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.

Hemolytic-uremic syndrome.

The hemolytic-uremic syndrome (HUS) has been recognized for more than 45 years and consists of the combination of hemolytic anemia, thrombocytopenia, and acute renal failure. HUS occurs predominantly in children younger than 4 years of age. It is the most frequent cause of acute renal failure in children. The most common form of the syndrome (D+ HUS) occurs in healthy young children (>6 mo to <5 y of age) and is preceded by watery diarrhea that can evolve to hemorrhagic colitis. The diarrhea precedes the hemolysis and thrombocytopenia by 5 to 7 days; oliguria/anuria follows several days later. Although the pathogenesis is unknown, available evidence strongly suggests that endothelial cell damage is necessary. The outcome for most patients who have D+ HUS is favorable: 65% to 85% recover completely, 5% to 10% die (usually during the acute illness), recurrence is uncommon, and only a few patients slowly progress to end-stage renal disease (ESRD).

Office evaluation of the child with hematuria.

Most children with an identifiable cause of hematuria will be properly diagnosed if an appropriate evaluation is completed. However, some children with persistent hematuria will not have an identifiable cause. This article provides clinical advice on properly diagnosing the child.

Angiotensin or thromboxane receptor antagonism in rats with congenital hydronephrosis.

A technique for the measurement of GFR without collection of urine in rats was experimentally validated and applied to experiments designed to: (1) evaluate the degree of reduction of GFR in rats with congenital, unilateral hydronephrosis; and (2) to determine if the reduction in renal function is mediated by angiotensin II and/or thromboxane A2 mechanisms. Simultaneous measurements of GFR by a constant-infusion technique and the traditional inulin clearance technique in rats with either one or two normal kidneys were highly correlated (r = 0.934; P < 0.001; N = 17). GFR was approximately 24% lower (P < 0.001) in rats with congenital unilateral hydronephrosis than in rats with a normal kidney. The GFR in rats with hydronephrosis infused with a receptor blocker for either angiotensin II or thromboxane A2 was greater than the GFR in hydronephrotic kidneys without blockade and was not significantly different (P > 0.05) from that in rats with normal kidneys. These results indicate that a constant inulin infusion technique without urine collections can be used to accurately measure GFR in congenitally hydronephrotic kidneys, rendering values free from possible residual pelvic volume artifact. In addition, these results also indicate that a significant 24% reduction in GFR occurs in congenital unilateral hydronephrosis and is mediated by angiotensin II and thromboxane A2 mechanisms.

Beckwith-Wiedemann syndrome and its association with type III polycystic kidney disease.

Two cases from our institution and another from the literature in which Beckwith-Wiedemann syndrome (BWS) and type III polycystic kidney disease (PKD) occurring simultaneously are discussed. The importance of recognizing the subtle signs of BWS is stressed, because of the increased risk of malignancies, as well as the need for continued evaluation of patients with BWS for the development and complications of PKD.

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.

Increased tacrolimus levels in a pediatric renal transplant patient attributed to chronic diarrhea.

Tacrolimus is an immunosuppressant used to prevent rejection of transplanted organs. It is metabolized in both the gut and the liver by the cytochrome P450 (CYP) 3A4 enzyme system and is a substrate for the P-glycoprotein (P-gp) drug efflux pump. As CYP3A4 enzymes and P-gp are present at differing concentrations throughout the gastrointestinal tract, the bioavailability of tacrolimus may be influenced by changes in gastrointestinal transit time in addition to changes in hepatic metabolism. We report the case of a pediatric renal transplant patient who experienced a three-fold increase in serum tacrolimus concentrations during an episode of gastroenteritis with chronic diarrhea.

Nephrosonography in the evaluation of renal failure and masses in infants.

