Pediatric health-related quality of life after intestinal transplantation.

As outcomes after ITx improve, greater emphasis is needed on HRQOL. The primary aims of this study were to (i) assess the feasibility of measuring HRQOL in pediatric ITx recipients, (ii) measure HRQOL using validated instruments, and (iii) compare HRQOL in ITx recipients to healthy normal (NL) children. The CHQ and Pediatric Quality of Life (PedsQL4.0) instruments were administered to both patients and parents at outpatient visits. All 24 eligible patients were enrolled. The median age at study enrollment was 6.0 yr (range: 2-18 yr), and the median time from transplant to study enrollment was 2.8 yr (range: 0.5-11.8 yr). The majority of subjects were male (58%), Latino (58%), and liver-inclusive (92%) recipients. For CHQ and PedsQL4.0, parental responses were significantly lower in multiple categories including physical health and social functioning compared to healthy norms. Patient responses were not different from NL using CHQ but using PedsQL4.0 were significantly lower in the school functioning subcategory and psychosocial health summary score. HRQOL as reported by children and families after ITx is significantly lower in multiple categories compared to NL.

Nutritional outcomes following pediatric intestinal transplantation.

BACKGROUND: This study sought to describe the long-term nutritional outcomes of children after intestinal transplant (SBT). METHODS: Between 1991 and March 2005, 30 children received 33 SBT at a single center. Eligibility criteria included patient and graft survival >6 months. Weight, height, albumin, prealbumin, zinc (Zn), and essential fatty acid (EFA) levels were reviewed retrospectively. RESULTS: The 19 patients who met inclusion criteria had a median age at SBT of 2.9 years. The majority of patients were male, Latino, transplanted for necrotizing enterocolitis and received combined liver-SBT. All patients were weaned off total parenteral nutrition to elemental formula at a mean of 39 days post-SBT. Seventeen of 19 patients were Zn deficient and four patients were EFA deficient post-SBT. CONCLUSIONS: Pre-SBT most subjects were significantly deficient in anthropometric and biochemical parameters. Post-SBT the mean Z score for weight and height improved significantly at year 1, then leveled off in year 2. Serum protein levels improved from pre-SBT, yet remained low-normal. Zn deficiency was seen frequently after SBT and is under investigation. Children who developed EFA deficiency were on the same formula, receiving inadequate EFA supplementation. Successful SBT was associated with growth and maintenance of serum nutritional parameters but not with significant catch-up growth.

Oerskovia infection caused by contaminated home parenteral nutrition solution.

Only three cases of human infection with Oerskovia have been reported. A woman receiving home total parenteral nutrition (TPN) was admitted for catheter-related sepsis caused by Oerskovia. She was discharged on an intravenous regimen of vancomycin, but symptoms recurred her first night home, and she was readmitted. Cultures of the TPN solution and peripheral blood yielded Oerskovia. The patient was successfully treated at home with 5 weeks of intravenous vancomycin therapy (30 mg/kg per day). Home TPN solutions provide an optimal incubation period for growth of microbial contaminants. Although quality control measures appropriate for hospital TPN solutions may be inappropriate for home TPN solutions, no standards currently exist for manufacturers of home TPN solutions. Thus, physicians should inquire about quality controls when choosing a company for home intravenous therapy referrals.

Choline pharmacokinetics during intermittent intravenous choline infusion in human subjects.

A study of choline pharmacokinetics was undertaken in four patients receiving long-term total parenteral nutrition. On consecutive days, 7, 14, 28, and 56 mmol choline chloride were intravenously infused over a 12-hour period in each subject. The choline concentration was determined in plasma at baseline, 1/4, 1, 3, 6, and 12 hours, and 3 and 12 hours after the infusion ended, and in daily 24-hour urine collections. Analysis of variance showed the data fit a two-compartment model in which elimination from the central compartment was saturable significantly better than a one-compartment model in all four subjects (p < 10(-8) in all cases), and significantly better than a nonsaturating model in three of the four subjects (p = 1.0 x 10(-9), 7.5 x 10(-6), 9.4 x 10(-11), respectively). The model allowed estimates of the rate constant for choline elimination at ambient levels, first-order rate constants for transfer between central and peripheral compartments, the dissociation constant for the saturable elimination process, the apparent volume of distribution in the central compartment, the steady-state volume of distribution, and the quantities of choline in the central compartment and in the readily exchangeable pool.

