A clinical predictive model of chronic kidney disease in children with posterior urethral valves.

BACKGROUND: Posterior urethral valves (PUVs) are associated with severe consequences to the urinary tract and are a common cause of chronic kidney disease (CKD). The aim of this study was to develop clinical predictive model of CKD in a cohort of patients with PUVs. METHODS: In this retrospective cohort study, 173 patients with PUVs were systematically followed up at a single tertiary unit. The primary endpoint was CKD ≥ stage 3. Survival analyses were performed by Cox regression proportional hazard models with time-fixed and time-dependent covariables. RESULTS: Mean follow-up time was 83 months (SD, 70 months). Sixty-five children (37.6%) developed CKD stage ≥ 3. After adjustment by the time-dependent Cox model, baseline creatinine, nadir creatinine, hypertension, and proteinuria remained as predictors of the endpoint. After adjustment by time-fixed model, three variables were predictors of CKD ≥ stage 3: baseline creatinine, nadir creatinine, and proteinuria. The prognostic risk score was divided into three categories: low-risk (69 children, 39.9%), medium-risk (45, 26%), and high-risk (59, 34.1%). The probability of CKD ≥ stage 3 at 10 years age was estimated as 6%, 40%, and 70% for patients assigned to the low-risk, medium-risk, and high-risk groups, respectively (P < 0.001). The main limitation was the preclusion of some relevant variables, especially bladder dysfunction, that might contribute to a more accurate prediction of renal outcome. CONCLUSION: The model accurately predicts the risk of CKD in PUVs patients. This model could be clinically useful in applying timely intervention and in preventing the impairment of renal function.

Comparison of outcomes with low-dose anti-thymocyte globulin, basiliximab or no induction therapy in pediatric kidney transplant recipients: a retrospective study.

It is unclear which induction therapy yields the best outcomes in pediatric kidney transplantation. Retrospective data of 88 children receiving a renal allograft between November 1996 and October 2003 were analyzed. Patients received ATGI (n = 12), BI (n = 29), or NAI (n = 47). The mean ATG dose was 5.1 +/- 2.1 mg/kg. At 12 months, graft survival rates were 91.7%, 100%, and 97.9% for ATGI, BI, and NAI groups, respectively. Acute rejection rates at 12 months were 0 (ATGI), 20.6% (BI), and 10.7% (NAI). The mean GFR for ATGI (42.4 +/- 25.9 mL/min) was lower than for BI (78.3 +/- 27.2 mL/min), and NAI (66 +/- 28.3 mL/min) at 12 months (p < 0.05). One ATGI patient developed CMV pneumonia but none developed post-transplant lymphoproliferative disorder. Although there was no renal allograft survival benefit with either ATGI or BI, relative to NAI, the absence of acute rejection and equivalent rates of viral infections in the higher-risk ATGI recipient group suggests that the treatment strategy is promising. A large prospective study is needed to better define the role of ATGI in pediatric kidney transplantation.

Proteinuria in pediatric renal transplant recipients during the first 60 post-transplant days.

Although normative values of post-transplant proteinuria have been reported in adults, data for pediatric renal transplant recipients have not been previously published. We hypothesized that pediatric renal transplant recipients achieve normal urinary protein to creatinine (UProt/UCr) ratios (<0.2) by 60 days post-transplant in the absence of early recurrent disease. Retrospective chart review of 108 consecutive pediatric renal transplant recipients at Stanford University was performed. Thirty-two (30%) patients who were eligible had > or = 1 UProt/UCr ratio obtained during the first 60 post-transplant days. Mean age at transplant was 13.9 +/- 4.2 yr. UProt/UCr ratios were grouped by week post-transplant for quantile analysis. Mean weekly UProt/UCr values were not lower than 0.2 until the ninth post-transplant week. No difference in post-transplant proteinuria existed between nephrectomized and non-nephrectomized transplant recipients. Experience with a single patient with proven focal segmental glomerulosclerosis (FSGS) recurrence suggests that normative UProt/UCr data may be useful in early identification of patients experiencing disease recurrence. Univariate correlations demonstrated that UProt/UCr negatively correlated with serum albumin levels (-0.415, p < 0.0001) and days post-transplant (-0.531, p < 0.0001). Independent of primary diagnosis, proteinuria persists throughout the first 60 days in most pediatric renal transplant patients, decreasing relative to time post-transplant.

