[Show abstract][Hide abstract] ABSTRACT: JC virus (JCV) viruria is more common than BK virus (BKV) viruria in healthy individuals but in kidney transplants (KT), polyomavirus nephropathy (PVAN) is primarily caused by BKV. Few cases of PVAN have been attributed to JCV. Systematic studies on JCV replication in KT are lacking.
Out of a cohort of KT patients screened with urine cytology, patients shedding decoy cells were studied (n=103). Molecular studies demonstrated BKV, JCV, or BKV+JCV shedding in 58 (56.3%), 28 (27.2%), and 17 (16.5%), respectively. Biopsy was performed when decoy cells persisted 2 months or serum creatinine increased >20%.
BKV viruria was strongly associated with BKV viremia (93%), PVAN (48%, P=0.01) and graft loss (P=0.03). Higher BKV viremia correlated with graft dysfunction (P=0.01), more advanced histological pattern of PVAN (P<0.0001), and more infected cells in biopsy (P=0.0001). BKV viremia of > or =10,000 copies/mL was significantly associated with histologically confirmed PVAN (P=0.0001). Reduction of immunosuppression lead to disappearance of decoy cells in patients shedding BK (>93%). JCV viruria, was more often asymptomatic (P=0.002) and affected older patients (P=0.02). JCV PVAN was less common (21.4%) and was characterized by sparse cytopathic changes but significant inflammation and fibrosis. JCV viremia was rare (14.2%), transient, and low (mean 2.0E+03/mL). After reduction of immunosuppression decoy cells persisted in >50% of patients with JCV (P=0.0001), but no graft loss occurred. During the period of the current study, the incidence of BKV-PVAN was 5.5% and the incidence of JCV-PVAN was 0.9%.
The data point to significant differences of BKV and JCV biology regarding replication and disease in KT patients, with important implications for screening and management.
[Show abstract][Hide abstract] ABSTRACT: Current K-DOQI recommendations call for an assessment of dialysis adequacy that depends critically on an estimate of total body water (TBW). Such estimates are problematic in children since the range of patient size is large, and often formulas derived in normals are not validated in end-stage renal disease. Gold standard methods of TBW measurement, such as deuterium dilution ((2)H(2)O), are not appropriate in the clinical setting, yet noninvasive methods such as bioimpedance analysis (BIA) and dual energy x-ray absorptiometry (DEXA) have not been independently validated.
We studied 14 stable pediatric dialysis patients on 1 to 3 occasions using (2)H(2)O dilution, BIA, DEXA, and anthropometry to measure TBW. We compared our data set to previously published formulae for TBW to determine root mean square error (RMSE) and skew of the estimate.
TBW prediction based upon the anthropometric formula proposed by the Pediatric Peritoneal Dialysis Consortium provided the best fit to our independent data set with RMSE = 2.15 L, and no skew by Bland-Altman analysis. Other formulas produced large, clinically relevant errors; obese subjects confounded many estimates. TBW calculated from hydrated lean body mass from DEXA scan was reliable with RMSE = 1.03 L and no skew. BIA-derived estimates can be useful, although the magnitude of RMSE ranged from 1.45 to 6.24 L, and one formula produced skewed results.
Techniques for estimating TBW in pediatric dialysis patients must be validated by independent data sets before being incorporated into clinical and research practice.
Kidney International 06/2005; 67(5):2056-62. DOI:10.1111/j.1523-1755.2005.00308.x · 8.56 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Septic arthritis (SA) typically occurs in young children, often from Staphylococcus. With chronic immunosuppression, however, pathogens may be atypical. A 15-year-old African-American female developed Mycoplasma hominis SA in her right hip 2 months following cadaveric renal transplant (Tx). Her presentation was subtle and indolent, without fever or leukocytosis. Although reported in adult Tx recipients, M. hominis infections have not been described in pediatric recipients. Early immunosuppression (basiliximab, prednisone, tacrolimus, mycophenolate mofetil and Thymoglobulin) may have increased her susceptibility to M. hominis. Optimal therapy for M. hominis SA is not well established and relapses occur. This patient underwent joint incision and drainage, treatment for 8 weeks with doxycycline and levofloxacin guided by in vitro sensitivities, and a reduction in immunosuppression. She has been free of ongoing infection for 3 years with stable graft function (Cr 1.1 mg/dL) on moderate immunosuppression with prednisone, tacrolimus and MMF.
