Role of Parathyroid Hormone in the Downregulation of Liver Cytochrome P450 in Chronic Renal Failure

Acute uremia is associated with increased calcium (Ca) in brain and changes in electroencephalogram (EEG), and both derangements are related to excess parathyroid hormone (PTH). Also changes in EEG in patients with chronic renal failure (CRF) correlated directly with blood levels of PTH, and fall in PTH was followed by improvement in EEG. We examined whether chronic uremia per se has an effect on brain calcium or EEG. Uremia was produced by 5/6 nephrectomy and maintained for 32-70 wk in seven thyroparathyroidectomized (TPTX) and seven control dogs. There were no differences in creatinine clearance and serum electrolytes except for HCO3, which was lower in control animals (P less than 0.01). Serum PTH was undetectable in TPTX dogs but was significantly elevated in control animals (32.3 +/- 3.3 mu leq /ml). Calcium in gray and white matter was significantly increased in both groups but much higher in control animals. The percent waves of less than 7 Hz in EEG were similar in both groups prior to uremia (TPTX 4.6 +/- 0.8 vs. control 4.2 +/- 0.5%) but remained unchanged in TPTX animals and increased significantly in control dogs (19.0 +/- 1.3%) after uremia. These data suggest that CRF per se is associated with marked rise in Ca in both gray and white matter and increment is higher in the presence of PTH. Disturbance in EEG in a state of CRF requires the presence of excess PTH and is prevented despite increased Ca in brain if hyperparathyroidism is not allowed to develop.

Download Full-text

Parathyroid hormone and extrarenal acid buffering

AJP Renal Physiology ◽

10.1152/ajprenal.1980.239.6.f533 ◽

1980 ◽

Vol 239 (6) ◽

pp. F533-F538

Author(s):

J. A. Arruda ◽

V. Alla ◽

H. Rubinstein ◽

M. Cruz-Soto ◽

S. Sabatini ◽

...

Keyword(s):

Renal Failure ◽

Acute Renal Failure ◽

Parathyroid Hormone ◽

Chronic Renal Failure ◽

Buffering Capacity ◽

Parathyroid Glands ◽

Blood Ph ◽

Acid Buffering ◽

Acid Load

The role of parathyroid hormone (PTH) on the extrarenal buffering of an acid load was examined during HCl infusion (5 meq x kg-1 x h-1) to bilaterally nephrectomized rats. Thyroparathyroidectomized (TPTX) rats replaced with PTH had significantly higher blood pH and HCO3 values than TPTX rats not infused with PTH. Administration of EDTA, in a dose shown to release PTH, was associated with a significant increase in buffering capacity in intact but not in TPTX rats. Colchicine, given in a dose capable of stimulating PTH release, was also associated with enhanced buffering capacity in intact but not in TPTX rats. In TPTX rats infused with acetazolamide and PTH, the hormone failed to enhance extrarenal buffering of an acid load. Animals with chronic renal failure, induced by infarction of the kidney, also had an enhanced capacity to buffer an acid load. This enhanced buffering capacity in chronic renal failure was abolished by TPTX. Acute renal failure induced by bilateral ureteral ligation was also associated with increased buffering only in the presence of parathyroid glands. These data demonstrated that PTH, from either an exogenous or endogenous source, enhances extrarenal buffering capacity of an acid load. Chronic and acute renal failure are associated with increased buffering capacity, which is dependent on the presence of parathyroid glands. The data suggest that this effect is mediated through carbonic anhydrase.

Download Full-text

Subtotal Parathyroidectomy: A Possible Treatment for Calciphylaxis

Ear Nose & Throat Journal ◽

10.1177/014556130308200516 ◽

2003 ◽

Vol 82 (5) ◽

pp. 390-393 ◽

Cited By ~ 13

Author(s):

Gideon Bahar ◽

Daniel Mimouni ◽

Meora Feinmesser ◽

Michael David ◽

Aharon Popovzer ◽

...

