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Ammonia functions as a regulatory molecule to mediate adjustments in glomerular filtration rate in response to changes in metabolic rate.

In mammals, varying in size from mouse to elephant there is a close linkage between metabolic rate (MR) and glomerular filtration rate (GFR). This linkage has evolved because of the necessity to excrete nitrogenous wastes generated predominately by amino acid catabolism. A similar linkage is observed in birds, reptiles and fish, although in the latter vertebrate group gill excretion rate and GFR need to be considered as an interdependent co-ordinated system. A change in the rate of amino acid catabolism will result in a change in the rate of production of nitrogenous wastes requiring excretion and hence GFR (or GFR plus gill excretory rate in fish) must be appropriately re-set. It is hypothesized that ammonia functions as a regulatory molecule to mediate adjustments in excretory rate (GFR or GFR plus gill excretory rate) in response to such changes in amino acid catabolism.

Amino Acids↗

Effect of feeding on glomerular filtration rate and proteinuria in conscious aging rats.

Food intake increases glomerular filtration and proteinuria in adult rats. That this postprandial hyperfiltration could be age dependent was investigated in 3-, 10-, 20-, and 30-mo-old rats. Glomerular filtration rate and protein excretion were measured in fed or 24 h fasted conscious animals. In the 3-mo-old rats food ingestion increased renal filtration by 45% from 1.17 +/- 0.08 to 1.73 +/- 0.11 ml.min-1.g kidney wt-1 (n = 6). As the animals became older, the differences between fed and fasted periods became smaller: in 30-mo-old rats glomerular filtration rate was 0.85 +/- 0.03 and 1.01 +/- 0.06 ml.min-1.g kidney wt-1 (n = 6) in fasted and fed conditions, respectively. Proteinuria, which was mainly albuminuria, increased slightly with age and was more markedly reduced by acute food restriction in the 30-mo-old than in the 3-mo-old rats. Because the renin-angiotensin system activity decreases with age, its role in postprandial hyperfiltration was assessed by measuring glomerular filtration in 3-mo-old animals whose angiotensin II converting-enzyme activity was chronically inhibited by daily administration of perindopril. In such experimental conditions there was no longer a difference in renal filtration between fed and fasted rats. These data indicate that 1) postprandial increase in glomerular filtration is to some extent related to the renin-angiotensin system activity; 2) short-term reduction of food intake reduces proteinuria even in senescent rats, although the feeding dependence of the glomerular filtration is blunted with age.

Animals↗

Genetic analysis of renal function in mice. 1. Glomerular filtration rate and its correlation with body and kidney weight.

Investigation of 18 inbred and 6 F1 hybrid mouse strains has shown that the glomerular filtration rate, bodyweight and kidney weight showed strain- and sex-dependent differences. Covariance analysis showed stronger correlations (genetic and environmental) between glomerular filtration rate and bodyweight than between glomerular filtration rate and kidney weight. This was predominantly due to a high within-strain variation of kidney weight (56%) in male mice. Therefore an allometric regression was calculated between the 48 strain means of glomerular filtration rate (GFR) and bodyweight (BW): GFR = 0.036 x BW0.74. Thus the term BW0.74, a suitable correction term for comparing the heat production of different species, is also suitable for the correction of glomerular filtration rate within one species.

Analysis of Variance↗

Evaluation of 99mTc-diethylenetriaminepentaacetic acid nuclear imaging for quantitative determination of the glomerular filtration rate of dogs.

The suitability of 99mTc-diethylenetriaminepentaacetic acid (99mTc-DTPA) as an agent to assess glomerular filtration rate (GFR) in dogs was evaluated. Glomerular filtration rates of 12 healthy dogs were determined on the basis of creatinine and/or inulin clearance. Glomerular filtration rates also were determined in 7 dogs after induction of acute renal failure by administration of amphotericin B. The healthy dogs and the amphotericin B-treated dogs were given 99mTc-DTPA (1 to 2 mCi) IV. The percentage of the 99mTc-DTPA dose in the kidneys (percentage dose) was determined, with background activity subtracted from total activity at 15-s intervals 0 to 6 minutes after 99mTc-DTPA infusion. Linear regression analyses (LRA) were performed to determine whether the percentage dose at various time intervals after injection correlated with GFR calculated on the basis of creatinine and inulin clearance data. One to 3 minutes after 99mTc-DTPA administration appeared to be the best period for analysis of the data. The percentage dose of 99mTc-DTPA (corrected for kidney depth differences) was determined and LRA against GFR were performed. The percentage dose correlated better with inulin clearance (r = 0.94) than with endogenous creatinine clearance (r = 0.83). Only inulin clearance correlations improved with kidney depth correction. The LRA was used to derive an equation that could be used to calculate GFR on the basis of the percentage dose. The equation derived from inulin regression was: GFR (milliliter/minute/kilogram of body weight) = 0.194 (depth-corrected percentage dose)--0.37; the equation derived from the creatinine regression was: GFR (milliliter/minute/kilogram) = 0.171 (depth-corrected percentage dose)-0.15.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗

Role of atrial natriuretic peptide in the increase in glomerular filtration rate induced by a protein meal.

