Effect of Thyroparathyroidectomy and Parathyroidectomy on Renal Function and the Nephrotic Syndrome in Rat Nephrotoxic Serum Nephritis

Abstract

A B S T R A C T Dietary phosphorus restriction (PR)prevents uremia in rats with nephrotoxic serum nephritis (NSN). One possible mechanism by which PR could be protective would be through the suppression of parathyroid hormone. To evaluate this possibility two separate protocols were designed. In the first rats were thyroparathyroidectomized (TPTX) before (n = 11) or 5 wk after (n = 7) NSN induction and compared to sham-operated parathyroid intact rats with NSN (n = 12). At the end of the 23-wk study, intact rats were azotemic, plasma creatinine 3.80±0.81 mg/100 ml vs. 0.65±0.07 for TPTX rats (P < 0.001). During the study 75% of intact rats died of uremia in contrast to none of the TPTX rats (P < 0.001). Renal histological damage was greatly diminished and calcification prevented in TPTX rats. The proteinuria of the heterologous phase was unaffected, but the protein excretion and hypertriglyceridemia (HTG) of the autologous phase were markedly decreased in the TPTX rats. The degree of HTG and proteinuria had a high positive correlation (P < 0.001). Late TPTX also produced significant decreases in proteinuria and HTG regardless of the degree of azotemia, and prevented azotemia if the plasma creatinine at the time of TPTX was -0.85 mg/ 100 ml.In additional studies selective parathyroidectomy (PTX) was performed. TPTX animals. However, selective PTX had no effect on proteinuria, histologic damage, or functional deterioration. These studies further showed that early, histologic damage and functional deterioration preceeded renal parenchymal calcification. Because animals were pair fed and both groups were given 1,25-dihydroxycholecalciferol to normalize serum Ca and P levels these studies exclude alterations in plasma Ca and P levels, dietary intake, urinary P excretion, and vitamin D administration in promoting the protective effect of TPTX on renal function.We conclude that TPTX is equally effective in preventing functional deterioration and more effective in reducing proteinuria in NSN than PR.

Fibroblast Growth Factor 23 (FGF23) Predicts Progression of Chronic Kidney Disease

“…Among factors that are related to calciumphosphate metabolism in patients with CKD, potential culprits for progression are hyperphosphatemia, hyperparathyroidism, lack of active vitamin D, and possibly excess of the recently discovered phosphaturic hormone fibroblast growth factor 23 (FGF23). 3,4 Early experimental work suggested a parathyroid hormone (PTH)-independent beneficial role of phosphate restriction on progres-sion in rats, 5 but it has to be pointed out that these animals have physiologic hyperphosphatemia. Furthermore, there is also little direct experimental or clinical evidence for a role of PTH in accelerating progression, 3 although results from recent experimental studies documented that progression is significantly attenuated by administration of calcimimetics or by parathyroidectomy.…”

Effect of Diets Containing Varying Concentrations of Essential Fatty Acids and Triglycerides on Renal Function in Uremic Rats and NZB/NZW F₁ Mice

“…A direct correlation between reduction of serum TG and renal function could be observed in the nephrotoxic serum nephritis model of the rat where the TG reduction was followed by thyroparathyroidectomy which resulted in a preservation of the glomerular filtration rate [5]. In this experiment a normal diet was used so that the hyper triglyceridemia seems to be a consequence of the chronic renal failure on its own.…”

Role of calcium-phosphorous disorders in the progression of renal failure

“…Beneficial effects of dietary phosphate restriction have mainly been shown in two experimental models (i.e., nephrotoxic nephritis [1,2] and remnant kidney model [3]). For several reasons these studies are complex.…”

“…Phosphate restriction causes secondary changes in calcemia and parathyroid hormone (PTH) concentrations. Although the latter confounder was carefully addressed in the study from Tomford et al [2], it still remains unclear whether the salutary effect of phosphate restriction is mediated via changes in renal hemodynamics, via less renal calcification or changes of cellular calcium/phosphate concentrations, respectively, or via other factors [4,5]. Almost no clinical data are available on this issue.…”