Long-term evaluation of cyclosporine and tacrolimus based immunosuppression in pediatric liver transplantation

Both calcineurin inhibitors (CNIs), cyclosporine and tacrolimus, are widely used in pediatric liver transplant recipients and currently data are limited with regards to long-term results using the one drug or the other in comparable low doses. We conducted the present study to assess the advantages and disadvantages of both drugs in children at least five yr post-liver transplantation. A total of 129 children were enrolled in the study. Thirty-eight of the children were switched to tacrolimus monotherapy for different reasons [steroid resistant graft rejection (n = 15), chronic rejection (n = 5), severe acute rejection (n = 4), repetitive acute graft rejection (n = 5), dysfunction of the transplant (n = 3), insufficient CsA metabolism (n = 3), hypertrichosis (n = 2), and CsA toxicity (n = 1)], four patients had primary tacrolimus therapy, and 87 patients are receiving cyclosporine. Mean trough levels were 5.3 +/- 2.3 ng/mL (tacrolimus) and 73.6 +/- 44.5 micro/L (cyclosporine), respectively at least five yr post-orthotopic liver transplantation (OLT). There was no significant difference in the calculated glomerular filtration rate between children on cyclosporine and tacrolimus (142.7 + 39.5 mL/min/1.73 m(2) vs. 151.1 +/- 44.1 mL/min/1.73 m(2)). The incidence of arterial hypertension was 7.1% vs. 9.2%, that of hepatotoxicity was 0% vs. 2.3%. Cosmetic changes were found in more than one-third of the patients on cyclosporine and in 4.8% of the patients receiving tacrolimus. Quality of life was excellent in both groups (self assessment). The impact of CNIs on chronic graft dysfunction cannot be assessed by our present study. We conclude from the results that cyclosporine and tacrolimus are both excellent drugs for maintenance immunosuppression in the long-term course following pediatric liver transplantation. However, this retrospective analysis is limited by the bias between children on CsA as compared with patients receiving tacrolimus. A prospective randomized controlled trial is needed in order to assess which CNI is the best for children following OLT.     

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.     

Persisting glomerular hyperfiltration in short-term diabetic children without microalbuminuria

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; pl less than 0.01). Eighteen out of 29 children exhibited a glomerular hyperfiltration (GFR greater than 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 less than 0.01) and remained elevated at both evaluations (794 +/- 163 and 812 +/- 157 ml/min/1.73 m2, p greater than 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 microgram/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 symptom 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.     

Reversal of loss of glomerular filtration rate in children with transplant nephropathy after switch to everolimus and low-dose cyclosporine A

Until now there have been no good therapeutic options in children with biopsy-proven transplant nephropathy (TN) and loss of glomerular filtration rate (GFR) while receiving cyclosporine A (CsA), mycophenolate mofetil (MMF) and prednisolone (Pred). In 13 kidney transplanted children (mean age 13 yr, SD 4) with CsA/MMF/Pred immunosuppression, renal biopsy revealed significant TN. MMF was discontinued, CsA dose was reduced to 50% and Everolimus was started (1.6 mg/m(2)/day). Pred was stopped in 10 of 13 patients. The mean GFR was 55 mL/min/1.73 m(2) (SD 24) one yr before switch, 45 mL/min/1.73 m(2) (SD 16, p < 0.05) at the time of switch and 47 mL/min/1.73 m(2) (SD 18, p < 0.05) 12 months later. There were no severe side-effects or acute rejections. Lactate dehydrogenase, cholesterol, creatine kinase, and U-albumin/creatinine ratio did not increase significantly. After six months, the mean certican-C0 level was 4.0 microg/L (SD 1.5) and mean CsA-C0 level was 52 ng/mL (SD 23). The GFR of transplanted kidneys in children with TN improved by changing immunosuppression from CsA/MMF/Pred to everolimus and low-dose CsA.     

