Lymphoproliferative disorder presenting as a tumor of the renal allograft

Post-transplant lymphoproliferative diseases (PTLDs) constitute a group of potentially life-threatening complications in solid organ transplantation, occurring in 1–2% of kidney transplant recipients. The absolute number of cases occurring at each transplant center remains small, making it difficult to assess incidence, prognosis, and treatment. We report a case of post-transplant lymphoproliferative disorder that developed in the allograft renal parenchyma 2 years after renal transplantation. This case implies that partial nephrectomy may be a safe and effective treatment protocol for renal lymphoma in allograft kidneys.     

Renal transplantations performed using non-heart-beating organ donors: going back to the future?

BACKGROUND: As more expanded-criteria organ donors are used to bridge the widening gap between organ supply and demand, non-heart-beating (NHB) donors will become increasingly important. The purpose of this study was to analyze renal transplant outcomes using this source of cadaveric (CAD) organs and compare the results with heart-beating organ sources. METHODS: Data from 98,698 adult CAD renal transplant recipients and 34,531 living donor renal transplant recipients registered in the U. S. Renal Data System database between January 1993 and June 2000 were analyzed. Kaplan-Meier survival curves were used to compare graft and patient survival rates between NHB, CAD, and living donor transplant recipients. Cox proportional hazards models were used to identify risk factors for NHB donor recipients, while adjusting for potential confounding variables. RESULTS: Recipients of NHB donor organs experienced nearly twice the incidence of delayed graft function (DGF) compared with heart-beating donors (42.4% vs. 23.3%, respectively). NHB donor transplants experienced comparable allograft survival when compared with CAD transplants at 6 years (73.2% vs. 72.5%, respectively; P=NS); patient survival was greater at 6 years for NHB compared with CAD renal transplant recipients (80.9% vs. 77.8%, respectively; P=NS). Significant factors for allograft loss for NHB donor organ recipients included the following: organ used for repeat transplants; DGF; donor age older than 35 years; and head trauma as a cause of initial injury (relative risk 2.74, 1.90, 1.78, and 1.41, respectively). CONCLUSIONS: Although exhibiting elevated DGF rates, allograft and patient survival rates of transplants from NHB donor sources are equivalent to those from conventional CAD sources. Donor age, recipient transplant number, female recipient, mechanism of injury, and DGF were the most pertinent variables leading to poor outcomes.     

Comparable renal graft survival in African-American and Caucasian recipients

In past years, many pediatric transplant centers found African-American renal transplant recipients to have poor graft survival. Since 1991 anti-lymphocyte induction therapy has been routinely used for pediatric cadaveric (CAD) and living-related donor (LRD) renal allograft recipients at the University of Tennessee, Memphis. Sixteen African-American first renal allograft recipients received induction therapy: 11 CAD allografts (10 OKT3, 1 ATGAM) and five LRD (all ATGAM). Sixteen Caucasian recipients received induction therapy; 3 CAD (all OKT3), 1 living-unrelated donor (OKT3), and 12 LRD (9 ATGAM, 3 OKT3). Mean age at renal transplantation was 11.8 and 10.5 years for African-American and Caucasian recipients, respectively. Predicted graft survival (PGS) estimated by the Kaplan-Meier method for the African-American patients was 94% at both 1 and 3 years, and for Caucasian patients was 94% and 85% at 1 and 3 years, respectively. Eleven African-American CAD recipients had a PGS of 91% at 1 and 3 years. Renal allograft survival for African-American and Caucasian pediatric recipients at our center appears to be comparable. This could be due, in part, to the use of anti-lymphocyte induction therapy. However, other factors, such as improved compliance or better immunological and pharmacological monitoring, may also have contributed. Received April 18, 1997; received in revised form January 14, 1998; accepted January 19, 1998     

Angiotensinogen and plasminogen activator inhibitor-1 gene polymorphism in relation to chronic allograft dysfunction