Bypass enteropathy: an inflammatory process in the excluded segment with systemic complications.

Evidence is presented that many of the enteric and systemic manifestations after jejunoileal bypass can be related to an inflammatory process within the bypassed small bowel rather than to the surgically induced sequelae of a short bowel syndrome with malabsorption. Invasion of the excluded segment by fecal flora was associated with a histologically demonstrable inflammatory response of the mucosa. The disorder was of variable severity and duration and occurred in the majority of 28 bypass patients. Progression to a clinical syndrome resembling an acute abdomen occurred in about 15% of the patients. Small bowel ileus and, in some patients, obstruction of the colon were suggested by physical signs and x-ray findings. Surgical exploration in such instances demonstrated an inflammaotry process of the excluded small bowel loops with severe distention of this segment and of the colon, but not organic obstruction. Pneumatosis cystoides intestinalis was a sequal in two patients. Exudative protein loss was documented in the severe cases. Most of the systemic sequelae are comparable to those seen with inflammatory diseases of the bowel such as Crohn's disease. Fever, excessive weight and lean tissue loss, and the involvement of skin, blood vessels, joints and possibly, the liver suggest an immune response as a common factor in the pathogenesis. The clinical improvement with antibiotics such as metronidazole or with restitution of normal bowel continuity indicates that the bacterial flora in the excluded small bowel segment or its byproducts are causally related to the systemic complications. Hyperoxaluria may be primarily the sequela of steatorrhea and not of the inflammatory process.

Taurine concentrations in plasma and blood cells of patients undergoing long-term parenteral nutrition.

Taurine concentrations were measured in plasma and blood cells of 40 adults undergoing long-term parenteral nutrition, without intravenous taurine, for 43.8 +/- 35.1 (SD) mo. Patients were classified into Group 1 (21 patients) or Group 2 (19 patients) according to whether their estimated enteral absorption of calories was less or greater than 25% of their daily requirement, respectively. In Group 1, taurine concentrations were reduced to 35-49% of normal control values in plasma (p less than 0.01), platelets (p less than 0.001), lymphocytes (p less than 0.005), and erythrocytes (p less than 0.001). Granulocyte taurine was not different from normal. A smaller decrease in taurine concentration was found in Group 2 patients; however, taurine levels were significantly below normal in their plasma and red cells. Thus, many patients undergoing long-term parenteral nutrition with little or no taurine intake are depleted of taurine in plasma and most blood cells. These findings suggest that taurine may be essential for these patients and should be added to solutions used for long-term parenteral nutrition.

Effect of intravenous taurine supplementation on plasma, blood cell, and urine taurine concentrations in adults undergoing long-term parenteral nutrition.

Thirty-four adults undergoing long-term parenteral nutrition (TPN) were treated either with or without intravenous taurine for less than or equal to 24 mo. Statistical comparisons were carried out in eight patients randomly assigned to receive intravenous taurine, usually 10 mg.kg-1.d-1, and 10 patients not receiving taurine. Compared with normal adults, baseline plasma taurine and urine taurine-creatinine ratios were decreased in both groups and platelet taurine was reduced in the taurine-treated group. During taurine treatment the mean of the mean values for taurine became normal in plasma and platelets and remained normal in erythrocytes, granulocytes, and lymphocytes; urine taurine-creatinine ratios rose to approximately five times normal. During follow-up, patients not given taurine had plasma, erythrocyte, and granulocyte taurine and urine taurine-creatinine ratios below normal values and the concentrations of taurine-treated patients. Their platelet taurine was also subnormal. Thus, 10 mg taurine.kg-1.d-1 intravenously normalizes plasma and blood cell taurine concentrations in long-term TPN patients.

