Effect of insulin on renal phosphorus handling in the rat: interaction with PTH and nicotinamide

1985 ◽  
Vol 249 (4) ◽  
pp. F610-F618 ◽  
Author(s):  
J. Guntupalli ◽  
A. Rogers ◽  
E. Bourke

Previous studies suggested an antiphosphaturic action of insulin. However, effects of parathyroid hormone (PTH), anti-natriuresis, or other variables were not vigorously controlled. Recently it has been suggested that nicotinamide restores phosphaturia in several antiphosphaturic states. Clearance studies were therefore performed in acutely parathyroidectomized rats to test the hypothesis that insulin abolishes the phosphaturic action of PTH and that this effect is prevented by nicotinamide. Superimposition of euglycemic hyperinsulinemia on PTH infusion (plasma insulin 19.1 +/- 2.7 vs. 9.8 +/- 1.1 microU/ml, P less than 0.05) during steady-state Pi excretion decreased fractional excretion (FE) of Pi compared with PTH-infused controls (3.16 +/- 0.61 vs. 18.02 +/- 0.81%, P less than 0.001). Renal cortical NAD+ was lower in the former than the latter group (455 +/- 22 vs. 689 +/- 30 pmol/mg, P less than 0.01). Nicotinamide pretreatment prevented the antiphosphaturic action of insulin and the decrease in cortical NAD+ in both the presence and absence of exogenous PTH. These studies offer direct evidence that in acutely parathyroidectomized rats insulin can abolish the phosphaturic action of PTH, independent of glomerular filtration rate, the filtered loads of Pi and glucose, FENa+, and cAMP excretion, an effect that is prevented by nicotinamide pretreatment. In the absence of nicotinamide pretreatment, superimposition of insulin on PTH infusion was associated with a decrease in renal cortical NAD+. A role for intracellular NAD+, probably indirect, in the antiphosphaturic action of insulin is suggested.

1987 ◽  
Vol 253 (1) ◽  
pp. F34-F40 ◽  
Author(s):  
J. Guntupalli ◽  
B. Matthews ◽  
B. Carlin ◽  
E. Bourke

The effects of respiratory acidosis on renal inorganic phosphate (Pi) handling are controversial. Clearance experiments, therefore, were performed in fasted, chronically parathyroidectomized (PTX), dietary Pi-deprived rats. The objectives were twofold: to study the effects of compensated and uncompensated hypercapnia per se on renal Pi excretion and to examine the interaction between acute hypercapnia, dietary Pi, and parathyroid hormone (PTH) on the renal handling of Pi. Acute hypercapnia increased the plasma Pi (delta 2.82 +/- 0.65 mg/dl, P less than 0.05) without altering the glomerular filtration rate (GFR). The FEPi increased (delta 7.26 +/- 0.48%, P less than 0.001) but the TRPi/GFR also increased. PTH (3 U X kg-1 X h-1) superimposed on hypercapnia resulted in a plasma Pi comparable to hypercapnia alone. The FEPi (7.56 +/- 0.78 vs. 24.43 +/- 2.20%; P less than 0.001) was higher and the TRPi/GFR (117 +/- 4 vs. 80 +/- 2 micrograms/min, P less than 0.01) lower, in the former group. PTH infusion during normocapnia resulted in a lower FEPi (0.20 +/- 0.10 vs. 24.43 +/- 2.20%, P less than 0.001) and a higher TRPi/GFR (106 +/- 2 vs. 80 +/- 2 micrograms/min, P less than 0.01) compared with PTH infusion during hypercapnia. Urinary adenosine 3',5'-cyclic monophosphate (cAMP) excretion was similar between the groups. During hypercapnia, when the extracellular acidemia was neutralized, the phosphaturic action of PTH persisted. These studies offer direct evidence that in chronically PTX, dietary Pi-deprived rats, the phosphaturic action of PTH is restored by hypercapnia per se. This effect appears to be independent of extracellular acidemia, changes in the plasma Pi and calcium, urinary pH and Na and cAMP excretion.


