Progression of asymptomatic nephrolithiasis in children: How often should patients receive follow-up ultrasound imaging?

INTRODUCTION: The natural history of asymptomatic nephrolithiasis (AN) in children is not well defined. Furthermore, there is no guidance on the utility of repeated renal ultrasound evaluations in this same population. Follow-up ultrasound studies are often obtained as frequently as every 6 months. The goal of this study is to assess the follow-up ultrasound interval in the management of these patients. METHODS: A retrospective IRB approved chart review was performed for patients seen for non-cysteine AN between 2012 and 2019. AN was defined as patients without obstructive uropathy abdominal, flank pain and/or gross hematuria. Asymptomatic stones were discovered incidentally or after an acute stone event. Patients with pre-existing renal anomalies and the timepoints with stone passage or stone procedure were excluded. Descriptive statistics were used for demographic information. Multiple linear regression was used to analyze risk factors. Statistical significance was set to p < 0.05. RESULTS: Twenty-nine patients had 90 ultrasounds. The average age at diagnosis was 10.8 ± 6.2 years. The average number of ultrasound studies per patient was 3.2 ± 1.7. The median time between follow-up ultrasounds was 5.2 months [IQR 2.8-10.0]. Median follow-up of patients was 10.6 months [IQR 4.9-21.9]. The change in total stone burden occurred at a rate of 0.11 mm/month (CI [-0.06-0.28], p = 0.20, r2 = 0.42) or 0.66 mm/6 months. Patients with more renal stones had almost a threefold increase in stone burden compared to patients with fewer renal stones (2.98 [CI 1.34-4.62], p=0.001, r2=0.33). Patients with a family history of stones had a twofold increase in the size of their largest stone when compared to patients without a family history (1.97 [CI 0.26-3.68], p=0.02, r2=0.60. CONCLUSION: A complex interplay of multiple factors influence the progression of AN in children. Children with a greater number of stones have a higher increase in total stone burden and children with a family history of stones have a faster increase in largest stone size. These patients may require more frequent imaging studies. The small change in stone size over time favors a longer than 6-month interval for many children.

Dextran-Sulfate Plasma Adsorption Lipoprotein Apheresis in Drug Resistant Primary Focal Segmental Glomerulosclerosis Patients: Results From a Prospective, Multicenter, Single-Arm Intervention Study.

Background: Focal segmental glomerulosclerosis (FSGS) causes end stage renal disease (ESRD) in significant proportion of patients worldwide. Primary FSGS carries poor prognosis and management of FSGS patients, refractory to standard treatments or resistant to steroids, remains a major challenge. Lipoprotein apheresis is a therapeutic approach for drug resistant primary FSGS and post-renal transplant primary FSGS recurrence. Objectives: To examine the safety and probable benefit at 1, 3, 6, 12, and 24-months following completion of apheresis treatment using Liposorber® LA-15 system in patients with nephrotic syndrome (NS), due to refractory primary FSGS or primary FSGS associated NS, in post renal transplant children. Material and Methods: Prospective, multicenter, single-arm intervention study using Liposorber® LA-15 system. Patients ≤21 years old with drug resistant or drug intolerant NS secondary to primary FSGS with glomerular filtration rate (GFR) ≥60 ml/min/1.73 m2 or post renal transplant patients ≤21 years old with primary FSGS associated NS were included in the study. Each patient had 12 dextran-sulfate plasma adsorption lipoprotein apheresis sessions over a period of 9 weeks. All patients were followed up at 1, 3, 6, 12, and 24-months following completion of treatment. Results: Of 17 patients enrolled, six were excluded from the outcome analysis (protocol deviations). Of the remaining 11 patients, all but one have completed apheresis treatments. Three patients were lost to follow-up immediately after completion of apheresis and excluded from outcome analysis. At one-month follow-up, 1 of 7 patients (14.3%) attained partial remission of NS while 2 of 4 subjects (50%) and 2 of 3 subjects (66.7%) had partial/complete remission at 3- and 6-months follow-up, respectively. One of two patients followed up for 12 months had complete remission and one patient had partial remission of NS after 24 months. Improved or stable eGFR was noted in all patients over the follow-up period. Conclusion: The results of our multicenter study showed improvement in the response rates to steroid or immunosuppressive therapy and induced complete or partial remission of proteinuria in some of the patients with drug resistant primary FSGS. The main limitation of our study is the small number of subjects and high dropout rate.