Altered diurnal regulation of blood ionized calcium and serum parathyroid hormone concentrations during parenteral nutrition.

BACKGROUND: Little is known about parathyroid gland function in patients receiving total parenteral nutrition (TPN). OBJECTIVE: Our objective was to determine whether parathyroid gland function is abnormal in TPN recipients. DESIGN: Six patients with a mean (+/-1 SD) age of 45.5 +/- 8.0 y who had been receiving TPN for 18.7 +/- 2. 8 y underwent bone biopsy, bone mass measurements with dual-energy X-ray absorptiometry, and dynamic tests of parathyroid gland function. Diurnal variations in blood ionized calcium (iCa(2+)) and serum parathyroid hormone (PTH) concentrations were also assessed. Results were compared with those of healthy volunteers. RESULTS: Bone mass and bone formation were subnormal in all patients. Basal serum PTH concentrations were moderately higher in the TPN recipients than in healthy volunteers, and values obtained every 30 min over 24 h were significantly higher (P < 0.001) in TPN recipients (5.0 +/- 0.9 pmol/L) than in healthy volunteers (2.6 +/- 0.6 pmol/L). The percentage increase in serum PTH during citrate-induced hypocalcemia was lower in the TPN recipients, consistent with secondary hyperparathyroidism. Evening infusions of calcium-containing TPN eliminated the nocturnal rise in serum PTH, increased the amplitude of change for iCa(2+) and PTH over 24 h, increased the orderliness of change for iCa(2+) and PTH as measured by approximate entropy (ApEn), and enhanced the synchrony of change between iCa(2+) and PTH. Treatment for 10 d with calcium-free TPN restored the nocturnal rise in serum PTH and increased ApEn for PTH. ApEn for iCa(2+) remained low, suggesting that a component of nutrient solutions, but not calcium per se, enhances the regularity of PTH release in TPN recipients. CONCLUSION: Parathyroid gland function is abnormal in long-term TPN recipients, which may contribute to disturbances in bone metabolism.

Visual function in patients undergoing long-term total parenteral nutrition.

To evaluate the effects of long-term total parenteral nutrition (TPN) on eye function, 27 adults and 12 children in the UCLA Home TPN Clinic underwent ophthalmoscopic examination and visual-function testing. Direct inspection of the fundus showed a marked granularity of the retinal pigmented epithelium in some patients. About one-half of the children and one-third of the adults tested had at least one and usually two abnormalities in their electroretinogram. Determination of blood nutrients thought to affect vision revealed that zinc and vitamin E were within normal range. Vitamin A concentrations were above normal in 10 of 19 adults and selenium concentrations were below normal in 10 of 10 children and 17 of 21 adults tested. Linoleic and linolenic acid concentrations were low; plasma, platelet, and urine taurine concentrations were significantly lower than normal. Despite these diffuse nutrient abnormalities, only zinc and vitamin E concentrations correlated significantly with any index of visual function.

Aluminum loading during total parenteral nutrition.

Patients on long-term total parenteral nutrition were found to have elevated aluminum (AI) levels in bone, and plasma, with the casein in the total parenteral nutrition solution the source of A1. Substitution of amino acids for casein was followed by a fall in urinary and plasma A1. Thus, parenteral loading with A1 increases tissue A1, particularly in bone. Whether A1 accumulation contributes to bone disease remains unclear, but the prolonged use of casein in total parenteral nutrition solutions may be inadvisable.

Metabolic bone disease of total parenteral nutrition: course after changing from casein to amino acids in parenteral solutions with reduced aluminum content.

