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PubMed2007

Evidence that postprandial reduction of renal calcium reabsorption mediates hypercalciuria of patients with calcium nephrolithiasis.

Idiopathic hypercalciuria (IH) is common among calcium stone formers (IHSF). The increased urinary calcium arises from increased intestinal absorption of calcium, but it is unclear whether increased filtered load or decreased renal tubular reabsorption of calcium is the main mechanism for the increased renal excretion. To explore this question, 10 IHSF and 7 normal subjects (N) were studied for 1 day. Urine and blood samples were collected at 30- to 60-min intervals while subjects were fasting and after they ate three meals providing known amounts of calcium, phosphorus, sodium, protein, and calories. Fasting and fed, ultrafiltrable calcium levels, and filtered load of calcium did not differ between N and IHSF. Urine calcium rose with meals, and fractional reabsorption fell in all subjects, but the change was significantly higher in IHSF. The changes in calcium excretion were independent of sodium excretion. Serum parathyroid hormone levels did not differ between N and IHSF, and they could not account for the greater fall in calcium reabsorption in IHSF. Serum magnesium and phosphorus levels in IHSF were below N throughout the day, and tubule phosphate reabsorption was lower in IHSF than N after meals. The primary mechanism by which kidneys ferry absorbed calcium into the urine after meals is via reduced tubule calcium reabsorption, and IHSF differ from N in the magnitude of the response. Parathyroid hormone is not likely to be a sufficient explanation for this difference.

Adult↗
PubMed1977

Autoregulation of nephron filtration rate in the dog assessed by indicator-dilution technique.

Micropuncture studies were conducted in anesthetized dogs to evaluate single nephron glomerular filtrate rate (SNGFR) and SNGFR autoregulation when assessed by means of an indicator-dilution technique (SNGFRID), which does not require interruption of distal volume delivery. In 18 dogs, control renal arterial pressure was 124 +/- 11 mmHg (SD), renal blood flow (RBF) was 185 +/- 58 ml/min, and whole kidney GRF was 37 +/- 7 ml/min. SNGFRID averaged 57 +/- 15 nl/min and was significantly lower than SNGFR determined on the basis of total collections (SNGFRTC) from proximal tubules (75 +/- 17 nl/min). However, SNGFRID was not significantly different from the overall average SNGFR of 62 +/- 12 nl/min estimated from whole kidney GFR and the total number of glomeruli (613,000 +/- 74,000). In 10 animals, renal arterial pressure was reduced to an average of 94 +/- 8 mmHg; whole kidney autoregulation was highly efficient and average RBF and GRF remained within 1 and 3% of their control values. Likewise, SNGFRID was not significantly altered at 52 +/- 17 and 52 +/- 16 nl/min. In contrast, SNGFRTC decreased significantly from 72 +/- 17 to 51 +/- 13 nl/min. These results indicate that the indicator-dilution technique provides a reliable assessment of SNGFR and allows the manifestation of single nephron autoregulatory behavior. They provide further support for the hypothesis that maintenance of distal volume delivery may be a necessary aspect of the autoregulation phenomenon.

Animals↗
PubMed1984

Mechanisms of escape from sodium retention during angiotensin II hypertension.

This study examined the role of increased renal arterial pressure (RAP) in renal escape from the chronic Na-retaining effects of angiotensin II (ANG II). When RAP was allowed to increase during ANG II infusion (5 ng X kg-1 X min-1), urinary Na excretion (UNaV) decreased transiently on the first day but there was no significant change in Na iothalamate space or cumulative Na balance when ANG II infusion was continued for 6 days. Mean arterial pressure (MAP) rose from 100 +/- 3 to 132 +/- 2 mmHg after 3 days and remained near that level for the next 5 days of ANG II infusion. When RAP was prevented from rising with a servo-controlled aortic occluder, UNaV remained below control even after 6 days of ANG II infusion, cumulative Na balance increased by 210 +/- 37 meq, and Na iothalamate space rose by 1,158 +/- 244 ml. MAP did not plateau when RAP was servo-controlled during ANG II infusion but continued to rise and after 6 days averaged 157 +/- 3 mmHg. In three of the eight dogs in which RAP was servo-controlled during ANG II infusion, Na and water retention became so severe that MAP increased to 165-180 mmHg and pulmonary edema developed within 4-6 days. These data suggest that a rise in RAP is essential in allowing the kidneys to escape from the chronic Na-retaining actions of ANG II and in attaining Na balance and a stable level of MAP without severe volume expansion.

