Increased incidence of insulin-dependent diabetes mellitus in pediatric renal transplant patients receiving tacrolimus (FK506)

BACKGROUND: Use of tacrolimus (FK506), a potent immunosuppressive agent, has been reported to have a 10-20% incidence of insulin-dependent diabetes mellitus (IDDM) in adults, but the incidence of IDDM in pediatric renal transplant recipients treated with this agent is unknown. In this article, we report our single-center experience with FK506-induced IDDM in children. METHODS: Five consecutive living related donor pediatric renal transplants were reviewed retrospectively. RESULTS: All five patients developed IDDM lasting longer than 6 months. Mean follow-up time was 18.6 months. CONCLUSIONS: Pediatric patients may be at high risk for developing FK506-induced IDDM.

A proposed method for the noninvasive evaluation of renal asymmetry in a living-related donor candidate.

This report proposes an adjunctive technique for the evaluation of asymmetry of renal size and function of undetermined etiology, discovered during the assessment of two living-related donor candidates. The method utilizes the observation of renal functional reserve measurement as demonstrated by oral protein loading in patients with normal and diseased kidneys. Renal function was measured as timed Ccr and estimation of differential GFR by technetium-99m diethylenetriaminepentaacetic acid (99mTcDTPA) scintigraphy. A comparison of renal function before and after protein loading in two such patients demonstrated the anticipated increase in GFR. No change in differential GFR as determined by renal scan in one patient was interpreted as supportive evidence for bilaterally normal parenchymal function. Follow-up of both donors shows continued normal renal function.

Glomerular macrophage phagocytic activity in experimental immune complex nephritis.

In rats with the proliferative immune complex glomerulonephritis of chronic serum sickness, kidney function deteriorates in three clearly distinguishable and discrete stages: mild, moderate and severe. The macrophage component of glomerular inflammation in each stage is also quantitatively and qualitatively distinct, with abnormal phenotypic markers appearing in the moderate stage and increasing in the severe stage. To determine whether there were distinct functional differences among macrophages from the three stages, Fc gamma receptor-mediated phagocytic capacity was measured. The phagocytic capacity of glomerular macrophages increased significantly in the moderate stage, then significantly decreased, as rats progressed to severe chronic serum sickness. This decline in phagocytic function was not associated with a decrease in the expression of Fc gamma receptors on the glomerular macrophage cell surface. Furthermore, the phagocytic function of peritoneal macrophages from rats with severe chronic serum sickness was not impaired. Whether or not this attenuation of glomerular macrophage phagocytic capacity is the cause, or result, of renal disease progression remains unclear. It may indicate a potentially protective role for intraglomerular macrophages, and can serve as an additional functional marker of disease progression.

Hypercalciuria and nephrocalcinosis in children.

Hypercalciuria has become a significant clinical focus both for pediatricians and for pediatric nephrologists after it was found that increased urinary calcium excretion is the most common abnormality in children with nonglomerular hematuria and with nephrolithiasis. The question of long-term implications of hypercalciuria in growing children, regardless of the underlying cause, remains unanswered. Whether dietary or pharmacologic therapy is warranted in children with hypercalciuria is controversial. One of the proposed consequences of hypercalciuria is nephrocalcinosis. With the availability of increasingly sensitive, noninvasive imaging techniques, nephrocalcinosis is being recognized more frequently. In some instances, concern about the risk and progression of nephrocalcinosis is provoking reevaluation of well-established metabolic therapies. New urinary inhibitors of crystal formation and aggregation have recently been identified. As the basic pathogenesis of nephrocalcinosis becomes clearer, clinical therapies will become more specific and effective.

A simple method for percutaneous renal biopsy.

A technique for percutaneous renal biopsy in children is described which combines the use of ultrasound guidance and a disposable automatic biopsy device. Twenty-five biopsies in 22 children were performed using the Bard Monopty biopsy instrument. Adequate tissue was obtained to aid in diagnosis in 24 of 25 cases. Complications inclused 2 small perinephric hematomas. We conclude that the Bard Monopty biopsy device in association with ultrasonography provides for a safe and reliable technique to perform percutaneous renal biopsy in children.

Applying decision analysis to management of adolescent idiopathic nephrotic syndrome.

Due to the concern that adolescents presenting with nephrotic syndrome are less likely to have minimal change disease than younger children, pediatric nephrologists have tended toward renal biopsy-tailored treatment rather than corticosteroid use in this population. The need for biopsy prior to treatment of nephrotic syndrome in adults has been challenged. A similar challenge to the clinical need for this procedure in adolescents with idiopathic nephrotic syndrome is raised here. The principles of medical decision analysis were applied and calculations were made with the Decision Maker computer program. The life expectancy of an adolescent who receives biopsy-tailored treatment was found to be no different from that of an adolescent who receives empiric corticosteroid treatment. We conclude that renal biopsy is not mandatory for the clinical management of adolescents with idiopathic nephrotic syndrome. Prognostically, a response, or lack thereof, to empiric corticosteroid therapy may be just as informative as a histological diagnosis.

Heptavax-B in pediatric dialysis patients: effect of systemic lupus erythematosus. Chesapeake Pediatric Nephrology Study Group.

Twenty-three pediatric dialysis patients [6 hemodialysis (HD) and 17 peritoneal dialysis (PD)], with a mean age of 13.9 years, were vaccinated against hepatitis B virus and their seroconversion rates were analyzed. There was no significant difference in the mean duration of dialysis between the HD and PD groups, or between responders and nonresponders to the vaccine. In the HD group, there was a response rate of 83.3% while the PD patients had a response rate of 88.2%. The only patients failing to seroconvert after the three vaccine series all had systemic lupus erythematosus and were taking oral corticosteroids.

