Mean Serum Creatinine Values Research Articles

Significance of Protocol Biopsies in Living Related Renal Transplant Recipients

Introduction Subclinical rejection (SCR) in a normally functioning renal allograft may have an impact on long-term graft outcome. SCR detection is best done by protocol biopsies in clinically normal grafts. Methods We evaluated 20 stable living related renal allografts with protocol biopsies on days 7 and 90 posttransplant. SCR when detected was treated with a 3-day pulse of methylprednisolone therapy. The outcomes of these grafts were compared with 63 other clinically stable renal allografts that did not undergo protocol biopsies. Results SCR was observed in 60% of cases. The patients who received antirejection therapy for SCR based on protocol biopsies showed better graft survival and mean serum creatinine values at the end of the follow-up period.

Age-related differences in renal function at onset of renal replacement therapy in chronic kidney disease stage 5 patients

Guidelines for initiating renal replacement therapy (RRT) are based on renal function and not age, so renal function at onset of RRT is expected to be similar across age groups. To evaluate renal function at initiation of RRT across age groups. Observational cross-sectional study. We extracted data for all incident chronic kidney disease (CKD) stage 5 patients (n = 322 064) commenced on chronic dialysis (haemodialysis and peritoneal) and renal transplant in the US from 1995 to 1999 from the US Renal Data Systems (USRDS). Subjects (n = 662) with incomplete data were excluded. The reminder (n = 321 402) were classified into five age groups: 0-19 years; 20-44 years; 45-64 years; 65-74 years; >/=75 years. Mean values of serum creatinine (Cr, mg/dl), creatinine clearance (CrCl, ml/min), body weight (kg) and body mass index (BMI, kg/m(2)) at onset of RRT were computed. Mean daily urinary creatinine excretion per kg body weight (CrCl x Cr/0.07/weight) was also calculated. Progressively lower serum creatinine levels were found in adult patients with increasing age (10.70, 8.56, 7.38 and 6.88 mg/dl in those aged 20-44 years, 45-64 years, 65-74 years, >/=75 years, respectively). CrCl was also lower in the same groups (14.76, 13.38, 11.63 and 11.60 ml/min, respectively). Older patients have a greater reduction in renal function than younger patients at onset of RRT, suggesting a delay in initiation of therapy.

Chromosomal substitution affects the severity of ischemia‐induced acute renal failure in BN and SS rats

This study sought to determine the potential location of alleles in the Brown-Norway (BN/Mcw) genome required for resistance to renal ischemia/reperfusion (I/R) injury. We compared BN/Mcw rats, Dahl S (SS/Mcw) rats and rats derived from these two strains in response to 40 min I/R. SS/Mcw rats were significantly injured as indicated by serum creatinine rising from 0.4±0.1 mg/dl pre-surgery to 3.0 ± 0.6 mg/dl at 24 hours of reperfusion and also histological evidence of tubular damage. In contrast, the rise in serum creatinine values in BN/Mcw was significantly less (0.8 ± 0.1 mg/dl) and there was little evidence of tubular damage. F1 generation rats derived from a BN/Mcw X SS/Mcw were injured to an equivalent degree as parental SS/Mcw rat, regardless of which strain was maternal. We then tested the sensitivity to renal I/R in consomic rat strains derived by introgressing chromosomes of the BN/Mcw rat into the SS/Mcw background. Of 17 consomic rat strains evaluated, 15 manifested substantial injury with mean serum creatinine values ranging between 2.5 and 4.3 mg/dl at 24 hours post surgery. In contrast, two consomic rat strains demonstrated an apparent resistance to renal I/R injury; these were the SS-BN8 and SS-BN5 (BN/Mcw chromosome 8 and 5 on SS/Mcw background). Mean serum creatinine values were 1.4 ± 0.2 and 1.8 ± 0.6 mg/dl at 24 hours post-ischemia, respectively. These data suggest that protection in the BN rat is primarily the result of autosomal recessive alleles likely residing on either chromosome 8 and/or 5 of the BN/Mcw genome.