Renal function outcome in pediatric liver transplant recipients

The orthotopic liver transplantation (OLT) allows survival of children followed for severe hepatic injury, provided that the immunosuppressive treatment is prolonged. The nephrotoxicity of cyclosporine predicts the long-term outcome of the adult patients receiving a liver transplant. The aim of this study was to determine the long-term outcome of renal function in children receiving OLT. This study included 12 children, with a median for age of 7.1 yr (2-15 yr) at the time of OLT. The duration of follow-up was at least 4 yr, being 7 yr in 10 patients and more than 10 yr in seven. Renal function was evaluated with the serum level of creatinine, calculated glomerular filtration rate (cGFR), and measurement of glomerular filtration rate using chrome 51 ethylenediaminetetraacetate ((51)Cr EDTA) clearance performed at least once during follow-up. The doses and the serum concentrations (C(0)) of cyclosporine were reported at each study time. The cGFR decreased significantly 2 yr after the OLT [median (range): 106 mL/min/1.73 m(2) (71-150) at the time of OLT vs. 85 mL/min/1.73 m(2) (57-128) 2 yr after the OLT, p = 0.03], and decreased again between 7 and 10 yr after OLT [median (range): 99 mL/min/1.73 m(2) (76-125) 7 yr after OLT vs. 81 mL/min/1.73 m(2) (66-140) 10 yr after OLT, p = 0.04]. Six patients developed chronic renal failure (cGFR from 57 to 80 mL/min/1.73 m(2)) 2 yr after OLT associated with high doses of cyclosporine [median (range): 8.8 mg/kg/day (3.5-13)]. The cGFR overestimated renal function by 16% compared with the isotopic measurement of GFR (p = 0.03). Using the (51)Cr EDTA measurement, six of seven patients followed up more than 10 yr after OLT presented mild (n = 3) or moderate (n = 3) chronic renal failure. In our study, the majority of OLT recipients developed a chronic renal failure 10 yr after transplantation. Cyclosporine seems to be the most important factor responsible for the impairment of renal function. The use of the mycophenolate mofetil, a new immunosuppressive agent, allowing a reduction in the dose of cyclosporine, could minimize renal dysfunction. While awaiting the results of a prospective long-term study, close drug monitoring is advised.     

Renal functional reserve in long-term survivors of unilateral Wilms tumor.

We hypothesized that long-term survivors of unilateral Wilms tumor would have a decreased renal functional reserve secondary to the consequences of hyperfiltration in the nephrons of the remaining kidney. Therefore we evaluated the renal functional reserve in 12 long-term survivors of Wilms tumor after unilateral nephrectomy (mean +/- SE: 15 +/- 1.1 years; range 9 to 23 years). We measured the creatinine clearance before and after an acute, oral protein load to determine the renal functional reserve. Study subjects and control subjects were matched for age, gender, and body surface area. The basal creatinine clearances were similar (Wilms group 132 +/- 13 vs control group 142 +/- 11 ml/min/1.73 m2; p = not significant (NS]. There was no significant difference in the renal functional reserve between long-term survivors of Wilms tumor and matched control subjects (Wilms group 17 +/- 11 vs control group 25 +/- 11 ml/min/1.73 m2; p = NS). The change in creatinine clearance was not secondary to volume expansion because the fractional excretion of sodium was unchanged with protein loading (Wilms group before loading 0.92 +/- 0.12 vs after loading 0.99 +/- 0.13 (p = NS); control group before loading 0.91 +/- 0.12 vs after loading 1.0 +/- 0.14 (p = NS)). We conclude that up to 15 years after nephrectomy for unilateral Wilms tumor in childhood, there is no evidence of hyperfiltration injury.     

Renal functional changes in relation to hemodynamic parameters during exercise test in normoalbuminuric insulin-dependent children

AIM: To examine the relationship between filtration fraction and systemic vasculopathy, in normoalbuminuric insulin-dependent diabetic adolescents. METHODS: We calculated filtration fraction from measured glomerular filtration rate and renal plasma flow during a hypotonic saline perfusion test in 30 normotensive adolescent diabetic patients (9-19 years), with a mean duration of diabetes of 7.4 years. Blood pressure and heart rate were measured in basal conditions, during a 24-h ambulatory monitoring and during a dynamic exercise test on a cycle ergometer and peripheral vascular resistance was calculated. RESULTS: Filtration fraction was increased in the diabetic children compared with controls (30+/-6% vs. 22+/-4%, p<0.001), while renal plasma flow was significantly lower (453+/-133 mL/min/1.73 m2 vs. 593+/-155 mL/min/1.73 m2, p<0.001). Peripheral vascular resistance was significantly higher at peak exercise in diabetic children compared to controls (16.3+/-1.3 mmHg/L min m2 vs. 11.4+/-0.5 mmHg/L min m2, p<0.01). CONCLUSION: These results indicate that in young patients with IDDM, without apparent nephropathy or apparent systemic vasculopathy, filtration fraction is increased, suggesting an increased intraglomerular pressure. The associated reduced decrease of peripheral vascular resistance (increased diastolic blood pressure during exercise) suggests that renal functional abnormalities may be partly explained by a systemic vasculopathy, also present in the kidney.     

