Sirolimus in chronic allograft nephropathy in pediatric recipients

CAN is a common cause of late graft loss. Nephrotoxicity due to CNIs is known to contribute to CAN. We retrospectively evaluated the efficacy and safety of SRL in pediatric renal Tx recipients showing CAN in their allograft biopsy. Twenty-one patients aged 10.4 +/- 4.6 yr at Tx time receiving CNIs as primary immunosuppression were converted to SRL at 58.9 +/- 49.1 months after Tx, due to progressive decline of renal function and biopsy proven CAN. Mean follow-up after switch was 19.7 +/- 9.5 months. All patients received CsA as part of the immunosuppressive regimen, at a mean dose 4.4 +/- 1.2 mg/kg/day. Mean daily dose of SRL three month after conversion was 2.6 +/- 0.8 mg/body surface area/day and the mean through levels where 6.9 +/- 2.5 ng/mL. Graft biopsies showed Grade I CAN in 12 children and Grade II CAN in nine. After SRL introduction, there were neither acute rejection episodes nor graft losses. GFR improved at three months and was sustained thereafter only in children with Grade I CAN. Post-Tx time at conversion was the only significant variable between patients who had Grade I CAN and Grade II CAN (33.6 +/- 33.3 vs. 92.7 +/- 47.5 months, p = 0.003). Nine patients had no AEs, six patients had nine SAE: five diarrhea, one herpes zoster, one pancreatic pseudo cyst, one pneumonia, and one Influenza A infection; 11 patients had 13 AEs: six oral aphthous ulcers, three urinary tract infections, two herpes simplex, one lymphedema, and one nephrotic proteinuria. Significant improvement of GFR occurred in Grade I CAN group at three months from conversion and was sustained during follow-up. Those who had Grade II CAN experienced no change in GFR. The incidence of AEs and SAE is of concern and further studies are necessary to assess their relevance.     

Linear growth in pediatric renal transplant recipients receiving sirolimus

SRL is a potent macrolide immunosuppressive agent that can be used as maintenance therapy for prevention of rejection and avoidance of CNI nephrotoxicity. However, animal studies indicate that SRL may inhibit skeletal and muscle growth. We analyzed linear growth in 25 children, age 1-15 yr old, maintained on SRL to determine whether SRL is detrimental to linear growth. Height z-scores at baseline were compared with those at 24 months. We also compared linear growth in children receiving SRL to patients maintained on TAC. Height z-scores over 24 months did not significantly change in the SRL group as a whole. Z-scores improved in 13 of 25 patients (52%). Children with improved z-scores were significantly younger than patents who did not display improved growth: 6 ± 5 yr vs. 11 ± 4 yr (p < 0.05). Height z-scores in SRL and TAC-based patients were no different initially and at 24 months, and a similar number of patients in each group displayed improved height scores. Height z-scores improved in 52% of patients on SRL and occurred predominantly in younger patients for the initial 24 months of treatment. Linear growth in SRL patients was also similar to the results in TAC-based patients. Therefore, our data did not identify a significant adverse effect of SRL on growth.     

Improved long-term graft function in pediatric transplant renal recipients with chronic allograft nephropathy

Abstract:  CAN is the leading cause of graft loss in pediatric renal transplant recipients. A retrospective single centre analysis of pediatric transplant patients with CAN treated with MMF in conjunction with CNI minimisation/withdrawal is reported. 35 children were successfully started on MMF. The mean age at transplant was 7.9 ± 0.1 years. MMF was introduced 3.5 ± 0.1 years after transplantation and patients were followed up for a mean of 32.2 ± 0.5 months. CAN was confirmed on biopsy in 31 patients. CNI was stopped in 23 patients at a mean time of 16.5 ± 0.6 months after MMF introduction and minimised in the remaining patients. Prior to MMF introduction, GFR was deteriorating by 21.6 ± 0.07 ml/min/1.73 m²/yr. After MMF, there was an overall improvement in GFR of 4.0 ± 0.03 ml/min/1.73 m²/yr. This was most marked in the first six months when the GFR improved by 20.8 ± 0.06 ml/min/1.73 m²/day. Mean acute rejection episode rate prior to MMF was significantly reduced after MMF introduction. MMF was discontinued in a total of 4 patients due to adverse effects. CNI minimisation/withdrawal with MMF introduction is safe and leads to significant initial improvement with subsequent stabilisation of GFR and improved long term graft survival in pediatric renal transplant recipients with CAN.     