The diagnostic accuracy of nephrosonography is compared with conventional radiologic techniques and surgical findings in 13 infants aged 1 day to 14 months, who were in renal failure or had abdominal masses. Ten of the 13 infants presented with marked renal failure and in half of them neither kidneys nor collecting systems were visualized on the first intravenous pyelogram. Normal renal architecture was demonstrated by nephrosonography in three, hypoplastic kidneys in three, hydronephrosis in three, and a combination of hydronephrosis and contralateral multicystic kidney in one. In the three infants without renal failure, only one kidney was demonstrated by IVP; The cystic contralateral kidney in each of them was demonstrated by nephrosonography. In all cases the diagnosis was confirmed by conventional radiologic techniques when renal function had improved or by surgical exploration. This technique appears to be a useful adjunct to conventional radiography in the differential diagnosis of the infant with abnormalities of the urinary tract. Nephrosonography is of especial value when a kidney is not visualized by IVP, and it may appropriately aid in therapeutic decisions regarding the use of invasive procedures in small critically ill infants.

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.

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.

The quest for living-related kidney donors for children with end-stage renal disease.

In a pediatric renal transplant program that actively seeks living-related kidney donors, we achieved a living donor rate of 55% in 119 children. This approximates the national average but is less than an idealized goal. For black children, the living-donor transplant rate was 41%, a disconcertingly low rate. In an attempt to define factors that negatively affected living-related donor availability, we analyzed our evaluation process by distinct phases (interview, histocompatibility testing and medical evaluation). We classified our families on the basis of locale (urban, suburban and rural), family unit (two or less parents, adult sibs or other relatives presenting at interview) and economic status (designating only economic-disadvantaged and other). While histoincompatibility is predictably a negative factor, the negative impacts of medical illness in the donor pool, economic disadvantage and single parent family are striking and cumulative. Our data validate the relative success of an aggressive recruitment policy in a patient population that includes many economically disadvantaged families. For pediatric renal transplant programs with low living-related donor rates, our data should encourage review and possible modification of the donor recruitment process.

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.

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.

Erythropoietin and inhibitors of in vitro erythropoiesis in the development of anemia in children with renal disease.

The relative roles of erythropoietin and potential inhibitors of erythropoiesis in the development of anemia in children with renal disease have been studied. Thirty-five children with renal disease of varied origins and severity were compared with 30 children with anemia of similar severity and with normal renal function. Serum erythropoietin was measured by radioimmunoassay; erythroid (CFU-E) and granulocytic (CFU-GM) progenitor cell growth were assessed in fetal mouse liver cell and normal human bone marrow cell cultures, respectively. The degree of serum inhibition of in vitro CFU-E growth in children with renal disease correlated with both creatinine clearance (r = 0.59, P less than 0.001) and hematocrit level (r = 0.55, P less than 0.005). Serum from children with renal disease inhibited in vitro CFU-E growth in a dose-related manner. Normal serum did not inhibit CFU-E growth in culture. The mean serum erythropoietin concentration was significantly (P less than 0.025) higher in children with anemia of renal disease (32.4 +/- 2.4 mU/ml) in comparison with serum values in normal children (19.6 +/- 1.5 mU/ml), but serum erythropoietin levels did not correlate with hematocrit level, creatinine clearance, or serum inhibition of in vitro erythropoiesis. In contrast, children with anemia and normal renal function showed a significant (P less than 0.001) linear increase in serum erythropoietin concentration (range 28.7 to 327 mU/ml), increased reticulocyte count, and stimulation of CFU-E formation with decreasing hematocrit levels. Coincubation of human urinary erythropoietin in the presence of serum from patients with uremia revealed markedly less immunoreactivity in the radioimmunoassay and less biologic activity in the fetal mouse liver CFU-E assay for erythropoietin than when erythropoietin was incubated with normal human serum, suggesting some alteration of erythropoietin in the presence of uremic serum, which reduced both the immunologic and biologic activity of erythropoietin. Normal and uremic sera inhibited CFU-GM growth to the same degree in comparison with controls. In conclusion, relative erythropoietin deficiency, direct alteration in the biologic activity of erythropoietin by uremic toxins, and serum inhibition of erythroid progenitor cells in the bone marrow are probably important factors in the pathogenesis of anemia in children with renal disease.