Mycophenolate mofetil and reduced doses of cyclosporine in pediatric liver transplantation with chronic renal dysfunction: changes in the immune responses

The aim of this study was to study the incidence of chronic renal dysfunction in patients with more than 5 yr of follow-up following liver transplantation and to evaluate the benefit of decreasing cyclosporine A (CsA) dose combined with mycophenolate mofetil (MMF) on renal function and immune response in these patients. Between 1988 and 1994, 60 children were transplanted, and 86% survived >5 yr post-liver transplantation. Fourteen patients developed chronic renal dysfunction secondary to CsA toxicity as evaluated by renal biopsy. In 11 patients CsA dose was decreased to 40-90 mg/ml target levels and MMF 600 mg/m(2) twice daily was added to the immunosuppressive regimen. Plasma creatinine decreased (from 1.0 +/- 0.03 to 0.8 +/- 0.03 ng/dl, p < 0.007), creatinine clearance increased (from 66.8 +/- 3.0 to 99.2 +/- 6.3 ml/min/1.73 m(2), p < 0.002) and microalbuminuria decreased (from 21.0 +/- 8.6 to 3.6 +/- 1.1 mg/24 h, p < 0.05) after 12 months of CsA combined with MMF therapy. During combined therapy the proliferative, cytolytic response and cytotoxic antibodies showed no significant changes, whereas CD4/CD8 ratio increased (from 1.2 +/- 0.2 to 1.4 +/- 0.1, p < 0.05). Tumor necrosis factor-alpha secretion increased (p < 0.005) during MMF therapy. The release of interleukin-10 was strikingly augmented under both immunosuppressive regimens, but the release of transforming growth factor-beta and interferon-gamma did not change. Our findings indicate that initiation of MMF combined with reduced doses of CsA allowed the recovery of renal function with minor changes in the immune response.     

Renal clearance of fluoride in children and adolescents

Renal function and fluoride excretion have been studied in 38 children. The children were divided into three groups according to their glomerular filtration rate: normal (92 to 136 mL/min/1.73 m2 of body surface area [BSA]), low (less than 92 mL/min/1.73 m2 BSA, and super-normal (greater than 136 mL/min/1.73 m2 BSA). Standard clearance technique with infusion of inulin and p-aminohippuric acid during water diuresis was used. Mean renal fluoride clearance was 45.0 +/- 9.8 (SD) mL/min in the group of children with normal glomerular filtration rates and 31.4 +/- 8.8 mL/min in the group with low glomerular filtration rates. This difference was statistically significant. There was a close linear relationship between renal fluoride clearance and glomerular filtration rate, urinary flow, and free water clearance. The fractional fluoride excretion did not differ between the groups. About 60% of the filtered fluoride was reabsorbed. No evidence for tubular secretion exceeding the reabsorption could be found. The results suggest that children have lower renal fluoride clearance rates than adults and indicate that a moderate impairment of the renal function could lead to increased retention of fluoride.     

Renal hypophosphatemic rickets. Growth and mineral metabolism after treatment with calcitriol (1,25-dihydroxyvitamin D3) and phosphate supplementation

To delineate the mineral metabolism of renal hypophosphatemic rickets and to update progress in linear growth after calcitriol (1,25-dihydroxyvitamin D3) therapy, the medical records of 19 patients were examined retrospectively from January 1978 through December 1985. With a mean (+/- SD) follow-up period of 42.0 +/- 5.4 months after calcitriol had been administered for at least 12 months, the growth measurements were as follows: the percentile weight (mean +/- SD) remained unchanged, with the initial being 12.3% +/- 17.3% and the final being 15.3% +/- 18.6%, and the length/height percentiles were -2.7% +/- 5.9% and -2.4% +/- 4.4%. The growth velocity index showed a significant improvement from mean values of 61.7% (at age 2 years) to mean values of 101.2% (at age 11.2 years). Serum phosphate concentrations rose from the initial value of 2.9 +/- 0.6 to 3.5 +/- 0.8 mg/dL (0.9 +/- 0.2 to 1.1 +/- 0.3 mmol/L). The effects of calcitriol on renal function were tested by creatinine clearance values, which were 127 +/- 22 mL/min/1.73 m2 (2.12 +/- 0.37 mL/s/1.73 m2) at the conclusion of the study, compared with 128 +/- 25 mL/min/1.73 m2 (2.13 +/- 0.41 mL/s/1.73 m2) obtained at the initiation of calcitriol therapy. We conclude that calcitriol treatment of renal hypophosphatemic rickets in children results in improvement of growth velocity and serum phosphate concentration without deterioration of renal function.     