Aldosterone↗
PubMed1998

The endogenous insulin-like growth factor system in radiocontrast nephropathy.

The response of insulin-like growth factor (IGF) I in acute renal failure was evaluated in a model of radiocontrast nephropathy associated with selective necrosis of medullary thick ascending limbs. In brief, rats were administered radiocontrast medium or vehicle injections for controls after combined inhibition of prostanoids and nitric oxide. Twenty-four hours after the insult, tissue mRNAs for IGF-I, the IGF-I receptor, and IGF-binding proteins (IGFBP) 1 and 3 were assayed in cortex, medulla, and liver by solution hybridization-RNase protection assay, and IGFBPs were measured in serum and tissue by Western ligand blotting. Cortical IGF-1 increased, whereas medullary IGF-I mRNA decreased. Renal IGFBPs decreased, whereas IGFBP-1 mRNA increased. The IGF system in the liver was unchanged. We conclude that general changes in renal IGFBPs in this experimental model of acute renal failure might increase the level of cortical IGF-I in a way that could modulate medullary recovery.

Acute Kidney Injury↗
PubMed1999

A simple, nonradioactive method for evaluating single-nephron filtration rate using FITC-inulin.

The determination of inulin concentration in nanoliter fluid samples is fundamental to micropuncture investigations of renal function, and this is generally accomplished through the use of radioisotopes. We report here a simple and reliable alternative to the use of radioisotopes that employs FITC-labeled inulin. Samples containing FITC-inulin are stored between oil columns in constant-bore microcapillary tubes, which are then used as cuvettes to determine fluorescence on a microscope fluorometer. Standard curves were generated and found to be linear, with correlation coefficients (R) exceeding 0.99 in every case. Although the fluorescence of FITC-inulin was found to be pH dependent, the pH and fluorescence of each 20- to 40-nl sample could be normalized by the addition of 1 nl of 0.5 M HEPES at pH 7.5. In mice prepared for standard micropuncture, simultaneous measurements of tubular fluid-to-plasma ratios (TF/P) using FITC-inulin and [125I]iothalamate were highly correlated (slope = 0.95, y-intercept = 0.01, R = 0.942), as were whole kidney measurements of glomerular filtration rate (GFR) (slope = 1.25, y-intercept = -53.5 microliter/min, R = 0.99). Micropuncture determinations of late-proximal samples from mice before and after treatment with acetazolamide showed expected changes: TF/P of FITC-inulin decreased from 1.89 +/- 0.07 to 1.48 +/- 0.10; single-nephron GFR (SNGFR) decreased from 9.64 +/- 1.1 to 6.65 +/- 1. 0 nl/min; and fractional fluid reabsorption decreased from 45.3 +/- 1.9 to 26.8 +/- 5.2%. Measurements of TF/P of FITC-inulin, volume, and SNGFR using this technique were stable for at least 2 wk when samples were stored in the dark at 4 degreesC. These data demonstrate that this simple method for determining inulin clearance represents a viable and accurate alternative to radioactive methods. This approach has the added benefits of being relatively inexpensive and leaving the micropuncture sample intact.

Absorption↗
PubMed1992

Effects of acute hypoxia on renal and endocrine function at rest and during graded exercise in hydrated subjects.