2000 ◽  
Vol 99 (4) ◽  
pp. 285-292 ◽  
Author(s):  
Christopher J. LOTE ◽  
Andrew THEWLES ◽  
Jeanne A. WOOD ◽  
Tariq ZAFAR

A side-effect of the immunosuppressive drug FK506 (Prograf; tacrolimus) is hypomagnesaemia. We have investigated the effects of short-term (7-day) treatment of rats with FK506, using a protocol designed to indicate whether there are modifications in the renal tubular handling of magnesium and other electrolytes, or in the tissue deposition of magnesium, which may account for the hypomagnesaemia. We have also investigated whether parathyroid hormone has a role in the observed hypomagnesaemia. Two studies have been performed; in the first we administered FK506 (0.5 mgċkg-1 body weightċday-1) or vehicle by intraperitoneal injection for 7 days, and then housed the rats in metabolic cages for the 24 h collection of urine. At the end of the metabolic cage period, the animals were anaesthetized, and blood and tissue samples were taken for analysis. In the second set of experiments the dosage regime was identical, but at the end of the treatment period the animals were anaesthetized for implantation of arterial and venous cannulae, and then received a saline (plus inulin) infusion for 6 h, during which time blood and urine samples were collected. The dose of FK506 employed did not decrease the glomerular filtration rate. FK506 elicited hypomagnesaemia in both sets of experiments, accompanied by inappropriately high fractional excretion of magnesium. There was also evidence of disruption of the normal renal reabsorption of calcium, but this did not result in hypocalcaemia. Plasma parathyroid hormone activity was not significantly different between the two groups, and there was no evidence of altered tissue content of magnesium in kidney, liver, heart, skeletal muscle or bone. The study confirms that hypomagnesaemia is a significant side-effect of FK506, even at a relatively low dose which did not decrease the glomerular filtration rate. The effect is not due to a decrease in parathyroid hormone release, or to translocation of magnesium from plasma to tissues, but does reflect decreased renal tubular magnesium (and calcium) reabsorption.


Author(s):  
Julie Mouron-Hryciuk ◽  
François Cachat ◽  
Paloma Parvex ◽  
Thomas Perneger ◽  
Hassib Chehade

AbstractGlomerular filtration rate (GFR) is difficult to measure, and estimating formulas are notorious for lacking precision. This study aims to assess if the inclusion of additional biomarkers improves the performance of eGFR formulas. A hundred and sixteen children with renal diseases were enrolled. Data for age, weight, height, inulin clearance (iGFR), serum creatinine, cystatin C, neutrophil gelatinase-associated lipocalin (NGAL), parathyroid hormone (PTH), albumin, and brain natriuretic peptide (BNP) were collected. These variables were added to the revised and combined (serum creatinine and cystatin C) Schwartz formulas, and the quadratic and combined quadratic formulas. We calculated the adjusted r-square (r2) in relation to iGFR and tested the improvement in variance explained by means of the likelihood ratio test. The combined Schwartz and the combined quadratic formulas yielded best results with an r2 of 0.676 and 0.730, respectively. The addition of BNP and PTH to the combined Schwartz and quadratic formulas improved the variance slightly. NGAL and albumin failed to improve the prediction of GFR further. These study results also confirm that the addition of cystatin C improves the performance of estimating GFR formulas, in particular the Schwartz formula.Conclusion: The addition of serum NGAL, BNP, PTH, and albumin to the combined Schwartz and quadratic formulas for estimating GFR did not improve GFR prediction in our population. What is Known:• Estimating glomerular filtration rate (GFR) formulas include serum creatinine and/or cystatin C but lack precision when compared to measured GFR.• The serum concentrations of some biological parameters such as neutrophil gelatinase-associated lipocalin (NGAL), parathyroid hormone (PTH), albumin, and brain natriuretic peptide (BNP) vary with the level of renal function. What is New:• The addition of BNP and PTH to the combined quadratic formula improved its performance only slightly. NGAL and albumin failed to improve the prediction of GFR further.


2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Uchenna Modestus Nnaji ◽  
Christian Chukwukere Ogoke ◽  
Henrietta Uche Okafor ◽  
Kingsley I. Achigbu