American Journal of Transplantation 02/2005; 5(1):183-8. DOI:10.1111/j.1600-6143.2004.00634.x · 5.68 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Evaluation of urine cytology (UC) for decoy cells and quantitative determinations of viruria (urine viral load [UPCR])and viremia (viral load in blood [VLB]) have been proposed as surrogate markers of polyomavirus allograft nephropathy (PVAN). In this study, we present the experience with the concurrent evaluation of UC, UPCR, and VLB in 349 patients (940 sets of samples). Results were correlated with each other and with a previous, concurrent, or subsequent biopsy diagnosis of PVAN. Patients were followed up for a mean of 27 months posttransplantation. We conclude that both UC and UPCR are useful for screening of renal transplant recipients. Simultaneous performance of both UC and UPCR does not add useful clinical information. In patients with positive UC, performance of UPCR, however, can allow for the distinction between BK and JC polyoma viruses. Quantitative measurement of viremia is not indicated in patients lacking viruria because no patients with PVAN present with this combination of findings. In patients with viruria, a positive viremia strongly correlates with PVAN. Rationale selection of screening protocols based on the current knowledge of the infection and tailored to the available laboratory capabilities in each transplantation center can optimize the use of resources.
[Show abstract][Hide abstract] ABSTRACT: Polyomavirus-associated nephropathy (PVAN) is a significant cause of allograft loss. The diagnosis requires allograft biopsy, but the impact of the histological features on diagnosis and outcome has not been described. We studied the distribution and extent of PVAN in 90 patients. Viral cytopathic changes, tubular atrophy/fibrosis and inflammation were semi-quantitatively scored and classified into histological patterns. The histological findings were correlated with viruria, viremia and graft survival. PVAN lesions were random, (multi-)focal and affected both cortex and medulla. Areas with PVAN coexisted with areas of unaffected parenchyma. In 36.5% (15/41) of biopsies with multiple tissue cores, discordant findings with PVAN-positive and -negative cores were observed. However, all patients with PVAN had decoy cells in urine as well as significant viruria and viremia (mean of 2.5 x 10(8) and 2.32 x 10(7) viral copies, respectively). Biopsies showing lesser degrees of renal scarring at the time of diagnosis were associated with, more likely, resolution of the infection, in response to decrease of immunosuppression (p = 0.001). More advanced tubulointerstitial atrophy, active inflammation and higher creatinine level at diagnosis correlated with worse graft outcome (p = 0.0002, 0.0001 and 0.0006). Due to the focal nature of PVAN, correlation of biopsy results with viruria and viremia are required for diagnosis.
American Journal of Transplantation 01/2005; 4(12):2082-92. DOI:10.1046/j.1600-6143.2004.00603.x · 5.68 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Polyoma virus allograft nephropathy often results in accelerated graft loss despite reduction of immunosuppression and/or treatment with antiviral agents. Irreversible renal fibrosis due to late diagnosis is likely to be one of the important causes of treatment failure. Early biopsy in 14 patients resulted in stable graft function after a mean follow-up of 22 months.
[Show abstract][Hide abstract] ABSTRACT: The polymerase chain reaction technique (PCR) has become a standard for the detection of Epstein-Barr virus ( EBV). Several studies have shown that solid organ transplant recipients fated to develop post-transplant lymphoproliferative disease (PTLD) have higher mean levels of EB viremia as measured by PCR. We directly compared PCR and immortalization assay (IA) for EBV detection from control cell lines as well as from peripheral blood monouclear cells (PBMC) and saliva samples from 9 pediatric solid organ transplant recipients. Results were expressed as the lowest amount of DNA and/or number of cells detected. All samples negative for EBV by PCR had amplifiable DNA detected using beta-actin primers. When control cell lines were assayed and positive in both assays, PCR was at least 200 times more sensitive than IA, as expected. When PBMC and saliva were compared, 1 patient, with a mononucleosis-like syndrome, was positive for EBV by IA only. When both IA and PCR were positive however, PCR was able to detect 5-500 times less EBV than IA, as expected. The associations of positive test with each assay and the diagnosis of PTLD were similar.
Pediatric Pathology and Molecular Medicine 07/2002; 21(4):433-43. DOI:10.1080/152279502760157777
[Show abstract][Hide abstract] ABSTRACT: Adequate nutrition is critical to the care of children with end-stage renal disease, and failure to reach the target dietary intake is associated with growth failure. Prospective studies of urea and nitrogen output in adults have led to the derivation of quantitative relationships, which allow assessment of dietary protein intake when only urea appearance is known. Such a clinically useful relationship has not been defined in children receiving chronic peritoneal dialysis (PD).
We studied 18 pediatric PD patients (ages 0.8 to 14.3 years) on 132 occasions and determined norms of urea nitrogen appearance (UNA), total nitrogen appearance (TNA), and nonurea nitrogen appearance (NUNA). We stratified data on UNA, TNA, NUNA, nonprotein nitrogen appearance, and the protein equivalent of nitrogen appearance by age groups (0 to 5, 6 to 10, and 11 to 15 years of age) and demonstrated significant differences. In addition, dietary protein and energy intake were measured in the outpatient setting with food scales and dietitian interviews, and the results were stratified by age, presence of residual renal function, and recombinant human growth hormone (rhGH) therapy.