Improvement in Dyslipidaemia after Switching Stavudine to Tenofovir and Replacing Protease Inhibitors with Efavirenz in HIV-Infected Children

To assess the impact on immunological, virological and metabolic parameters of replacing protease inhibitors (PIs) with efavirenz and replacing stavudine with tenofovir in HIV-infected children. A 48-week prospective evaluation of 28 HIV-infected children, with stable undetectable HIV-1 loads, who were taking highly active antiretroviral therapy (HAART) containing lamivudine, stavudine and a PI. Individuals were randomized to switch PI to efavirenz and stavudine to tenofovir at baseline (Group 1) or at week 24 (Group 2). Patient assessment included: clinical evaluation, viral load, CD4+ T-cell count, fasting blood levels and urine samples. All individuals maintained HIV RNA <50 copies/ml and unchanged CD4+ T-cell count through week 48. In Group 1 individuals, a significant decrease in cholesterol (P < 0.05), cholesterol:high-density lipoprotein (HDL) ratio (P < 0.01) and triglycerides (P < 0.05) was observed 24 and 48 weeks after the switch of HAART. The percentage of Group 1 children with increased cholesterol and triglycerides markedly decreased over the study period (from 43% to 0% and from 36% to 7%, respectively). In Group 2 individuals, unchanged lipids in the 24 weeks prior to the switch of HAART and a significant improvement on cholesterol (P < 0.05), cholesterol:HDL ratio (P < 0.01) and triglycerides (P < 0.05) were observed 24 weeks after the switch of HAART. The percentage of Group 2 children with increased cholesterol and triglycerides markedly decreased 24 weeks after the switch of HAART (from 46% to 7% and from 54% to 0%, respectively). Proteinuria and glucosuria were not detected in any individual. The mean values of serum creatinine, serum phosphorus, serum bicarbonate, estimated glomerular filtration rate, urinary microalbumin/creatinine, alpha-1-microglobulin/creatinine ratio and maximal tubular phosphate reabsorption remained unchanged in both groups. In HIV-infected children, switching PI to efavirenz and stavudine to tenofovir is virologically and immunologically safe, is not associated with renal impairment and provides a significant improvement in lipid profile.

Effect of Amyloidosis on Long-Term Survival in Kidney Transplantation

Amyloidosis is characterized by the accumulation of an amorphous material in various organs and tissues secondary to a variety of inflammatory, immune, infectious, and hereditary diseases. Since 1975, our transplantation team has performed 1470 renal transplantations. Between 1985 and July 2004, among 1159 kidney transplantations, 953 (82.3%) were from living donors and 206 (17.7%) from cadaveric donors. There were 32 recipients (28 men, 4 women; mean age, 31.4 ± 1.7 years; range, 21 to 48 years) with amyloidosis, including, 28 (87.5%) who received grafts from living donors and 4 (12.5%) from cadaveric donors. Amyloidosis was secondary to familial Mediterranean fever in 22 (68.7%) patients and rheumatoid arthritis in 1 (3.1%). The remaining 9 (28.1%) patients had primary amyloidosis. The mean follow-up time was 51.2 ± 5.7 months (range, 2–124 months). Mean HLA mismatch rate was 2.2 ± 1. Twenty-six (81.2%) patients are alive at this time with functioning grafts, and a mean serum creatinine value of 2.1 ± 1.5 ng/dL. The 1- and 5-year patient and graft survival rates were 90.6% and 84.3%, and 81.2% and 68.7%, respectively. We conclude that patients with amyloidosis may undergo kidney transplantation safely expecting outcomes similar to those patients who receive transplantations for other reasons.

