Melinda McVicar

Transient urodynamic dysfunction of infancy: relationship to urinary tract infections and vesicoureteral reflux.

PURPOSE Urinary tract infections and vesicoureteral reflux are more common in male than female infants. Since these problems can result from voiding dysfunction, we obtained a detailed history of voiding patterns and urodynamic testing in infants with urinary tract infections in the first year of life. MATERIALS AND METHODS We evaluated 39 male and 22 female infants, including 40 with primary vesicoureteral reflux and 21 with no reflux or obstruction. RESULTS Voiding abnormalities were noted in 97% of the male and 77% of the female infants, including high voiding detrusor pressure of greater than 40 cm. water in 92% of the male and 66% of the female infants, residual urine greater than 2 ml./kg. in 13% of the male and 23% of the female infants, and detrusor hyperreflexia with filling pressure greater than 40 cm. water in a third of the male infants. Voiding detrusor pressure was significantly higher in male than female infants and in male infants with grade IV to V reflux than those with lower grades of reflux or no reflux. Followup urodynamic testing in 15 infants with high voiding detrusor pressure revealed resolution of detrusor hyperreflexia and improvement in post-void residual in all and decreased voiding detrusor pressure in 14. CONCLUSIONS We coined the term transient urodynamic dysfunction of infancy to describe this constellation of abnormalities, which predisposes infants to urinary tract infections and vesicoureteral reflux but improves spontaneously. The higher incidence of urinary tract infections and reflux in male infants may be related to higher intravesical pressures.

Hypertension secondary to renin-secreting juxtaglomerular cell tumor: case report and review of 38 cases.

A 15-year-old girl with severe high renin hypertension caused by a juxtaglomerular cell tumor (JCT) was successfully treated with the calcium channel blocker nifedipine until surgical removal effected a permanent cure. This case was incorporated into a review of the 37 cases previously published. Comparison of the children and adolescents with the adult population showed that the features of JCT were similar in the two groups except for the average duration of symptoms prior to diagnosis (pediatric group 2.6 years vs. 6.0 years for the adult group). Analysis of all 38 cases demonstrated the following:1.Teenagers constituted the largest single population with JCT (39%) and approximately two-thirds of the entire population were female.2.Many patients failed to show persistent hypokalemia despite high plasma renin activity and secondary hyperaldosteronism.3.Renal angiography was initially negative in more than half the cases.4.Renal vein renin failed to show lateralization to the affected kidney in 52% of the cases.5.Computerized tomography demonstrated a renal mass in all of the cases in which it was performed, even when other imaging studies were negative.6.Calcium channel blockers may evolve as the preferred treatment for the high renin hypertension of JCT.

Experimental Lead Poisoning and Intestinal Transport of Glucose, Amino Acids, and Sodium

Summary: Juvenile rats fed a diet containing 1% lead acetate for 7 weeks, in addition to an impaired growth rate and renal function derangements, suffered malabsorption of glucose and certain amino acids, as assessed by an in vivo perfusion technique. The reduction in glucose absorption ranged between 10% and 31% when the carbohydrate was pumped in concentrations of 2–80 mM. This alteration was compatible with a noncompetitive type of transport inhibition. The intestinal absorption of glycine, lysine, and phenylalanine were, respectively, decreased 22, 18, and 15% when these amino acids were present at 1 mM levels. Sodium transport was severely reduced (57.6 ± 17.9 (SEM) vs. 124.2 ± 17.4 μEq/min-cm) and intestinal mucosa (Na+-K+ )-ATPase was concomitantly lower in the lead-intoxicated rats (186.4 ± 19.0 vs 268.4 ± 29.8 nmol P/minmg protein). However, this enzyme was not altered in liver and kidney. Furthermore, intestinal mucosa fructose-1,6-diphosphatase, succinie de-hydrogenase, pyruvate kinase, and tryptophan hydroxylase were not different in experimental and control animals. These studies substantiate the presence of functional and biochemical abnormalities in the intestinal mucosa of young rats when fed substantial amounts of a soluble lead salt. It is, therefore, reasonable to accept the possibility that physiologic damage occurs in tissues directly subjected to high and persistent levels of a toxic agent, as it occurs in other organs, underscoring the parallelism between transport mechanisms at the renal and intestinal levels.Speculation: The gastrointestinal symptoms often associated with chronic lead intoxication may be related to physiologic damage of the intestinal mucosa transport mechanisms. Therefore, intestinal mucosa could be considered another primary target organ for lead poisoning, as the kidney, the erythropoietic system, and nervous tissue are known to be.

