Question: 

Loss of renal tissue results in an increase in function and mass of the remaining intact nephrons. The initial signals that induce this compensatory renal hypertrophy are largely unknown. Since plasma concentration of atrial natriuretic peptide ANP increases after uninephrectomy (UNx), we investigated kidney growth and function in response to UNx in mice lacking the ANP receptor guanylyl cyclase-A (GC-A).

Results: 

Except for heart weight, which was higher in GC-A-/- compared to wildtypes, no differences in organ weights were detected (kidneys, spleen, liver, brain) between the genotypes under control conditions. Moreover, glomerular filtration rate, urine volume and sodium excretion were not different between the genotypes. UNx of the left kidney for 5 days resulted in a compensatory growth of the remaining right kidney in GC-A+/+ (right/left ratio of kidney weight: 1.15±0.02, p<0.001, n=12) but not in GC-A-/- (ratio: 1.07±0.02, n.s., n=12). GFR of wildtypes 5 days post UNx was 71±10% of baseline values before uninephrectomy indicating functional adaptation of kidney function, while in GC-A-/- GFR was 53±8% of baseline values. 24h urine volume and sodium excretion did not differ between genotypes. 16 days after UNx no significant differences of kidney weight, urine and sodium excretion were detected between GC-A-/- and GC-A+/+.

Conclusion: 

Natriuretic peptides that signal via GC-A are involved in the functional adaptation of GFR and renal mass of the remaining kidney 5 days after UNx. Additional mechanisms contribute to the long term adaptation to renal tissue loss as well as in the regulation of urine and salt excretion.