Comparison of Long-Term Actual Renal Allograft Survival in Mycophenolate Mofetil and Azathioprine-Based Triple Drug Immunosuppression Protocols

Introduction The use of mycophenolate mofetil (MMF) in renal transplantation results in a 50% lower incidence of acute rejection compared to azathioprine (AZA). However, the graft survival reports are conflicting: the European trial and US database analysis suggest better survival with MMF, an observation that was not seen in the US and tricontinental studies. Methods We retrospectively reviewed our single-center experience (60% African-Americans) comparing the serum creatinine (SCr) values and 3-year actual graft survival with MMF versus AZA-based immunosuppression. Group I included patients transplanted between January 1990 and December 1992 on cyclosporine (CSA), AZA, and steroids; group II subjects, from January 1996 to December 1998 on CSA, MMF, and steroids. We analyzed SCr and all causes of graft losses at 3, 6, 12, 18, 24, and 36 months posttransplantation. Results The patient demographics were similar in both groups as was the mean SCr values at different times. The time-group interaction for SCr, the Kruskal-Wallis test for SCr for different categories (<1.5, 1.5 to 2.0, 2.0 to 2.5, and >2.5 mg/dL) and the all-cause graft loss between the two groups were not significantly different. Conclusion Our results failed to show better long-term actual graft survival despite the 6-year interval between the two groups. These findings agree with the results of the United States and the tricontinental studies. A lower incidence of acute rejection early after transplantation observed with MMF may not always translate into a long-term benefit, possibly due to the influence of nonimmunological factors, such as hypertension, calcineurin inhibitor toxicity, more frequent cytomegalovirus infections, and increased attempts to withdraw steroids using MMF-based protocols.

Effect of Feeding Ammoniated Wheat Straw Treated with Hydrochloric Acid on Blood Biochemical Profile in Growing Male Buffalo (Bubalus bubalis) Calves

An experiment was conducted to study the effect of feeding ammoniated wheat straw treated with HCl on blood biochemical profiles in growing male buffalo (Bubalus bubalis) calves. Twenty-four growing male buffalo calves (one year of age, 88.54±3.81 kg average body weight) were divided into three groups in a completely randomized design on the basis of their body weight. Animals in all the three groups were fed on concentrate mixture. In addition, they were offered wheat straw, ammoniated wheat straw (4% urea at 50% moisture level) and HCI treated ammoniated wheat straw (4% urea at 50% moisture level and HCl added to trap 30% of the NH3 evolved) in groups I, II and III, respectively for a period of 180 days, as per Kearl (1982) for body weight gain of 500 g/d. In all diets, concentrate:roughage ratio was fixed at 50:50 and were made isonitrogenous by adjusting CP levels of conc. mixtures. Blood was collected from jugular vein of each buffalo calf at the beginning and subsequently at two months interval of experimental feeding. Due to urea-ammoniation, the CP content of wheat straw increased from 2.90 to 6.96% and addition of HCl along with urea further increased the CP content to 10.09%. In all the three groups, the mean values of plasma glucose (mg %) and serum globulin (g %), showed a decreasing trend, while the mean value of serum TP (g %), serum A:G ratio, serum urea (mg %), serum creatinine (mg %), serum ALP (KA units), SGOT (units/ml.), SGPT (units/ml), serum T3 and T4 (ng/ml) showed an increasing trend with the advancement of feeding period. The cumulative period mean values of serum TP (6.15 to 6.20 g %), serum albumin (3.07 to 3.18, g %), serum globulin (2.98 to 3.09, g %), serum A:G ratio (1.03 to 1.10), serum ALP (23.15 to 23.63, KA units), serum T3 (1.20 to 1.23 ng/ml) and serum T4 (21.33 to 21.88 ng/ml) were comparable among the groups. The cumulative period mean plasma glucose (mg %) in group III (57.28) was similar to groups I (55.31) and II (59.41), however, the cumulative period mean plasma glucose in group II was significantly (p<0.01) higher than group I. The cumulative period mean serum urea (mg %) in group III (47.34) was significantly (p<0.001) higher than group I (38.38) and II (42.24), which were statistically alike. However, the cumulative period mean serum creatinine values (mg %) in groups II (1.43) and III (1.52) were similar and were significantly (p<0.01) higher than group I (1.24). The cumulative period mean SGOT (units/ml) in groups I, II and III was 91.71, 96.04 and 96.64, respectively. Similarly the cumulative period mean SGPT (units/ml) was 19.00, 19.93 and 20.01 in groups I, II and III, respectively. The cumulative period mean values of SGOT (p<0.05) and SGPT (p<0.001) in groups II and III were similar and were significantly higher than group I. The cumulative period mean serum T3 and T4 values in groups I (1.21 and 21.81), II (1.23 and 21.42) and III (1.20 and 21.33) were comparable. From the present study it may be concluded that feeding of AWS treated with and without HCI to growing male buffalo calves for 180 days had no significant adverse effect on blood biochemical profile. (Asian-Aust. J. Anim. Sci. 2005. Vol 18, No. 2: 185-191)

