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.     

Standardizing resistive indices in healthy pediatric transplant recipients of adult-sized kidneys

Gholami S, Sarwal MM, Naesens M, Ringertz HG, Barth RA, Balise RR, Salvatierra O. Standardizing resistive indices in healthy pediatric transplant recipients of adult-sized kidneys.
Pediatr Transplantation 2010: 14: 126–131. © 2009 John Wiley & Sons A/S.
Abstract:  Small pediatric recipients of an adult-sized kidney have insufficient renal blood flow early after transplantation, with secondary chronic hypoperfusion and irreversible histological damage of the tubulo-interstitial compartment. It is unknown whether this is reflected by renal resistive indices. We measured renal graft resistive indices and volumes of 47 healthy pediatric kidney transplant recipients of an adult-sized kidney in a prospective study for six months post-transplant. A total of 205 measurements were performed. The smallest recipients (BSA ≤0.75 m²) had higher resistive indices compared to recipients with a BSA between 0.75 and 1.5 m² (p < 0.0001) and to recipients with a BSA ≥ 1.5 m² (p < 0.0001). Resistive indices increased during the first six months in the smallest recipients (p = 0.02), but not in the two larger recipient groups (BSA 0.75–1.5 m² and ≥1.5 m²). All three BSA groups showed a reduction in renal volume after transplantation, with the greatest reduction occurring in the smallest recipients. In conclusion, renal transplant resistive indices reflect pediatric recipient BSA dependency. The higher resistance to intra-renal vascular flow and significant decrease in renal volume in the smallest group likely reflect accommodation of the size discrepant transplanted adult-sized kidney to the smaller pediatric recipient vasculature with associated lower renal artery flow.     

Transplantation of adult‐sized kidneys in low‐weight pediatric recipients achieves short‐term outcomes comparable to size‐matched grafts

Goldsmith PJ, Asthana S, Fitzpatrick M, Finlay E, Attia MS, Menon KV, Pollard SG, Ridgway DM, Ahmad N. Transplantation of adult‐sized kidneys in low‐weight pediatric recipients achieves short‐term outcomes comparable to size‐matched grafts.
Pediatr Transplantation 2010: 14:919–924. © 2010 John Wiley & Sons A/S. Abstract: Low‐weight pediatric recipients are disadvantaged by scarcity of size‐matched donors. ASK have been successfully used for pediatric recipients. We report the results of renal transplantation using ASK in low‐weight pediatric recipients and compare outcomes in weight‐matched and unmatched donor–recipient pairs. The outcomes of renal transplants using ASK grafts in low‐weight (<20 kg) recipients from a single center over a 10‐yr period were reviewed. Two groups, comprising recipients of grafts from weight‐matched and mismatched donors, were compared. Primary outcome was one‐yr graft survival. Secondary outcomes were one‐ and two‐yr calculated eGFR, changes in recipient body weight, perioperative cardiovascular stability, rates of AR and DGF. Twenty‐three low‐weight recipients were transplanted. Eleven received ASK grafts from high‐weight donors and 12 grafts from low‐weight donors. One patient in each group had early graft loss. No significant difference was observed in rates of DGF, AR, one‐yr graft or patient survival and perioperative cardiovascular parameters. ASK with considerable donor:recipient weight discrepancies can be safely transplanted into small pediatric recipients with comparable outcomes to grafts with less weight discrepancy.     

The profile of renal function over time in a cohort of pediatric heart transplant recipients

Abstract:  To assess the burden over time of renal dysfunction in pediatric heart transplant patients using an objective measure on an annual basis for serial comparison. GFR was measured at regular interval by nuclear medicine scintigraphy. Results were analyzed in relation to age, time post-transplantation, gender, and average calcineurin-inhibitor dose for the first two months post-transplantation. Results were compared with cGFR using the Schwartz equation. A total of 91 patients (56 males) transplanted between 1990 and 2004 underwent 373 GFR measurements. Median age at transplantation was 3.3 yr (birth – 17.8). Median first GFR at 0.7 yr (0.1–4.1) post-transplant was normal (94 mL/kg/1.73 m²). Freedom from at least mild renal insufficiency was 84% and 33% at one and five years post-transplant. Females had better renal function early post-transplant (GFR 105 mL/min/1.73 m²) but an increased probability of an abnormal GFR over time. Higher calcineurin inhibitor dose in the first two months post-transplantation was associated with an increasing probability of an abnormal GFR over time. The cGFR overestimated the measured GFR by 33 ± 26 mL/kg/1.73 m². Renal insufficiency is an important morbidity after pediatric transplantation with the majority of patients experiencing at least mild renal dysfunction. Calculated GFR significantly underestimates the burden of renal insufficiency in this patient population.     