Bone disease with total parenteral nutrition (TPN) has been attributed to aluminum loading or vitamin D therapy. We studied 17 patients who first received TPN containing casein hydrolysate with high Al and ergocalciferol (25 micrograms/d) for 6-72 mo followed by TPN containing amino acids with reduced Al and ergocalciferol (5 micrograms/d) for 9-58 mo. We also did a cross-sectional study of 22 patients receiving casein and ergocalciferol (25 micrograms/d) compared with 46 patients receiving amino acids and ergocalciferol (5 micrograms/d) for 6-58 mo. Bone formation was higher and osteoid area, bone-surface stainable Al and total bone Al were lower with amino acid TPN than with casein TPN. Bone formation varied inversely with both plasma Al and bone-surface Al, suggesting that plasma or bone-surface Al, acquired during TPN, can reduce bone formation and lead to patchy osteomalacia. Serum levels of iPTH and 1,25-dihydroxyvitamin D were higher with amino acid TPN.

The histologic spectrum and clinical outcome of refractory and unclassified sprue.

The vast majority of patients with celiac disease respond to a gluten-free diet; yet, a small number of refractory patients do not respond and have persistent malabsorption and residual mucosal abnormalities of the small intestine. The histologic features of refractory/unclassified sprue have been published as case reports, often without long-term follow up, and no clear histologic picture has emerged. We present the results of a long-term study of the clinical and histologic features of 10 patients with refractory/unclassified sprue. The histologic features of small bowel biopsies in this group of patients were compared with those of 10 patients with responsive celiac disease and with 10 patients without malabsorption who had normal duodenal biopsies. Five of the 10 refractory patients ultimately developed collagenous sprue as a distinct histologic marker of refractory disease. Additional distinctive findings found in small bowel biopsies in the refractory group were subcryptal chronic inflammation (10 of 10) and marked mucosal thinning in three patients. Other nonspecific findings included acute inflammation and gastric metaplasia. One patient with collagenous sprue developed a B-cell lymphoma of the ileum, and in general collagenous sprue was associated with a poor prognosis. Two of five patients died whereas two others require total parenteral nutrition for survival. Pathologists evaluating small bowel biopsies in the setting of malabsorption should be aware of the subtle histologic changes described here that may portend a refractory course.

A comparison of renal function in cyclosporine- and FK-506-treated patients after primary orthotopic liver transplantation.

In this randomized controlled trial comparing FK-506 to CsA, we report parameters of nephrotoxicity in adult patients surviving > 90 days after orthotopic liver transplant (OLT). Patients randomized to FK-506 first received 0.15 mg/kg IV/day followed by 0.3 mg/kg PO/day. Doses were modified to avoid toxicity and to achieve FK-506 levels of 0.5 to 1.5 ng/ml. CsA was administered in the usual manner with dose adjustments to whole blood HPLC levels. A pre-OLT glomerular filtration rate (GFR) of > or = 30 ml/min/1.73/m2 and/or serum creatinine < or = 2.0 mg/dl were required for inclusion in the study. GFRs were obtained at post OLT days 28, 180, and 360. Other parameters of renal function evaluated were creatinine, magnesium, serum electrolytes, blood pressure, use of antihypertensives, and magnesium supplements. There were 38 patients in the FK-506 group and 34 in the CsA group. The mean days of follow up for each group was similar: 456 +/- 135 days for the FK-506 group and 451 +/- 112 days for the CsA group. The mean oral dose for the FK-506 group ranged from 0.13-0.16 mg/kg/day with mean FK-506 levels of 0.6-0.8 ng/ml. In the FK-506 group, there was a significant fall in the pre-transplant GFR from 89 +/- 31 ml/min/173 m2 to 43 +/- 15 ml/min/173 m2 at day 360. Similarly, for the CsA group, the pre-transplant GFR of 75 +/- 31 ml/min/1.73 m2 fell to 49 +/- 17 ml/min/1.73 m2 at day 360. At each time point studied, there was no significant difference in mean GFR between the two groups. There were no significant differences in the monthly mean values for creatinine, electrolytes, magnesium, or blood pressure between the two groups. Magnesium levels were in the low normal range (1.4-1.6 mEq/L), and the mean potassium levels in the high normal range (4.4-4.7 mEq/L). In both groups, a similar number of patients required magnesium supplementation or hypertensive medications. The nephrotoxicity of FK-506 given at low oral doses and with concomitant low levels was comparable to that of CsA. The two drugs were remarkably similar in their spectrum of electrolyte disturbances and incidence of hypertension.

