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Biomedical subjects

R L Chevalier

Publications and source records attributed to R L Chevalier.

At least 127 records · Page 7Linked to original sources

Chronic partial ureteral obstruction in the neonatal guinea pig. II. Pressure gradients affecting glomerular filtration rate.

Neonatal guinea pigs with chronic partial ureteral obstruction (CPUO) and contralateral nephrectomy develop hydroureteronephrosis and reduced glomerular filtration rate (GFR) without significant reduction of renal blood flow. To investigate the role of pressure gradients in determination of GFR, micropuncture studies were performed in animals 23 +/- 3 days of age subjected to left ureteral constriction and right nephrectomy within the first 2 days of life and compared to uninephrectomized controls. Resulting ureteral dilatation was variable, with kidney weight and ureteral diameter being proportional to the rise in ureteral pressure (PU). In individual animals with severe CPUO (ureteral diameter greater than or equal to 3 mm), distal tubular transit time was either normal (31-90 s) or prolonged (greater than 120 s). Superficial single nephron GFR (SNGFR) was inversely correlated with PU. Glomerular capillary pressure and afferent arteriolar colloid oncotic pressure were not affected by CPUO while peritubular capillary, proximal and distal intratubular hydrostatic pressure increased as a function of PU. As a result, afferent effective filtration pressure (EFPA) was reduced in severe (10.0 +/- 1.1 mm Hg) compared to mild CPUO (13.4 +/- 0.5 mm Hg), but was not different from controls (11.3 +/- 0.9 mm Hg). For both control and CPUO groups, superficial SNGFR increased by 0.5 nl/min for each mm Hg increase in EFPA but for a given EFPA, SNGFR was 6 nl/min lower in guinea pigs with CPUO. These results indicate that higher EFPA in animals with mild compared to severe CPUO contributes to maintenance of higher SNGFR.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Prognostic factors in neonatal acute renal failure.

Sixteen infants, 2 to 35 days of age, had acute renal failure, a diagnosis based on serum creatinine concentrations greater than 1.5 mg/dL for at least 24 hours. Eight infants were oliguric (urine flow less than 1.0 mL/kg/h) whereas the remainder were nonoliguric. To determine clinical parameters useful in prognosis, urine flow rate, duration of anuria, peak serum creatinine, urea (BUN) concentration, and nuclide uptake by scintigraphy were correlated with recovery. Nine infants had acute renal failure secondary to perinatal asphyxia, three had acute renal failure as a result of congenital cardiovascular disease, and four had major renal anomalies. Four oliguric patients died: three of renal failure and one of heart failure. All nonoliguric infants survived with mean follow-up serum creatinine concentration of 0.8 +/- 0.5 (SD) mg/dL whereas that of oliguric survivors was 0.6 +/- 0.3 mg/dL. Peak serum creatinine concentration did not differ between those patients who were dying and those recovering. All infants who were dying remained anuric at least four days and revealed no renal uptake of nuclide. Eleven survivors were anuric three days or less, and renal perfusion was detectable by scintigraphy in each case. However, the remaining survivor (with bilateral renal vein thrombosis) recovered after 15 days of anuria despite nonvisualization of kidneys by scintigraphy. In neonates with ischemic acute renal failure, lack of oliguria and the presence of identifiable renal uptake of nuclide suggest a favorable prognosis.

Acute Kidney Injury↗

Early onset of clinical diabetic nephropathy in children--a new subgroup?

The onset of fixed proteinuria and hypertension in insulin-dependent diabetic is generally associated with eventual renal insufficiency due to diabetic nephropathy or with a superimposed glomerulopathy. We report three adolescents with normal renal function who developed fixed proteinuria and hypertension after only 7 to 11 years of insulin-dependent diabetes mellitus. Blood pressure ranged from 130/95 to 165/104 mmHg, urinary protein excretion was 1.31 to 1.37 g/24 hours, and creatinine clearance ranged from 98-133 ml/min/1.73 m2. Renal biopsy revealed changes consistent only with diabetic glomerulosclerosis. Follow-up evaluation for 11 months to 3 1/2 years revealed blood pressure reductions to 125/78-140/85 mmHg as a result of antihypertensive medications. Creatinine clearance increased by 12-20% and urinary protein excretion remained unchanged. We conclude that these patients may represent an unusual subgroup of insulin-dependent diabetics with early development of clinical and pathological diabetic nephropathy in the face of normal renal function.