Renal failure in children with hepatic failure undergoing liver transplantation

Over a 3 1/2 year period, 133 children with hepatic failure underwent orthotopic liver transplantation (OLT) at our center. Renal failure (creatinine clearance less than 20 ml/min/1.73 m2) was present in 19 (14.3%) of these children. In seven of the 19 children, renal failure was present before OLT, and in the other 12 after OLT. The causes of renal failure included hepatorenal syndrome in seven, postischemic acute tubular necrosis in five, severe prerenal azotemia in five, and cyclosporine nephrotoxicity in two. Eight other patients died of renal failure while awaiting emergency transplantation. Of the total of 31 deaths among 133 children who underwent OLT, nine occurred in the 19 patients with renal failure. Thus patients with OLT and renal failure had a significantly higher mortality than other patients with transplants (P less than 0.025). Dialysis was not associated with improved survival. The majority of deaths in patients with renal failure were related to severe hemorrhage, thromboembolic events, and systemic fungal infections. Our experience suggests that renal failure is common in children with hepatic failure and is associated with reduced patient survival after OLT.     

Correlation of serum parathormone level with biochemical parameters in chronic renal failure

A prospective study was carried out to assay the level of serum intact parathormone and its correlation with biochemical parameters in patients with chronic renal failure (CRF). The study included 64 children (44 with CRF, and 20 age and sex matched controls). Serum intact parathormone (iPTH), serum creatinine, urea, calcium, inorganic phosphate and alkaline phosphatase were estimated. Creatinine clearance (Ccr) was estimated by Schwartz formula. Patients with CRF were divided into four groups based on their Ccr (mild CRF with mean Ccr 59.17 +/- 1:18.53 mL/min/1.73 m2 (n = 6) moderate CRF with mean Ccr 34.98 +/- 7.75 mL/min/1.73 m2 (n = 7); severe CRF with mean Ccr 17.71 +/- 5.40 mL/min/1.73 m2 (n = 15); and end-stage renal disease with mean Ccr 6.46 +/- 1.71 mL/min/1.73 m2 (n = 16). Mean serum iPTH levels were 93.00 +/- 46.62 pg/mL in CRF and 16.52 +/- 9.35 pg/mL in controls. Groupwise mean serum (iPTH) levels were 48.50 +/- 4.76, 67.29 +/- 7.91, 82.42 +/- 9.67 and 130.66 +/- 58.74 pg/mL in mild, moderate, severe CRF and endstage renal failure respectively. Mean serum iPTH level of CRF (93.00 +/- 46.42 pg/mL) negatively correlated with mean Ccr (22.02 +/- 18.53 mL/min/l.73 m2) (P < 0.001) and mean serum calcium (7.30 +/- 1.02 mg/dL) (P < 0.001) and positively correlated with mean inorganic phosphate (5.76 +/- 1.1 mg/dL) (P < 0.05) and mean alkaline phosphatase (355.14 +/- 185.53 UL) (P < 0.001). We conclude that increased iPTH level occur even early in the course of CRF and progressive hypocalcemia and hyperphosphatemia are the initiating factors for the development of hyperparathyroidism.     

Evolution of individual renal function in children with unilateral complex renal duplication

OBJECTIVE: To assess the evolution of individual renal function during the maturation process in terms of single kidney glomerular filtration rate (SKGFR) and split function in children with unilateral complex renal duplication. STUDY DESIGN: We retrospectively reviewed the records of 44 children with unilateral complex duplex kidney. All affected kidneys had a poor or nonfunctioning dysplastic moiety, 28 in the upper pole and 16 in the lower pole. At least 2 radioisotopic examinations, including a 99mTc-mercaptoacetyltriglycine (99mTc-MAG3) renogram and a plasma clearance of 51Cr-ethylenediaminetetraacetic acid (Cr-51 EDTA), were performed in all children, the first one performed at a median age of 3 months (range 2 to 15 months) and the last one at 24 months (range 12 to 120 months). They allowed a precise estimation of split renal function, overall glomerular filtration rate (GFR), and SKGFR. RESULTS: Mean overall kidney GFR increased significantly between the two measurements from 63 +/- 12.7 mL/minute/1.73 m2 to 95 +/- 21 mL/minute/1.73 m2 (P <.0001). SKGFR of the duplex side similarly increased from 26 +/- 7.7 mL/minute/1.73 m2 to 38 +/- 12.6 mL/minute/1.73 m2 (P <.0001). In terms of split function, the affected kidney had a remarkable stable function between the two measurements, 40% +/- 8.6 and 39% +/- 8.3 (P=.94), respectively. However, cases with the lowest initial split function (<30%) had the lowest initial SKGFR and the worst further evolution. CONCLUSION: In children with unilateral complex renal duplication, we found on the affected side a significant increase of SKGFR because of renal maturation, whereas mean split function remained stable during follow-up.     