Renal function evaluated by measured GFR during follow-up in pediatric liver transplant recipients

Abstract:  Calcineurin inhibitors form the mainstay of immunosuppression in pediatric liver transplantation, but may cause significant nephrotoxicity. We evaluated renal function in liver transplant recipients treated with a tacrolimus-based immunosuppressive regimen. GFR was measured using 99 mTc-DTPA in patients pretransplant and annually thereafter. GFR calculated by Schwartz formula was compared with the measured values. Sixty patients who underwent 69 transplants were followed for at least one yr post-transplant (median three yr). In children over two yr of age at transplant GFR fell significantly from pretransplant (140 mL/min/1.73 m²) to one yr post-transplant (112 mL/min/1.73 m²) (p = 0.01) but thereafter there was no significant decline. In younger children the picture was confounded by maturation of renal function, but again there was no significant fall to five yr post-transplant. Although 13 (22%) patients developed renal dysfunction post-transplant, none required renal replacement therapy. cGFR correlated poorly with measured values (r = 0.21). Use of a tacrolimus-based immunosuppressive regimen is associated with an initial decline in GFR, though this picture is confounded in younger children by normal maturation of renal function. There is no further significant fall in GFR in the medium-term. The Schwartz formula is inaccurate in determining GFR in this patient group.     

Outcomes of children receiving en bloc renal transplants from small pediatric donors

The utilization of en bloc renal allografts from small pediatric donors has been adopted as an effective strategy to expand the organ donor pool in adult recipients. Data in children are limited. The aim of our study is to describe the outcomes of en bloc renal transplants in children from our center. Medical records of children receiving pediatric en bloc renal transplants at our institution from January 2007 were abstracted. Data collected included recipient and donor demographics, operative technique and complications, and post‐operative studies. Eight children received en bloc renal transplants at a median age of 17 yr; median follow‐up was 0.9 yr. Donor body weight ranged from 4 to 22 kg. One kidney was lost to intra‐operative thrombosis, while the other kidney from this en bloc graft remained viable. All grafts showed increased renal size at follow‐up ultrasound. Surveillance biopsies showed glomerulomegaly in two patients. At last follow‐up, the median eGFR was 130 mL/min/1.73 m². The urinary protein to creatinine ratio was normal in four of seven patients. Our data suggest that in experienced centers, en bloc renal transplantation from young donors into pediatric recipients is effective. Long‐term follow‐up to monitor for complications, including hyperfiltration injury, is warranted.     

Optimizing the utilization of kidneys from small pediatric deceased donors under 15 kg by choosing pediatric recipients

Currently, most kidneys from small pediatric deceased donors are transplanted into adult recipients (i.e., PTA). However, due to the weight mismatch, there is a high discard rate and a high ratio of EBKTs if adopting PTA. Here, we sought both to optimize utilization of these challenging but scarce donor grafts by selecting pediatric recipients and to characterize the feasibility and efficacy of this PTP allocation strategy. From February 2012 to October 2014, kidneys from 27 infant donors ≤15 kg were procured and distributed to 38 pediatric candidates in our center. The grafts were utilized for EBKT if the donor weighed 2.5–5 kg and for SKT if the donor weighed 5–15 kg, leading to 10 EBKTs and 28 SKTs. The overall utilization rate from small pediatric deceased donors was 94.12%. After a follow‐up of 3–26 months, the graft survival rate was 89.47%, with four graft losses due to vascular thrombosis. Kidneys from low‐body‐weight donors should be applied to pediatric recipients, and the kidneys from infant donors ≥5 kg can be used in single‐kidney‐transplant procedures at experienced centers to optimize utilization.     