Background. Sickle cell nephropathy (SCN) is a serious complication of sickle cell anaemia (SCA) with asymptomatic onset in childhood and possible progression to chronic kidney disease (CKD). In Southeast Nigeria, few studies have evaluated renal function in paediatric SCA patients for early detection of renal impairment and early intervention to reduce morbidity and mortality. Therefore, this study evaluated the renal function of paediatric SCA patients in a steady state based on glomerular filtration rate and urinalysis findings (proteinuria and haematuria). Methods. A cross-sectional study of consecutively recruited sixty haemoglobin SS (HbSS) children in a steady state and sixty age- and sex-matched haemoglobin AA (HbAA) controls aged 2–18 years was done. Renal function of HbSS subjects was evaluated using estimated glomerular filtration rate (eGFR) which was compared with healthy HbAA subjects. The prevalence of significant proteinuria and haematuria, its association with eGFR, and the effect of past sickle cell crisis (in the preceding 24 months) on renal function were also evaluated. Results. Mean eGFR was significantly higher in HbSS subjects than in the HbAA subjects (p=0.001) and decreased with age. Significant proteinuria and haematuria were more prevalent in the HbSS group (3.4% and 6.7%, respectively) compared to the HbAA subjects (0% and 0%, respectively) (p=0.496 and 0.119, respectively). No significant association was observed between eGFR and proteinuria (p=1.000) or haematuria (p=1.000). There was a positive correlation between eGFR and frequency of past painful crisis that required hospitalization (r=0.138, p=0.295) and between eGFR and frequency of blood transfusion (r=0.679, p≤0.001). Conclusions. Asymptomatic paediatric HbSS (SCA) patients had higher mean eGFR indicating an increased risk of nephropathy. There was no association between eGFR and proteinuria or haematuria. Frequent sickle cell crises especially one requiring transfusion were positively correlated with hyperfiltration.


1993 ◽  
Vol 84 (2) ◽  
pp. 237-242 ◽  
Author(s):  
Niels Vidiendal Olsen ◽  
Michael Hecht Olsen ◽  
Niels Fogh-Andersen ◽  
Bo Feldt-Rasmussen ◽  
Annelise Kamper ◽  
...  

1. The effect of a single dose of lithium on renal function before and during intravenous infusion of dopamine (3 μg min−1 kg−1) was investigated in 12 healthy males. In a double-blind and randomized design, 450 mg or 600 mg of lithium carbonate or placebo was administered orally at 22.00 hours on three different occasions. After an overnight fast, the subjects were water-loaded and clearance studies were started at 09.00 hours with a 1 h baseline period and three 1 h periods during dopamine infusion. 2. Baseline sodium clearance with placebo was 0.65 ± 0.35 ml/min, but with lithium it increased to 1.25 ± 0.44 (P < 0.001) and 1.17 ± 0.46 ml/min (P < 0.01) after 450 and 600 mg, respectively. Urine flow rates were unchanged compared with placebo. Lithium did not significantly affect glomerular filtration rate, but both doses slightly increased effective renal plasma flow by 7% (P < 0.05) and 10% (P < 0.01), respectively. 3. The maximal natriuretic and diuretic effects of dopamine were not reduced by lithium, but the percentage increases in sodium clearance were significantly diminished after 450 mg (P < 0.01) and 600 mg (P < 0.001) of lithium. Lithium had no effect on dopamine-induced changes in effective renal plasma flow, glomerular filtration rate or osmolal clearance. Neither lithium nor dopamine influenced plasma concentrations of renin, aldosterone or atrial natriuretic peptide. 4. In conclusion, single test doses of lithium, as normally used in lithium clearance studies, increase baseline values of sodium clearance and effective renal plasma flow. Although these effects of lithium do not reduce the maximal renal responses to low-dose dopamine, they result in an underestimation of the percentage increase in sodium excretion.


1993 ◽  
Vol 85 (4) ◽  
pp. 479-485 ◽  
Author(s):  
Francesco P. Cappuccio ◽  
Pasquale Strazzullo

1. The associations between the renal clearance of ingested lithium (used as a marker of renal proximal tubular sodium handling) and a number of biological variables have been investigated in an unselected sample of 592 healthy and untreated white men (aged 21–68 years) under their usual living conditions and drawn from a population at work. 2. Renal excretion of lithium was expressed both as clearance of lithium and as fractional excretion of lithium, i.e. normalized for unit of glomerular filtrate. 3. Clearance of lithium was positively associated with a number of anthropometric variables such as weight (r = 0.215; P <0.001), height (r = 0.212; P <0.001), body mass index (r = 0.122; P <0.01) and body surface area (r = 0.244; P <0.001). However, when expressed as fractional excretion of lithium many of these associations were lost or tended to be negative (weight, r = −0.107, P <0.01; body mass index, r = −0.119, P <0.01), greatly depending on the strong relationship between body size and/or mass and glomerular filtration rate. The associations between clearance of lithium and other renal variables reflected, in part, a spurious association mediated by the common relationship with glomerular filtration rate. However, when expressed as fractional excretion of lithium, only some associations were apparent (fractional excretion of sodium, r = 0.256, P <0.001; fractional excretion of uric acid, r = 0.336; P <0.001), probably indicating some plausible biological relationships. These results were confirmed by analysis of co-variance by quintiles of clearance of lithium and fractional excretion of lithium. 4. The results of the present study show that the renal excretion of ingested lithium (an approximate index of proximal tubular sodium handling in man) could be used in an epidemiological setting. However, the use of the fractional excretion of lithium rather than the clearance of lithium as such would be advisable to remove the confounding effects of age and anthropometry, at least in a white middle-aged male working population.