Pathologic characterization of a renin-secreting juxtaglomerular cell tumor in a child and review of the pediatric literature.

We describe a rare case of renal hypertension in a 15-year-old caused by juxtaglomerular cell tumor and compare our findings with those of 20 children reported in the literature. These tumors are usually encapsulated and composed microscopically of polyhedral cells with bland nuclei separated by fibrovascular septa. Characteristic renin granules can be demonstrated by Bowies stain or electron microscopy. These tumors are benign. Pathologists should recognize the morphologic characteristics of these tumors when dealing with renin-producing neoplasia.

Idiopathic arterial calcification of infancy: a case with prolonged survival

We describe a patient with idiopathic arterial calcification of infancy and the following unusual features of the disease: (1) prolonged survival until age 11 years, (2) discordance between the extent of vascular calcification and clinical manifestations of arterial luminal occlusion, (3) a large area of myocardial calcification, (4) symptoms of cerebral-vascular insufficiency, and (5) spontaneous resolution of hypertension.

Normalization of hematocrit in a uremic patient receiving hemodialysis: Role of erythropietin**

of the kidney biopsy revealed thickened capillary walls with swollen endothelial cells and focal fibrin deposition. Pathologic changes of myoglobinuric renal failure (tubular necrosis with myoglobin casts in the tubules) were not detected. 4 Immunofluorescence studies revealed focal and segmental intracapillary deposits of fibrin, IgM, IgG, and IgA in a pattern suggestive of intracapillary thrombosis. Electron microscopy studies showed typical widening of the subendothelial space with electron-lucent material.

Intraperitoneal production of erythropoietin with continuous ambulatory peritoneal dialysis

Higher hematocrit and serum erythropoietin (EPO) levels have previously been shown in end-stage renal disease patients treated with continuous ambulatory peritoneal dialysis (CAPD) compared with hemodialysis. We investigated whether EPO was produced intraperitoneally in CAPD patients. EPO concentration was 3.5±0.3 mU/ml by radioimmunoassay in 26 samples of peritoneal dialysis effluent obtained from 15 CAPD patients. EPO was not detectable in the fresh unused dialysate. No correlation was observed between EPO levels in the serum and dialysis effluent. Peritoneal macrophages were isolated from the dialysis effluent of 9 CAPD patients after an overnight dwell. The culture supernatant obtained after 24 h of in vitro culture of a million cells yielded EPO of 3.5±0.3 mU/ml. Our study demonstrated that peritoneal macrophages from CAPD patients produce EPO on in vitro stimulation, and EPO is present in the dialysis effluent of CAPD patients.

Effects of amino acid additives during hemodialysis of children

The intradialytic losses into the dialysate of free amino acids (AA) and alpha-amino nitrogen were determined during the dialysis of three children. Variations in plasma AA were determined pre- and postdialysis. The effect of these losses with the addition of an Abbott General Amino Acid Mixture to the dialysate in concentrations of 8.5, 17, and 34 mg/100 ml was studied. The major determinant of AA losses was the plasma concentration of the AA before beginning the dialysis treatment. Dialysance of individual AA varied inversely with their molecular weights. A zero flux of alpha-amino nitrogen occurred at a derived concentration of 22 mg/100 ml of the AA additive in the dialysate. Plasma concentrations of nonessential amino acids were little affected by the dialysate additive. In contrast, total essential amino acid nitrogen which fell during baseline dialyses showed significant improvement when the AA solution was added to the dialysate. This study suggests that the addition of AA to the dialysate bath may be effective in decreasing AA nitrogen losses during dialysis.

