Frank G. Boineau

Ultrafast Contrast Enhanced Magnetic Resonance Imaging of Congenital Hydronephrosis in a Rat Model

Since new ultrafast magnetic resonance imaging (MRI) might offer unique advantages for evaluating renal blood flow, anatomy and urinary excretion, we used this technique to characterize a rat model with congenital partial ureteropelvic junction obstruction. MRI of 9 rats from an inbred colony with unilateral congenital (nonsurgical) hydronephrosis was compared with the contralateral nonhydronephrotic kidney serving as control. Our new imaging technique consisted of a 1-minute ultrafast gradient recalled imaging sequence during the first minute (64 images per imaging time 960 milliseconds) after contrast bolus injection with gadolinium-diethylenetriaminepentaacetic acid for assessment of renal blood flow followed by a 30-minute period with image acquisition every 30 seconds to study contrast distribution and excretion. Signal intensities were analyzed continuously over selected, different regions of interest. Anatomic analysis of MRI noncontrast studies showed precise delineation of the hydronephrotic pelvis and corticomedullary junction. After contrast gadolinium-diethylenetriaminepentaacetic acid injection signal intensity from the region of interest from hydronephrotic kidneys differed from nonhydronephrotic kidneys by showing less cortical decrease, suggesting decreased blood flow, less medullary decrease and delayed contrast excretion. Clear contrast distribution among the cortex, medulla and collecting system allowed selective estimation of different regions of interest and excellent anatomic evaluation. Renal anatomy and renal pelvic pressures were confirmed after scans were completed. Ultrafast contrast enhanced MRI allows simultaneous assessment of renal morphology, blood flow and function. In hydronephrotic partially obstructed kidneys distinct flow and excretion patterns measured with contrast enhanced MRI allow differentiation between the obstructed and nonobstructed kidney on physiological rather than purely anatomic means. This imaging technique may provide a useful method of evaluating congenital hydronephrosis obviating the need for multiple different diagnostic procedures.

Congenital Unilateral Hydronephrosis in a Rat Model: Continuous Renal Pelvic and Bladder Pressures

We investigated a rat model with inbred unilateral congenital hydronephrosis. Simultaneous bladder and renal pelvic pressures were measured during different urinary flows, and during bladder filling and voiding in these congenitally hydronephrotic rats (approximately 45 days old) and normal nonhydronephrotic rats from the same colony. Differential pressures between pelvis and proximal ureter were determined. Upon termination of the experiment the urinary tract was removed and processed for histological examination. Hydronephrotic rats had significantly higher renal pelvic pressures throughout bladder filling at all urinary flow rates than normal rats. These elevated renal pelvic pressures exceeded bladder pressures at high flows (for example bladder pressure at 50% capacity was 8.9 +/- 3.1 cm. water and corresponding pelvic pressure was 20.8 +/- 2.1 [hydronephrosis] versus pelvic pressure 7.4 +/- 1.1 [control]). While pressures in the proximal ureter were higher than in the pelvis in normal rats the hydronephrotic rats showed significantly higher pressures in the pelvis, suggesting that the site of obstruction is the ureteropelvic junction. Histological evaluation of the excised kidneys revealed only minimal tubular changes. This study represents a unique animal model with unilateral hydronephrosis from a partially obstructing ureteropelvic junction. Moreover, the data indicate that partial urinary obstruction and the associated renal pelvic pressures should be defined with reference to bladder fullness and urinary flow rates.

Reversible vasoconstriction in rats with congenital unilateral hydronephrosis

We studied the effects of inhibition of either prostaglandins or the role of prostanoids and the renin-angiotensin system on renal function in rats with congenital unilateral hydronephrosis. Wistar rats with congenital unilateral hydronephrosis were infused with normal saline (control), captopril dissolved in normal saline or indomethacin dissolved in a solution of sodium chloride and sodium carbonate. In the control group both glomerular filtration rate (GFR) and effective renal plasma flow were reduced in the right hydronephrotic kidney (RHK) compared with the normal left kidney. Indomethacin did not improve renal function in the RHK. Captopril significantly improved GFR in the RHK. These results support the conclusion that the renin-angiotensin system is an important mediator of reduced GFR in congenital unilateral hydronephrosis in rats.

Reversible myopathy due to labetalol

A severe, generalized myopathy developed in 2 children treated with labetalol. An 11-year-old girl and a 14-year-old boy demonstrated proximal weakness and markedly elevated creatine kinase levels during labetalol therapy. Clinical improvement began immediately when labetalol administration was halted; muscle strength was normal within 2 months. Muscle biopsies were consistent with rhabdomyolysis.

Estimation of parenteral fluid requirements.

This article reviews the normal physiologic losses of water and electrolytes from the body, the source of the loss, and the increased body loss of water associated with fever. The three different methods for estimating replacement of water and electrolyte losses are described in this review.

Effect of urinary tract infection on ureteropelvic junction obstruction in a rat model.