Effect of low dose dopamine on hemodynamic and renal function in children

The purpose of the study was to investigate the effect of low doses of dopamine in children. Fourteen cases were studied after open heart surgery. Cardiac output and renal parameters were determined under baseline conditions and under continuous infusion of dopamine 2.5 and 5 micrograms/kg/min. During the control period cardiac index was 2.62 +/- 0.19 L/min/m2, renal plasma flow was decreased at 269 +/- 41 mL/min/1.73 m2, GFR was 86.6 +/- 9.2 mL/min/1.73 m2, and filtration fraction was elevated at 37.1 +/- 1.9%. Plasma concentration of aldosterone correlated with the filtration fraction. At 5 micrograms/kg/min dopamine increased significantly cardiac output, renal plasma flow, and to a lesser extent GFR, thus decreasing the filtration fraction. At 2.5 micrograms/kg/min dopamine, increased renal plasma flow only in patients older than 5 y and had no effect on the other parameters. The increase of cardiac output in response to dopamine was abolished by propranolol pretreatment. By contrast, the hemodynamic renal response to dopamine was not altered by beta-blockade. These results indicate that 5 micrograms/kg/min of dopamine could prevent renal failure after open heart surgery in children by increasing renal blood flow and attenuating renal compensatory mechanisms.     

Glomerular filtration rate in children with solid tumors: normative values and a new method for estimation

Many chemotherapy regimens used in children are nephrotoxic. Accurate dosing of these medications requires that some estimation of glomerular filtration rate (GFR) be performed prior to initiating chemotherapy. However, few studies evaluating normal GFR in children exist. The authors report normal values for GFR for children with nonhematogenous malignancies using a highly accurate method of directly measuring GFR and an equation for estimating absolute GFR in these children. Children with nonhematogenous malignancies with no evidence of renal involvement or prior use of nephrotoxic agents had their GFR measured using an iothalamate infusion methodology. A total of 111 children (males and females) with a mean age = 7.95 years (range 2.8 months-19.5 years) were included in the study. GFR adjusted for body surface area (mL/min/1.73 m(2)) increases in the first 2 years of life and then plateaus at a level comparable to adult values. GFR adjusted for body surface area for males >2 years = 131.3 +/- 22.5, females = 126.8 +/- 24.4 mL/min/1.73 m(2) (p value not significant). Absolute GFR in mL/min can be easily estimated by a simple formula (r(2) =.97) based on the child's weight and serum creatinine: GFR (mL/min) = k sqrt[ ( (agemos+ 6)* wt) / Cr serum ] where agemos is age in months, wt is weight in kg, and k = 1.05 for males and 0.95 for females. The accurate measurement of GFR remains vitally important in the safe and effective treatment of pediatric solid tumors. This study provides a set of normal GFR values for these children and an equation for easy estimate of absolute GFR.     