C4d in pediatric renal allograft biopsies: a marker for negative outcome in steroid-resistant rejection

Recently, deposition of C4d, reflecting complement activation via the classical pathway, has been established as marker of antibody-mediated rejection. As C4d can be detected in paraffin sections, it allows for retrospective analysis in populations with low case loads, such as in pediatric transplantation. In this study we re-evaluated consecutive renal transplant biopsies obtained since 1990 in 36 children (18 boys, 18 girls) who had received their allograft (nine living, 27 cadaveric) at an age of 10.12+/-4.4 yr. Clinical indications for biopsy were 16 acute steroid resistant rejections (ASRs), 11 chronic rejections and nine other diagnoses. Overall, C4d deposition was found in nine cases (25%), eight of them with diagnosed ASR. Six out of these eight allografts were lost during 36 months of clinical follow-up, a significantly higher rate than in C4d-negative biopsies (p<0.05). C4d status therefore turned out to be an excellent predictor for inferior graft survival following ASR. None of the other histopathologic markers were sensitive for humoral rejections. In conclusion, the high prevalence of C4d-positive staining in ASR demonstrates the importance of the humoral part of the immune system in pediatric transplantation. The worse outcome of C4d-positive rejections despite massive immunosuppressive therapy clearly indicates the need for innovative therapies in this high-risk population.     

The predictive value of resistive index obtained by Doppler ultrasonography early after renal transplantation on long‐term allograft function

DUSG is a useful diagnostic tool for the follow‐up of renal transplant recipients. The measurement of intrarenal arterial RI by DUSG has been proven to predict short‐term AF. The aim of the study was to evaluate the predictive value of DUSG performed during the early after RTx on long‐term AF. Seventy patients were enrolled into study. DUSG was performed at third and seventh days after RTx. Patients were divided into two groups according to rate of recovery of graft function as patients with normal graft function and abnormal graft function. Although the RI values were correlated with the AF early after transplantation, they were not correlated with long‐term AF. However, the rate of recovery of graft function at early period after RTx was correlated with creatinine level at first year and with glomerular filtration rate at first year and last visit. Although the RI has no predictive value for long‐term AF, the rate of recovery of graft function at early post‐transplantation period has predictive value for long‐term AF; patients with higher RI values early after RTx should be followed carefully for the development of chronic allograft injury.     

Improved long-term allograft function in pediatric renal transplantation with mycophenolate mofetil

MMF has been shown to decrease the incidence of acute rejection in children and adults at 1 and 3 yr. Other beneficial effects of MMF have been more difficult to demonstrate. Our open-labeled study presents a 5-yr data for patients and graft survival, allograft function, and growth in MMF-treated patients. The trial included 29 patients who were treated with MMF in combination with cyclosporine and methylprednisone. Patients were compared with a preceding group of 29 patients treated with AZA instead of MMF. Patient and graft survival rate 5 yr after transplantation were 97 and 90% in the MMF group vs. 93 and 83% in the AZA group (p: NS). Acute rejection was 20.6% in the MMF group vs. 58.6% in the AZA group (p < 0.01). Chronic rejection was 10.3% in the MMF group and 25% in the AZA group (p: NS). The changes in the creatinine clearance from baseline to 5 yr (Delta) were different between groups (-6.0 +/- 5.1 mL/min/1.73 m(2) in the MMF group vs. -22.2 +/- 7.6 mL/min/1.73 m(2) in the AZA group, p < 0.05). Also, the slope of 1/Scr showed a significant lower incidence of worsening renal function after the second year of renal transplantation (p < 0.0001) in the MMF group compared with the AZA group. Delta Height SDS in prepubertal patients was 0.3 +/- 0.4 SDS in the MMF group vs. -0.8 +/- 0.2 SDS in the AZA group (p < 0.05). This study shows that long-term MMF therapy has resulted in a decrease in acute rejection and was associated with a protection against renal function deterioration. The use of MMF enables a reduction in the dose of steroids and leads to a linear growth improvement of children after renal transplantation.     

