Serial Glomerular and Tubular Dynamics in Thyroidectomized Rats With Remnant Kidneys

Abstract

Serial measurements were performed in Munich-Wistar rats with five-sixths nephrectomy that had undergone prior selective thyroidectomy (Tx group) or thyroidectomy with thyroxine replacement (TxT4 group) to determine the effects of Tx on glomerular and tubular dynamics in relation to Tx attenuation of renal failure progression. At 1 week, inulin clearance rates (CIn) in TxT4 and Tx rats were 0.367 ± 0.171 and 0.120 ± 0.036 mL/min, respectively, different at P < 0.01. Corresponding single-nephron filtration rate (SNGFR), glomerular plasma flow (QA), glomerular transcapillary hydraulic pressure (ΔP), and proximal tubular reabsorption (Jv) were all reduced in Tx compared with TxT4 rats (P < 0.01). Protein excretion (UPROT) was 151 ± 40 in TxT4 rats, and 9 ± 5 mg/d in Tx animals. Glomerular mesangial matrix expansion and focal tubulointerstitial changes were more frequent in TxT4 than Tx rats. By 4 weeks, CIn, SNGFR, QA, glomerular ultrafiltration coefficient (K1) and Jv were similar in Tx and TxT4. Only glomerular capillary pressure (PGC) remained lower in Tx rats (35 ± 3 v 50 ± 3 mm Hg in TxT4, P < 0.001). UPROT was 161 ± 24 in TxT4 and 17 ± 12 mg/d in Tx rats. While 7% ± 4% of glomeruli showed focal sclerosis in TxT4 rats, there was none in the Tx group. Maximal glomerular planar area increased between 1 and 4 weeks in the TxT4 group, but not in the Tx group. However, this measurement was not significantly different between TxT4 and Tx glomeruli at 1 or 4 weeks. Minimal focal tubulointerstitial changes were found in TxT4, but these were not progressive from those observed at 1 week. The reduced PGC at 1 week was the result of a disproportionately greater increase in afferent (RA) than efferent arteriolar resistance (RE) in Tx rats (P < 0.025); however, at 4 weeks, both RA and RE had decreased to values identical to those in TxT4 animals and the lower PGC in Tx rats was the result of a reduced mean arterial pressure. In conclusion, a reduced PGC was the sole functional correlate of decreased proteinuria and glomerulosclerosis afforded by Tx in this partial nephrectomy model. Suppression of either nephrectomy-related hypertrophy or tubulointerstitial injury by Tx could not be excluded as at least partially protective factors.