1. The increase in glomerular filtration rate after a protein meal is believed to be mediated by hormonal factors. Since natriuresis is often observed after a protein meal, it was postulated that the increase in glomerular filtration rate after a protein meal might be mediated by atrial natriuretic peptide. 2. Subjects were given a low, medium or high protein meal. Fluid intake was controlled so as to avoid significant extracellular fluid volume expansion. It was found that the creatinine clearance, the urea excretion, the fractional sodium excretion and the potassium excretion were elevated in all subjects after protein meals (P less than 0.05). These effects were not observed in subjects given a carbohydrate control meal. 3. The plasma atrial natriuretic peptide concentrations remained unchanged in all subjects except those given a high protein meal (P less than 0.05). There was no significant relationship between plasma atrial natriuretic peptide concentrations and creatinine clearance before or after a protein meal. 4. The data suggest that a high protein meal induces a minor increase in plasma atrial natriuretic peptide concentration, whereas a low or medium protein meal does not. It is unlikely that the change in creatinine clearance after a protein meal can be explained by a change in plasma atrial natriuretic peptide levels.

Adult↗

Correlation between single nephron glomerular filtration rate and filtration area in superficial glomeruli of developing rats.

Single nephron glomerular filtration rate (SNGFR) was correlated to the area of the glomerular basement membrane (GBM) determined by stereological techniques in rats between 20 and 40 days of age. Single nephron glomerular filtration rate increased 8.4 times in parallel with a twofold increase in GBM area. The much greater postnatal increase in SNGFR than in GBM area demonstrates that the increase in GBM area cannot account for the entire increase in SNGFR. Instead a combination of other factors influencing SNGFR most likely determines the largest part of the increase in SNGFR during this period. Thus, the drop in vascular resistance known to occur during maturation will increase the renal blood flow and may cause the filtration process to turn from a state of filtration equilibrium to or close to disequilibrium, thereby increasing GFR. Additional increase in GFR may be due to an increased net driving force for filtration and/or changed hydraulic permeability.

Age Factors↗

The natural history of postoperative renal function in patients undergoing ileal conduit diversion for cancer measured using serial isotopic glomerular filtration rate and 99m technetium-mercaptoacetyltriglycine renography.

PURPOSE: There is little consensus regarding long-term followup of renal function in patients who undergo urinary diversion. We established the usefulness of combined serial isotopic glomerular filtration rate measurement and diuresis renography in the early identification of patients at risk for deterioration of renal function following ileal conduit diversion. MATERIALS AND METHODS: A total of 340 patients with ileal conduit diversion who were followed between 1990 and 2000 were identified. We analyzed data on 178 patients who had more than 4 years of followup. Renal function was assessed by serial estimation of serum creatinine, isotopic glomerular filtration rate and diuresis renographic measurements. RESULTS: Of the patients 52 (29%) demonstrated a worsening glomerular filtration rate. Mean followup +/- SEM was 8.2 +/- 0.4 years (range 4 to 30) and 67% of patients had more than 6 years of followup. In this group we found that hypertension, recurrent urinary sepsis and an initial post-diversion glomerular filtration rate of less than 50 ml per minute per 1.73 m were prevalent risk factors. Hypertension was an independent predictor of a decreased glomerular filtration rate in this group. Of 52 patients with a deteriorating glomerular filtration rate 19 had type II or IIIb curves on followup renography, of whom 13 underwent revision surgery. Renal function subsequently stabilized or improved in this group. CONCLUSIONS: Of patients with an ileal conduit 29% have renal function deterioration in the long term. No surgical cause for glomerular filtration rate deterioration was found in 18%. Important predisposing factors in nonobstructed cases were hypertension, recurrent urinary sepsis and a glomerular filtration rate of less than 50 ml per minute per 1.73 m. Hypertension was an independent predictor of a decreased glomerular filtration rate in the group with worsening glomerular filtration rates. In 11% of patients deterioration was due to upper tract obstruction. This was identifiable using renography and the glomerular filtration rate. A type IIIb curve was an early indicator of obstruction.