Chronic allograft dysfunction (CAD) is the most common cause of allograft failure in the long-term, and current immunologic strategies have little effect on this condition. The renin-angiotensin system (RAS) plays important roles progression of chronic renal disease. It is thought that plasminogen activator inhibitor-1 (PAI-1) functions in the RAS, in addition to involvement in thrombotic risk and fibrosis. This study investigated possible links between angiotensinogen (AGT) genotypes (M235T/MM, MT, TT) and PAI-1 genotypes (4G4G, 4G5G, 5G5G) and CAD assessments of both types of polymorphism were performed in 82 renal allograft recipients. One hundred healthy subjects were also investigated for AGT polymorphism, and 80 healthy subjects for PAI-1 polymorphism. Genotypes were determined using polymerase chain reaction (PCR) sequence-specific primers, and PCR followed by restriction fragment length polymorphism analysis. Kidney recipients with CAD had significantly lower frequencies of the MM genotype and the M allele than the recipients without CAD (p < 0.05 and <0.001). The transplant recipients with CAD also had significantly lower frequencies of the 5G5G genotype and the 5G allele than those without CAD (p < 0.001 and <0.05). Determination of AGT M235T and PAI-1 genotypes prior to transplantation may help identify patients who at risk for chronic renal transplant dysfunction.     

Capillary deposition of complement split product C4d in renal allografts is associated with basement membrane injury in peritubular and glomerular capillaries: a contribution of humoral immunity to chronic allograft rejection

Endothelial deposition of the complement split product C4d is an established marker of antibody-mediated acute renal allograft rejection. A contribution of alloantibody-dependent immune reactions to chronic rejection is under discussion. In this study, the association of immunohistochemically detected endothelial C4d deposition in peritubular capillaries (PTC) with morphologic features of chronic renal allograft injury was investigated in a large study cohort. C4d deposits in PTC were detected in 73 (34%) of 213 late allograft biopsies performed in 213 patients more than 12 mo after transplantation (median, 4.9 yr) because of chronic allograft dysfunction. Endothelial C4d deposition was found to be associated with chronic transplant glomerulopathy (CG) (P < 0.0001), with basement membrane multilayering in PTC (P = 0.01), and with an accumulation of mononuclear inflammatory cells in PTC (P < 0,001). Furthermore, C4d deposits in PTC (in biopsies with normal glomerular morphology) were associated with development of CG in follow-up biopsies. Other morphologic features of chronic allograft nephropathy (with exception of tubular atrophy) were not associated with C4d deposits in PTC. Analyses of previous and follow-up biopsies revealed that C4d deposits may occur de novo and may also disappear at any time after transplantation. In conclusion, the data suggest that complement activation in renal microvasculature, indicating humoral alloreactivity, contributes to chronic rejection characterized by chronic transplant glomerulopathy and basement membrane multilayering in PTC.     

Cost of Traveling to Follow-up Appointments at Kidney Transplant Clinics

BackgroundThe number of kidney transplant (KT) recipients has increased in recent years, saturating kidney transplant visits at transplant centers (TCs). Furthermore, some patients live far from TCs, which adds displacement costs to their expenses. To solve these problems, joint follow-up of KT recipients has been initiated at TCs and referral hospitals.MethodsWe performed a cross-sectional study in a cohort of 64 KT recipients during joint follow-up in TCs and the Hospital Arnau de Villanova (HAV) using a survey that evaluated the displacement costs as well as the advantages and disadvantages of each.ResultsDistance (320 km [IQR, 300-340 km] vs 15 km [IQR, 4-60 km]; P < .001), time (240 minutes [IQR, 210-240 minutes] vs 40 minutes [IQR, 30-68 minutes]; P < .001), total economic cost per visit (€60 [IQR, €50-90] vs €10 [IQR, €2-15]; P < .001), and annual CO₂ emission (32.3 kg vs 1.4 kg; P < .05) were greater when patients traveled to TCs. Nephrologists at both TCs and HAV were rated positively by patients, while the displacement costs associated with travel to the TCs and the smaller size of the HAV were seen as negative aspects. Overall, 93.75% of the KT recipients preferred joint follow-up.ConclusionsThis study suggests that joint follow-up between TCs and referral hospitals is an economic and ecological solution for follow-up in KT recipients living far away and visiting their referral hospital, which is the preferred choice for most patients.     