Serial decrease in glomerular filtration rate in long-term pediatric liver transplantation survivors treated with cyclosporine.

Serial calculations of glomerular filtration rate were made in 31 pediatric liver transplant recipients surviving more than 1 year. GFR was computed from the Schwartz formula, (cGFR = KL/S Cr), before orthotopic liver transplantation, and at 3-6 monthly intervals thereafter. At the same time points, CsA dose/kg, CsA level, blood pressure, and liver functions were recorded. The mean difference between the pre-OLT cGFR and the most-current cGFR for all patients was -50 ml/min/1.73 m2 (P = less than 0.005). In 17/31 (55%), the current cGFR was less than 80 ml/min/1.73 m2, indicative of renal impairment. The cGFR continued to decrease in 24 patients followed beyond 1 year (26.8 ml/min/1.73 m2 per year decrease, P less than 0.005). More patients with a cGFR less than 80 ml/min/1.73 m2 had outpatient hypertension. There was no correlation of cGFR with CsA levels, CsA dose, or liver function. We conclude that a significant decrease in cGFR is seen in children treated with CsA for more than 1 year, which is progressive in the majority.

Differences in oral FK506 dose requirements between adult and pediatric liver transplant patients.

The oral dose recommendation for FK506 (Fujisawa Pharmaceutical, Deerfield, IL) after liver transplantation has, to date, made no distinction between adult and pediatric patients. Sixteen pediatric and 33 adult liver transplant patients treated long term with oral FK506 were studied. Initial FK506 doses were 0.3 mg/kg/day p.o. or 0.15 mg/kg/day i.v. Thereafter, doses were adjusted to achieve therapeutic FK506 serum levels (0.5-3.0 ng/ml, ELISA liquid/liquid separation) and to maintain an acceptable serum creatinine. FK506 (in mg/kg/day), FK506 levels, and liver function were assessed at monthly intervals on outpatient visits. The mean age of 16 pediatric patients was 5.3 +/- 3.5 years and of 33 adult patients was 49 +/- 12 years. Mean days of FK506 therapy were 284 +/- 136 for pediatric patients and 239 +/- 112 for adult patients. For each time period, pediatric patients required a significantly higher dose of FK506 compared to adult patients (P < 0.001). The overall mean pediatric dose for the first year was 0.46 +/- 0.4 mg/kg/day compared to the mean adult dose of 0.13 +/- 0.01 mg/kg/day. The ratio of pediatric to adult oral FK506 dose requirements ranged from 2.7 to 4.4 over the 1 year of followup. FK506 levels monitored at the same time points showed no significant differences at any month between pediatric and adult patients. We conclude that the oral dose per kilogram per day of FK506 required to maintain similar FK506 levels is significantly greater in pediatric patients compared to adult recipients during the first year of follow-up. Pediatric recipients require substantially more, and adult recipients substantially less, than the recommended oral FK506 dose to achieve a therapeutic effect.

Red cell aplasia in children on tacrolimus after liver transplantation.

Hematological toxicity of tacrolimus has been rarely reported. We report two pediatric recipients of liver transplantation with anemia. They were treated with tacrolimus for 8 and 47 months, respectively, before developing pure red cell aplasia (PRCA) confirmed by bone marrow biopsy. The children recovered quickly on withdrawal of tacrolimus. The clinical profile of these children is compared with the only other patient reported in the literature with PRCA due to tacrolimus. All three patients had similar hematological findings. However, the mechanism of the tacrolimus-induced PRCA in these children appears to be different from that reported in the adult patient.