Adrenocorticotropic Hormone for Childhood Nephrotic Syndrome: The ATLANTIS Randomized Trial.

BACKGROUND AND OBJECTIVES: There is renewed interest in adrenocorticotropic hormone (ACTH) for the treatment of nephrotic syndrome. We evaluated the efficacy and safety of ACTH in children with frequently relapsing or steroid-dependent nephrotic syndrome in a randomized trial. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Participants aged 2-20 years old with frequently relapsing or steroid-dependent nephrotic syndrome were enrolled from 16 sites in the United States and randomized 1:1 to ACTH (repository corticotropin injection) or no relapse-preventing treatment. ACTH treatment regimen was 80 U/1.73 m2 administered twice weekly for 6 months, followed by 40 U/1.73 m2 administered twice weekly for 6 months. The primary outcome was disease relapse during the first 6 months. Participants in the control group were offered crossover to ACTH treatment if they relapsed within 6 months. Secondary outcomes were relapse after ACTH dose reduction and treatment side effects. RESULTS: The trial was stopped at a preplanned interim analysis after enrollment of 31 participants because of a lack of discernible treatment efficacy. Fourteen out of 15 (93%) participants in the ACTH arm experienced disease relapse in the first 6 months, with a median time to first relapse of 23 days (interquartile range, 9-32), compared with 15 out of 16 (94%) participants and at a median of 21 days (interquartile range, 14-51) in the control group. There was no difference in the proportion of relapsed patients (odds ratio, 0.93; 95% confidence interval, 0.05 to 16.40; P>0.99) or time to first relapse (hazard ratio, 1.03; 95% confidence interval, 0.50 to 2.15; P=0.93). Thirteen out of 16 participants in the control group crossed over to ACTH treatment. Three out of 28 participants completed 12 months of ACTH treatment; the others exited the trial because of frequent relapses or side effects. There were no disease relapses after ACTH dose reduction among the three participants. Most side effects were mild and similar to side effects of corticosteroids. CONCLUSIONS: ACTH at 80 U/1.73 m2 administered twice weekly was ineffective at preventing disease relapses in pediatric nephrotic syndrome.

Ambulatory hypertension in a pediatric cohort of sickle cell disease.

Hypertension is an established risk factor for subsequent cardiovascular and renal disease in children as well as adults. Sickle cell disease (SCD) is a genetic disorder associated with chronic hemolytic anemia with the major manifestation of vaso-occlusive crises. Although this disease entity involves most organ systems causing vascular and pulmonary injury, little is known about blood pressure (BP) levels or prevalence of hypertension in children with SCD. A cross-sectional study was conducted on 56 children with SCD (54 with hemoglobin SS disease; 2 with hemoglobin Sß0 thalassemia; 29 females). Study participants underwent 24-hour ambulatory BP monitoring (ABPM). Serum creatinine and cystatin C were obtained to assess estimated glomerular filtration rate with age-based formulas. A random urine sample was obtained to estimate urine osmolality and urine albumin to creatinine ratio. Mean age range was 11.9 (±4.5) years. Seventeen participants (30%) met criteria for hypertension based on ABPM. Of the 17 participants classified with hypertension, three had office hypertension with ambulatory hypertension, and 14 had masked hypertension detected on ABPM. Another 28 participants (50%) had some abnormal ABPM parameters in the form of either prehypertension and/or lack of normal nocturnal dipping status. The prevalence of confirmed hypertension, largely manifest by masked hypertension, is high in children, as young as 6 years of age with SCD. Early identification of hypertension in SCD children can confer benefit as it is an important modifiable risk factor for progression of cardiovascular and renal disease.

The clinical impact of humoral immunity in pediatric renal transplantation.

The development of anti-donor humoral responses after transplantation associates with higher risks for acute rejection and 1-year graft survival in adults, but the influence of humoral immunity on transplant outcomes in children is not well understood. Here, we studied the evolution of humoral immunity in low-risk pediatric patients during the first 2 years after renal transplantation. Using data from 130 pediatric renal transplant patients randomized to steroid-free (SF) or steroid-based (SB) immunosuppression in the NIH-SNSO1 trial, we correlated the presence of serum anti-HLA antibodies to donor HLA antigens (donor-specific antibodies) and serum MHC class 1-related chain A (MICA) antibody with both clinical outcomes and histology identified on protocol biopsies at 0, 6, 12, and 24 months. We detected de novo antibodies after transplant in 24% (23% of SF group and 25% of SB group), most often after the first year. Overall, 22% developed anti-HLA antibodies, of which 6% were donor-specific antibodies, and 6% developed anti-MICA antibody. Presence of these antibodies de novo associated with significantly higher risks for acute rejection (P=0.02), chronic graft injury (P=0.02), and decline in graft function (P=0.02). In summary, antibodies to HLA and MICA antigens appear in approximately 25% of unsensitized pediatric patients, placing them at greater risk for acute and chronic rejection with accelerated loss of graft function. Avoiding steroids does not seem to modify this incidence. Whether serial assessments of these antibodies after transplant could guide individual tailoring of immunosuppression requires additional study.

