BK virus nephropathy in the native kidneys of a pediatric heart transplant recipient.

BK virus is a human polyoma virus that may cause nephropathy in immunosuppressed patients. It is a well-recognized cause of renal allograft dysfunction and allograft loss in renal transplant recipients, but it is an infrequent cause of nephropathy outside this setting. There are a few case reports of BK virus nephropathy in the native kidneys of immunosuppressed adult patients with non-renal transplants, but so far it has not been reported in pediatric non-renal solid organ transplant recipients. We report a case of a seven-yr-old heart transplant patient who was diagnosed with BK virus nephropathy, eight months after his second heart transplant. Despite intervention, his renal dysfunction progressed to renal failure. He is currently receiving maintenance hemodialysis and awaiting renal transplantation. It is important to recognize BK virus infection as a possible cause of renal dysfunction in immunosuppressed children who are non-renal transplant recipients.

Mycophenolate mofetil in pediatric renal transplantation: non-induction vs. induction with basiliximab.

North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) reports have shown anti-T cell antibody, OKT3, to be deleterious in pediatric renal transplant recipients treated with mycophenolate mofetil (MMF). Unlike OKT3, basiliximab is a chimeric monoclonal antibody to the alpha subunit of the interleukin-2 receptor on activated T-lymphocytes. We sought to examine the outcome of MMF with or without basiliximab induction therapy in pediatric renal transplantation. Between January 1998, and June 2001, 49 pediatric renal transplants were performed at our center and 41 met the criteria for this study. We retrospectively analyzed the records of 25 patients who received MMF, Prednisone, CSA or TAC, alone (group I) and 16 patients who received MMF, CSA or TAC, and Prednisone in combination with basiliximab (group II). The two groups were similar with respect to recipient or donor age, gender, ethnicity, donor source (LD vs. CAD), cold ischemia time, and primary diagnosis. The basiliximab group had a shorter follow up period because of its more recent addition to our pediatric immunosuppression protocol, 12.9 +/- 5.9 months vs. 35.5 +/- 7.2 months for group I (p < 0.0001). At 6 months, the acute rejection rate was 16% (group I) compared with 25% (group II) (p = 0.689). The patient and graft survival at 6 and 12 months were 100% respectively for both groups. Basiliximab was well tolerated without significant adverse events. At 6 months, there was no significant difference between the groups in the incidence of urinary tract infection or cytomegalovirus infection. These data suggest that in the short-term, MMF with or without basiliximab induction therapy appears to yield excellent and statistically similar outcomes. However, further controlled studies are necessary to verify these findings as well as to define the role of basiliximab in MMF-treated pediatric renal transplant recipients.

Use of basiliximab with mycophenolate mofetil in kidney transplantation.

INTRODUCTION: Randomized, placebo-controlled studies have determined that administration of basiliximab (chimeric IL-2 receptor antagonist) decreases the acute rejection rate in kidney transplantation when used in combination with cyclosporine, azathioprine, and steroids. We report our experience using basiliximab with mycophenolate mofetil, a calcineurin inhibitor, and steroids in kidney transplantation. METHODS: We retrospectively analyzed 127 patients who received their first kidney transplant between September 1, 1998, and December 30, 2000, including 59 who received basiliximab (22 living and 37 cadaveric donor recipients) and the 68 that did not receive this antibody (31 living and 37 cadaveric donor recipients). The groups were demographically comparable for risk factors such as race, peak of panel-reactive antibody, delayed graft function, donor age, and cold ischemia time. The analysis assessed serum creatinine levels, acute rejection, cytomegalovirus infection, and posttransplant lymphoproliferative disease incidence as well as patient and graft survival at 6 months. RESULTS: Serum creatinine levels were 3 +/- 3.1 and 2.6 +/- 2.5 mg/dL (P =.346) at discharge, 1.5 +/- 0.6 and 1.7 +/- 1.1 mg/dL (P =.098) at 1 month, and 1.5 +/- 0.7 and 1.6 +/- 0.7 mg/dL (P =.454) at 6 months posttransplantation for patients treated with versus without basiliximab, respectively. Only one episode of acute rejection was seen among patients treated with basiliximab within 1 month posttransplantation versus three episodes among patients treated without basiliximab (P =.382). Three patients (5.1%) treated with basiliximab and two patients (2.9%) treated without basiliximab developed acute rejection within 6 months posttransplantation (P =.536). Patient and graft survivals at 6 months posttransplantation were not significantly different between patients treated with versus without basiliximab (100% and 100% versus 100% and 98.3%, respectively). There was no increased incidence of cytomegalovirus infection with the use of basiliximab (5.1% vs 5.9%, P =.844). There was only one case of posttransplant lymphoproliferative disease within 6 months posttransplantation in a patient treated without basiliximab. CONCLUSION: These data suggest that the routine addition of basiliximab to a mycophenolate mofetil-based regimens does not appear to be warranted. A larger prospective randomized study with longer follow-up is needed to confirm these results.