Growth of pediatric recipients after renal transplantation from small pediatric deceased donors weighing less than 15 kg

RTx is currently the best treatment for children with ESRD. This study retrospectively analyzed the outcomes of growth after RTx using the pediatric‐to‐pediatric allocation strategy and some factors that may affect it. From March 2012 to August 2016, 8 en bloc and 38 single pediatric RTxs were performed at our center using organs from small pediatric deceased donors (weight < 15 kg). Growth before and after RTx was analyzed according to the height‐for‐age z‐score at RTx, the 3‐year follow‐up, and adulthood and compared between the procedures. The chi‐square test and multiple linear regression analysis were used for statistical analyses. Overall, 79.2% of children were diagnosed with chronic nephritis before RTx; 14.6% of cases were due to congenital urinary tract malformation, and 6.3% of cases were due to unknown causes. All grafts and patients survived postoperatively. The mean estimated GFRs were 92.7 ± 28.6 mL/min/1.73 m², 100.9 ± 32.3 mL/min/1.73 m², and 110.1 ± 34.8 mL/min/1.73 m² at 1, 2, and 3 years’ postoperatively, respectively. The children's postoperative growth and development, particularly during the first year postoperatively, improved but were negatively correlated with age and the height‐for‐age z‐score before RTx. The growth of children after RTx was moderate and accelerated during prepubescence. The rate of post‐RTx growth during the first year postoperatively was unrelated to the recipient's sex or duration of dialysis (P > 0.05) but was negatively correlated with age at RTx (r = ?0.349, P = 0.043). Future studies on the long‐term outcomes are still needed.     

Conversion from calcineurin inhibitor to sirolimus in pediatric chronic allograft nephropathy

Chronic allograft nephropathy is a major cause for allograft loss in renal transplantation. Sirolimus was recently introduced as a potent non-nephrotoxic alternative to calcineurin inhibitors. In the present study, effects of a conversion protocol were investigated in pediatric chronic allograft nephropathy with declining glomerular filtration rate (GFR), defined by a Schwartz formula clearance below 60 mL/1.73 m(2)/min, steadily increasing serum creatinine and allograft biopsy. In eight children with a median age of 12.8 yr, sirolimus was started at median 32 months after transplantation with a loading dose of 0.24 mg/kg bodyweight (BW), followed by 0.2 mg/kgBW/day, aimed at trough levels of 15-20 ng/mL. Calcineurin inhibitors were reduced to 50% at the start of sirolimus and discontinued at median 7 days when target levels of sirolimus were reached. Following conversion, changes of GFR significantly stabilized (-2.9 vs. +0.4 mL/min/1.73 m(2)/month, p = 0.025). Individual GFR increased in five out of eight patients (p = 0.026), and only one child exhibited unaltered progression of graft failure. In the responders, mean serum creatinine improved by 0.3 mg/dL (p = 0.043). Effects were not dependent on GFR at conversion, or on time post-transplantation. Blood pressure, hematological parameters and proteinuria remained stable during the observation period, and serum lipids increased transiently. About half of the children suffered from infectious complications. No child had to be taken off sirolimus; there was no graft loss during the observation period. In conclusion, conversion from calcineurin inhibitors to sirolimus is an effective protocol with tolerable side effects to stabilize renal graft function for at least one yr in the majority of children with biopsy-proven chronic allograft nephropathy.     