Keyword(s):

Renal Failure ◽

Parathyroid Hormone ◽

Chronic Renal Failure ◽

Treatment Options ◽

Lower Extremities ◽

Skin Lesions ◽

Rare Disorder ◽

Subtotal Parathyroidectomy ◽

Hormone Levels

Calciphylaxis is a rare disorder in patients with chronic renal failure that is characterized by ischemic necrotic skin lesions. The prognosis is grave and mortality is high (80%). The precise mechanism of calciphylaxis is still unknown, but in addition to chronic renal failure, elevated parathyroid hormone levels appear to play a role. The role of parathyroidectomy in treating affected patients is questionable. In this article, we describe the case of a patient with chronic renal failure who developed rapidly progressive subcutaneous calcifications and ulcerations in the lower extremities. These lesions regressed following subtotal parathyroidectomy. We also review the literature on calciphylaxis, with a focus on treatment options.

Download Full-text

Regulation of NaPi-IIa mRNA and transporter protein in chronic renal failure: role of parathyroid hormone (PTH) and dietary phosphate (Pi)

Pflügers Archiv - European Journal of Physiology ◽

10.1007/s00424-004-1298-x ◽

2004 ◽

Cited By ~ 1

Author(s):

Michal Dranitzki Elhalel ◽

Hanna Wald ◽

Dvora Rubinger ◽

Anka Gal-Moscovici ◽

Makoto Inoue ◽

...

Keyword(s):

Renal Failure ◽

Parathyroid Hormone ◽

Chronic Renal Failure ◽

Transporter Protein ◽

Dietary Phosphate

Download Full-text

Inhibition of Erythropoiesis in Chronic Renal Failure: The Role of Parathyroid Hormone

American Journal of Kidney Diseases ◽

10.1016/s0272-6386(84)80087-6 ◽

1984 ◽

Vol 3 (5) ◽

pp. 380-384 ◽

Cited By ~ 7

Author(s):

John D. Lutton ◽

Karim B. Solangi ◽

Nader G. Ibraham ◽

Alvin I. Goodman ◽

Richard D. Levere

Keyword(s):

Renal Failure ◽

Parathyroid Hormone ◽

Chronic Renal Failure

Download Full-text

Downregulation of Hepatic Cytochrome P450 in Chronic Renal Failure

Journal of the American Society of Nephrology ◽

10.1681/asn.v122326 ◽

2001 ◽

Vol 12 (2) ◽

pp. 326-332 ◽

Cited By ~ 1

Author(s):

FRANCOIS LEBLOND ◽

CARL GUÉVIN ◽

CHRISTIAN DEMERS ◽

ISABELLE PELLERIN ◽

MARIELLE GASCON-BARRÉ ◽

...

Keyword(s):

Gene Expression ◽

Renal Failure ◽

Cytochrome P450 ◽

Chronic Renal Failure ◽

Protein Expression ◽

Liver Microsomes ◽

Liver Cytochrome ◽

Cytochrome P450 Activity ◽

And Control

Abstract. Chronic renal failure (CRF) is associated with a decrease in drug metabolism. The mechanism remains poorly understood. The present study investigated the repercussions of CRF on liver cytochrome P450 (CYP450). Three groups of rats were defined: control, control paired-fed, and CRF. Total CYP450 activity, protein expression of several CYP450 isoforms as well as their mRNA, and the in vitro N-demethylation of erythromycin were assessed in liver microsomes. The regulation of liver CYP450 by dexamethasone and phenobarbital was assessed in CRF rats. Compared with control and control paired-fed rats, creatinine clearance was reduced by 60% (P < 0.01) in CRF rats. Weight was reduced by 30% (P < 0.01) in control paired-fed and CRF rats, compared with control animals. There was no difference in the CYP450 parameters between control and control paired-fed. Compared with control paired-fed rats, total CYP450 was reduced by 47% (P < 0.001) in CRF rats. Protein expression of CYP2C11, CYP3A1, and CYP3A2 were considerably reduced (>40%, P < 0.001) in rats with CRF. The levels of CYP1A2, CYP2C6, CYP2D, and CYP2E1 were the same in the three groups. Northern blot analysis revealed a marked downregulation in gene expression of CYP2C11, 3A1, and 3A2 in CRF rats. Although liver CYP450 was reduced in CRF, its induction by dexamethasone and phenobarbital was present. N-demethylation of erythromycin was decreased by 50% in CRF rats compared with control (P < 0.001). In conclusion, CRF in rats is associated with a decrease in liver cytochrome P450 activity (mainly in CYP2C11, CYP3A1, and 3A2), secondary to reduced gene expression.

Download Full-text