UNA (3.05 +/- 1.38 g/day, 103 +/- 42 mg/kg/day) and TNA (4.67 +/- 1.86 g/day, 159 +/- 52 mg/kg/day) varied significantly between different age groups. NUNA in pediatric subjects (56 +/- 24 mg/kg/day) was significantly greater than previously published adult norms. A linear relationship was defined between UNA and TNA that was specific to pediatric PD patients [TNA (g/day) = 1.26(UNA) + 0.83]. When the relationship was scaled to body mass, the y intercept was significantly different in the youngest subjects [TNA = 1.03 (UNA) + 0.02 (weight in kg) + 0.56 (for subjects age 0 to 5) or 0.98 (for subjects age 11 to 15 or 6 to 10), r2 = 0.91]. Dietary protein intake was significantly greater in subjects receiving rhGH therapy, although nitrogen excretion was unchanged.
Markers of protein metabolism in pediatric PD patients are age dependent and differ from adult values. An age-specific relationship between TNA and UNA is defined for pediatric subjects; it does not vary with rhGH or the presence of residual renal function.
Kidney International 01/2001; 58(6):2564-70. DOI:10.1046/j.1523-1755.2000.00442.x · 8.56 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Infection is an important complication of peritoneal dialysis that often limits technique survival. Recurrent episodes of peritonitis caused by the same organism may be the result of catheter infection, necessitating removal. We performed 34 single-step catheter replacement procedures in children and young adults for recurrent peritonitis or refractory exit site and tunnel infections. The success rate of the procedure was high (85%), with rare instances of intraoperative contamination. The presence of Staphylococcus aureus infection or exit site and tunnel infection were not risk factors for worse outcome. All patients continued on peritoneal dialysis through catheter change without requiring interval hemodialysis. Eighteen peritoneal dialysis catheters were replaced in a staged procedure with an interval off peritoneal dialysis. There was one early reinfection of the new catheter. Patients with Pseudomonas sp infections were more likely to be treated with a staged procedure; S aureus infections were equally likely to be managed by staged or simultaneous catheter removals. Simultaneous removal and replacement of infected peritoneal dialysis catheters is an effective management strategy when compared with two-step catheter replacements.
American Journal of Kidney Diseases 06/1997; 29(5):706-11. DOI:10.1016/S0272-6386(97)90123-2 · 5.90 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Peritoneal equilibration test (PET) curves have been standardized in adult peritoneal dialysis (PD) patients. However, it appears that norms for pediatric PD patients may be different. A series of PET in 29 stable, chronic PD patients < or = 14 yr old performed at dwell volumes of 33 +/- 6 mL/kg with 2.5% Dianeal is reported. PET results for glucose and creatinine transport were compared between patients age < or = 2 and those 3 to 14 and published adult values by analysis of variance. Children < or = 2 transport glucose and creatinine more rapidly than do children 3 to 14 and adults. Children 3 to 14 transport glucose more rapidly than do adults; creatinine transport is not significantly different. These data demonstrate that transport characteristics differ between very young children, older children, and adults. Because PET are usually performed to plan mode of therapy, to address inadequate ultrafiltration, or to increase clearance, awareness of these results should assist in the clinical care of children on PD.
Journal of the American Society of Nephrology 10/1995; 6(4):1309-12. · 9.34 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We measured urea [weekly urea clearance/total body water (KT/Vurea)] and creatinine (CCr) clearances on 35 occasions in 15 stable chronic peritoneal dialysis patients to determine the feasibility and reproducibility of such measurements in children. In addition, we performed peritoneal equilibration tests (PETs) to characterize our patients' peritoneal membranes and to estimate weekly clearances. We demonstrated that dialysis delivery can be quantified by these standard measurements in children of widely varying size. Further, we found that clearances predicted from PET data were similar to measured values in all patients. However, predicted and measured values were most significantly correlated in patients with high and high-average peritoneal membrane permeability. KT/Vurea and CCr were correlated overall, but differences in scaling affected the validity of the relationship. When both clearances were scaled to weight, the correlation was closer, but still differed between PET-determined peritoneal membrane types.
[Show abstract][Hide abstract] ABSTRACT: The authors performed peritoneal equilibration tests (PET) in children and young adults of widely varying sizes to characterize membrane transport type, and used data (D/P ratios) obtained to predict clearances of urea (KT/Vurea) and creatinine (CrCl). Overall, PET predicted and measured values for KT/Vurea and CrCl were not significantly different. KT/Vurea could be reliably predicted from PET data for all membrane transport types. However, the relationship between predicted and measured CrCl was only significant for patients with high and high average membrane transport. In addition, the relationship between KT/Vurea and CrCl was significant only in patients with high and high average membrane transport.