Experimental Focal Segmental Glomerulosclerosis: Correlation with Protein Excretion, Glomerular Filtration Rate, and Renal Plasma Flow

ABSTRACT. A rat model of focal segmental glomerulosclerosis (FSGS) produced by repeated injections of amino-nucleoside (AMN) of puromycin was used to evaluate the relative roles of hemodynamic alterations and AMN-induced glomerular visceral epithelial cell injury in the development of FSGS.Twenty rats received three intraperitoneal injections of AMN on days 1, 21, and 28 and developed significant proteinuria. On day 50, 14 rats (group 1) underwent selective left renal perfusion with AMN and six rats (group 2) received left renal perfusion with saline. At sacrifice on day 70 or 110, group 2 rats had similar values in left and right kidneys for glomerular filtration rate (GFR), effective renal plasma flow (ERPF), and the amount of FSGS (13.1 ± 5.6% in left and 12.9 ± 7.8% in right). In contrast, group 1 rats manifested a significantly higher amount of FSGS in right kidneys as compared to left kidneys (3.1 ± 1.3% in left and 6.3 ± 2.0% in right, as well as significantly diminished GFR and ERPF in left as compared to right kidneys. A higher degree of FSGS was seen in kidneys with a higher GFR and ERPF. A positive correlation was observed between the mean 24-h protein excretion of the rats and the percentage of FSGS in left and right kidneys (r = 0.66, p < 0.01).

Intestinal transport of glucose and amino acids in experimental uremia.

Summary: The effects of chronic uremia on the intestinal transport of amino acids and glucose were assessed by an in vivo perfusion technique in young uremic rats and pair-fed controls. The experimental rats were rendered uremic by a modification of the conventional nephrectomy, and control animals were sham operated. All intestinal perfusions were performed 4 to 6 wk after completion of surgical induction of uremia. The mean BUN of the experimental group at the time of evaluation of intestinal transport was 79 ± 18 mg/dl (mean ± S.E.) compared to 23 ± 9 mg/dl (P < 0.02) in control animals. A 20-cm-long segment of proximal jejunum was perfused in vivo with Krebs-Henseleit buffers containing amino acids and carbohydrates with 14C-and 3H-labeled tracers. The jejunal absorption of tyrosine was significantly increased in uremic rats: 5.63 ± 0.42 as compared to 3.47 ± 0.28 nmoles/min cm in the controls (P < 0.001). Similarly, the absorption of phenylalanine was increased in the uremic rats; 5.79 ± 0.41 versus 3.74 ± 0.32 nmoles/min cm in the control rats (P < 0.001). Confirmation that increased phenylalanine absorption represented a true lumen-to-blood flow was obtained by measurement of [3H]phenylalanine in blood drawn from the aorta after 60 min of perfusion. The blood count in uremic rats was 2,307 ± 257 dpm/ml versus 1173 ± 172 dpm/ml in controls (P < 0.01). The absorption of glucose along the jejunum was also increased in the uremic rats over the controls both at 4 and 40 mM. At 4 mM, the absorption in uremic rats was 27.79 ± 1.84 versus 21.02 ± 1.66 nmoles/min cm (P < 0.01) in controls. At 40 mM, the values were 228.5 ± 16.3 and 170.9 ± 16.9 nmoles/min cm, respectively (P < 0.02). In contrast, the absorption of histidine and alpha-aminoisobutyric acid was not significantly different between uremic and control animals. The alterations in jejunal transport were associated with a decreased incorporation of [3H]phenylalanine into protein in the cell membrane-rich portion of intestinal mucosal scrapings (43.7 ± 4.7 nCi/g protein versus 94.2 ± 13.1 nCi/g protein in controls; P < 0.01). There was also secretion of glucose from blood-to-intestinal lumen, which was significantly greater in uremic than in control animals: 1.41 ± 0.16 versus 0.87 ± 0.05 nmoles/min cm (P < 0.01). These results are consistent with an alteration of the integrity of the jejunal mucosa in uremia which affects its permeability and alters the transport of nutrient.Speculation: The decreased incorporation of phenylalanine into membrane-bound material of the jejunal mucosa and the increased blood-to-lumen flux of glucose in uremic rats may indicate a defect in the integrity of the intestinal mucosa. This may be associated with an altered premeability, which facilitates increased intestinal absorption of solutes. These kinds of changes in uremia seem to be different in pathogenesis from those induced by malnutrition per se. The observed changes in jejunal absorption appear to compensate for, rather than to contribute to, the malnutrition and growth failure typical of chronic uremia.