Polymorphism of the renin-angiotensin-aldosterone system in patients with chronic allograft dysfunction

Polymorphism of the gene encoding components of the renin-angiotensin-aldosterone synthase system (RAAS) represents an area of intense research of cardiovascular disease associations. Numerous studies have addressed the role of RAAS gene polymorphisms in the development and progression of renal disease. Also, it has been reported that patient with ACE (DD) and angiotensinogen AGT (TT) genotypes are associated with chronic allograft dysfunction (CAD). We investigated the effects of gene polymorphisms of the renin-angiotensin-aldosterone system in renal transplant patients (81 males and 50 females; mean age 29.6+/-10.2 years). Genotypes were determined using polymerase chain reaction sequence specific primers and PCR followed by RFLP analysis. Renal allograft recipients with chronic allograft dysfunction had significantly higher frequencies of the MM genotype than those without CAD (P<0.05). The other genetic polymorphisms of the RAAS were not associated with CAD. This study proves that determination of AGT M235T genotype before transplantation may help identify patients who are at risk for chronic renal transplant dysfunction.     

Ctla-4 exon 1 (+49) and promoter (-318) gene polymorphisms in kidney transplantation

To investigate the association between kidney transplant rejection and the polymorphisms of CTLA-4 gene exon 1(+49) and promoter (-318), genomic DNA of 70 renal transplant recipients and 110 healthy blood donors were genotyped by PCR-RFLP and PCR-SSP, respectively. The patients were classified in two groups: G1 included 33 HLA-identical recipients and G2, 37 one haplo-identical recipients. Thirty-one recipients experienced an acute rejection episode: 10 in G1 and 21 in G2. Ten G2 patients developed chronic allograft dysfunction (CAD). Allelic frequencies and genotype distribution were similar among patients and controls. CTLA-4 exon 1 genotype A/A and CTLA-4 promoter genotype C/C were significantly higher among G2 patients with CAD than without CAD (P < .01). The distribution of CTLA-4 exon 1-promoter genes did not reach significance between graft recipients and controls. The genotype frequency of (G/G-C/C) was increased among controls (42.72%) compared with graft recipients (G1 and G2; 35.71%). CTLA-4 polymorphisms gene were associated with susceptibility to chronic allograft dysfunction.     

Cost-effectiveness of colorectal cancer screening in renal transplant recipients

BACKGROUND: Colorectal cancer screening is now standard practice in most developed countries. The aim of this study was to determine the cost-effectiveness of colorectal cancer screening, with annual fecal occult blood testing, in renal transplant recipients. METHOD: A Markov model was developed to compare the effects of annual fecal occult blood testing (FOBT) as screening for colorectal cancer in a cohort of renal transplant recipients ages 50-70 years, versus no screening. Data on cancer risk and survival were obtained from the ANZDATA Registry. Accuracy of FOBT, cancer stage distribution of the screened and unscreened arms, and adverse effects of colonoscopy were extrapolated from general population data because of unavailability of equivalent data in renal transplant recipients. RESULTS: When the participation rate was 50%, the average cost for annual FOBT was $5076. The estimated incremental cost-effectiveness ratio was $22,309 per life year saved. Using a series of sensitivity analyses, the choice of screening strategy was most sensitive to the prevalence of disease, test specificities, and participation rate. When the base-case analyses were tested over the worst and best-case scenarios, the incremental cost-effectiveness ratio varied from $32,863 to $95,668 per life year saved. CONCLUSION: Under the most favorable conditions, immunochemical FOBT screening in renal transplant recipients appears good value for money. Uncertainties, however, exist in the model's influential estimates. Primary research into these uncertainties is necessary to confirm whether population colorectal cancer screening is cost-effective in renal transplant population.     