Adolescent↗

Autoregulation of renal blood flow in the rat: effects of growth and uninephrectomy.

As a result of normal maturation or after reduction in renal mass, renal blood flow (RBF) progressively increases. However, the effects of renal growth on the relationship of RBF to renal perfusion pressure (RPP) have not been systematically investigated. We examined RBF as a function of RPP in anesthetized young and adult rats that had been subjected to uninephrectomy or sham operation 3-4 wk previously. As a result of normal growth, mean arterial blood pressure increased from 94.1 +/- 2.7 (SE) to 118.9 +/- 4.2 mmHg. The calculated autoregulation factor, in which a value less than 1 indicates the presence of autoregulation, was 0.44 +/- 0.10 over RPP 70-100 mmHg and 1.74 +/- 0.25 over RPP 40-70 mmHg in sham-operated young animals. In adult sham-operated rats, the factor was 0.38 +/- 0.07 over RPP 100-130 mmHg and 1.03 +/- 0.07 over RPP 70-100 mmHg. Uninephrectomy in adults resulted in a 30% rise in RBF over RPP 100-130 mmHg, and there was no change in the autoregulation factor. Uninephrectomy in young rats, however, resulted in a 35% rise in RBF at RPP = 100 mmHg with only a 17% rise at RPP = 70 mmHg, and the autoregulation factor increased to 0.91 +/- 0.10 over this range of RPP. We conclude that the autoregulatory range shifts with increasing blood pressure during normal growth and that autoregulation is "reset" to higher RBF in the uninephrectomized adult rat. Although autoregulation takes place in the young animal, uninephrectomy alters the relationship of RBF to RPP such that autoregulation is impaired.

Aging↗

Reduced renal mass in early postnatal development. glomerular dynamics in the guinea pig.

As shown previously in the neonatal guinea pig, unilateral nephrectomy at birth results in an earlier rise in superficial nephron glomerular filtration rate. To evaluate the role of glomerular dynamics in this compensatory adaptation, pressure gradients responsible for glomerular ultrafiltration in superficial nephrons were measured by micropuncture techniques in developing euvolemic guinea pigs subjected to uninephrectomy or sham operation at birth. Uninephrectomy resulted in a significant rise in mean arterial blood pressure and glomerular capillary pressure by 10 days of age. Effective filtration pressure was 30% higher in 10- and 21-day-old uninephrectomized guinea pigs compared to sham-operated littermates. However, there ws no significant increase in effective filtration pressure with normal growth from 10 to 21 days of age. Augmented pressure gradients for glomerular ultrafiltration therefore contribute significantly to early compensatory renal adaptation but not to the transitional sharp increase in superficial glomerular filtration which characterizes normal renal growth from 10 to 21 days of age. The apparent acceleration of functional glomerular maturation resulting from uninephrectomy of birth may result from the summation of differing responses to the demands of somatic growth and reduced renal mass.

Adaptation, Physiological↗

Hemodynamic adaptation to reduced renal mass in early postnatal development.

Radioactive microspheres, clearance methodology, and glomerular counting techniques were used to compare hemodynamic changes resulting from uninephrectomy at birth with those of sham-operated guinea pigs 8-13 days of age and 18-24 days old. Left renal blood flow doubled from 10-20 days of age, and was approximately 65% higher in animals with reduced renal mass. Cardiac output also doubled from 10-20 days of age but was not significantly affected by uninephrectomy whereas mean arterial blood pressure rose with normal or compensatory renal growth. There was a progressive fall in renal vascular resistance that paralleled the drop in total peripheral resistance during normal growth, but the fraction of cardiac output supplying the remaining kidney of renoprival guinea pigs rose significantly from 7% at 10 days to 11% at 20 days of age. Whole kidney filtration fraction averaged 0.25-0.29 for all groups. There was no change in cortical blood flow distribution with age or after uninephrectomy: 50, 30, and 20% supplied outer, middle, and inner thirds, respectively. Glomerular perfusion rate increased proportionately in all cortical levels during normal or compensatory renal growth, and was higher in outer and inner cortical thirds than in the middle cortex. It is concluded that systemic and intrarenal hemodynamic responses to uninephrectomy at birth are similar to the pattern of normal maturation. Reduction in renal mass and normal somatic growth provide additive stimuli resulting in maintenance of homeostasis.

