Single donor-derived strongyloidiasis in three solid organ transplant recipients: case series and review of the literature.

Donor-derived Strongyloides stercoralis infections in transplant recipients are a rare but recognized complication. In this case series, we report donor-derived allograft transmission of Strongyloides in three solid organ transplant recipients. Following detection of infection in heart and kidney-pancreas recipients at two different transplant centers, a third recipient from the same donor was identified and diagnosed. S. stercoralis larvae were detected in duodenal aspirates, bronchial washings, cerebrospinal fluid, urine and stool specimens. Treatment with ivermectin and albendazole was successful in two of the three patients identified. The Centers for Disease Control and Prevention was contacted and performed an epidemiologic investigation. Donor serology was strongly positive for S. stercoralis antibodies on retrospective testing while all pretransplant recipient serum was negative. There should be a high index of suspicion for parasitic infection in transplant recipients and donors from endemic regions of the world. This case series underscores the need for expanded transplant screening protocols for Strongyloides. Positive serologic or stool tests should prompt early treatment or prophylaxis in donors and recipients as well as timely notification of organ procurement organizations and transplant centers.

Short-course versus conventional length antimicrobial therapy for uncomplicated lower urinary tract infections in children: a meta-analysis of 1279 patients.

OBJECTIVE: The objective was to compare the efficacies of single-dose, short-course (4 days or less), and standard course (5 days or greater) antimicrobial therapy for uncomplicated childhood cystitis. METHODS: Prospective, randomized, controlled trials comparing 4 days or less of therapy (short courses) with 5 days or more of therapy (conventional therapy) were included if all of the subjects were <18 years of age, the initial infection was documented by urine culture, at least 1 subsequent culture was obtained between 3 and 30 days of enrollment, and some attempt was made to separate upper tract from lower tract infection. Composite differences among treatment groups were compared with a fixed or random effects model, depending on the test for heterogeneity. RESULTS: Of the 517 citations identified by literature search, 37 were selected for detailed review, and 22 were included in the final meta-analysis. The overall difference in cure rates between short and conventional courses of therapy was significant (6.38%; 95% CI: 1.88% to 10.89%), favoring the conventional course. Similar results were obtained when only studies comparing the same agents in the short and conventional courses were included (7.92%; 95% CI: 2.09% to 13.8%). Short-course amoxicillin was inferior to conventional length course (difference in cure rate, 13%; 95% CI: 4% to 24%); no difference was found between short-course and conventional length courses of trimethoprim-sulfamethoxazole (difference in cure rate, 6.24%; 95% CI = -3.74% to 16.2%). CONCLUSIONS: We conclude that single-dose amoxicillin is inadequate therapy for uncomplicated cystitis of childhood. Three days of trimethoprim-sulfamethoxazole therapy appears to be as effective as conventional length courses of the drug.

Renal transplantation in a patient with common variable immunodeficiency.

A 15-year-old girl developed end-stage renal disease requiring renal transplantation. Posttransplantation immunosuppression therapy consisted of antithymocyte globulin, glucocorticosteroids, cyclosporine A, and azathioprine. The patient's clinical course after transplantation was complicated by several episodes of graft rejection, chronic anemia, oral candidiasis, and numerous infections of the sinopulmonary tract that were recalcitrant to antibiotics and surgical intervention. An immunologic evaluation showed marked immune abnormalities beyond that expected by the transplant immunosuppression. Examination of serum samples taken before the transplant confirmed a diagnosis of common variable immunodeficiency. The difficulties of managing posttransplantation immunosuppression in a patient with a primary immunodeficiency are discussed. Patients with end-stage renal disease and a history of recurrent sinopulmonary infections may require immunologic screening before renal transplantation.

Evolution of chronic nitric oxide inhibition hypertension: relationship to renal function.