Gingival enlargement in pediatric organ transplant recipients in relation to tacrolimus-based immunosuppressive regimens.

PURPOSE: Tacrolimus, in contrast to cyclosporine, has not been found to be associated with gingival enlargement (GE) among adult transplant recipients. The purpose of this study was to explore the prevalence of GE in relation to tacrolimus and cyclosporine-based immunosuppressive regimens among pediatric solid-organ transplant recipients, controlling for the use of calcium channel blockers (CCB) and the presence of supragingival plaque. METHODS: A standardized questionnaire was administered and a comprehensive oral examination was performed among pediatric renal and liver transplant recipients who were at least 6 months post-transplant. RESULTS: The prevalence of GE among 133 participants was 26%, with the highest incidence among subjects receiving cyclosporine and CCB (60%) and the lowest among those receiving tacrolimus without CCB (13%). A multivariate model showed that the odds of having GE were 5 times higher among children receiving cyclosporine than in those not receiving this medication, and 4 times higher among boys than girls. Supragingival plaque and the use of CCB, however, were not found to be associated with GE. CONCLUSION: This study revealed that tacrolimus was not associated with gingival enlargement while cyclosporine remains a risk factor for the development of this condition in pediatric renal and liver transplant recipients.

Oral disease burden and utilization of dental care patterns among pediatric solid organ transplant recipients.

OBJECTIVES: We conducted a study among pediatric renal (RTRs) and liver transplant recipients (LTRs) to determine: a) the overall burden of oral disease; and b) the frequency with which this population utilizes dental care services in relation to sociodemographic factors and oral disease burden. METHODS: In this cross-sectional survey, study procedures included the completion of a standardized questionnaire (by parents/guardians), oral mucosal examination, assessment of caries, gingival enlargement, and plaque index. RESULTS: The 142 children (82 RTRs and 60 LTRs) enrolled from April 2002 to November 2005 were predominantly Latino (41 percent) and Caucasian (34 percent). Forty-three percent had at least one carious surface (in either a deciduous or permanent tooth), 19 percent had five or more carious surfaces, and 25 percent had gingival enlargement. We found only one case of oral candidiasis. Even though 72 percent of parents/guardians reported their child had a regular source of dental care, only 49 percent had a dental cleaning and 44 percent had dental radiographs in the past year, reflecting a low prevalence of preventive dental care. Among children with no regular source of dental care, there were statistically significantly higher proportions of Latinos, younger children, and families with an annual household income <$35,000. CONCLUSION: While the prevalence of oral mucosal disease and gingival enlargement was low, the prevalence of children with caries was high, and there was low use of preventive dental care. Strategies to improve this population's utilization of preventive dental care are needed.

The effect of fluoride on enamel and dentin formation in the uremic rat incisor.

Renal impairment in children is associated with tooth defects that include enamel pitting and hypoplasia. However, the specific effects of uremia on tooth formation are not known. In this study, we used rat mandibular incisors, which continuously erupt and contain all stages of tooth formation, to characterize the effects of uremia on tooth formation. We also tested the hypothesis that uremia aggravates the fluoride (F)-induced changes in developing teeth. Rats were subjected to a two-stage 5/6 nephrectomy or sham operation and then exposed to 0 (control) or 50 ppm NaF in drinking water for 14 days. The effects of these treatments on food intake, body growth rate, and biochemical serum parameters for renal function and calcium metabolism were monitored. Nephrectomy reduced food intake and weight gain. Intake of F by nephrectomized rats increased plasma F levels twofold and further decreased food intake and body weight gain. Uremia affected formation of dentin and enamel and was more extensive than the effect of F alone. Uremia also significantly increased predentin width and induced deposition of large amounts of osteodentin-like matrix-containing cells in the pulp chamber. In enamel formation, the cells most sensitive to uremia were the transitional-stage ameloblasts. These data demonstrate that intake of F by rats with reduced renal function impairs F clearance from the plasma and aggravates the already negative effects of uremia on incisor tooth development.