Mycophenolate mofetil without antibody induction in cadaver vs. living donor pediatric renal transplantation.

Mycophenolate mofetil (MMF) is a new immunosuppressive agent that blocks de novo purine synthesis in T and B lymphocytes via a potent selective inhibition of inosine monophosphate dehydrogenase. MMF has been shown to significantly reduce the incidence of acute rejection in both adult and pediatric renal transplantation. The impact of MMF on routine antibody induction therapy in pediatric renal transplantation has not been defined. Remarkably, a recent North American Pediatric Transplant Cooperative Study concluded that T-cell antibody induction therapy was deleterious for patients who received MMF. Our study examines the use of MMF in an evolving immunosuppressive strategy to avoid antibody induction in both living (LD) and cadaver (CAD) donor pediatric renal transplantation. We retrospectively analyzed the records of 43 pediatric renal transplants that received MMF-based triple therapy without antibody induction therapy between November 1996 and April 2000. We compared CAD (n = 17) with LD (n = 26). The two groups were similar demographically except that CAD had significantly younger donors than LD, 26.1 +/- 13.7 vs. 36.2 +/- 9.2 yr (p = 0.006). All the patients received MMF at 600 mg/m2/b.i.d. (maximum dose of 2 g/d) and prednisone with cyclosporine (86%) or tacrolimus (14%). Mean follow-up was >36 months for each group. Acute rejection rate at 6 months was 11.8% (CAD) vs. 15.4% (LD) (p = 0.999) and at 1 yr was 23.5% (CAD) vs. 26.9% (LD) (p = 0.999). Mean estimated glomerular filtration rate (ml/min/1.73 m2) at 6 months was 73.3 +/- 15.3 (CAD) vs. 87.6 +/- 24.2 (LD) (p = 0.068). Patient survival at 1, 2, and 3 yr was 100, 100, and 100% for CAD vs. 100, 96, and 96% for LD, respectively. Graft survival at 1, 2, and 3 yr was 100, 100, and 94% for CAD vs. 96, 88, and 71% for LD, respectively. Graft loss in CAD was because of chronic rejection (n = 2) while in LD it was because of non-compliance (n = 6), post-transplant lymphoproliferative disorder (n = 1), and sepsis (n = 1). In conclusion, MMF without antibody induction in both CAD and LD pediatric renal transplantation provides statistically similar and effective prophylaxis against acute rejection at 6 months and 1 yr post-transplant. The short-term patient and graft survival rates are excellent, however, non-compliance remains a serious challenge to long-term graft survival. Additional controlled studies are needed to define the role of MMF without antibody induction therapy in pediatric renal transplantation.

Renal biopsy in infants and children.

Renal biopsy is a technically difficult procedure in children. Some centers are still using general anesthesia, fluoroscopy, and/or open renal biopsies in young infants. We evaluated the safety and efficacy of two different types of 18-gauge, automated, spring-loaded disposable biopsy needles in 43 children, aged 8 months to 16 years, under ultrasound guidance. Microinvasive ASAP18 (Boston Scientific Corp, Watertown, MA) needles retrieve 19-mm long specimens only, while Ultra-Cut needles (Medical Device Technologies, Inc, Gainesville, FL) are adjustable and can retrieve 6-, 13-, or 19-mm specimens. Technically, Ultra-Cut needles are easier to use in infants or when small kidneys are biopsied. While two infants required intravenous ketamine, the remaining biopsies were done with intravenous sedation. Ultrasound-guided renal biopsy with 18-gauge microinvasive needles and intravenous sedation is a safe and reliable method for obtaining biopsy specimens in older children, as well as in small infants.