Induction of metallothionein synthesis with preservation of testicular function in rats following long term renal transplantation

Metallothionein (MT), as an acute phase or stress-response protein and free radical scavenger, is related to inflammation and cellular protection from oxidative damage. In order to evaluate long-term testicular damage and the role of MT following renal transplant, nine allogenic (Fisher 344 → Lewis) and seven isogenic (Lewis → Lewis) renal transplants were performed and the recipient rats were followed for 140 days when allografts develop chronic transplant rejection. Testicular weight, light microscopic morphology, and lactate dehydrogenase-X enzyme activity were assessed. Testicular MT was determined by Cd-heme assay, and was localized immunocytochemically using a polyclonal rabbit antibody. No differences in testis weight, morphology, or LDH-X enzyme activity were found between allograft and isograft recipients. Testicular MT level was significantly increased in the testis of allograft recipients. Testicular zinc (Zn) and copper (Cu) levels, but not iron (Fe) level, were significantly higher in testis with allograft kidney than that with isograft kidney. In addition, Cu/Zn ratio was also significantly high in the allograft group. However, the MT level did not show any significant correlation either with Cu and Zn alone or with Cu/Zn and Fe/Zn ratios. These data suggest that allogenic stimuli may induce MT synthesis in the recipient testis. The increased MT level in an allograft may offer a protective action from oxidative damage in the testis. Received: 9 March 1999 / Accepted: 1 October 1999     

Colonisation with methicillin‐resistant Staphylococcus aureus prior to renal transplantation is associated with long‐term renal allograft failure

Renal transplant recipients are at an increased risk of developing Methicillin‐resistant Staphylococcus aureus due to their immunosuppressed status. Herein, we investigate the incidence of MRSA infection in patients undergoing renal transplantation and determine the effect of MRSA colonisation on renal allograft function and overall mortality. Between January 1st 2007 and December 31st 2012, 1499 consecutive kidney transplants performed in our transplant unit and a retrospective 1:2 matched case‐control study was performed on this patient cohort. The 1‐, 3‐ and 5‐year overall graft survival rates were 100%, 86% and 78%, respectively, in MRSA positive recipients compared with 100%, 100% and 93%, respectively, in the control group (P < 0.05). The 1‐, 3‐ and 5‐year overall patient survival rates were 100%, 97% and 79%, respectively, in MRSA positive recipients compared with 100%, 100% and 95%, respectively, in the control group (P = 0.1). In a multiple logistic regression analysis, colonisation with MRSA pre‐operatively was an independent predictor for renal allograft failure at 5 years (hazard ratio: 4.6, 95% confidence interval: 1–30.7, P = 0.048). These findings demonstrate that the incidence of long‐term renal allograft failure is significantly greater in this patient cohort compared with a matched control population.     

Long-term renal function and survival of renal transplant recipients admitted to the intensive care unit

Arulkumaran N, West S, Chan K, Templeton M, Taube D, Brett SJ. Long‐term renal function and survival of renal transplant recipients admitted to the intensive care unit.
Clin Transplant 2012: 26: E24–E31.
© 2011 John Wiley & Sons A/S. Abstract: Introduction: We determined the long‐term mortality and renal allograft function of renal transplant recipients admitted to the intensive care unit (ICU). Methods: A single institution retrospective observational cohort study of all renal transplant patients admitted to the ICU was performed. Serum creatinine was recorded up to one yr after hospital discharge and survival data were collected for three yr. Results: Chest sepsis was the commonest reason for ICU admission. ICU and hospital mortality were 32% and 19% respectively. Predictors of hospital mortality included the presence of sepsis and duration of mechanical ventilation (MV). Of the patients who were discharged from ICU, three‐yr mortality was 50%. Renal function at one yr was worse than that at hospital discharge and at baseline, though not statistically significant. Death‐censored allograft loss was 11% over the three‐yr follow up period. Conclusions: Sepsis and requirement for MV are independent predictors of mortality in renal transplant recipients admitted to ICU. Renal transplant recipients with chest sepsis may warrant earlier ICU admission. Any loss of renal allograft function during an episode of critical illness appears to have a lasting effect, and longterm patient and allograft survival is poor.     