Exercise capacity and physical fitness in pediatric dialysis and kidney transplant patients.

Studies of exercise capacity in children with chronic kidney disease (CKD) are limited. We tested 25 pediatric kidney transplant (TX) recipients and 15 pediatric dialysis (DX) patients. Nine children in the DX group received kidney transplants and were retested 3 months following surgery (pre/post). Testing involved treadmill testing with measurement of peak oxygen uptake (VO(2peak)), muscle strength, body composition (percent fat), and "field" tests of physical fitness using the FITNESSGRAM, which included the PACER test. Values obtained were compared with gender- and age-based criterion-referenced standards [healthy fitness zone (HFZ)]. The previous day physical activity recall (PDPAR) was used to assess physical activity participation. There were no differences between TX and DX subjects for VO(2peak) and muscle strength measurements, and all values were below the normative values. The TX group achieved significantly higher PACER scores, but only one TX and no DX subjects achieved the HFZ for the PACER test. No improvement in any measures were observed from pre- to post-TX in the nine subjects tested, except for a significant increase in percent fat, which negatively affected the change in muscle strength and VO(2peak). All subjects were physically inactive, with less than 10% of nonschool time being physical activity participation. Pediatric patients with CKD had low exercise capacity, were physically inactive, and gained significant fat weight following TX. Counseling and encouragement for more physical activity is warranted as a part of routine medical care in these children.

Outcomes of dialysis initiated during the neonatal period for treatment of end-stage renal disease: a North American Pediatric Renal Trials and Collaborative Studies special analysis.

OBJECTIVE: We sought to determine the outcomes of initiating long-term dialysis of neonates and children aged > 1 to 24 months with end-stage renal disease. PATIENTS AND METHODS: By querying the North American Pediatric Renal Trials and Collaborative Studies database, we obtained information on 193 neonates (< or = 1 month of age) and 505 children (> 1-24 months of age) with a presumptive diagnosis of end-stage renal disease who initiated long-term dialysis. Dialysis characteristics and likelihood of hospitalization were compared using the chi2 test, and duration of hospitalization was compared using the Wilcoxon 2-sample test. Product limit methods were implemented, and the log rank test was used to compare time-to-event analyses. Multivariate analyses were performed using Cox proportional hazards models. RESULTS: Neonates with end-stage renal disease were more likely to receive peritoneal dialysis versus hemodialysis than older children with end-stage renal disease. Moreover, neonates who initiated dialysis during the first month of life were just as likely to terminate dialysis as were the older children. Rates of renal transplantation were significantly lower in the neonates compared with the older children, but neonates were more likely to recover function of the native kidney. Although neonates were more often hospitalized, their overall risk of mortality was similar to that observed in older children. CONCLUSIONS: Neonates with a presumptive diagnosis of end-stage renal disease may initiate long-term dialysis during the first month of life with outcomes comparable to those of patients who initiate dialysis later in infancy.

Redo ureteroneocystostomy using an extravesical approach in pediatric renal transplant patients with reflux: a retrospective analysis and description of technique.

PURPOSE: Vesicoureteral reflux and pyelonephritis following transplantation may significantly contribute to renal damage and premature graft loss. We report our retrospective experience with redo ureteral reimplantation of refluxing pediatric renal transplants and describe our surgical technique. MATERIALS AND METHODS: We identified 20 children with a diagnosis of symptomatic post-transplant vesicoureteral reflux, of whom 16 underwent redo ureteral reimplantation. Patient characteristics including etiology of end stage renal disease, presenting symptoms, serum creatinine and postoperative followup were documented. The presence or absence of lower urinary tract dysfunction was documented and values between the 2 groups were analyzed for significance. RESULTS: All 20 patients presented after assessment for a febrile urinary tract infection, and 35% had concurrent lower urinary tract dysfunction. Median interval between transplantation and vesicoureteral reflux diagnosis was 1.3 years, and mean vesicoureteral reflux grade was 3.2. Patients with lower urinary tract dysfunction presented significantly earlier and had a higher postoperative serum creatinine than those without lower urinary tract dysfunction (1.1 vs 1.7 years, p = 0.048). Redo reimplantation was performed in 94% of patients using an extravesical approach with ureteral stent placement. Seven of 16 patients underwent followup voiding cystourethrogram, with 5 demonstrating resolution and 2, both with lower urinary tract dysfunction, exhibiting persistent vesicoureteral reflux. At a mean followup of 3.6 years 25% of patients experienced recurrent pyelonephritis, while 75% were asymptomatic. One instance of anastomotic stricture occurred in a patient with lower urinary tract dysfunction. CONCLUSIONS: Effective repair of post-transplantation vesicoureteral reflux can be performed using an extravesical technique, facilitated by preoperative ureteral stent placement. Patients with lower urinary tract dysfunction are likely to present earlier after transplantation than those without lower urinary tract dysfunction, and may have an increased risk of persistent vesicoureteral reflux and renal damage despite surgical correction.