Renal effects of altitude hypoxia are unclear. Renal and hormonal function was investigated in eight males at rest and during graded exercise at sea level (SL) and 48 h after rapid ascent to 4,350 m (HA). HA did not change resting values of effective renal plasma flow (ERPF), glomerular filtration rate (GFR), sodium clearance (CNa), urine flow, or lithium clearance (CLi), which was used as an index of proximal tubular outflow. At rest, HA increased plasma norepinephrine concentration and decreased plasma concentrations of renin and aldosterone. Exercise decreased ERPF similarly in both environments. Normoxic exercise progressively reduced GFR, but at HA GFR only decreased during heavy exercise. This resulted in a higher filtration fraction during light and moderate hypoxic exercise. However, calculated absolute proximal reabsorption rate (GFR-CLi) at HA was higher during low-intensity exercise, and there were no significant differences between exercise-induced decreases in CLi, CNa, and urine flow at HA compared with SL. Exercise gradually increased plasma norepinephrine, but values were higher at HA during light and moderate exercise. The small changes in the renal response to low-intensity hypoxic exercise may be secondary to increased adrenosympathetic activity. However, antidiuretic and antinatriuretic effects of exercise were maintained in hypoxia and in both environments seemed to be the consequence of decreased proximal tubular outflow. The results demonstrate that renal glomerular and tubular function is well preserved in acute hypoxia despite marked hormonal changes.

Adult↗
PubMed1998

Ejaculatory duct obstruction: TRUS-guided opacification of seminal tracts.

OBJECTIVE: To assess the usefulness of TRUS-guided aspiration and opacification of seminal tracts in the evaluation and management of patients with ejaculatory duct obstruction (EDO). METHODS: In 21 men who had dilated seminal vesicles and/or midline cysts on TRUS, a mixture of contrast media and indigocarmine was injected and then pelvic radiographs were taken. RESULTS: The diagnoses based on the findings of TRUS-guided opacification were bilateral EDO in 9 patients, unilateral EDO in 1, and midline cyst with EDO in 11. Midline cysts had communication with seminal tracts in 7. Transurethral unroofing was performed in 12, in all of whom blue color of the injected indigocarmine facilitated the surgical procedure. CONCLUSION: TRUS-guided opacification of the seminal tracts with a mixture of contrast media and indigocarmine may be valuable in the evaluation and management of the patients with EDO.

Adult↗
PubMedDate not supplied

Effect of radiocontrast agents on intrarenal nitric oxide (NO) and NO synthase activity.

BACKGROUND/AIMS: Contrast media (CM) induce a biphasic renal hemodynamic response, with late prominent cortical vasoconstriction and marked outer medullary vasodilation. The objective of the study was to explore a possible role for altered nitric oxide (NO) production or bioavailability in these hemodynamic responses. METHODS: We explored the impact of CM (sodium iothalamate) upon rat renal NO synthase (NOS) activity (citrulline recovery) and NO (using a NO electrode). RESULTS: The cortical NOS activity following CM was 11.5 +/- 1.0 versus 13.8 +/- 1.1 nmol/gww/min (gww = gram wet weight) in controls (p = 0.16, NS). In rats pretreated with the nonselective endothelin antagonist bosentan, CM reduced the cortical NOS activity to 8.5 +/- 1.2 nmol/gww/min (p < 0.005 vs. controls). Cortial NO readings declined over 30 min following CM by 13 +/- 8% (p < 0.05, Anova), in parallel with the decline in cortical blood flow. The outer medullary NOS activity was not affected by CM (5.2 +/- 1.5 vs. 5.5 +/- 1.3) nmol/gww/min in controls) or bosentan. Nevertheless, the outer medullary NO reading increased by 36 +/- 23% (p < 0.05), with a concomitant increase in regional blood flow. CONCLUSION: In the cortex, CM might reduce the NOS activity (an effect blunted by endothelin release). This may potentiate the effect of endothelin to induce regional vasoconstriction. In the outer medulla, the vasodilatory response to CM does not seem to be mediated by enhanced NOS activity and might reflect increased local NO bioavailability as the result of regional hypoxia.

Animals↗
PubMed1991

Nephrotoxicity of contrast media in high-risk patients with renal insufficiency: comparison of low- and high-osmolar contrast agents.