The effect of immunosuppression on posttransplant lymphoproliferative disease in pediatric liver transplant patients.

BACKGROUND: Posttransplant lymphoproliferative disease (PTLD) is a serious complication associated with the use of chronic immunosuppression for solid organ transplantation. This study represents a retrospective analysis of UCLA's experience with PTLD in all pediatric liver transplant recipients between 1984-1997. We assessed the clinical presentation, risk factors, incidence density, immunological characteristics, management, and outcome of patients who developed PTLD when receiving either primary cyclosporin A (CsA) or tacrolimus. METHODS: A total of 251 children received primary CsA therapy of which 70 required OKT3 for steroid resistant rejection and 29 required tacrolimus rescue for OKT3 resistance and/or chronic rejection. One hundred forty one children received tacrolimus as primary therapy. Sixty patients who survived for less than 6 months after transplantation were excluded from the study. RESULTS: The total incidence density (ID) rate of PTLD was 1.8+/-0.4 per 100 patient-years (30/392). The overall ID rate of PTLD in the CsA group was 0.93+/-0.2 per 100 patient-years (15/251). Within this group of primary CsA-treated patients, the ID rate of PTLD was 0.49+/-0.1 without OKT3 or tacrolimus, 0.67+/-0.2 with OKT3, and 6.42+/-1.1 with tacrolimus rescue. The overall PTLD ID rate in the primary tacrolimus-treated patients was 4.86+/-1.2 per 100 person-years (15/141). There was a 5-fold increase in the ID rate of PTLD in the primary tacrolimus group when compared to the comparable, primary CsA group (P<0.001). The mean time to PTLD was 5-fold longer (49.7+/-20.7 months) in the CsA group when compared to the CsA/tacrolimus rescue group (9.8+/-3 months, P<0.05) or the tacrolimus primary group (12.6+/-5.1 months, P<0.05). Five patients had monoclonal disease in the CsA group, but only one in the tacrolimus group (P<0.05). Clinical presentations with enlarged lymph nodes, fevers, malaise, anorexia, weight loss, hypoalbuminemia, and gastrointestinal blood loss were common. Mortality was 20%, three patients died in each group. CONCLUSION: The use of primary tacrolimus therapy was associated with a significant 5-fold higher rate of PTLD when compared to those treated with primary cyclosporine. Early diagnosis, decrease and/or discontinuation of potent immunosuppressive agents may contribute to decrease morbidity and mortality of this entity.

Serum lipid abnormalities in pediatric liver transplant patients.

UNLABELLED: Little is known about serum lipid abnormalities in pediatric liver transplant recipients. We performed a longitudinal cohort review of 102 outpatient pediatric liver recipients surviving greater than 6 months and immunosuppressed with cyclosporine and prednisone (+/- azathioprine). The median age was 6 years, median months posttransplant 25, and male-to-female ratio 1:1.5. The average cholesterol (mean of individual means) was 177 +/- 45 mg/dl and average triglyceride level 158 +/- 71 mg/dl. The mean percent of cholesterol levels greater than 170 mg/dl and triglyceride levels greater than 140 mg/dl was 47% and 50%, respectively. Age, obesity, sex, and family history of risk factors had no significant effect on cholesterol or triglyceride levels. Bivariate regression analysis showed no meaningful association between cholesterol or triglyceride levels and cyclosporine levels, cyclosporine dose, prednisone dose, or diastolic blood pressure. Triglyceride and cholesterol neither increased nor decreased with time posttransplant. The rate of change of triglyceride or cholesterol could not be predicted by the rate of change of cyclosporine levels (or dose), or prednisone dose. We found no evidence that rises or falls in cholesterol or triglyceride levels coincided with rises or falls in either cyclosporine level or prednisone dose. Cholestasis was significantly associated with increased cholesterol and triglyceride levels (P = 0.05). A multivariate analysis was unable to predict cholesterol or triglyceride levels from three predictors: cyclosporine level, prednisone dose, and liver function. The mean dietary intake of fat and cholesterol was above RDA and exercise patterns were suboptimal in school-aged children. CONCLUSIONS: 50% of children had a mean cholesterol greater than 75th percentile (170 mg/dl); 20% were above the 95th percentile; 56% had a mean triglyceride level greater than 140 mg/dl. By these criteria the majority of pediatric liver transplant patients have lipid abnormalities that may predispose them to atherosclerosis in later life.