Limited-Dose Daclizumab Versus Basiliximab: A Comparison of Cost and Efficacy in Preventing Acute Rejection

The purpose of this study was to compare the efficacy and cost of the limited-dose Daclizumab regimen to that of the standard-dose Basiliximab regimen. Two antibody induction regimens were compared in patients aged 18 years and older who received renal transplants from January 2002 to September 2003 and completed interleukin (IL)-2R antibody induction with standard-dose Basiliximab (20 mg × 2 doses) or limited-dose Daclizumab (1 mg/kg × 2 doses). The primary outcome measure was the incidence of acute rejection. Secondary outcomes included cost, changes in serum creatinine level, and delayed graft function. Of the 46 patients randomized, 42 patients completed the 6-month follow-up. Mean serum creatinine level at time of discharge was originally higher in the limited-dose Daclizumab group than the standard-dose Basiliximab group (1.89 vs 1.57, respectively). By 1, 3, and 6 months, mean serum creatinine values were similar between both groups, with a trend toward lower mean serum creatinine values in the limited-dose Daclizumab group. The incidence of acute rejection was also similar between the groups (6% vs 7%). The average cost difference between the 2 regimens was approximately $715. This study suggests that a limited-dose Daclizumab regimen may be an efficacious and less costly alternative to the standard-dose Basiliximab regimen for antibody induction therapy following renal transplantation.

Renal artery stenosis in hypertensive patients with antiphospholipid (Hughes) syndrome: outcome following anticoagulation

We have demonstrated a point prevalence of 26% renal artery stenosis in patients with antiphospholipid syndrome (APS) and uncontrolled hypertension. We describe the effect of anticoagulation on blood pressure control and renal function. We studied 23 patients retrospectively with renal artery stenosis (RAS). Fourteen received oral anticoagulation for more than 1 yr (target International Normalized Ratio (INR) of 3.0-4.5). Five patients had primary APS. Patients were divided into two groups based on their INR (< 3.0 and > or = 3.0). Nine patients had repeat magnetic resonance angiography (MRA) or an angiogram of the renal arteries after 2 yr. Only 8/14 patients managed to maintain their INR > or = 3.0 (median INR 3.1, range 2.8-3.7) while six had a INR < 3.0 (median INR 1.9, range 1.2-2.4). Patients with a median INR < 3.0 had poorly controlled blood pressure and there was significant deterioration in mean serum creatinine values (Wilcoxon's test, P < 0.03). Nine patients underwent follow-up renal artery imaging. Three of nine patients with an INR < 3.0 (median INR 1.9) had re-stenosis and a fourth developed bilateral renal artery stenosis. Five patients with INR > or = 3.0 (median INR 3.1) did not show re-stenosis of the renal arteries; their renal function was stable and blood pressure was well controlled. One other patient with secondary APS (mixed connective tissue disorder) with INR > 3.0 showed recanalization of the stenosed renal artery. Anticoagulation with INR maintained > or = 3.0 helped to control the blood pressure and prevent the progression of renal disease.