Adult↗

[Could cystatine C replace creatinine as a market of glomerular filtration rate?].

Measurement of glomerular filtartion rate (GFR) is crucial for the detection and follow-up of an early renal impairment. Inulin clearance or radio-isotopes are the gold standard but they cannot be used routinely. Serum creatinine and creatinine clearance are the most widely used, but they lack sensibility to detect an early renal impairment and in cases of obesity, malnutrition or advanced age. Looking for a more reliable marker is necessary and cystatin C seems to be interesting. This molecule is constantly produced by nucleated cells, then freely filtrated and catabolized in the proximal tube. Clinical studies showed that cystatin C might be a more reliable marker of GFR in determined groups of patients. Moreover this molecule may have an other interest as a predictive risk factor or mortality, especially for cardiovascular events.

Biomarkers↗

Mechanisms of amphotericin B-induced reduction of the glomerular filtration rate: a micropuncture study.

Amphotericin B infusions cause acute reductions in renal plasma flow and glomerular filtration rate. The exact mechanism by which these changes occur has not been identified fully, nor have the effects of the drug on the renal microcirculation been studied adequately. In this study, we examined the effect of intrarenal amphotericin B infusions (0.05 mg/kg/min) on glomerular hemodynamics in the anesthetized rat. Amphotericin B did not affect systemic blood pressure and slightly increased hematocrit (5%), but significantly decreased renal blood flow and glomerular filtration rate by 40 and 35%, respectively. Glomerular micropuncture revealed decreases in single nephron plasma flow and glomerular filtration rate (from 142 +/- 12 to 89 +/- 14 and from 35.3 +/- 2.2 to 22.8 +/- 2.8 nl/min, respectively). These changes were due to significant increases in pre- and postglomerular resistances (from 1.91 +/- 0.17 to 3.95 +/- 0.38 and from 1.30 +/- 0.10 to 2.08 +/- 0.12 10(10) dyn.sec.cm-5, respectively), and to a significant decrease in the glomerular capillary ultrafiltration coefficient which fell from 0.043 +/- 0.008 to 0.032 +/- 0.009 nl/(sec.mm Hg). These results provide further insight into the mechanisms of the acute renal effects of amphotericin B, and suggest possible mediators that may be involved in these effects.

Amphotericin B↗

[The relationship between creatinine clearance and glomerular filtration rate in the critically ill patient].

A study was undertaken to show that the determination of glomerular filtration rate with radio-labelled sodium chromate ethylenediaminetetra-acetic acid is a repeatable, easily performed and accurate examination in the critically ill patient. Differences in glomerular filtration rate were relatively small, with a phase difference of between -10,59 and 5,34. Creatinine clearance showed a greater variation over a corresponding period, with a difference of between -27,50 and -4,10. The study indicated that this method of determining glomerular filtration rate can be very useful in an intensive care unit, because it seems to be more accurate and easier to perform. Information is obtained more quickly than when the glomerular filtration rate is determined by means of creatinine clearance.

Acute Disease↗

Effects of a K+ channel blocker on glomerular filtration rate and electrolyte excretion in conscious rats.

Effects of a K+ channel blocker on glomerular filtration rate and electrolyte excretion in conscious rats were observed. Effects of K+ channel modulation on glomerular filtration rate and electrolyte excretion were studied using the adenosine-triphosphate- (ATP)-sensitive K+ channel blocker 4-morpholinecarboximidine-N-1-adamantyl-N'-cyclohexylhydr ochloride (U-37883A) in conscious rats previously equipped with catheters for clearance studies. In saline-loaded rats, i.v. doses of U-37883A of 1.7, 5.0 and 15 mg/kg increased absolute and fractional Na+ excretion dose-dependently without changing K+ excretion. The glomerular filtration rate remained constant during diuresis. In water-loaded (hypotonic dextrose) rats, free-water clearance studies revealed that the ATP-sensitive K+ channel blocker significantly decreased an index of solute reabsorption (free-water clearance adjusted for chloride clearance) in the diluting segment during peak natriuretic activity. In addition, U-37883A significantly decreased the osmolality of renal papillary interstitial fluid, indicative of an effect in the medullary portion of the diluting segment. Together, these findings suggest that ATP-sensitive K+ channels, possibly those located at the apical boarder, play a pivotal role in Na+ reabsorption in the thick ascending limb of the loop of Henle.

Adamantane↗

Abnormal glomerular filtration rate, renal plasma flow, and renal protein excretion in recent and short-term diabetics.