1982 ◽  
Vol 63 (3) ◽  
pp. 48P-48P
Author(s):  
P. A. Lucas ◽  
R. C. Brown ◽  
J. S. Woodhead ◽  
G. A. Coles

1987 ◽  
Vol 65 (11) ◽  
pp. 2219-2224 ◽  
Author(s):  
J. Krayacich ◽  
R. L. Kline ◽  
P. F. Mercer

Denervation supersensitivity in chronically denervated kidneys increases renal responsiveness to increased plasma levels of norepinephrine. To determine whether this effect is caused by presynaptic (i.e., loss of uptake) or postsynaptic changes, we studied the effect of continuous infusion of norepinephrine (330 ng/min, i.v.) and methoxamine (4 μg/min, i.v.), an α1 adrenergic agonist that is not taken up by nerve terminals, on renal function of innervated and denervated kidneys. Ganglionic blockade was used to eliminate reflex adjustments in the innervated kidney and mean arterial pressure was maintained at preganglionic blockade levels by an infusion of arginine vasopressin. With renal perfusion pressure controlled there was a significantly greater decrease in renal blood flow (−67 ± 9 vs. −33 ± 8%), glomerular filtration rate (−60 ± 9 vs. −7 ± 20%), urine flow (−61 ± 7 vs. −24 ± 11%), sodium excretion (−51 ± 15 vs. −32 ± 21%), and fractional excretion of sodium (−50 ± 9 vs. −25 ± 15%) from the denervated kidneys compared with the innervated kidneys during the infusion of norepinephrine. During the infusion of methoxamine there was a significantly greater decrease from the denervated compared with the innervated kidneys in renal blood flow (−54 ± 10 vs. −30 ± 14%), glomerular filtration rate (−51 ± 11 vs. −19 ± 17%), urine flow (−55 ± 10 vs. −39 ± 10%), sodium excretion (−70 ± 9 vs. −59 ± 11%), and fractional excretion of sodium (−53 ± 10 vs. −41 ± 10%). These results suggest that vascular and tubular supersensitivity to norepinephrine in chronically denervated kidneys is due to postsynaptic changes involving α1-adrenergic receptors.


2014 ◽  
Vol 12 (2) ◽  
pp. 47-51
Author(s):  
ES Ajibola ◽  
SA Rahman ◽  
KT Biobaku ◽  
N Okwelum ◽  
JA Oyewusi ◽  
...  

This study was done to evaluate the effect of an increased dose of ketamine on some renal function indices of Ketamine−Xylazine anaesthetised dogs. Five adult female mongrel dogs assigned to two different treatment groups in a randomized cross over design were used for this study. Each of the dogs received either 10mg/kg or 20mg/kg ketamine at a week interval. The mean glomerular filtration rate (GFR) of creatinine, absolute and fractional excretion of sodium (UNaV, FENa), urine flow rate (UFR), and plasma sodium clearance were all found to be insignificantly increased in dogs that received the higher dose regime of ketamine. All the dogs in the two treatment groups exhibited levels of glycosuria and hyposthenuria. When plasma sodium concentration of dogs treated with 10mg/kg was correlated with UNaV it was found to be significant and strong (P < 0.05; r =0.86). It was however strong but insignificant with sodium clearance (P>0.05; r = 0.82) and creatinine clearance (P> 0.05; r = 0.39). At 20mg/kg, the UNaV, sodium clearance and glomerular filtration rate all correlated weakly and insignificantly with plasma sodium concentration. The enhanced diuresis and natriuresis observed in the two treatment groups could be attributed to the effect of xylazine on either the alpha-2 adrenoceptor of the brain or those on the tubules of the kidney. These effects of xylazine could not be reversed by attempting to competitively antagonize it with a 100% increase in ketamine dose.Keywords: Diuresis, GFR fractional excretion, Ketamine, Natriuresis, xylazine


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