We have compared the renal effects of ioxitalamate, ioxaglate, and iopamidol in patients with chronic renal failure. Sixty consecutive patients with an estimated creatinine clearance (ECRCl) less than 60 ml/min were randomly assigned to receive either ioxitalamate, iopamidol, or ioxaglate. All patients received 500 cm3 isotonic saline before the procedure. Serum creatinine and ECRCl were estimated before, 1 and 2 or 3 days after the procedure. There was no statistical difference between the three groups with respect to age, sex, weight, renal function, amount of iodine, and type of procedure. Mean serum creatinine and ECRCl remained unchanged after administration of contrast media. No patient had nephrotoxicity or acute oliguria requiring dialysis as a result of the administration of contrast material. The number of patients with an increase in the serum creatinine level greater than 10% from the basal value did not differ in the treatment groups. The maximal increases in serum creatinine were 52 mumol/l (29%) in the ioxitalamate group, 56 mumol/l (18%) in the ioxaglate group, and 57 mumol/l (23%) in the iopamidol group (p = NS). Using a population carefully randomized and matched for renal insufficiency, we could not show any differences in nephrotoxicity between these three contrast agents. Clinically serious renal impairment was uncommon in our study, regardless of the contrast agent used. However, the interpretation of these favorable findings requires a cautionary note. All patients in this study were well hydrated before and after uro-/angiography, and none had a recent renal injury or a treatment with a nephrotoxic agent that would predispose to injury from contrast material.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1995

Comparison of simultaneous renal clearances of true endogenous creatinine and subcutaneously administered iothalamate in man.

125I-iothalamate and true endogenous creatinine clearances, measured over two short collections periods of 1 and 2 h, were compared simultaneously in 70 patients with a variety of renal diseases and a wide range of renal function. Reproducibility of the iothalamate clearance was 18.5% and that of the creatinine clearance 12.2%. The slope of the regression was not significantly different from 1 (95% confidence interval, CI, 0.964-1.155) for the whole group, nor in any subgroup chosen. The intercept at 12.6 ml/min (CI = 5.0-20.2) indicates that there is some creatinine secretion, but this was constant at all levels of GFR. It is concluded that although the clearance of true creatinine obtained during short collection periods consistently overestimates GFR by a constant proportion, it is a reproducible and accurate measure of GFR suitable for use in the clinical setting.

Adult↗
PubMed1995

Association of post-renal transplant erythrocytosis and microalbuminuria: response to angiotensin-converting enzyme inhibition.

Angiotensin-converting enzyme (ACE) inhibitor therapy has recently been shown to be effective in the treatment of post-renal transplant erythrocytosis (PTE). In an attempt to assess the effect of drug treatment on serum erythropoietin level, glomerular filtration rate, and urinary protein excretion, we prospectively evaluated 8 consecutive cadaveric renal transplant recipients with PTE treated with ACE inhibitor therapy for 3 months. In response to ACE inhibition, the mean hematocrit (HCT) value decreased from 53.7 +/- 0.6% before treatment to 42.7 +/- 2.2% at the conclusion of the study (p = 0.03). However, 1 patient failed to respond to ACE inhibition (HCT > 50%), and 2 patients with PTE developed anemia (HCT < 35%) while maintained on drug treatment. Although the mean serum erythropoietin level decreased during ACE inhibition (from 22.8 +/- 8.4 to 9.4 +/- 5.3 mU/ml; p = 0.06), a consistent change in individual erythropoietin levels was not identified. At the conclusion of the study, the serum erythropoietin levels were undetectable in 4 patients, decreased in 1, unchanged in 2, and increased in the only patient with PTE who failed to respond to drug treatment. All patients tolerated the ACE inhibitor therapy without developing cough or hyperkalemia. In addition, serum creatinine levels, 125I-iothalamate clearances, and mean arterial blood pressures were unchanged throughout the study. Microalbuminuria (spot urinary albumin/creatinine ratio between 30 and 200 mg/g) developed in 5 patients with PTE and coincided with the onset of erythrocytosis (25.2 +/- 7 mg/g before PTE and 76.3 +/- 36.7 mg/g at the time of PTE detection).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