OBJECTIVES When a partially obstructed kidney becomes infected, more rapid and extreme renal parenchymal damage appears to occur than might result from either infection or obstruction alone. Previously, we showed that either bacteriuria or partial obstruction in congenital unilateral hydronephrosis causes elevated renal pelvic pressures in a rat model. In this same model, we examined the combined effects of partial upper tract obstruction and bacteriuria on renal pelvic and bladder pressures. METHODS Female rats from an inbred colony in which more than one half are born with unilateral obstructive hydronephrosis were studied. Type 1 piliated Escherichia coli was instilled into the bladder. Two to 6 days later, the bladder and renal pelvic pressures were measured during varying urinary flows (less than 2 to more than 30 mL/kg/hr). All animals were killed and the kidneys and bladder grossly and histologically assessed. Hydronephrosis was determined at pathologic examination. RESULTS Eight rats had congenital unilateral hydronephrosis; five were normal. Acute inflammation was found in all bladder and renal specimens. In hydronephrotic, infected kidneys, the renal pelvic pressures exceeded those in nonhydronephrotic, infected kidneys at all urinary flow rates. Bladder capacity and pressures did not differ between the two groups. CONCLUSIONS This model demonstrates that the combination of infection and obstructive hydronephrosis in this model causes renal pelvic pressure elevation that is higher than that associated with either infection or obstructive hydronephrosis alone. These data demonstrate the compound effect that infection and obstruction may have on the kidney and offers an explanation for why this clinical situation is more likely to be associated with greater renal parenchymal injury than either alone.

DIAGNOSIS OF CONGENITAL NEPHROTIC SYNDROME: A CLINICAL AND A PATHOLOGIC CHALLENGE

The diagnosis of congenital nephrotic syndrome (NS) is a challenge both for clinicians and for pathologists. We observed three cases in a series of 50 children with NS nonresponsive to therapy, corresponding to one case each of minimal change disease, Finnish-type glomerulopathy, and diffuse mesangial sclerosis--two histopathologic studies were performed in each case. The age at presentation did not predict the diagnosis nor the prognosis: The NS presented at 7 months of age in the patient with diffuse mesangial sclerosis, but it was present at birth in the patient with minimal change disease. In these 2 patients the final diagnosis was made with the first renal biopsy. Conversely, in the patient with Finnish-type glomerulopathy, the diagnosis was only possible in the repeat biopsy, as the early pathologic changes were nonspecific. This study shows the essential role of the renal biopsy in determining the etiologic diagnosis and prognosis in patients with congenital nephrotic syndrome.

The Renal Quantitative Scintillation Camera Study for Determination of Renal Function

The renal quantitative scintillation camera study assesses glomerular filtration rate and effective renal plasma flow based upon renal uptake of 99mtechnetium-iron ascorbate and 131iodine-hippuran, respectively. The method was compared to inulin, para-aminohippuric acid and creatinine clearance studies in 7 normal subjects and 9 patients with various degrees of reduced renal function. The reproducibility of the technique was determined in 15 randomly selected pediatric patients. The values of glomerular filtration rate and effective renal plasma flow were not significantly different from those of inulin and para-aminohippuric acid studies. The reproducibility of the technique was comparable to that of inulin and para-aminohippuric acid studies. Patient acceptance of the technique is excellent and the cost is minimal. Renal morphology and excretory dynamics also are demonstrated. The technique is advocated as a clinical measure of renal function.

Oxybutynin lowers elevated renal pelvic pressures in a rat congenital unilateral hydronephrosis.

We investigated whether oxybutynin could lower elevated renal pelvic pressures measured in a rat with an inbred unilateral congenital hydronephrosis. Simultaneous renal pelvic and bladder pressures were measured in 8 hydronephrotic rats and compared to those of 10 hydronephrotic rats treated with intravenous injection of 1.6 mg./kg. oxybutynin. Pressures were recorded at different urinary flow rates and during bladder filling and emptying. Hydronephrotic rats not given oxybutynin showed significantly higher renal pelvic pressures (e.g. p-bladder at 50% capacity = 8.9 +/- 3.1 cm. H2O, corresponding p-pelvis = 20.8 +/- 2.1 at very high urinary flow rates) than rats treated with oxybutynin. The latter had renal pelvic pressures similar to rats with normal non-hydronephrotic kidneys (e.g. p-bladder at 50% capacity = 10.1 +/- 3.5 cm. H2O, corresponding p-pelvis = 6.3 +/- 1.1 at very high urinary flow rates). Renal pelvic pressures were, moreover, lower than corresponding bladder pressures in contrast to the untreated hydronephrotic pelvic pressure that exceeded bladder pressure. This effect of oxybutynin in lowering elevated renal pelvic pressures in the obstructed kidney has not been described before and suggests a possible role for oxybutynin in this condition.

Serum osteocalcin concentrations in children with chronic renalinsufficiency who are not undergoing dialysis

This report describes the serum osteocalcin values in children with mild to moderate, but relatively stable, renal dysfunction followed in the Growth Failure in Children With Renal Diseases Study. This report is derived from data obtained during the control period (6 months) before the initiation of vitamin D therapy. Up to three measurements per patient were obtained. Serum osteocalcin concentration was compared with creatinine clearance (glomerular filtration rate) calculated by the Schwartz formula; with serum concentrations of alkaline phosphatase, parathyroid hormone, and bicarbonate; and with the percentages of the recommended dietary allowances of calories and protein ingested. By standard correlation techniques, there appeared to be an inverse correlation between calculated creatinine clearance and serum osteocalcin concentration, and a direct correlation between serum osteocalcin and parathyroid hormone values. However, when we employed a statistical technique that takes into account repeated measures in the same patient, no correlation was found between calculated glomerular filtration rate and serum osteocalcin concentration, and no direct correlation was found between serum osteocalcin and parathyroid hormone values. The lack of a correlation between calculated glomerular filtration rate and serum osteocalcin values may be due to large fluctuations in the serum osteocalcin concentration, even though renal function is relatively stable.