Modeling the economic benefit of targeted mild hypothermia in deceased donor kidney transplantation

Delayed graft function (DGF) in kidney transplant significantly increases inpatient and outpatient cost. Targeted, mild hypothermia in organ donors after neurologic determination of death significantly reduced the rate of DGF in a recent randomized controlled clinical trial. To assess the potential economic benefit of national implementation of donor hypothermia, rates of reduction DGF were combined with estimates of the impact of DGF on hospital cost and total health expenditure for standard and extended criteria donor organs (SCD and ECD). DGF increases the cost of the transplant episode by $9487 for ECD transplant and $10 342 for SCD transplant. Medicare recipients with DGF incur an additional $18 513 spending for ECD and $14 948 in SCD transplants over the first year. An absolute reduction in DGF rate after kidney transplantation consistent with trial results (ECD 25%, SCD 7%) has the potential to lower annual hospital cost for kidney transplant by $13 178 746 and annual Medicare spending by $20 970 706 compared to standard donor management practice using static cold storage. Targeted mild hypothermia improves care of renal transplant patients by safely reducing DGF rates in both ECD and SCD transplant. Broader application of this safe, effective, and low‐cost intervention could reduce healthcare expenditures for providers and insurers.     

Outcomes of Pediatric Kidney Transplantation in Recipients of a Previous Non‐Renal Solid Organ Transplant

Children who receive a non‐renal solid organ transplant may develop secondary renal failure requiring kidney transplantation. We investigated outcomes of 165 pediatric kidney transplant recipients who previously received a heart, lung, or liver transplant using data from 1988 to 2012 reported to the United Network for Organ Sharing. Patient and allograft survival were compared with 330 matched primary kidney transplant (PKT) recipients. Kidney transplantation after solid organ transplant (KASOT) recipients experienced similar allograft survival: 5‐ and 10‐year graft survival was 78% and 60% in KASOT recipients, compared to 80% and 61% in PKT recipients (p = 0.69). However, KASOT recipients demonstrated worse 10‐year patient survival (75% KASOT vs. 97% PKT, p < 0.001). Competing risks analysis indicated that KASOT recipients more often experienced graft loss due to patient death (p < 0.001), whereas allograft failure per se was more common in PKT recipients (p = 0.01). To study more recent outcomes, kidney transplants performed from 2006 to 2012 were separately investigated. Since 2006, KASOT and PKT recipients had similar 5‐year graft survival (82% KASOT vs. 83% PKT, p = 0.48), although 5‐year patient survival of KASOT recipients remained inferior (90% KASOT vs. 98% PKT, p < 0.001). We conclude that despite decreased patient survival, kidney allograft outcomes in pediatric KASOT recipients are comparable to those of PKT recipients.     

The Role of Microscopic Hematuria in the Evaluation of Urologic Malignancy in Renal Transplant Recipients

Urologic malignancy is a relatively uncommon but serious complication following kidney transplantation. The reported prevalence of renal cell carcinoma (RCC) of the native kidneys is 4.4% and of bladder malignancy is 2.6%. However, presently there are no universal guidelines for prospective screening of urologic malignancies after kidney transplantation. We routinely monitored all renal transplant recipients for microscopic hematuria and persistent hematuria (>3 separate occasions) results in imaging studies (ultrasound or computed tomography scan) of both native kidneys and the allograft. Cystoscopy is performed if imaging studies are negative. This retrospective study identified a total of 18 urologic malignancies among the study cohort, which consisted of 539 patients with an incidence of 3.3% (12 cases of RCC of native kidneys [10/12 had hematuria], and six cases of bladder and ureteral malignancies [6/6 had hematuria]). There were no significant differences between cyclosporine- and tacrolimus-based immunosuppression (IS). Among RCC recipients, two lost the allograft from chronic allograft nephropathy and one patient died unrelated to malignancy. Among patients with bladder and ureteral malignancies, two lost the graft possibly from IS reduction and one had BK virus nephropathy prior to diagnosis of bladder carcinoma. In conclusion, screening transplant recipients routinely for persistent microscopic hematuria may identify urologic malignancies in renal transplant recipients.     

Growth after renal transplantation

Growth may be severely impaired in children with chronic renal insufficiency. Since short stature can have major consequences on quality of life and self-esteem, achieving a ‘normal’ height is a crucial issue for renal transplant recipients. However, despite successful renal transplantation, the final height attained by most recipients is not the calculated target height. Catch-up growth spurts post-transplantation are usually insufficient to compensate for the retardation in growth that has occurred during the pre-transplant period. Longitudinal growth post-transplantation is therefore influenced by the age at transplantation but also by subsequent allograft function and steroid exposure, both of which interfere with the growth hormone/insulin-like growth factor axis. The management of growth retardation in renal transplant recipients includes adequate nutritional intake, correction of metabolic acidosis, prevention of bone disease, steroid-sparing strategies and a supraphysiological dose of recombinant human growth hormone in selected cases.     