Animals↗

Hypercalciuria in a child with primary Fanconi syndrome and hearing loss.

A hitherto undescribed association of sensorineural hearing loss and Fanconi syndrome (FS) is reported in a 10 year old black male. The patient presented with growth failure developing at the age of 6 and rachitic changes were detected the following year. No known cause for FS was identified, and renal biopsy was within normal limits. Distal tubular acidification and the threshold for proximal tubular bicarbonate reabsorption were normal, as was urine concentrating capacity. He was found to have significant hypercalciuria (urine calcium excretion 10 mg/kg/day) despite dietary calcium restriction, and urine calcium excretion increased further following an oral calcium load. Dietary sodium restriction to 16 mEq/kg/day resulted in a fall in urine calcium loss, which remained elevated at 6 mg/kg/day. Serum parathyroid hormone and 1,25 dihydroxy vitamin D3 (1,25(OH)2D3) concentrations were in the normal range. Treatment with neutral phosphate dietary supplementation resulted in partial healing of rickets and normal growth rate. Hypercalciuria resolved during phosphate administration (urine calcium excretion 3 mg/kg/day) without a fall in urine sodium excretion. It is concluded that in this patient with FS, hyperphosphaturia resulted in phosphate depletion and secondary hypercalciuria. A similar mechanism of hypercalciuria may be operative in a variety of renal tubular disorders affecting children and adults.

Calcium↗

Percutaneous transluminal angioplasty: the treatment of choice for renovascular hypertension due to fibromuscular dysplasia.

Twenty-three renal artery stenoses in 21 hypertensive patients, caused by fibromuscular dysplasia, were treated with percutaneous transluminal angioplasty (PTA). Follow-up over a period of 1 to 30 months, including angiography, renal vein renin assay, and radionuclide flow studies, was performed in 8 patients, each with one stenosis. Dilatation was initially successful in all cases and was successfully repeated in 1 case. The mean systolic pressure decreased by 61.81 mm Hg and the mean diastolic pressure by 36.28 mm Hg in response to treatment. Thirteen patients were cured, 8 were felt to have better control of blood pressure on medication, and there was no failures. This study demonstrates that PTA is a clinically effective method of treating renovascular hypertension due to fibromuscular dysplasia.

Adult↗

Functional adaptation to reduced renal mass in early development.

To determine whether reduced renal mass in the newborn results in acceleration of normal renal development, the response to unilateral nephrectomy (N) before 36 h of age was compared with sham-operated (S) guinea pigs during the period of most rapid nephron maturation. Studies were performed at 7-13 days (group I) and 19-25 days (group II). Mean arterial blood pressure (AP), left kidney glomerular filtration rate (LKGFR), and urine sodium excretion (UNaV) were measured. Superficial single nephron GFR (sSNGFR) and proximal fractional water reabsorption (FRH2O) were measured by micropuncture, and the number of glomeruli (NG) was determined by India ink perfusion. In view of the susceptibility of the neonate to extracellular fluid loss, groups I and II were plasma infused to maintain euvolemia and group II was compared with 19- to 25-day-old hydropenic animals (group III). Increase in body weight with age was unaffected by neonatal N. In group IN, the compensatory increase in sSNGFR was greater than SNGFR for deeper nephrons, which normally contribute most to GFR at this age. In group IIN there was an 80% adaptive increase in LKGFR that could not be entirely explained by the rise in SNGFR. Since NG in group IIN was greater than in group IIS and similar to that in adulthood, the enhanced adaptation in LKGFR in group IIN may be due in part to earlier recruitment of a population of underperfused glomeruli. FRH2O did not change significantly with age and did not differ in N and S groups. Animals in group III developed a rise in hematocrit during the experiment, and AP, LKGFR, and UNaV were lower in group IIIN than in group IIN. It is concluded that following N at birth, the sequence of renal functional maturation is accelerated while glomerulotubular balance is preserved. As a result of these adaptative changes, homeostasis is maintained and body growth proceeds without impairment.