Prevalence of renal dysfunction in tacrolimus‐treated pediatric transplant recipients: A systematic review

Renal dysfunction after non‐renal transplantation in adult tacrolimus‐treated transplant patients is well documented. Little is known about its prevalence in children. Age‐related changes in both disposition and effect of tacrolimus as well as renal function may preclude extrapolation of adult data to children. To systematically review the literature on renal dysfunction in non‐renal pediatric transplant recipients treated with tacrolimus. PubMed/Medline, Embase, and Google were searched from their inception until April 19, 2012, with the search terms “tacrolimus,” “renal function,” “transplantation,” and “children.” Eighteen of 385 retrieved papers were considered relevant. Twelve dealt with liver, four with heart transplant, one with heart and lung transplant, and one with intestinal recipients. Reported prevalences of mild and severe chronic kidney disease ranged from 0% to 39% and 0% to 71.4%, respectively, for liver, and from 22.7% to 40% and 6.8% to 46%, respectively, for heart and/or lung transplant recipients. Ranges remained wide after adjusting for follow‐up time and disease severity. Possible explanations are inclusion bias and definitions used for renal dysfunction. A considerable proportion of pediatric non‐renal transplant patients who receive tacrolimus‐based immunosuppression, appear to suffer from chronic kidney disease. This conclusion warrants further research into the real risk, its risk factors, and individualization of immunosuppressant therapy.     

Cyclosporine drug monitoring with C0 and C2 concentrations in children with stable renal allograft function

Cyclosporin A (CsA) has a narrow therapeutic window and necessitates monitoring of blood concentration. We aimed to evaluate trough (C0) and second hour (C2) level after ingestion of drug monitoring in renal allograft recipients. In this retrospective study, 12 children eight boys and four girls; mean age at transplantation 14.6 +/- 3.7 yr (ranges: 7.0-19.0), mean age post-transplant 17.8 +/- 4.9 yr (ranges: 9.0-24.0) who were transplanted >6 months were enrolled in this evaluation. Ten were recipients of a living related donor and two deceased donor grafts. While six children were receiving CsA, steroids and azathioprine, the other six received CsA, steroids and mycophenolate mofetil. Clinical course, blood pressure, renal and liver function tests were recorded. Mean C0 and C2 were 96.2 +/- 59.5 and 504 +/- 305.4 ng/mL respectively. Mean serum creatinine level was 1.2 +/- 0.45 mg/dL and mean creatinine clearance (CrCl) was 89.2 +/- 36.8 mL/min/1.73 m2. There was a correlation between serum creatinine level, CsA dose and C2 levels,whereas,there was no correlation between age, blood pressure, CrCl and C2 levels. However, no correlation was found between C0 levels and any of the above parameters. In conclusion, our data suggest that C2 levels are correlated better with dose and serum creatinine level.     

Adiponectin levels and arteriosclerotic risk factors in pediatric renal transplant recipients

ADPN, a recently discovered adipocytokine, has attracted great attention because of its anti-atherogenic properties. It was suggested as a protective factor for the cardiovascular system because of its close correlation with several risk factors. Our aim was to investigate serum ADPN levels in pediatric RTR and to document possible relationships between ADPN and arteriosclerotic risk factors. Twenty-one RTR, aged 16.3 +/- 4.0 yr, and 23 healthy age and sex-matched control subjects were enrolled in this study. Serum lipid/lipoprotein fractions, homocysteine and ADPN levels as well as intima-media thickness of the cIMT were determined in both groups. Significantly higher serum ADPN (p < 0.001) and homocysteine (p < 0.05) levels as well as higher cIMT (p < 0.001) were found in RTR compared with the control subjects, whereas apolipoprotein B and lipoprotein (a) levels were not significantly different. HDL cholesterol was positively correlated with log ADPN (r = 0.585, p < 0.01). There were inverse correlations between log time post-transplantation and log ADPN as well as HDL cholesterol (r = -0.438, p < 0.05 and r = -0.578, p < 0.05, respectively). There were no correlation between log ADPN, log homocysteine, log apolipoprotein B, lipoprotein (a), creatinine clearance and cumulative steroid dose. Despite reasonable lipid profiles and remarkably elevated ADPN levels, our pediatric RTR with stable graft function displayed a risk for arteriosclerosis because of increased cIMT and mild hyperhomocysteinemia. Regarding the close positive correlation between ADPN and HDL cholesterol, it could be speculated that ADPN is a novel negative surrogate marker of arteriosclerosis. To our knowledge, this is the only report investigating levels and diverse correlates of ADPN in a pediatric RTR group. Further studies in larger groups of recipients are needed to clarify the interaction between arteriosclerotic risk factors and ADPN.     