A technique for rapid exchange of continuous renal replacement therapy.

Re-initiation of continuous renal replacement therapy (CRRT) in neonates and young infants weighing less than 15 kg often necessitates a blood prime of the blood circuit path or a concurrent packed red blood cell (PRBC) transfusion to avoid causing hemodynamic instability due to acute hemodilution. The significant amount of time required for a routine CRRT circuit change can be associated with worsening electrolyte and acid-base abnormalities, fluid retention, greater hemodynamic instability and reducing effective hemofiltration time. In an attempt to limit the time without CRRT and to eliminate the requirement for additional blood exposure, a new technique, rapid exchange of continuous renal replacement therapy (RECRRT), was developed. Rapid exchange of continuous renal replacement therapy is a sequential technique that transfers citrated blood from one CRRT machine to another machine connected in series. The technique effectively negates the requirement for CRRT circuit path blood priming or PRBC transfusion. The amount of time without CRRT is markedly reduced by RECRRT to 2-3 min. The RECRRT technique has been utilized more than 30 times for at least 15 patients without an adverse event. RECRRT may benefit children who weigh less than 15 kg and in those patients who experience hemodynamic or clinical instability while CRRT is discontinued for only a brief period.

Hyperhomocysteinemia in pediatric and young adult renal transplant recipients.

Hyperhomocysteinemia (HHcy) has been recently identified as an important and reversible cardiovascular risk factor in adult and pediatric renal transplant recipients. A retrospective cross-sectional analysis of 70 pediatric and young adult renal transplant recipients was performed to determine the prevalence, and important clinical and laboratory correlates of HHcy. Total homocysteine concentration, free and protein bound, was determined by fluorescence polarization immunoassay using an IMX analyzer. Hyperhomocysteinemia was defined as a serum homocysteine (Hcy) level above the 95th percentile for age. Fifty-four of 70 patients (77%) had HHcy. Comparison of patients with HHcy with patients without HHcy demonstrated no statistical difference in age (p = 0.35), gender (p = 0.76) or donor type (p = 0.20). Patients with HHcy had significantly lower calculated creatinine clearance values (Ccr) (p = 0.02), 67.3 +/- 21.2 mL/min/1.73 m(2) vs. 90.7 +/- 32.3 mL/min/1.73 m(2) for patients without HHcy. Immunosuppression did not correlate with the diagnosis of HHcy. Stepwise logistic regression identified patient age (0.18, p = 0.013) and Ccr (-0.04, p = 0.011) as significant variables. In conclusion, HHcy is more common than expected in pediatric renal transplant recipients. Patients with Ccr <80 mL/min/1.73 m(2) were statistically more likely to have a diagnosis of HHcy. We recommend that Hcy levels should be evaluated in this high risk population.

The use of art therapy to detect depression and post-traumatic stress disorder in pediatric and young adult renal transplant recipients.

Pediatric and young adult renal transplant recipients may experience feelings of depression and emotional trauma. A study was conducted to (1) determine the prevalence of depression and emotional trauma and (2) assess the utility of the Formal Elements of Art Therapy Scale (FEATS). Sixty-four renal transplant recipients, 6-21 yr of age, were evaluated using self-report measures (CDI and Davidson) and art-based assessments. Subject art was analyzed by art therapists using seven of the 14 elements of the (FEATS), to assess depression. Unlike CDI and Davidson self-report testing, all patients were able to complete the art-based directives. When self-report measures and art-based assessments were combined, 36% of the study population had testing results consistent with depression and/or post-traumatic stress. The FEATS assessments identified a subset of patients who were not identified using the self-report measures. There was a correlation between CDI and Davidson scores (p < 0.0001), Davidson scores correlated with hospital days (p = 0.05), and FEATS correlated with height Z score (p = 0.04) and donor type (p = 0.01). Patients who required psychological interventions including antidepressant therapy, psychological counseling and psychiatric hospitalization during the year after the study were identified as depressed. Sensitivity for FEATS and CDI were 22 and 50% respectively. The results suggest that while art therapy may be of utility in the identification of pediatric and young adult transplant recipients who are suffering from depression, FEATS analysis appears to lack sufficient sensitivity to warrant its use in this population. Study of other quantitative art-based assessment techniques may be warranted.