Ramadan fasting in kidney transplant recipients with normal renal function and with mild-to-moderate renal dysfunction

Background  Fasting during Ramadan is prescribed for every healthy Muslim after the age of puberty. However, many patients ask their physicians whether it is safe for them to fast. Aim  The aim of this study was to evaluate the influence of voluntary Ramadan fasting on patients with transplanted kidneys. Methods  We conducted a prospective study on 41 kidney transplant recipients who chose to fast during Ramadan and 41 recipients who had not fasted at five transplant centers in the month of Ramadan (September–October 2007). All 82 recipients underwent transplantation at least 1 year prior to the study, and all had had stable renal function for at least 6 months prior to the study. Results  The mean ages of the fasting and control groups were 42 ± 12 years and 43 ± 12 years, respectively, and the corresponding duration since transplantation was 10–210 (average: 65) months and 11–180 (average: 69) months. Our results showed that estimated GFR did not significantly change during Ramadan for either group (mean estimated GFRs pre- and post-Ramadan were 72.8 ± 27.8 and 73.1 ± 29.3 ml/min in the fasting group, and 73.4 ± 18.8 and 73.1 ± 18.5 ml/min in non-fasters, respectively). In patients with GFR < 60 ml/min, renal function remained stable during Ramadan. Conclusion  The results did not show any adverse effects of fasting, especially on allograft function, in kidney recipients who had normal as well as mild to moderate impaired but stable renal function prior to fasting.     

Flow cytometry-detected IgG is not a contraindication to renal transplantation: IgM may be beneficial to outcome

BACKGROUND: At our transplant center, primary recipients of either a haplo-identical (haplo-ID) living related (LRD) or a cadaveric (CAD) donor renal allograft are transplanted after a negative donor-specific IgG anti-human globulin (AHG) cross-match (XM). Testing included the historically highest panel-reactive antibody and the immediate (0-7 days) pretransplant sera. A positive donor specific IgM-AHG XM has not been a contraindication to transplant. Reports suggest that donor-specific flow cytometry cross-matches (FCXM) may be more clinically informative than the AHG-XM. METHODS: We therefore evaluated the impact of a positive FCXM (IgG or IgM) on the rejection frequency (0-12 months after transplant) and 1-year graft survival for cyclosporine-prednisone-treated primary (haplo-ID and CAD) renal allograft recipients. All transplants were performed after a negative donor-specific IgG AHG-XM regardless of the IgM-AHG XM status. RESULTS: Rejection frequencies (26% vs. 31%, P = NS) and 1-year graft survivals (92% vs. 89%, P = NS) were comparable for haplo-ID LRD FCXM-negative and IgG-FCXM-positive recipients. However, IgM-FCXM-positive LRD recipients experienced significantly fewer rejections (13% vs. 26% P<0.02) and an improved 1-year graft survival (100% vs. 92%, P<0.02) than FCXM-negative LRD recipients. Similar results were observed for primary CAD recipients. Rejection frequencies (40% vs. 44%, P = NS) and 1-year graft survivals (83% vs. 81%, P = NS) were comparable for primary CAD FCXM-negative and IgG-FCXM-positive recipients. Again, IgM-FCXM-positive primary CAD recipients experienced significantly fewer rejections (22% vs. 40%, P<0.02) and improved 1-year graft survivals (89% vs. 83%, P<0.05) than FCXM-negative recipients. CONCLUSION: These data suggest that, after a negative donor-specific IgG-AHG XM, an IgG-positive FCXM is not a contraindication to transplantation. The presence of IgM may be beneficial in reducing the occurrence of rejection episodes and improving graft survivals.     