Glomerular filtration rate in children following renal transplantation

Most studies evaluating renal function post-renal transplantation in children have used serum creatinine (S(Cr)) or estimates of its clearance (C(SCH)). When renal function is impaired both S(Cr) and the C(SCH) overestimate glomerular filtration rate (GFR), especially during cyclosporine therapy. This study measured GFR in 64 children (age range: 4-19 years) with stable renal function who received renal allografts at the Childrens Medical Center of Dallas, 31 from live related donors (LRD) and 33 from cadaveric donors (CAD). 125I-iothalamate clearance (C(IO)) was used as the reference standard for measuring GFR. Data from 100 C(IO) studies, were analyzed and results reported as mean +/- S.E.M. C(IO) performed during the first year after renal transplantation in 23 children who received allografts from LRD was 72.4+/-5.5 ml/min per 1.73 m2 compared to 50.4+/-7.4 ml/min per 1.73 m2 in 18 children who received allografts from CAD (p<0.05). Beyond the first year post-renal transplantation there was no difference in C(IO) between LRD and CAD allografts. When S(Cr) was compared to C(IO), the relationship was nonlinear. C(IO) was also compared to the simultaneous estimation of creatinine clearance by C(SCH). The overestimation of GFR by C(SCH) was inversely proportional to the level of renal function. When renal function was normal or mildly reduced (C(IO) > 50 ml/min per 1.73 m2), C(SCH) closely approximated C(IO). When renal function was moderately to severely curtailed (C(IO) < or = 50 ml/min per 1.73 m2), C(SCH) overestimated C(IO) by 43.6+/-5.6%. The study concludes that in children with renal transplant: 1) C(IO) is higher in allografts from LRD compared to CAD kidneys only in the first 12 months following renal transplantation; 2) S(Cr) is a poor predictor of C(IO); and 3) C(SCH) consistently overestimates GFR children following renal transplantation unless renal function is normal or only mildly decreased.     

Mycophenolate mofetil introduction stabilizes and subsequent cyclosporine A reduction slightly improves kidney function in pediatric renal transplant patients: a retrospective analysis

Chronic allograft nephropathy (CAN) is the major cause of late graft loss. Among others, chronic calcineurin inhibitor toxicity (CNI) contributes to the development of CAN. Therefore, reduction in CNI dosage may delay the development of CAN, leading to longer graft survival. It was the aim of the present retrospective analysis to investigate the effect of mycophenolate mofetil (MMF) addition with subsequent cyclosporine A (CSA) reduction on renal function in pediatric kidney allograft recipients. Seventeen patients (aged 8.3-17.6 yr) with monotherapy with CSA and progressive loss of renal function at a median of 3.4 yr after kidney transplantation were enrolled. After at least three months of MMF treatment, CSA dosage was stepwise reduced to trough levels of 100, 80, and 60 ng/mL. In all patients, introduction of MMF prevented a further decrease of glomerular filtration rate (GFR). The mean GFR 12 months before study enrollment was 96.1+/-24.5 and 71.0+/-21.0 mL/min/1.73 m2 at start of MMF. After introduction of MMF and unchanged CSA dosage GFR was stabilized to 71.1+/-23.8 mL/min/1.73 m2. After CSA reduction to trough levels of 60 ng/mL, GFR was slightly ameliorated up to 76.3+/-24.1 mL/min/1.73 m2. Within the follow-up period, one borderline rejection occurred in a patient in whom the CSA trough level was 60 ng/mL since seven months. In pediatric kidney allograft recipients with progressive loss of renal function reduction of CSA after introduction of MMF may stabilize and even slightly ameliorate renal function.     

The effect of growth hormone on growth and blood urea levels in children with chronic renal failure

It has been claimed that low protein diets slow deterioration of chronic renal failure (CRF) by reducing renal solute load. The anabolic effect of recombinant human growth hormone (rhGH) also has potential to reduce renal solute load and thereby slow progression of renal failure. The aim of this study was to determine the effect of rhGH on growth, renal solute load and renal function in children with CRF.
Seven prepubertal children, aged 2-14 years, with moderately severe CRF (creatinine clearance 7.7-23.4 mL/min per 1.73 m²) were treated with daily subcutaneous rhGH, 1 U/kg per week for 10-12 months. As expected, mean height velocity standard deviation scores (SDS) increased, from - 2.87 before treatment to + 3.39 on rhGH, and mean height increased from - 3.1 to - 2.4 SDS. Serum urea concentrations decreased in most patients during the first month of growth hormone treatment from a mean of 20.0pm7.7 mmol/L to 14.8pm5.8 mmol/L ( P = 0.006). The serum urea then returned to pretreatment levels over the next few months.
In the 12 months before treatment with growth hormone, mean creatinine clearance decreased from 19.3 mL/min per 1.73 m² to 16.7 mL/min per 1.73 m². In the next 12 months on rhGH mean creatinine clearance decreased further to 13.5 mL/min per 1.73 m². Therefore the rate of deterioration of renal function was unaffected during treatment with growth hormone. Initial treatment with rhGH is associated with decrease in serum urea concentrations in children with CRF, probably mediated by stimulation of anabolic incorporation of dietary nitrogen into body protein. Despite this reduction in renal solute load, renal function deterioration continued unchanged in most children.     

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.     

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

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