We conducted longitudinal measurements of blood pressure and renal function in the conscious, chronically catheterized rat before and during acute nitric oxide synthase inhibition (N-nitro-L-arginine methylester [L-NAME], 37 micromol/kg IV) and then chronic administration of oral L-NAME (approximately 37 micromol/kg per 24 hours). These studies specifically investigate the impact on plasma and renal renin as well as volume status during the evolution of this hypertension in rats not subjected to acute experimental stress. Blood pressure progressively increased with chronic administration of L-NAME and reached values greatly above those seen with acute administration of L-NAME. There were parallel increases in renal vascular resistance and development of proteinuria, and glomerular filtration rate began to decline at day 21, coincident with the appearance of renal damage. Twenty-four-hour urinary nitrite and nitrate excretion remained depressed, reflecting reduced nitric oxide synthesis. The plasma renin activity was variable and only increased transiently at 21 days, thus the angiotensin II dependence of this hypertension is not caused by stimulated plasma renin activity. Despite severe hypertension, sodium intake and excretion were unchanged over the 21 days of L-NAME administration. Plasma volume was significantly reduced at days 2 and 12 of L-NAME administration; thus the prolonged plasma volume contraction must result from the acute natriuretic response to the initial acute L-NAME administration.

Persistent severe hypertension in an infant with posterior urethral valves.

Severe hypertension, an infrequent problem in pediatrics, usually has a single secondary cause. We report an infant with severe hypertension and left reflux nephropathy, a known cause of secondary hypertension. The severity of hypertension and poor response to pharmacological therapy prompted further investigation, including a renal arteriogram that showed a right segmental renal artery stenosis.

Regulation of the renal response to atrial natriuretic peptide by sodium intake in preweaned rats.

The neonate conserves sodium avidly, and sodium intake is normally limited to that present in maternal milk. To evaluate the role of atrial natriuretic peptide (ANP) in this adaptation, preweaned rat pups were artificially reared and fed a formula with either normal sodium (25 mEq/L) or high sodium (145 mEq/L) for 7-8 d. To determine whether increased dietary sodium decreases ANP clearance receptor activity, animals were anesthetized, and the plasma ANP concentration (ANPp), urine flow (V), urinary sodium (UNa V), and cGMP excretion (UcGMP V) were measured before and after infusion of ANF(4-23), an ANP clearance receptor inhibitor (C-ANF), at 50 micrograms/kg/ min. Infusion of C-ANF increased ANPp 10-fold in both normal and high sodium groups, but V, UNa V, and UcGMP V increased only in animals receiving the high sodium diet (p < 0.05). Incubation of isolated glomeruli with 0.1 microM ANP increased extracellular cGMP more in high sodium than normal sodium groups (p < 0.05). We conclude that ANP clearance receptors in the neonate are highly activated regardless of sodium intake. Increased dietary sodium increases the renal diuretic and natriuretic response to circulating ANP through enhanced generation of cGMP.

Salt intake modulates the developmental expression of renal kallikrein and bradykinin B2 receptors.

The mechanisms involved in the postnatal induction of renal kallikrein gene transcription and enzymatic activity are unknown. The present study was designed to test the hypothesis that salt (NaCl) intake regulates the ontogeny of renal kallikrein gene expression and enzymatic activity and urinary kallikrein excretion. Newborn rats were artificially fed via a gastric tube with a milk formula containing either normal (25 meq/l, same as in maternal milk) or high (145 meq/l) NaCl content from day 7 to 14 of postnatal life. High-salt feeding decreased renal kallikrein mRNA levels (P < 0.05) and kallikrein-like activity (P < 0.05) compared with rat pups on normal salt intake. However, urinary kallikrein excretion (Ukal) was not different on chronic high vs. normal salt intake. Furthermore, acute volume expansion (0.9% saline, 1% body wt iv) did not alter Ukal in either group of developing rats. In adult rats, 1% NaCl in the drinking water for 10 days decreased renal active kallikrein contents (P < 0.05) but did not alter kallikrein mRNA levels compared with pair-fed rats on normal salt diet. Acute volume expansion in adult rats decreased active Ukal in the high-salt group only (P < 0.05). High-salt feeding upregulated bradykinin B2 receptor mRNA in the developing rats (P < 0.05). We conclude that chronic salt loading suppresses the postnatal rise in renal kallikrein gene expression and enzymatic activity, indicating that sodium intake is an important factor in the maturation of renal kallikrein synthesis. The data also suggest that bradykinin B2 receptor gene expression in the developing kidney may be subject to reciprocal feedback regulation by endogenous kallikrein-kinin activity.