Monocyte chemoattractant protein-1 in chronic proliferative immune complex nephritis.

In rats with chronic serum sickness, proliferative immune complex glomerulonephritis progresses in three discrete stages, designated mild, moderate, and severe. One distinguishing immunopathologic feature, the progressive increase in the number of glomerular macrophages, is closely correlated with decreasing kidney function. We hypothesized that monocyte chemoattractant protein-1, a beta-subfamily chemokine with potent monocyte-specific chemotactic activity, might contribute to this macrophage accumulation. Immunohistochemical methods were used to identify monocyte chemoattractant protein-1 in kidney tissue sections. Total RNA was extracted from the kidneys of rats at each stage of chronic serum sickness, and age-matched controls, and Northern blot analysis was performed with a rat monocyte chemoattractant protein-1 cDNA probe. Tissue staining localized monocyte chemoattractant protein-1 to the glomerular capillary wall and mesangium in chronic serum sickness. Minimal quantities of monocyte chemoattractant protein-1 mRNA were detected in the kidneys of normal control rats, with marked increases in mRNA as chronic serum sickness nephritis progressed to the moderate stage. There was then an apparent decrease in monocyte chemoattractant protein-1 mRNA in the severe stage. The degree of protein staining and mRNA levels paralleled each other. We conclude that monocyte chemoattractant protein-1 is a potentially important chemotactic agent in chronic serum sickness nephritis.

Hyponatremia in the very young chronic peritoneal dialysis patient.

Two anuric infants had recurrent hyponatremia during chronic peritoneal dialysis (PD). This occurred because at normal serum sodium concentrations ([Na]), Na losses from ultrafiltration (UF) were greater than the Na ingested from infant formula. Hyponatremia was corrected with increased oral Na intake or with increased dialysis solution [Na]. Anuric infants undergoing PD have hyponatremia because of their high UF requirements/body weight and the low Na content of proprietary infant formulas.

Relief of respiratory distress with leukapheresis in a child with chronic myelocytic leukemia.

Therapeutic leukapheresis of a 10-year-old girl with adult-type chronic myelocytic leukemia is described. The efficiency of WBC removal was noted to improve significantly after addition of hydroxyethyl starch to the anticoagulant infusion. In fact, the percentage of white cells removed more than doubled (39% vs. 16%) when comparing procedures of similar duration, with and without the sedimenting agent. Of particular interest was the relief of the patient's respiratory distress concomitant with the decline in her leukocyte count, a finding that has not previously been documented in pediatric patients. The arterial oxygen pressure remained greater than 95 mmHg after the procedure with hydroxyethyl starch compared with 70 mmHg after the procedures without it. In addition, her respiratory rate decreased from 70 on admission to the low 20s after the final procedure. Leukapheresis with hydroxyethyl starch was shown to be a safe procedure, and the use of hydroxyethyl starch was shown to be of particular benefit for prevention of prolonged apheresis procedures.

The effects of IL-1, IL-2, and tumor necrosis factor on polymorphonuclear leukocyte Fc gamma receptor-mediated phagocytosis. IL-2 down-regulates the effect of tumor necrosis factor.

It has been reported that the Fc gamma R-mediated phagocytic activity of polymorphonuclear leukocytes (PMN) from patients with acute bacterial infections is markedly enhanced when compared with healthy controls. Inasmuch as several potent cytokines are known to be involved in inflammatory and infectious processes, we studied the effects of three such cytokines (IL-1 beta, IL-2, and TNF-alpha) on normal PMN Fc gamma R-mediated phagocytosis. IL-1 beta and TNF alpha both caused a significant increase in the ingestion of EIgG by adherent PMN. In combination, IL-1 beta and TNF-alpha had an additive effect, even when each was used at its optimal concentration. In contrast to the enhancing effects mediated by IL-1 beta and TNF-alpha, IL-2 alone had no significant effect on PMN phagocytosis. Notably, however, IL-2 at a concentration of 10(4) U/ml partially inhibited TNF-alpha-mediated enhancement of phagocytosis by decreasing TNF binding to the PMN cell surface. This inhibitory effect of IL-2 on TNF was reversed by anti-IL-2 antibody and mAb directed against the low affinity IL-2R (anti-Tac), whereas mAb directed against the intermediate affinity receptor (mik-beta 1) had no such effect. These findings may have important physiologic implications, because patients receiving IL-2 therapy have been shown to have increased susceptibility to infection.

Increased expression of Fc gamma RI on isolated PMN from individuals of African descent.

Fc gamma R plays an important role in host defense, triggering and/or facilitating many immunologic responses. Of the three defined Fc gamma Rs, Fc gamma RI (CD64) is not known to be constitutively expressed on normal PMN. We report here that there is markedly increased expression of Fc gamma RI on the PMN of normal, healthy blacks, detected by binding of monoclonal antibody to this receptor. This may have significant implications when multiracial data are pooled in studies of receptor expression as markers of response to various chemotherapeutic agents.

End-stage renal disease in two pediatric patients with Fechtner syndrome.

Fechtner syndrome, a disease in the spectrum of the hereditary nephridites, is a macrothrombocytopenia associated with sensorineural hearing loss, cataracts, nephritis, and characteristic leukocyte inclusions. Renal biopsy findings are consistent with those of Alport syndrome, and the associated renal disease is said to be unusual before mid to late adulthood. Here, we review the available literature on this disease and report two African-American pediatric patients with Fechtner syndrome who rapidly progressed to end-stage renal disease during adolescence. We conclude that chronic renal failure can occur at a young age in patients with Fechtner syndrome, with a possible relation to race/ethnicity. Fechtner syndrome, or other variants of Alport syndrome, need to be considered in patients presenting with proteinuria and thrombocytopenia.