Outcomes and predictive factors of pediatric kidney transplants: An analysis of the Thai Transplant Registry

As universal coverage for pediatric kidney transplantation (KT) was introduced in Thailand in 2008, the number of recipients has been increasing. We evaluated predictive factors for graft failure to understand how to improve clinical outcomes in these children. Using data obtained from the National Transplant registry, we assessed the risk of graft failure using the Kaplan–Meier method and Cox proportional hazards regression. Altogether, 201 recipients aged <21 yr at the time of KT were studied. Living donors (LD) were significantly older than deceased donor (DD). Mean cold ischemia time of DD was 17 h. The mean donor glomerular filtration rate (GFR) was 84.0 mL/min/1.73 m². Induction immunosuppressive therapy was administered more frequently in DD than in LDKT. Delayed graft function (DGF) occurred in 36 transplants. Over 719 person years of follow‐up, 42 graft failures occurred. Graft survival at one, three, and five yr post‐transplant were 95%, 88% and 76%, respectively. Two factors independently predicted graft failure in multivariate analysis. The hazard ratios for graft failure in patients with DGF and in patients with donor GFR of ≤30 mL/min/1.73 m² were 2.5 and 9.7, respectively. Pediatric recipients should receive the first priority for allografts from young DD with a good GFR, and DGF should be meticulously prevented.     

Long-term outcome of intensive initial immunosuppression protocol in pediatric deceased donor renal transplantation

Olaitan OK, Zimmermann JA, Shields WP, Rodriguez-Navas G, Awan A, Mohan P, Little DM, Hickey DP. Long-term outcome of intensive initial immunosuppression protocol in pediatric deceased donor renal transplantation.
Pediatr Transplantation 2010: 14: 87–92. © 2009 John Wiley & Sons A/S.
Abstract:  To report the long-term outcome of deceased donor kidney transplantation in children with emphasis on the use of an intensive initial immunosuppression protocol using R-ATG as antibody induction. Between January 1991 and December 1997, 82 deceased donor kidney transplantations were performed in 75 pediatric recipients. Mean recipient age at transplantation was 12.9 yr and the mean follow-up period was 12.6 yr. All patients received quadruple immunosuppression with steroid, cyclosporine, azathioprine, and antibody induction using R-ATG-Fresenius^®. Actual one, five, and 10 yr patient survival rates were 99%, 97%, and 94%, respectively; only one patient (1.2%) developed PTLD. Actual one, five, and 10 yr overall graft survival rates were 84%, 71%, and 50%, respectively; there were five cases (6%) of graft thrombosis and the actual immunological graft survival rates were 91%, 78%, and 63% at one, five, and 10 yr, respectively. The use of an intensive initial immunosuppression protocol with R-ATG as antibody induction is safe and effective in pediatric recipients of deceased donor kidneys with excellent immunological graft survival without an increase in PTLD or other neoplasms over a minimum 10-yr follow up.     

Successful transplantation of four kidney grafts from two small pediatric donors with anuric acute renal failure into adult recipients

Background

Kidneys from infants with anuric acute kidney injury (AKI) only rarely get accepted for transplantation despite encouraging data that such kidneys can have very good long-term outcome.

Methods

We report the transplantation of four kidney grafts from two pediatric donors (3 and 4 years) with anuric acute kidney injury as single kidneys into four adult recipients.

Results

All grafts gained function within 14 days posttransplantation, only one recipient needed dialysis after transplantation. None of the recipients suffered from surgical complications. One month after transplantation, all recipients were free of dialysis. Estimated glomerular filtration rates (eGFR) 3 months after transplantation were 37, 40, 50, and 83 mL/min/1.73 m². eGFR increased further through month 6, reaching 45, 50, 58, and 89 mL/min/1.73 m².

Conclusion

These cases highlight the feasibility of successful transplantation of single pediatric kidney grafts into adult recipients despite anuric AKI of the donor.     

Multicenter trial of everolimus in pediatric renal transplant recipients: results at three year