Colonic hydrogen elimination and methane production in infants with and without infantile colic syndrome.

Our objective was to investigate the relationship between demographic factors, nutrition, stool gas production, and the existence of infantile colic (IC) syndrome. Hydrogen and methane production from stool specimens of infants with and without infantile colic was quantified at two separate time points, the age at presentation of colic (<12 weeks) and at >6 months of age. The relationship between demographic variables and IC was also studied. A total of 59 infants with ages ranging from 2 to 12 weeks were enrolled in the study. Of these, 30 infants developed symptoms of colic. No correlation was found between IC and birth weight, gestational age, sex, type of feeding, mean time of feeding, stool frequency, and consistency. There was also no correlation between IC and the parents' age or education or the infant's number of siblings. Analysis of the stool samples revealed that methane was produced at concentrations >2 ppm by 15.3% of the infants at age <3 months and by 46.4% of infants at age >6 months. The mean methane concentrations produced by stool increased with age (0.95 +/- 0.58 ppm at 3 months of age vs 1.29 +/- 0.65 ppm at 6 months of age. There was no difference in stool hydrogen concentration between infants with and without IC. In contrast, the mean methane level at 3 and 6 months of age was higher in infants without IC than with IC, but reached statistical significance only at 6 months of age (0.97 +/- 0.68 vs 0.93 +/- 0.46) (NS) at 3 months of age, and 1.56 +/- 0.55 vs 0.93 +/- 0.62 (P < 0.05) at 6 months of age respectively. Furthermore, infants that produced higher methane levels at 3 and 6 months of age had significantly (p < 0.05) less colic in the first months of life. In conclusions, methane production may play a role in the alleviation of IC. Future studies are needed to confirm our findings.

Anemia in children after transplantation: etiology and the effect of immunosuppressive therapy on erythropoiesis.

Anemia in children after renal transplantation is more common than previously appreciated. Multiple factors appear to play roles in the development of post-transplant anemia, the most common of which is absolute and/or functional iron deficiency anemia. Most experts recommend that iron limited anemias in transplant patients should be diagnosed using the same criteria as for chronic renal failure patients. Serum erythropoietin (EPO) levels are expected to normalize after a successful renal transplantation with a normal kidney function, yet both EPO deficiency and resistance have been reported. While no large controlled trials comparing the effect of different immunosuppressive agents on erythropoiesis after transplantation have been performed, generalized bone marrow suppression attributable to azathioprine (AZA), mycophenolate mofetil (MMF), tacrolimus, antithymocyte preparations has been reported. Pure red cell aplasia (PRCA) occurs rarely after transplantation and is characterized by the selective suppression of erythroid cells in the bone marrow. PRCA has been reported with the use of AZA, MMF, tacrolimus, angiotensin converting enzyme inhibitors (ACEI), but not with cyclosporine (CSA) use. Post-transplant hemolytic uremic syndrome has been reported with orthoclone anti T-cell antibody (OKT3), CSA and tacrolimus therapy. Viral infections including cytomegalovirus, Epstein-Barr virus and human parvovirus B19 have been reported to cause generalized marrow suppression. Management of severe anemia associated with immunosuppressive drugs generally requires lowering the dose, drug substitution or, when possible, discontinuation of the drug. Because this topic has been incompletely studied, our recommendation as to the best immunosuppressive protocol after renal transplantation remains largely dependent on the clinical response of the individual patient.

Unexpectedly high prevalence of posttransplant anemia in pediatric and young adult renal transplant recipients.