Glomerular filtration rate and renal plasma flow were simultaneously determined in comparable groups of 43 diabetics less than 40 years of age and with a duration of diabetes less than 10 years and 32 control subjects. The average glomerular filtration rate in the diabetic group was significantly higher than that in the control group (P <0.01). The average renal plasma flow in the diabetic group was found to be significantly lower than that in the control group (P <0.05). The filtration fraction in both male and female diabetics was significantly higher than in the male and female control groups (P <0.001). These changes were found to be present even in recent juvenile diabetics with disease of a duration of less than one year. No correlation was apparent between the average levels of serum growth hormone and glomerular filtration rate.The urinary protein excretion was determined in 36 diabetic and 38 healthy subjects comparable with regard to glomerular filtration rate. In the diabetic group there was a greater frequency of cases with higher protein excretion rates (P <0.02). The average protein excretion rate was increased even in diabetics with less than one year's duration of the disease.The results of the changes in renal haemodynamics in subjects with recent and short-term diabetes are compatible with the presence of a constrictive state of the vas efferens leading to an increase in the filtration pressure. The increase in protein excretion rate may similarly be a consequence of this process or of an increase in the glomerular permeability with augmented molecular sieving of proteins or both.

Adolescent↗

Diagnosis of renal artery stenosis: feasibility of combining MR angiography, MR renography, and gadopentetate-based measurements of glomerular filtration rate.

OBJECTIVE: Our aim was to evaluate the feasibility of combining in a single test (1) structural evaluation of renal arteries with MR angiography, (2) functional evaluation of global glomerular filtration rates calculated on the basis of plasma disappearance of gadopentetate dimeglumine, and (3) renographic analysis of individual kidneys based on the dynamic changes in signal intensity that occur after administration of gadopentetate dimeglumine. SUBJECTS AND METHODS: We used unenhanced MR angiography to measure patency of the renal arteries in 10 healthy volunteers and in 10 patients with renal artery stenosis. Calculations of global glomerular filtration rate were based on measurements of plasma disappearance of gadopentetate dimeglumine as shown by MR relaxometry. For renography with gadopentetate dimeglumine, we generated curves that showed changes in signal intensity in both kidneys over time; intrarenal kinetics were studied by measuring the time of arrival of gadopentetate dimeglumine in the cortex and outer medulla of the kidney. Conventional angiograms, measurements of global glomerular filtration rate based on plasma disappearance of 99mTc-DTPA, and 99mTc-DTPA renograms were used as reference standards. We compared the two different methods of determining global glomerular filtration rates by computing the correlation coefficient of the linear regression of rates derived from studies with gadopentetate dimeglumine versus rates derived from studies with 99mTc-DTPA. RESULTS: In all volunteers, renal arteries were well visualized, and global glomerular filtration rates based on plasma clearance of gadopentetate dimeglumine were normal. In nine of 10 patients, correlation was good between findings on MR angiograms and findings on conventional arteriograms. Finding were discordant in one patient because the patient moved during the MR angiography. For all six patients studied, correlation was good between measurements of global glomerular filtration rates based on plasma clearance of gadopentetate dimeglumine and those based on clearance of 99mTc-DTPA (r = 98%). CONCLUSION: Our results suggest the potential of magnetic resonance for a comprehensive approach for detection of renal artery stenosis. This novel approach provides structural evaluation of renal arteries with unenhanced MR angiography. MR renography is done and global glomerular filtration rates are determined by using MR relaxometry after injection of contrast material. Corticomedullary transit times can be determined on the basis of the dynamic changes in signal intensity that occur after administration of gadopentetate dimeglumine.

Adult↗

Long-term followup of maximum concentrating ability and glomerular filtration rate in adult obstructed kidneys after pyeloplasty.

We investigated 34 patients with obstructed kidneys preoperatively and 8 to 10 years postoperatively concerning the separate glomerular filtration rate and maximum concentration ability. The mean glomerular filtration rate for the obstructed kidneys was approximately 10 per cent lower compared to that for the contralateral kidneys preoperatively and at followup. Although the mean value for obstructed kidneys was not improved at followup, kidneys with a decreased glomerular filtration rate preoperatively improved significantly after pyeloplasty. The maximum concentration ability was low preoperatively for the obstructed kidneys compared to the contralateral kidneys. The lowest maximum concentration ability was found in patients with a history of repeated upper urinary tract infections. At followup marked improvement was noted, which was most obvious for kidneys with severely reduced concentration ability preoperatively. However, the restoration was not total. There was a positive correlation between the improvement in glomerular filtration rate and improvement in maximum concentration ability.

Adult↗