Abstract:  There are few prospective clinical trials of mTOR inhibitors (or proliferation signal inhibitors) combined with CNI inhibitors in de novo pediatric renal transplantation. Results reported here are from a multicenter, open-label study in de novo pediatric renal transplant patients (≤16 yr), in which patients received everolimus with cyclosporine and corticosteroids for one yr, then entered an extension study for a further two yr. Nineteen patients completed the one-yr study, of whom three discontinued study medication. Fifteen of the remaining 16 patients entered the extension study, eight of whom were aged <10 yr (Group 1) and seven were aged 10–16 yr (Group 2). Mean daily dose of everolimus during the first 36 months was 1.53 mg/m² BSA. Biopsy-proven acute rejection occurred in three patients in Group 2 and in one patient in Group 1. Biopsy-proven chronic allograft rejection was reported in four patients (two in each age group). Graft survival at one yr was 100%; one patient in Group 2 lost their graft subsequently during the extension. For patients entering the extension, patient survival at three yr was 100%. There were three cases of viral infection, including one case of cytomegalovirus infection. At three yr, mean total cholesterol was 5.5 ± 0.8 m m /L (213 ± 31 mg/dL) and four patients received statin therapy. Mean serum creatinine at 36 months was 96 ± 36 μ m /L (1.1 ± 0.4 mg/dL). This is the first long-term prospective study to demonstrate that a regimen of everolimus, cyclosporine, and corticosteroids provides good efficacy, tolerability, and safety in de novo pediatric renal transplant patients.     

Very small pediatric donor kidney transplantation in pediatric recipients

Kidneys from very small pediatric donors (age <5 years, weight <21 kg) may be a means to increase the donor pool for pediatric recipients. Transplantation of small pediatric kidneys is more commonly performed in adult recipients due to the increased risks of technical complications, thrombosis, and early graft failure. While these risks are abrogated in adult recipients by limiting the donor weight to ≥10 kg and using the EB technique, it is unknown whether pediatric recipients achieve comparable results. US national data were assessed for all first‐time, deceased‐donor, kidney‐only pediatric recipients, 1/1996‐10/2013, who received very small pediatric donor grafts or grafts from ideal adult donors. We identified 57 pediatric EB, 110 pediatric SK, and 2350 adult transplants. The primary outcome was 3‐year all‐cause graft survival. Kaplan‐Meier curves showed worse outcomes for pediatric grafts compared to adult ideal grafts (P=.042). On multivariate analysis, pediatric recipients of SK grafts had significantly higher HRs (aHR 2.01, 95% CI 1.34‐3.00) and pediatric recipients of EB grafts had somewhat higher non‐significant HRs (1.57; 95% CI 0.88‐2.79) for graft survival. These results suggest cautionary use of very small pediatric donors as a source to expand the donor pool for pediatric candidates.     

The use of porcine dermal collagen implants in assisting abdominal wall closure of pediatric renal transplant recipients with donor size discrepancy

Children may have kidneys transplanted from donors larger than themselves. Abdominal wall closure may be difficult, with risks of abdominal compartment syndrome and graft compromise. Meshes used to facilitate closure may cause dense intra-abdominal adhesions, making further surgery or peritoneal dialysis difficult. We present five cases in which abdominal wall closure was facilitated by porcine dermal collagen implant. Five children (2-15 yr) received transplanted kidneys from adult donors of significantly greater weight. In four recipients, the kidney was transplanted onto the aorta and vena cava intra-abdominally using a midline incision. In the fifth, the kidney was anastomosed onto the iliac vessels. The skin overlying the implant was closed normally. Maximum follow-up was three yr. In all cases, primary closure was achieved. One child received a second intra-abdominal transplant as an emergency, which later failed. The other kidneys are functioning well. One recipient developed a small incisional hernia three yr post-transplant. Another developed a skin dehiscence over the implant 23 days post-operatively. The implant was removed and skin closed. The other two recipients recovered well. Porcine dermal collagen implant is a helpful adjunct to abdominal wall closure following organ transplantation in children with donor size discrepancy.     

Using pediatric liver grafts (≤6 yr) for adult recipients: A considerable option?

In LT, the common policy is to allocate pediatric liver grafts to pediatric recipients. Pediatric organs are also offered to adults if there is no pediatric recipient. However, they are rarely accepted for adult recipients. So far, there is no information available reporting outcome of LT in adult recipients using pediatric livers from donors ≤6 yr. In this study, we included nine adult recipients (seven females and two males) who received grafts from children ≤6 yr from January 2008 to December 2013. We evaluated the graft quality, the GBWR and analyzed the recipients’ perioperative course. Laboratory samples and graft perfusion were analyzed. Nine adults with a median age of 49 yr (range: 25–65) and a median weight of 60 kg (range: 48–64) underwent LT with a pediatric donor graft. Median donor age was five yr (range: 3–6). Median GBWR was 1.02 (range: 0.86–1.45). After a median follow‐up of 3.9 yr (range: 11 months–6.6 yr), patient survival was 100%; graft survival was 89%. One patient needed re‐transplantation on the second postoperative day due to PNF. Eight recipients were discharged from the ICU after 2–9 days with a regular graft function. Doppler scans revealed regular flow patterns at any time. Only if denied for pediatric recipients, the use of pediatric livers from donors ≤6 yr for adult recipients is a considerable option.     