BACKGROUND: Although posttransplant anemia (PTA) is recognized as a common problem in adult renal transplant recipients, few pediatric studies have been published. METHODS: In this retrospective cohort study of 162 pediatric renal transplant recipients treated at Stanford University, the authors sought to determine the prevalence, severity, and the predictive factors of PTA. Anemia was defined as a hematocrit (HCT) level greater than 2 SD below published means for age or as erythropoietin dependency to maintain a normal HCT. RESULTS: Sixty-seven percent of pediatric renal transplant recipients were anemic at the time of transplantation. The prevalence of anemia increased to 84.3% in the first month posttransplant. From 6 months to 60 months posttransplant, the prevalence of anemia remained high at 64.2% to 82.2%. Only 4 patients (2.5%) were never anemic. Iron depletion was detected in 19 of 26 and 23 of 23 anemic patients 12 and 60 months posttransplant, respectively. Serum erythropoietin levels were low relative to hematocrit levels in 38 of 56 anemic patients. Logistic regression at 3 months posttransplant showed that discharge hematocrit level (P < 0.0001), calcium (P = 0.0004), and cyclosporine dose (P = 0.0002) correlated with anemia. Creatinine clearance (P = 0.002) and white blood cell count (P = 0.004) correlated with anemia at 12 months posttransplant, but only creatinine clearance (P = 0.011) correlated with anemia 60 months posttransplant. CONCLUSION: Nearly all pediatric renal transplant recipients experience PTA. However, few children less than 2 years of age were anemic during the first year posttransplant. Antirejection therapy, bone disease, iron depletion, and creatinine clearance appear to play pivotal roles in the development of PTA in children.

Limited surgical interventions in children with posterior urethral valves can lead to better outcomes following renal transplantation.

There is currently no consensus as to the most appropriate means by which children with posterior urethral valves (PUV) are to be managed prior to transplantation. We compared (i) renal allograft survival and function in patients with PUV vs. those with non-obstructive causes of ESRD and (ii) graft outcomes in children who had limited interventions (Group 1) vs. those with more extensive urologic surgeries to decompress the urinary tract (Group 2). Twenty-six pediatric renal transplant recipients had ESRD due to PUV (Group 1, n = 16; Group 2, n = 10). The study group was compared to 23 matched controls with ESRD due to non-obstructive causes. Five yr patient and graft survival was similar in all patients with PUV (Groups 1 and 2) when compared to all other kidney recipients in the transplant program, 96.2% vs. 98.0% and 87.5% vs. 87.0%, respectively. Although calculated creatinine clearance (Ccr), was similar between the PUV group and controls for the first 4 yr, the 5 yr graft function was significantly lower in the PUV group. (53.7 +/- 15.7 vs. 70.2 +/- 21.0 mL/min/1.73 m2; p = 0.03). When the two PUV groups were compared, graft survival was equivalent, but graft function was significantly better at 5 yr in Group 1(60.4 +/- 10.8 vs. 33.8 +/- 9.3 mL/min/1.73 m2; p = 0.02). Thus, patients with PUV managed by a limited intervention approach of vesicostomy with delayed valve ablation or primary valve ablation, had better outcomes. When ESRD is virtually certain, additional pre-transplant surgeries affecting the urinary tract should be avoided.

Late post-transplant anemia in adult renal transplant recipients. An under-recognized problem?

Post-transplant anemia (PTA), a frequent complication during the first 3-6 months after transplant, is thought to be uncommon during the late post-transplant period. A study population of adults (> 18 years) transplanted during 1995 at Stanford University (n = 88) and University of North Carolina (n = 40) was selected. Data-collection points were 0, 1, 2, 3, 4 and 5 years post transplant. Anemia was defined as a hematocrit < 33 volume percentage. Thirty percent of patients were anemic at some time during the post-transplant period. The prevalence of PTA increased over time; by 5 years post transplant, 26% of the patients were anemic. Anemia occurred in 62.5% of patients converted from azathioprine to mycophenolate mofetil. A multivariate logistic regression model demonstrated a correlation between anemia and serum total CO2 (p = 0.002), BUN (p = 0.04), and creatinine (p = 0.045) at 1 year post transplant. At 5 years post transplant, only serum total CO2 (p = 0.0004) correlated with anemia. Thus, diminished renal excretory function and metabolic acidosis appear to be the most important correlates of late PTA. These findings should be interpreted in view of the fact that the newer immunosuppressive agents may have an even more profound effect on anemia and its recovery after transplantation.