A family study of renal dysplasia.

A family study was undertaken to investigate genetic involvement in renal dysplasia, which is defined as abnormal metanephric differentiation. Probands were ascertained through the retrospective examination of necropsy records and the reevaluation of available material, which included microscopic examinations of the kidneys, gross descriptions of organs, and gross photographs. We obtained family histories and performed physical examinations and renal ultrasonography on parents and sibs of the 21 probands. In only one family a sibling with renal dysplasia was discovered; both the proband and the previous stillborn sib had renal dysplasia in association with posterior urethral values. Renal dysplasia could have resulted from urinary tract obstruction secondary to the urethral valves, with inheritance of the valves as the primary abnormality. However, we cannot exclude primary inheritance of the renal abnormality, perhaps with multifactorial determination with a threshold. The empiric recurrence risk of 2.1%, calculated from this family study, was statistically not significantly different from zero. We can assume, therefore, that the multicystic and aplastic types of renal dysplasia, which predominated in this study, are sporadic or rarely familial, but certain other types of renal dysplasia, identified in the literature as familial, probably carry a higher recurrence risk.

Hemoglobin sickle cell disease and systemic lupus erythematosus.

An unusual association of hemoglobin sickle cell disease with systemic lupus erythematosus in an 11-year-old girl highlights the diagnostic dilemma that may arise because of the similarity of symptomatology.

Adult polycystic kidney disease: presymptomatic diagnosis for genetic counselling.

We evaluated 30 first degree relatives of 9 patients with end-stage renal disease secondary to adult polycystic kidney disease. The diagnostic accuracy of renal ultrasonography was compared with intravenous pyelogram with nephrotomography. In 27 patients the two tests were in agreement. In 3 patients both tests were abnormal but findings on IVP did not completely agree with ultrasonography. For early detection and genetic counselling, we recommend ultrasonography as the initial screening procedure for the evaluation of asymptomatic family members of a patient with APKD. IVP should only be considered if ultrasonogram is abnormal but not diagnostic of APKD.

Hemoperfusion in theophylline neurotoxicity.

Four patients with severe theophylline toxicity (theophylline levels of 60 to 180 micrograms/ml) are reported. Three patients with neurotoxicity were treated with hemoperfusion. Two of these were hemoperfused early after the onset of seizures; they recovered with no neurologic deficit. In the third patient hemoperfusion was delayed for 16 hours after uncontrolled seizures; severe brain damage resulted. The fourth patient, who had the highest peak theophylline level but no seizures, was successfully treated with conservative management and peritoneal dialysis. The role of hemoperfusion in severe theophylline intoxication is discussed.

Genetic counseling in adult polycystic kidney disease.

We evaluated 22 patients with end-stage renal disease (ESRD) due to adult polycystic kidney disease (APKD) to assess their knowledge of the hereditary nature of the condition and to determine whether they received adequate genetic counseling. Patients were evaluated by means of a questionnaire and a review of their medical records. Only 5 of 22 (23%) knew their disorder was hereditary at the time of diagnosis, and in only 4 (18%) was genetic counseling suggested. In no instance had proband and spouse received genetic counseling together. Diagnostic studies of children at risk were rarely suggested. We also evaluated the children of 9 probands for APKD. Of 26 children evaluated, 17 had APKD (65%). Sixteen had no children at the time of testing. All but two of the 26 were less than 25 years old. Of the probands' children over 15 years of age, 55% knew the name of the condition in the family but only 9% knew they should be tested. Our study demonstrated inadequacy of genetic counseling and follow-up in this group of patients; we suggest that referral for counseling become a routine part of their management. Early diagnosis and effective counseling has the potential benefit for the individuals of making rational reproductive decisions appropriate for their situation. Counseling may have to be repeated during the course of the patients' disease, as their perception of risk may change with time. With advances in dialysis and transplantation, ESRD may not be as devastating in years to come as it is now.