Fetal compensatory renal growth due to unilateral ureteral obstruction

To determine whether fetal compensatory renal growth occurs in response to early gestational unilateral renal obstruction and to help elucidate the characteristics of this response, a fetal lamb model was developed in which unilateral ureteral obstruction was created at 60 days of gestation (term 135 to 140 days) and the effects of the obstruction were studied at varying periods thereafter. Kidneys were retrieved at 2 weeks (75 days in 3 cases), 5 weeks (95 days in 4) and 10 weeks (135 days in 9) after obstruction, weighed and preserved for histology and biochemical studies. Deoxyribonucleic acid (DNA), ribonucleic acid and protein were quantitated using standard assays. Morphometric studies to estimate glomerular number were performed using standard stereological methods. Contralateral kidney weight was increased compared to normals in 55 cases at all ages. The relative difference increased from 75 to 95 days. The fractional increase at 135 days (49.5%, p < 0.001 versus normal) was not different from 95 days (46.4%, p = 0.87), indicating that growth rate acceleration occurred predominantly before 95 days. Total renal DNA was increased above normal at each time point, with an ultimate increment proportionate to weight. Protein concentration was unchanged, suggesting that weight increase was not due to changes in renal water. Protein/DNA ratios were unchanged, indicating a predominantly hyperplastic process. Ribonucleic acid/DNA ratios decreased, possibly indicating a high rate of proliferation. Total glomerular number at term did not increase with in utero compensatory renal growth. Unilateral ureteral obstruction created early in gestation produced compensatory renal growth of the intact kidney in the fetal lamb. This process demonstrates an early but transient growth rate acceleration, hyperplasia and no increase in total glomerular or nephron number. The occurrence of compensatory renal growth in the fetal kidney with minimal functional renal demand would suggest that its mechanisms may be independent of functional demand. This model is unique and well suited to study compensatory renal growth.