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.     

The outcome of pediatric cadaveric renal transplantation in the UK and Eire

An analysis of all pediatric cadaveric renal transplant recipients in the UK and Eire was undertaken to review the outcomes of pediatric cadaveric renal transplantation and to consider the implications for organ allocation procedures for pediatric recipients. Factors influencing the outcome of 1,252 pediatric cadaveric renal transplants in the UK and Eire in the 10-yr period from 1 January 1986 to 31 December 1995 were analyzed by Cox proportional hazards regression, including analysis of four distinct post-transplant epochs (0-3 months, 3-12 months, 12-36 months, and beyond 36 months). At the time of analysis (December 2000), 113 (11%) recipients had died and 47% of grafts had failed. In the multi-factorial modelling, the factors significantly affecting transplant outcome were cold ischaemia time, donor and recipient age and human leucocyte antigen (HLA) matching. Epoch analysis demonstrated that these factors operated at different times post-transplant. Cold ischaemia time had a strong influence on outcome at 3 months. A highly significant increased risk of graft failure was associated with donors under 5 yr of age. Young recipients had an increased risk of failure in the short term, but beyond 1 yr post-transplant there were few failures in young recipients while a steady rate of graft loss persisted in the older children. In terms of HLA matching, the worst outcome was observed for two HLA-DR mismatched grafts, while 000 and favorably matched kidneys (100, 010, 110 HLA-A, -B, -DR mismatches) survived longest. Hence, a policy of exchanging organs on the basis of HLA matching is justified for 000 mismatched and favorably matched kidneys. The poor outcome associated with very young donors should discourage pediatric units from transplanting kidneys from such young donors. The reasons for late losses in older recipients need investigation.     

Pediatric kidney transplantation is safe and available for patients with urological anomalies as well as those with primary renal diseases

The aim of the current study was to evaluate long-term outcomes of pediatric live kidney transplantation in patients with genitourinary anomalies relative to those with primary kidney diseases. The study included 35 pediatric patients who received a live kidney transplantation during the last 25 yr (28 males, six females). Median age at the time of transplantation was nine yr (range 1-15 yr), and the median follow-up period was 151 months (range 6-239 month). The patients were divided into two groups. The urological group (n = 14) included patients with primary obstructive/reflux nephropathy. The renal group (n = 20) included patients with primary renal disorders. Differences between groups in graft survival, clinical course, and final graft function were evaluated. Original diseases represented in the urological group included five cases with primary VUR and eight cases with secondary VUR. Diseases in the renal group included eight cases with bilateral hypo-dysplastic kidney, three cases with focal/segmental glomerular sclerosis, two cases with membranous proliferative glomerulonephritis, two cases with congenital nephrotic syndrome and five cases with other forms of chronic nephritis. Ten of 14 cases in the urological group, relative to six of 20 in the renal group, were preemptive. Median age at transplantation was 7.5 or 10 yr old, respectively, in the urological or renal group. Twelve kidney recipients in the urological group had also undergone other urinary surgeries, including upper urinary tract drainage, ureteroneocystostomy, augmentation cystoplasty, endoscopic incision of posterior-urethral valve, urethroplasty, etc. Cumulative post-operative complications occurred in nine or 16, respectively, in the urological or renal group. The acute rejection free and overall graft survival were similar in both groups. One patient in the urological group lost his graft while six patients in the renal group lost their grafts. Thus, the post-transplant clinical outcome of pediatric transplantation in patients with urological anomalies is comparable to that of recipients with primary renal disease. Appropriate urinary tract reconstruction and management is essential to reduce the risk of graft dysfunction because of urinary problems.     