Chronic sodium loading augments natriuretic response to acute volume expansion in the preweaned rat.

Positive sodium balance is necessary for normal somatic growth of the neonate, and the neonatal renal response to volume expansion (VE) is attenuated compared with the adult. To test the hypothesis that dietary sodium modulates the developmental response to VE, preweaned rats were artificially reared with either a normal (25 meq/l)- or high-sodium (145 meq/l) diet for 7-8 days and were compared with adult rats receiving normal or high sodium. Serum sodium concentration remained normal in adults on high sodium, whereas neonates became hypernatremic. Glomerular filtration rate (GFR), urinary flow (V), and urinary sodium (UNaV) were measured before and after acute saline VE (1% body wt). While remaining constant in preweaned rats, GFR increased > 50% in adult rats after VE (P < 0.05). High sodium intake augmented V and UNaV after VE but was not sustained in neonates as in adults. Plasma atrial natriuretic peptide (ANP) and guanosine 3',5'-cyclic monophosphate excretion (UcGMPV) were measured, and baseline UcGMPV was lower in preweaned rats receiving normal sodium but increased to levels similar to adult levels after VE. Postexpansion plasma ANP was higher in preweaned rats than in adult rats and was not affected by dietary sodium regardless of age. We conclude that the attenuated postexpansion natriuresis in the neonate is due in part to an adaptive response to limited sodium intake. However, neonatal compensation to increased sodium intake is incomplete and independent of plasma ANP.

Dietary sodium modulates neonatal but not adult cardiac atrial natriuretic peptide in rats.

After an initial postnatal diuresis, neonates are in positive sodium balance. Because atrial natriuretic peptide (ANP) contributes to sodium homeostasis, this study was designed to evaluate the maturational effects of increased dietary sodium intake on cardiac ANP production. Preweaned Sprague-Dawley rat pups were artificially reared by feeding them either a normal-sodium or high-sodium diet for 7 d and were compared with maternally reared rat pups. Adult rats were divided into three groups: the first group was given ad libitum rat food and 1% sodium chloride to drink, the second group was pair-fed with this group but given tap water to drink, and the third group was fed ad libitum rat food and water for 10 d. Atrial and ventricular pro-ANP and ANP contents and plasma ANP concentrations were measured by RIA. Steady state atrial and ventricular ANP mRNA expression was determined by Northern and dot-blot analysis. There was a 2-fold increase in atrial pro-ANP and ANP content and a 50% decrease in plasma ANP concentration in preweaned rat pups fed a high-salt diet. In contrast, atrial pro-ANP and ANP content and plasma ANP concentration were not affected by increased sodium intake in adult rats. Atrial and ventricular ANP mRNA levels and ventricular pro-ANP and ANP contents were not altered by dietary sodium at either age. We conclude that chronic increase in sodium intake in the preweaning period results in increased storage of atrial pro-ANP. The decrease in plasma ANP concentration in these preweaned rats may be due to reduced basal secretion or enhanced degradation of the peptide.

Prenatal maternal indomethacin use resulting in prolonged neonatal renal insufficiency.

The short-term use of indomethacin has been shown to be relatively safe and effective in halting premature labor. Its use has been associated with adverse renal effects in both the fetal and newborn periods that are generally transient and resolve on discontinuation of the drug. However, limited data suggest that prolonged prenatal exposure to indomethacin may be harmful to the fetus. We report a case of prolonged severe renal dysfunction characterized by oligohydramnios and postnatal anuria, azotemia, and ultrasonographic kidney abnormalities associated with the long-term prenatal use of indomethacin. Although partial resolution was observed, a moderate decrease in renal function persists. Prenatal maternal indomethacin use represents a potential cause of renal dysfunction in the newborn infant that may be only partially reversible.