The comprehensive assessment of physical fitness in children following kidney and liver transplantation.

BACKGROUND: Pediatric organ transplant recipients may have elevated cardiovascular (CV) risk. Low cardiorespiratory fitness (CRF) may contribute to CV risk; however, studies of CRF in children following kidney transplantation (KTx) and liver transplantation (LTx) are limited. METHODS: Laboratory testing included assessment of CRF (VO2peak), muscle strength, and body composition (%fat). Field testing (FITNESSGRAM) included the PACER, curl-up, and sit-and-reach tests. Values obtained were compared to sex- and age-based criterion-referenced standards (Healthy Fitness Zone, HFZ). The Previous Day Physical Activity Recall was used to assess after-school physical activity (PA) participation. Independent t tests were used to compare groups. RESULTS: Twenty-five KTx and 11 LTx recipients were tested. The groups were similar in all measures. Both groups demonstrated below normative values for VO2peak and muscle strength. Only 4% of the KTx and 9% of the LTx recipients achieved the HFZ for the PACER and 24% of the KTx and 45% of the LTx attained the HFZ for the curl-up test. Approximately 44% of both groups had percent fat greater than the upper criterion value of the HFZ. Both groups reported spending only 8% of their after-school time participating in physical activity. CONCLUSIONS: Pediatric KTx and LTx recipients have significantly reduced CRF, muscle strength, and physical activity. Routine counseling and encouragement for increased physical activity is recommended as a part of routine care. A randomized clinical exercise intervention trial after pediatric solid organ transplantation is warranted to determine the impact of such lifestyle intervention on improving physical fitness and cardiovascular health.

Persistent secondary hyperparathyroidism after renal transplantation in children.

Secondary hyperparathyroidism (HPTH) is a frequent complication of chronic kidney disease (CKD). Renal transplantation corrects the biochemical abnormalities that cause HPTH; however, HPTH persists in some patients. The factors that contribute to the persistence of HPTH after transplantation in children are poorly understood. We examined 57 children who underwent renal transplantation and determined whether baseline clinical and biochemical parameters could predict the persistence of HPTH at 1 year post-transplantation, using multivariate logistic regression. At the time of transplantation, serum parathyroid hormone (PTH) levels were >300 pg/ml in 60%, 150-300 pg/ml in 17%, and <150 pg/ml in 23% of recipients. HPTH (PTH >73 pg/ml) persisted in 78% of patients at 6 months and in 56% at 1 year after transplant. Older age at transplantation was the strongest predictor of HPTH at 1 year (OR=1.17, P<0.05). After adjustment for age, other baseline clinical or laboratory parameters were not predictive of HPTH at 1 year. The relationship between older age and persistent HPTH may be explained by longer duration of CKD. Given the potential morbidities associated with persistent HPTH, the role of interventions that would prevent or reverse persistent HPTH post-transplantation requires further investigation.

Nephrogenic syndrome of inappropriate antidiuresis.

The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is a common cause of hyponatremia. We describe two infants whose clinical and laboratory evaluations were consistent with the presence of SIADH, yet who had undetectable arginine vasopressin (AVP) levels. We hypothesized that they had gain-of-function mutations in the V2 vasopressin receptor (V2R). DNA sequencing of each patient's V2R gene (AVPR2) identified missense mutations in both, with resultant changes in codon 137 from arginine to cysteine or leucine. These novel mutations cause constitutive activation of the receptor and are the likely cause of the patients' SIADH-like clinical picture, which we have termed "nephrogenic syndrome of inappropriate antidiuresis."

Growth and metabolic consequences of bladder augmentation in children with myelomeningocele and bladder exstrophy.