Patient selection critical for calcineurin inhibitor withdrawal in pediatric kidney transplantation

Abstract:  CNI withdrawal may be employed as a "rescue" strategy for patients with established renal allograft injury and/or declining allograft function, with the aim at eliminating CNI-associated nephrotoxic effects. This analysis reviews outcomes in a pediatric population and identifies risk factors for adverse events post-CNI withdrawal. We performed a retrospective analysis of 17 pediatric renal transplants who underwent CNI withdrawal, with conversion to sirolimus and MMF. Mean CrCl decreased from 64.3 ± 22 to 59.38 ± 28.6 mL/min/1.73 m² (p = 0.04) at six months and 57.46 ± 31.1 mL/min/1.73 m² (p = 0.02) at 12 months post-withdrawal. Forty-one percent of patients experienced AR. Increased risk for AR was associated with prior AR history, lower sirolimus trough levels, and lower CNIT biopsy scores. Graft loss (24%) was associated with worse CrCl, proteinuria, and histologic chronicity. Proteinuria (spot protein/creatinine ratio) increased from 0.75 ± 1.0 to 1.71 ± 2.0 (p = 0.03), unrelated to de novo sirolimus use. Four patients returned to CNI-based immunosuppression due to AR (n = 3) and gastrointestinal side effects (n = 1). Careful selection of pediatric candidates for CNI withdrawal is recommended. Worsening graft function and graft loss may be minimized by selecting patients with high CNIT scores and low biopsy chronicity and excluding patients with prior AR history.     

Rapid discontinuation of corticosteroids in pediatric renal transplantation

Abstract:  Corticosteroid immunosuppression has permitted the development of successful allotransplantation; however, corticosteroids are associated significant post-transplant complications. To circumvent these problems, we implemented a protocol of rapid discontinuation of corticosteroids in 19 consecutive pediatric primary kidney transplant recipients. Mean age at time of transplant was 13.4 (±4.5) yr, 52.6% were male, 63.2% underwent living donor transplantation. All patients were administered Thymoglobulin^® [anti-thymocyte globulin (rabbit)] as induction immunosuppression with a rapid tapering dose of corticosteroids (total of five daily doses), and maintained on mycophenolate mofetil and tacrolimus. Two patients had immediate recurrence of primary disease (FSGS), requiring further corticosteroid therapy. Otherwise, remaining 17 patients were maintained off corticosteroids, with excellent graft function; mean baseline eGFR of 112 mL/min/1.73 m² (±19) at 28 months (±14) post-transplantation. There was 100% patient and rejection-free graft survival at 27 months (range 5–58 months) post-transplantation; 47% underwent renal transplant biopsy secondary to acute rise in serum creatinine with or without worsening hypertension. All biopsies had no evidence of acute rejection; 62.5% had findings consistent with tacrolimus toxicity. Renal transplantation utilizing a rapid discontinuation of corticosteroid protocol in pediatric patients appears to be safe and effective, without increasing the risk of acute rejection or graft loss.     

Persisting Glomerular Hyperfiltration in Short-term Diabetic Children without Microalbuminuria

ABSTRACT. The renal function in a group of diabetic children ( n =29; age: 4–17 yr; IDDM duration: 1.5–13 yr) was studied with a 3 year interval. At the first evaluation glomerular filtration rate (GFR) as assessed by inulin clearance was significantly increased compared to control values (167±32 vs. 124±18 ml/min/1.73 m²; p ≤0.01). Eighteen out of 29 children exhibited a glomerular hyperfiltration (GFR ≥ 160). Three years later mean GFR was identical (169±25 ml/min/1.73 m²) and 16 children were hyperfiltrating. Among them, 11 have had a persisting glomerular hyperfiltration over the 3-year period. Renal plasma flow (RPF) was positively correlated to GFR ( r =0.7; p ≤0.01) and remained elevated at both evaluations (794±163 and 812±157 ml/min/1.73 m², p ≤0.01 vs. control values). When the children were separated into 3 groups according to IDDM duration no significant differences were observed in the results for GFR and RPF. Mean urinary albumin excretion was comparable at the 3-year interval, and not significantly different from the control values (5.2±3.7 and 8.2±6.6 respectively vs. 8.65±4 |ig/min). None of the children demonstrated a persistent microalbuminuria. This study reveals a high proportion of diabetic children with a persisting glomerular hyperfiltration, without any other symmptom of incipiens nephropathy. If elevated GFR plays an important role in the development of diabetic nephropathy, this study emphasizes the value of regular evaluation of renal function in diabetic children.