the solitary kidney cases (after doubling the kidney weight) was 1.26 ? 0.35 (SD). This significant increase leads us to hypothesize that the increased weight may be due to a n induced negative feedback system involving a renotropic factor. From histologic studies a uniform increase in all nephron elements was found. Why should a fetus with adequate placental clearance of metabolic wastes need increased renal size?

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During the past 60 years there have been numerous studies dealing with the controversial subject of compensatory renal growth in subjects with solitary kidneys. In most mammals studied, unilateral nephrectomy results i n a compensatory growth of the remaining kidney (Arataki, '26; Hayslett and Kashgarian, '68; Dicker and Shirley, '73; Johnson and Rome, '66). This increase in size occurs via a combined cellular hypertrophy and hyperplasia. However, additional studies indicate a n actual nephron hyperplasia as the most significant factor in compensatory growth, especially in younger animals (Bonvalet and Monique, '72; Karp et al., '71; Rollason, '69). Despite the confusion over the growth process, there remains even more uncertainty as to whether or not compensatory renal growth occurs prenatally when the placenta transfers metabolic waste products. We have found no published data on compensatory renal growth in human or experimental animal fetuses. Establishing whether or not this compensatory growth occurs prenatally might add a valuable clue with regard to the mechanisms involved. To study compensatory growth in human fetuses we have used a unilateral renal agenesis model (URA). URA is a primary malformation due to the failure of differentiation of the anlage from which it normally 0 1991 WILEY-LISS, INC.

develops. The prevalence of URA is 2.5-20: 10,000individuals (Collins, '39; Potter, '72). It is more frequently found in males and the missing kidney is nearly always the left one (Potter, '72). MATERIALS AND METHODS

A retrospective analysis of 20 fetuses with unilateral renal agenesis was made. Specimens were drawn from the Departments of Pediatrics and Pathology of the University of Washington and the Teratology Unit of the University of Michigan. Autopsies and weights were performed on fresh unfixed specimens. The absence of pathologic changes in the solitary kidney and of nonrenal malformations was verified by detailed postmortem examination. None of the cases had evidence of contralateral remnant of the metanephric blastema. Fetal radiographs were performed when the prosecutor felt they were indicated. Control specimens were chosen by using the preceding fetal autopsy record that exhibited no gross or microscopic pathology. Kidneys were removed through a ventral approach and were dissected away from the adrenals with minimal damage to the perire-

Received July 23, 1990; accepted January 8, 1991

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N. HARTSHORNE ET AL.

nal capsule. After removal of the perirenal tissue the kidneys were blotted on filter paper and weighed to the nearest 0.1 g. Control kidneys were measured a s a combined weight. Despite the wide range in body weight of fetus& studied, there is a linear relationship between fetal kidney and body weight over this range (Shepard et al., '88). Accordingly, we compared the combined-kidney:body weight ratios of the 20 controls to solitary kidney x 2: body weight ratios of the URA fetuses. Unpaired comparisons between the two groups were made by using Student's unpaired t-test (for comparing two means). The level of significance chosen was P

Compensatory renal growth in human fetuses with unilateral renal agenesis.

To determine whether compensatory growth of the kidney occurs during fetal life we studied 20 human specimens with a unilateral kidney as an isolated ...
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