Hyperuricemia and gout following pediatric renal transplantation

Hyperuricemia and gout are common complications in adult renal transplant recipients. In pediatric recipients, however, hyperuricemia seems to be rare, but data are scarce. Thirty-two children (21 males, 11 females) were investigated for a median time of 4.8 years (range: 0.4–11.2 years) following renal transplantation. The median age of this pediatric study group was 13.9 years (range: 5.7–20.3 years), and the calculated glomerular filtration rate (GFR) was 61 ml/min per 1.73 m² (range:12–88 ml/min per 1.73 m²). All patients were given calcineurin inhibitors, with 22 and ten children receiving cyclosporine A (CSA) and tacrolimus (TAC), respectively. The median plasma uric acid was 385 μmol/l (range: 62–929 μmol/l); 15 children (47%) were above the age-related normal range. Only one patient experienced gouty arthritis. There was a significant correlation between plasma uric acid concentration and both time span after transplantation and plasma creatinine, and an inverse correlation to GFR (p<0.05). No significant correlation was found between plasma uric acid and body mass index (BMI). Plasma uric acid concentrations were neither different among CSA- and TAC-treated children, nor did they correlate with drug exposure or blood trough levels of CSA or TAC. Plasma uric acid concentration was not different when compared to children with chronic renal failure (CRF) of a similar degree in native kidneys. We conclude that hyperuricemia is common among pediatric renal transplant recipients and rather a consequence of chronic renal transplant dysfunction than the use of calcineurin inhibitors. Gout, however, is rare.     

Economic analysis of basiliximab in renal transplantation.

BACKGROUND: Basiliximab is a chimeric monoclonal directed against the alpha-chain of the interleukin-2 receptor. International studies have shown that it is highly effective in preventing acute rejection in patients receiving Neoral, and causes no measurable incremental toxicity, but its economic value remains unknown. METHODS: This study employed an economic model to examine the potential economic benefit of basiliximab. Parameter estimates were derived from a randomized, prospective, double-blind study conducted in 21 renal transplant centers in seven countries in which 380 adult primary allograft recipients were randomized within center to receive basiliximab (20 mg i.v.) on days 0 and 4 or placebo in addition to dual immunosuppression with Neoral and steroids. Key clinical events included primary hospitalization, immunosuppressive drug use, patient and graft survival, graft rejection, treatment of rejection, dialysis, and repeat hospitalization. Health resources were valued via a comprehensive electronic cost dictionary, based upon a detailed economic evaluation of renal transplantation in Canada. Medication costs were calculated from hospital pharmacy acquisition costs; basiliximab was assessed a zero cost. RESULTS: The average estimated cost per patient for the first year after transplant was $55,393 (Canadian dollars) for placebo and $50,839 for basiliximab, rising to $141,690 and $130,592, respectively, after 5 years. A principal component of the cost in both groups was accrued during the initial transplant hospitalization ($14,663 for standard therapy and $14,099 for basiliximab). An additional $15,852 and $14,130 was attributable to continued care, graft loss, and dialysis in the two groups, whereas follow-up hospitalization consumed an additional $15,538 for placebo and $13,916 for basiliximab. The mean incremental cost of dialysis was $5,397 for placebo compared with $3,821 for basiliximab, whereas incremental costs of graft loss were $2,548 compared with $2,295 in the two treatment groups. The principal costs associated with repeat admission to the transplant ward and the general ward were marginally higher for placebo ($7,395 vs. $6,300 and $5,986 vs. $4,625). Treatment of acute rejection and maintenance immunosuppressive drug use were associated with only limited savings as a result of basiliximab (savings <$200 each). Sensitivity analysis indicated that the most influential parameters affecting the savings as a result of using basiliximab were a reduction in the duration of initial and repeat hospitalization followed by the reduced risks of acute rejection and graft loss. CONCLUSIONS: Before accounting for the cost of the therapy itself, basiliximab produces an estimated economic saving of $4,554 during the first year after transplant, of which $3,344 is attributable to the reduced costs of graft dysfunction, including graft loss and dialysis ($1,722) and follow-up hospitalizations ($1,622). When marketed, basiliximab is expected to cost approximately $3,000 per course (two doses of 20 mg), resulting in a net first-year saving of $1,554. Under these circumstances, basiliximab can be considered a dominant therapy in renal transplantation.