The relationship of donor source and age on short- and long-term allograft survival in pediatric renal transplantation

Abstract:  Limited pediatric data on allograft survival from advanced aged kidney donors exist. To determine the influence of donor source and age on allograft survival in pediatric renal transplant recipients, we analyzed the OPTN database. Allograft survival for 7291 pediatric renal transplants was evaluated. Up to five yr post-transplantation, graft survival was higher for LD vs. DD recipients. At seven yr, allograft survival was 71% in 18–54 yr-old LD recipients, 59.1% in ≥55 yr-old LD, and 45.1% in ≥50 yr-old DD recipients. An approximate 35% improvement in allograft survival in 18–54 yr-old LD recipients was observed. Multivariate results showed that recipients of LD 35–49 (aRR 0.66, 95% CI 0.55–0.80) and LD 50–54 (aRR 0.65, 95% CI 0.45–0.94) have a graft survival advantage over the ideal DD. In LD ≥55 yr, no improvement in graft survival was observed when compared with the 18–34 yr-old DD. In summary, we observed in a pediatric population, <55 yr-old LD kidneys afford improved long-term allograft survival when compared with DD kidney recipients. Increasing awareness of the long-term graft survival advantage for children receiving an LD kidney, even from older donors, should be a priority.     

Predictors of cardiac allograft vasculopathy in pediatric heart transplant recipients

CAV remains a leading cause of late graft loss and mortality among survivors of pediatric heart transplantation. We sought to define the incidence of CAV and identify its predictors in pediatric heart transplant recipients. The OPTN/UNOS database was analyzed for pediatric recipients who underwent heart transplant between 1987 and 2011. The primary end‐point is time from heart transplantation to development of CAV (CAV‐free survival). To identify predictors of CAV‐free survival, demographic and transplant data were analyzed by the Kaplan–Meier survival method and Cox proportional hazards regression. Of 5211 pediatric heart transplant recipients with at least one‐yr follow‐up, the incidence of CAV at five, 10, and 15 yr was 13%, 25%, and 54%, respectively. Multivariate analysis found that risk of CAV was associated with the following variables: Recipient age 1–4 yr (HR 1.25), 5–9 yr (1.45), 10–18 yr (1.83), donor age >18 yr (1.34), re‐transplantation (2.14), recipient black race (1.55), and donor cigarette use (1.54). Older recipient and donor age, recipient black race, donor cigarette use, and re‐transplantation were highly associated with shorter CAV‐free survival.     

Fibroblast growth factor‐23 and chronic allograft injury in pediatric renal transplant recipients: a Midwest Pediatric Nephrology Consortium study