OBJECTIVE: Bladder augmentation using intestinal segments is reported to cause decreased linear growth in bladder exstrophy and myelomeningocele patients. We studied changes in calcium metabolism, height, bone chemistry, and bone density in exstrophy and myelomeningocele patients after bladder augmentation. METHODS: Thirty-three patients were prospectively admitted to the Pediatric Clinical Research Center at the University of California San Francisco for 24 hours. Blood and urine were analyzed for electrolytes, and serum was obtained for markers of calcium metabolism. Dual radiograph bone densitometry of the forearm was performed. Myelomeningocele patients were compared with nonaugmented myelomeningocele patients matched by age, gender, level of defect, and ambulatory status. Exstrophy augmented patients were compared with nonaugmented exstrophy patients. The bone densities in both groups were compared with normal children. Laboratory values and percentile heights were statistically analyzed using the Student t test; bone densitometry was analyzed using the Tukey test. RESULTS: Twenty-two patients with myelomeningocele and 11 with bladder exstrophy were studied. Mean follow-up was 3.7 years postaugmentation (range: 1-13 years). The results indicate a significant difference in serum bicarbonate and chloride levels between myelomeningocele patients who underwent ileal augmentation and those who did not. Although this may be indicative of chronic metabolic acidosis, there was no affect on growth or bone density when compared with controls. There were no other significant differences in laboratory values, or percentile heights, nor were any differences noted in patients who underwent gastrocystoplasty. In the exstrophy group, there were no observable differences in percentile height or laboratory values between the augmented and nonaugmented group. There were no significant differences in bone density between these 2 groups when matched for age and gender. No significant difference was seen in bone density when these groups were compared with normal children. CONCLUSION: Bladder augmentation is safe and does not impact negatively on the linear growth or bone densities of patients with myelomeningocele or bladder exstrophy.

Glucocorticoids prolong Ca(2+) transients in hippocampal-derived H19-7 neurons by repressing the plasma membrane Ca(2+)-ATPase-1.

Calcium ions (Ca(2+)) play an important role in mediating an array of structural and functional responses in cells. In hippocampal neurons, elevated glucocorticoid (GC) levels, as seen during stress, perturb calcium homeostasis and result in altered neuronal excitability and viability. Ligand- and voltage-gated calcium channels have been the presumed targets of hormonal regulation; however, circumstantial evidence has suggested the possibility that calcium extrusion might be an important target of GC regulation. Here we demonstrate that GC-induced repression of the plasma membrane Ca(2+)-ATPase-1 (PMCA1) is an essential determinant of intracellular Ca(2+) levels ([Ca(2+)](i)) in cultured hippocampal H19-7 cells. In particular, GC treatment caused a prolongation of agonist-evoked elevation of [Ca(2+)](i) that was prevented by the expression of exogenous PMCA1. Furthermore, selective inhibition of PMCA1 using the RNA interference technique caused prolongation of Ca(2+) transients in the absence of GC treatment. Taken together, these observations suggest that GC-mediated repression of PMCA1 is both necessary and sufficient to increase agonist-evoked Ca(2+) transients by down-regulating Ca(2+) extrusion mechanisms in the absence of effects on calcium channels. Prolonged exposure to GCs, resulting in concomitant accumulation of [Ca(2+)](i), is likely to compromise neuronal function and viability.

Increased incidence in post-transplant diabetes mellitus in children: a case-control analysis.

There is limited information regarding the incidence and features of post-transplant diabetes mellitus (PTDM) in pediatric renal transplant recipients. We noted a recent increased frequency of PTDM and reviewed charts of children who underwent renal transplantation from 1 September 1986 to 31 August 1999 to characterize the risk factors and natural history of PTDM. Sixteen children were identified with PTDM, and were each matched with two transplanted controls who did not develop PTDM. Clinical presentation varied from asymptomatic hyperglycemia to hyperosmolar dehydration or diabetic ketoacidosis. The mean time from transplantation to PTDM presentation was 1.2 years (range 1 day to 6.2 years). Significant risk factors for PTDM included: first degree family history of type 2 DM [odds ratio (OR) 23.9]; second degree family history of type 2 DM (OR 5.8); tacrolimus use (OR 9.1 versus cyclosporin); and hyperglycemia in the 2 weeks immediately after transplantation (OR 4.7). Seven of eight children with persistent PTDM continue to receive insulin. Patients with persistent PTDM had later onset disease (mean 1.9 years) compared to those with transient PTDM (0.3 years), suggesting different pathophysiologic processes. We suggest that all children undergoing renal transplantation be screened routinely for PTDM after transplantation, and that such patients may benefit from the avoidance of tacrolimus, as it may cause permanent beta-cell injury.