Clinicopathologic correlates predict the outcome in children with steroid-resistant idiopathic nephrotic syndrome treated with pulse methylprednisolone therapy.

Although pulse methylprednisolone therapy (PMT) has been used successfully in the management of children with steroid-resistant nephrotic syndrome (SRNS), the relationship between initial presenting findings and renal histological characteristics to the subsequent clinical response to PMT is unknown. A retrospective analysis was conducted in a study cohort of 42 children (30 boys, 12 girls; mean age, 7.4 +/- 4.7 years) with SRNS administered PMT between June 1976 and July 1994 at Stanford University (Stanford, CA). Four diagnostic categories were created: group I, minimal change disease with or without mesangial hypercellularity (n = 10); group II, mesangial proliferation (n = 7); group III, focal segmental glomerulosclerosis (FSGS) with or without mesangial hypercellularity (n = 10); and group IV, FSGS plus mesangial proliferation (n = 15). Primary variables analyzed were remission in response to PMT with or without alkylating agent therapy and end-stage renal disease (ESRD). Remission rates were best in group I (90%) and worst in group IV (46%). With the exception of hematuria, presenting clinical features did not correlate with outcome. Segmental sclerosis, glomerular adhesion to Bowman's capsule, epithelial sloughing, corona (segmental scar surrounded by visceral epithelial cells), subepithelial deposits, inflammatory cells, and percentage of interstitium, immunoglobulin M (IgM), IgG, and C3 deposition univariately correlated with ESRD in univariate analysis. In a multivariate logistic regression model, only segmental sclerosis (P = 0.008) correlated with ESRD. Histological analysis is important because it identifies features, including segmental sclerosis, that portend a poor prognosis in children with SRNS.

Successful renal transplant outcome after intravenous gamma-globulin treatment of a highly sensitized pediatric recipient.

Approximately 10% of patients on the renal transplant (Tx) cadaver waiting list have high (> 20%) panel-reactive antibody (PRA) levels to human leukocyte antigens (HLA). Intravenous gamma-globulin (IVIG) has been shown to reduce anti-HLA cytotoxic antibody levels through an anti-idiotypic antibody-blocking effect. We report a successful renal Tx outcome in a 7-yr-old-girl with high PRA levels owing to a failed renal Tx who experienced a significant reduction in PRA levels (from 96% to 0%) concomitant with IVIG therapy. IVIG was infused weekly (500 mg/kg/week) for 3 consecutive weeks every 12 weeks. Thirty-four months after starting IVIG therapy, the PRA activity dropped to zero and IVIG was stopped. Then IVIG therapy was resumed after 8 months due to a rebound in PRA activity to 52%. Forty-four months after starting IVIG therapy, the patient was cross-matched with a cadaver donor who shared three antigens with the first living donor. The cross-match was positive with the recipient's sera obtained prior to IVIG therapy and negative with the recipient's sera obtained post-IVIG therapy. A successful cadaver renal Tx was performed using anti-thymocyte globulin (ATGAM) induction therapy and a tacrolimus-based immunosuppression protocol. IVIG was given (1 g/kg) prior to Tx and at day 4 post-operatively. A single mild acute rejection episode occurred 10 days post-transplantation that responded to pulse methylprednisolone therapy and an increase in the tacrolimus oral dose. We conclude that a prolonged course of IVIG infusions, without immunosuppressive medications or plasmapheresis, is likely to have been beneficial in modulating the immune response in this highly sensitized recipient. Randomized multicenter trials are required to define the role of IVIG in this specific population.