The chronic kidney disease‐mineral bone disorder (CKD‐MBD) produces fibroblast growth factor‐23 (FGF‐23) and related circulating pathogenic factors that are strongly associated with vascular injury and declining kidney function in native CKD. Similarly, chronic renal allograft injury (CRAI) is characterized by vascular injury and declining allograft function in transplant CKD. We hypothesized that circulating CKD‐MBD factors could serve as non‐invasive biomarkers of CRAI. We conducted a cross‐sectional, multicenter case–control study. Cases (n = 31) had transplant function >20 mL/min/1.73 m² and biopsy‐proven CRAI. Controls (n = 31) had transplant function >90 mL/min/1.73 m² and/or a biopsy with no detectable abnormality in the previous six months. We measured plasma CKD‐MBD factors at a single time point using ELISA. Median (range) FGF23 levels were over twofold higher in CRAI vs. controls [106 (10–475) pg/mL vs. 45 (8–91) pg/mL; p < 0.001]. FGF23 levels were inversely correlated with transplant function (r² = ?0.617, p < 0.001). Higher FGF23 levels were associated with increased odds of biopsy‐proven CRAI after adjusting for transplant function, clinical, and demographic factors [OR (95% CI) 1.43 (1.23, 1.67)]. Relationships between additional CKD‐MBD factors and CRAI were attenuated in multivariable models. Higher FGF23 levels were independently associated with biopsy‐proven CRAI in children.     

Proteinuria in pediatric renal transplant recipients

Proteinuria has been shown to be an important and potentially treatable risk factor for graft loss. The aim of this study was to evaluate prevalence, etiology, and outcome of proteinuria during the follow‐up of children with renal transplantation. We retrospectively reviewed the files of renal transplanted children between 2006 and 2016 in our center. All patients were interpreted with respect to the demographic data and clinical and laboratory features including information about proteinuria. Chi‐square test and Mann‐Whitney U test were used for analysis. Fifty‐two children were eligible for the study. Proteinuria was observed in 34 (65%) and nephrotic range proteinuria was detected in 5 (9.6%) patients. Etiology of proteinuria could be identified in 21 patients. Acute rejection and uncontrolled hypertension were the most frequent causes of proteinuria. Proteinuria had resolved during the follow‐up in 59% of the patients. We found that children with and without proteinuria had similar glomerular filtration rate at the end of 50 months of follow‐up period. Proteinuria seems to be a common complication in renal transplant recipients. Graft functions can be preserved by immediate evaluation of increasing proteinuria, and by fixing treatable causes rapidly and efficiently during the follow‐up in majority of the patients.     

Predominance of nocturnal hypertension in pediatric renal allograft recipients

Hypertension is common in children with end-stage renal disease who have undergone renal transplantation. We performed ambulatory blood pressure monitoring (ABPM) in renal allograft recipients who were on stable maintenance immunosuppressive medications and were more than six months post-transplant. Echocardiographic measurement of left ventricular mass index (LVMI) was obtained at the time of ABPM. Twenty-nine children with a mean age of 14.8 yr (8-18 yr) were evaluated 4.3 yr (0.6-12.8 yr) after deceased donor (n = 13) or living donor (n = 16) transplantation. BP levels were higher during sleep compared with when awake using the 95th percentile to standardize mean BP for each period: mean BP was expressed as a standard deviation score (SDS) for each time period, awake vs. sleep: systolic (s) BP SDS were 0.43 +/- 1.3 vs. 1.29 +/- 1.2 (p < 0.001) and diastolic (d) BP SDS were 0.04 +/- 1.3 vs. 1.34 +/- 1.2 (p < 0.001). Significant differences between awake and sleep BP were also confirmed using the mean BP for each period expressed as a BPI. Hypertension (HTN) during sleep was more common than awake HTN. Based upon BPI, 21% had sHTN when awake compared with 48% during sleep and 7% had dHTN when awake compared with 41% during sleep (p < 0.05). Based upon mean BP load, 38% had sHTN when awake compared with 55% during sleep and 21% demonstrated dHTN when awake compared with 52% during sleep (p < 0.05). Left ventricular mass (LVM) was abnormally increased in six of 17 children (35%); LVM was not correlated with BP. Children prescribed angiotensin converting enzyme inhibitors or angiotensin II receptor blockers (ACEi/ARB) had significantly lower systolic BP compared with those on calcium channel blocking agents (CCB). Mean sSDS was -0.11 +/- 1.1 in those children on ACEi/ARB compared with 1.6 +/- 1.2 in those on CCB (p = 0.02): sSDS during sleep was significantly lower in the ACEi/ARB group compared with CCB (0.70 +/- 1.1 vs. 2.0 +/- 1.1, p = 0.04). Isolated nocturnal HTN is more common than daytime HTN among clinically stable pediatric renal allograft recipients. Detection and treatment of nocturnal HTN in pediatric allograft recipients could potentially affect graft survival.     