Adaptation, Physiological↗

Glomerular number and perfusion during normal and compensatory renal growth in the guinea pig.

Changes in glomerular number and perfusion during maturation of the guinea pig were compared with the response to uninephrectomy at birth or 84 days of age. From birth to adulthood, there was a 21% increase in number of glomeruli identified by the presence of India ink previously injected in vivo. For animals uninephrectomized at birth, a similar increase occurred several wk earlier than in sham-operated littermates; however, uninephrectomy in adulthood resulted in no further increment. Although the number of glomeruli in the left kidney varied by 25% within each group, the difference in number between right and left kidneys of individual animals averaged only 4%. Additional glomeruli not identified by India ink were subsequently revealed by application of Wright's stain. These comprised 13-17% of the glomeruli containing India ink in 1 and 22-day-old sham groups, but only 2% in 22-day-old uninephrectomized or adult animals. Approximately 3/4 of all glomeruli identified by India ink were present in the outer cortex of 22-day-old uninephrectomized and sham-operated guinea pigs; the cortical distribution of Wright-stained glomeruli in the latter group was similar. Paraffin sections of kidneys revealed scattered glomeruli not containing India ink in 1-day-old and 22-day-old sham guinea pigs, but almost none in 22-day-old uninephrectomized animals. There were no glomeruli in an early stage of formation in any of the sections examined. It is concluded that during development, an increase in number of glomeruli identified by India ink represents nephrons which are underperfused in the neonate but are completely perfused at maturity. This process is accelerated by uninephrectomy in early development, but is unaffected by uninephrectomy in adulthood, at which time glomerular perfusion is virtually homogeneous.

Adaptation, Physiological↗

Prolonged anuria and aortic insufficiency in a child with Wegener's granulomatosis.

A 16 year-old boy developed generalized Wegener's granulomatosis with rapidly progressive renal insufficiency resulting in prolonged anuria. He was treated with cyclophosphamide, prednisone and anticoagulants, and was maintained on peritoneal dialysis for seven weeks, after which he regained a GFR of 35 ml/min. Recovery of renal function following prolonged anuria has not been previously reported in a child with Wegener's granulomatosis. The patient also developed aortic regurgitation, a cardiac lesion not previously described in this disorder.

Adolescent↗

The neonate with adult-type autosomal dominant polycystic kidney disease.

A premature infant with severe respiratory distress syndrome was found to have bilaterally enlarged kidneys and normal renal function. Renal ultrasonography confirmed renal enlargement but revealed no hydronephrosis or cysts. Family history was consistent with autosomal dominant polycystic kidney disease (ADPKD), and renal ultrasonography in the mother revealed bilateral multiple cysts of which she was previously unaware. The infant died of respiratory failure and septicemia, and autopsy revealed multiple microscopic renal cysts characteristic of early ADPKD. This case, along with 16 other affected newborns previously reported, illustrates the difficulty and importance of diagnosing ADPKD in the neonate. It is anticipated that awareness of this unusual cause of renal enlargement in the newborn will result in earlier diagnosis and appropriate genetic counselling.

Female↗

Effects of propranolol on post-ischemic acute renal failure.

The effects of constant intravenous infusion of propranolol, 1 mg/kg/h, on acute renal failure produced by 1 h occlusion of the left renal artery in the rat were investigated by clearance and micropuncture techniques. Propranolol infusion resulted in a significantly smaller rise in proximal intratubular pressure than that observed following renal ischemia in the saline-infused group. When compared with saline-infused animals, this effectwas accompanied by a significant improvement in inulin clearance without commensurate increase in renal blood flow or stop flow pressure and suggests attenuation of intratubular obstruction by the drug. A complex metabolic effect may be involved.