The long-term outcome of OKT3 compared with cyclosporine prophylaxis after liver transplantation.

We report the long-term follow-up (greater than 1 year) of 46 patients (12 pediatric) randomized to receive OKT3 for the first 14 days after OLT with low-dose steroids compared with 39 patients (8 pediatric) who received cyclosporine, steroids, and azathioprine. The mean period of follow-up for survivors was 648 +/- 261 days for the OKT3 group and 682 +/- 216 days for the cyclosporine group. Of the OKT3 patients, 46% were rejection-free in the first month compared with 31% of CsA-treated patients (P = NS). Rejection occurred after 1 month in 21% of the OKT3 group patients compared with 19% of the CsA group patients. One patient in each group developed vanishing bile duct syndrome. Eight patients in the OKT3 group and 13 in the CsA group experienced steroid-resistant rejection and required OKT3 rescue. In the 8 patients in whom OKT3 was reused, 4 had a positive ELISA after prophylaxis, and in 6, CD3-positive cells were greater than 10% during OKT3 reuse. Five patients resolved the episode. Of patients receiving OKT3 prophylaxis, 39% developed anti-OKT3 antibodies. In the OKT3 group 83% of patients and in the CsA group 75% currently have normal liver function. There was no difference in serum creatinine for either adult or pediatric recipients at 12 months in the two groups. Eight episodes (2 CMV) of severe infection occurred after 1 month in the OKT3 group compared to 11 (4 CMV) in the CsA group. Graft survival, 63% for the OKT3 group and 73% for the CsA group, and patient survival, 67% for the OKT3 group and 84% for the CsA group, were not significantly different in the two groups. We recommend reserving the use of OKT3 for resistant rejection or when cyclosporine is contraindicated, as we can show no long-term benefit from its routine prophylactic use.

The impairment of true glomerular filtration rate in long-term cyclosporine-treated pediatric allograft recipients.

We performed indium-111-DTPA plasma clearance studies in 61 pediatric kidney and liver recipients treated with cyclosporine to compare true glomerular filtration rate with calculated GFR (cGFR). The mean true GFR of 61.9 +/- 36.6 ml/min/1.73 m2 indicated renal impairment. The mean cGFR of 85.2 +/- 22.4 ml/min/1.73 m2 was significantly higher (P less than 0.001), and overestimated GFR by 38%. cGFR alone did not accurately reflect the degree of renal dysfunction. A group of 48 pediatric orthotopic liver transplant recipients was studied in more detail: 73% of these patients had a true GFR less than 70 ml/min/1.73 m2, while 85% had a true GFR below 90 ml/min/1.73 m2, the lower limit for normal GFR in children. The mean true GFR for patients treated more than 24 months with CsA was lower (P = 0.02) than patients treated with CsA for 12 to 24 months. OLT patients with normal true GFR (greater than 90 ml/min/1.73 m2) had significantly lower plasma CsA levels, and 50% of patients with a true GFR less than or equal to 50 ml/min/1.73 m2 had hypertension. There was no effect on true GFR of age, liver function, azathioprine use, or peritransplant treatment with other nephrotoxic drugs. We conclude that true GFR is significantly impaired in long-term CsA-treated allograft pediatric recipients. Calculations of GFR underestimate the degree of renal dysfunction. As patients treated greater than 24 months had the lowest true GFRs, the fall in GFR may be progressive.