Masked hypertension and allograft function in pediatric and young adults kidney transplant recipients

Masked hypertension is a common complication of pediatric kidney transplantation. While office hypertension is known to be associated with worse short‐ and long‐term graft function, the role of masked hypertension in allograft dysfunction is not clear. We conducted a retrospective cross‐sectional analysis of 77 consecutive pediatric kidney transplant recipients who had routine 24‐h ambulatory blood pressure monitoring with the aims to estimate the prevalence of masked hypertension and examine its association with allograft function. Masked hypertension was defined as a 24‐h systolic or diastolic blood pressure load ≥25%. Twenty‐nine percent of patients had masked hypertension. Patients with masked hypertension had significantly lower allograft function estimated using the creatinine‐based Schwartz‐Lyon formula, a cystatin C‐based formula, and combined cystatin C and creatinine‐based formulas than patients with normal blood pressure (all p values <0.05). In a multivariable analysis, masked hypertension remained independently associated with worse allograft function after adjustment for age, sex, race, time post‐transplant, rejection history, antihypertensive treatment, and hemoglobin level. We conclude that in young kidney transplant recipients, masked hypertension is common and is associated with worse allograft function. These results support the case for routine ambulatory blood pressure monitoring as the standard of care in these patients to detect and treat masked hypertension.     

Long-term renal function in pediatric liver and heart recipients

Long-term survivors of pediatric liver and heart transplantation are at risk for progressive renal dysfunction as a result of chronic exposure to calcineuron inhibitors. This class of drugs causes alterations in renal perfusion that can result in irreversible renal injury including afferent arteriopathy, glomerulosclerosis, tubular atrophy and interstitial fibrosis. Approximately 3-6% of pediatric liver and heart recipients will develop end stage renal failure. A much larger percentage has chronic renal insufficiency and hypertension. Children with significant renal compromise in the pretransplant period and those with significantly elevated serum creatinine levels during the first post-transplant year may be at the highest risk to develop irreversible renal injury in long-term follow-up. Serum creatinine is a poor screening tool as it rises late in the course when the injury may no longer be reversible. Strategies to minimize long-term exposure to calcineuron inhibitors may reduce the prevalence of renal insufficiency in this vulnerable population.     

Transient renal enlargement in pediatric hematopoietic cell transplant recipients

Age‐dependent renal length tables are routinely used when interpreting pediatric ultrasound. Standard renal length tables may not be accurate for HCT patients due to treatment effects on kidney size. The purpose of this study was to determine whether renal size changes from expected lengths based on age after HCT in the absence of other markers of renal disease. Four hundred and fifty renal measurements were made on 101 patients who underwent HCT between 2006 and 2010. Renal length was measured at 1–90 days pre‐HCT and at 0–30, 31–90, 91–180, and 181+ days post‐HCT. Values were compared with normal renal length tables. Average post‐HCT renal lengths were greater than established normative renal length data within every age group. Age‐adjusted average renal lengths measured at 0–30 and 31–90 days post‐transplantation were significantly larger than pre‐HCT renal lengths, with relative increases of 6.9% (4.5, 9.4; p < 0.001) and 3.9% (1.4, 6.4; p = 0.003), respectively. Average renal length did not differ significantly after 90 days post‐transplantation. HCT patients may have larger kidneys in the absence of renal disease. Awareness of the potential phenomenon of transient renal enlargement following HCT can prevent misdiagnosis and eliminate unnecessary diagnostic evaluations, interventions, anxiety, resource allocation, and financial costs.