Acute Kidney Injury↗

Recovery from postischemic acute renal failure in the rat.

To define the pattern of recovery from postischemic acute renal failure (ARF), we performed clearance and micropuncture studies at intervals of 1, 2, 4, and 8 weeks following 60 min of complete unilateral renal artery occlusion in the rat. At 1 week, the inulin clearance (CIn) of the postischemic kidney was less than 2% of normal. The presence of marked preglomerular vasoconstriction was indicated by the reductions in renal blood flow (RBF), and stop-flow (SFP) and estimated glomerular capillary hydrostatic pressures (GCPe). In additon, there was evidence of tubular obstruction. Proximal intratubular pressures (PITP) were elevated, and intratubular casts could be seen in vivo and on histologic sections. At 2 weeks CIn had increased more than tenfold. This change occurred in the absence of any significant elevation in RBF, SFP, or GCPe. PITP had fallen, however, to normal values, and histologic sections revealed a marked reduction in the extent of intratubular casts. Ipsilateral urinary recovery of 3H-inulin microinjected into proximal convolutions was complete. At 4 and 8 weeks, there were further but more gradual rises in CIn, which were associated with progressive increases in RBF, SFP, and GCPe. These observations indicate that recovery from postischemic ARF occurred in a biphasic pattern. The initial rise in CIn was associated with the relief of intratubular obstruction, whereas subsequent rises in CIn occurred in association with progressive renal vasodilation.

Acute Kidney Injury↗

Chronic ureteral obstruction in the rat suppresses renal tubular Bcl-2 and stimulates apoptosis.

Unilateral ureteral obstruction (UUO) results in widespread tubular apoptosis in obstructed kidneys of both adults and neonates. The oncoprotein bcl-2 inhibits many forms of apoptosis, whereas the related protein bax promotes apoptosis. To evaluate the interaction of bcl-2, bax, and apoptosis in the renal response to UUO, adult and neonatal rats were subjected to UUO or sham operation, and kidneys were harvested 14 days later. Apoptotic cells were identified by the Tunel technique, and the distribution of bcl-2 and bax was determined by immunochemistry. In both adults and neonates, tubular and interstitial apoptosis was present in the obstructed kidney, but not in intact kidneys. In both adults and neonates, there was diffuse tubular bcl-2 and bax staining of sham-operated and intact kidneys. While bcl-2 was increased in scattered nonapoptotic tubules of the obstructed kidney, there was minimal staining of dilated apoptotic tubules. These results are consistent with the premise that bcl-2 normally suppresses renal tubular apoptosis. The distribution of bax staining in tubules of the obstructed kidney overlapped that of bcl-2. We conclude that chronic UUO inhibits bcl-2 expression in selected tubules of the obstructed kidney which contributes to activation of apoptosis and progressive renal damage in either neonatal or adult kidneys. Dysregulation of apoptosis may be a response to renal injury similar to that underlying the development of cystic kidney disease or renal dysplasia.

Animals↗

Seizures and blindness following intravenous pulse methylprednisolone in a renal transplant patient.

Seizures in renal transplant recipients may be due to a variety of causes. Although intravenous pulse methylprednisolone used to treat acute rejection episodes has been reported to be associated with acute central nervous system (CNS) manifestations in adult renal transplant patients, this complication has not previously been described in pediatric patients. We report a 12 year old renal transplant recipient who developed transient blindness and focal seizures 72 hours following intravenous pulse methylprednisolone. Serum creatinine and urea nitrogen were 1.5 and 31 mg/dl respectively; serum electrolytes, calcium, magnesium, phosphate, and glucose were normal. Although usually due to other etiologies, seizures in the pediatric transplant recipient may be secondary to acute CNS toxicity resulting from intravenous glucocorticoid infusion.

Blindness↗