Renal transplantation in children with abnormal lower urinary tract

Objective This retrospective study reports the outcomes as well as pre- and posttransplant urologic treatments of renal transplantation for children with an abnormal lower urinary tract (LUT). Methods Between March 1981 and December 2001, 195 children (≤18 years of age) received live-donor kidney transplants. The 15 recipients (14 boys and 1 girl, mean age 13.5 ± 3 years) who had lower urinary tract disorders included posterior urethral valves (PUV) with valve bladder ( n = 12) and neuropathic bladders secondary to meningomyelocele ( n = 3). These children were evaluated by voiding cystourethrogram, cystourethroscopy, and cystometry. The children with PUV were maintained on clean intermittent catheterization (CIC) and a detrusor relaxant at least 3 months before transplantation. Augmentation ileocystoplasty or continent cutaneous diversion were used in three patients. The graft and patient survivals as well as complications in this cohort was compared with a group of children with normal LUT, who underwent renal transplantation during the same period. Results One child died in the early posttransplant period due to rupture of the external iliac artery. Follow-up ranged from 6 months to 16 years (mean = 4.5 years). During the same period the graft and patient survival rates were comparable between the group of children with versus without abnormal LUT. Furthermore, mean serum creatinine and creatinine clearance values were also comparable. The group with an abnormal LUT showed a higher incidence of urinary fistula (3/14) and recurrent UTI and/or bacteremia (4/14). Conclusions Renal transplantation is feasible with good results for children with abnormal LUT. Pre- and posttransplant urologic management is critical for a successful outcome. However these children display a high incidence of urologic and infectious complications.

Methenamine silver staining quantitative digital histochemistry in chronic allograft nephropathy

Renal function and final outcome of renal allografts have been correlated with irreversible damage. This study describes a quantitative histochemical method relying on periodic acid methenamine silver (PAMS) staining of all renal compartments. Among 60 renal allograft biopsies from 43 patients, 15 biopsies showing pure chronic allograft nephropathy were selected to determine PAMS-stained area percentage (SAP), using image analysis with quantitative histochemistry. Of the 15 cases, 9 (60%) were grade I and 6 (40%) were grade II chronic allograft nephropathy (CAN). The mean serum creatinine (sCr) value was 1.86 ± 0.47 for allograft biopsies. The mean (±SD) SAP for the implantation biopsies was 10.58 ± 1.87%, and for allograft biopsies 25.26 ± 9.67 ( P << .000). The serum creatinine (sCr) values for grade I versus II CAN were 1.63 ± 0.24 versus 2.20 ± 0.54 mg/dL, respectively ( P = .019), and SAP values were 18.97 ± 0.24 versus 34.7 ± 5.89 ( P = .003). There was a strong positive correlation between sCr values and SAP ( P = .005; r = 0.64). These findings show the PAMS approach to be a useful alternative method for reflecting damage in more than one compartment of the renal tissue. Also, the method can discriminated implantation and allograft biopsies as well as grade I and II CAN cases. The series is small for a multivariate analysis of the value of SAP measurements in PAMS-stained sections as a prognosticator, but the data support its use.

Clinical Use of Caspofungin in Immunocompromised Children: A Multicenter Survey.

Background: Caspofungin (CAS) is a novel echinocandin, which is approved for several antifungal indications in adults. Although the compound is not licensed in pediatric patients (pts), it is being used in children with refractory infections or intolerance to standard antifungal agents.Methods: We conducted a multicenter retrospective survey to obtain data on clinical use, safety, and outcome in immunocompromised pediatric pts who received therapy with CAS.Results: The survey identified 71 immunocompromised children and adolescents [mean age (range) 11.4 years (5 months –26 years)]. Out of the 29 females and 42 males, 53 suffered from hematological malignancies, 10 from bone marrow failure syndromes, 3 from solid tumors, 2 from congenital immunodeficiency, and 3 from non-malignant hematological disorders. Forty-two pts (59%) had undergone allogeneic blood stem cell transplantation, and 36 pts (51%) had an ANC of less than 500/μL at baseline. CAS was administered for proven (n=18), probable (15), and possible (20) invasive fungal infection, or as empirical antifungal treatment (18). All but one pt had received prior systemic antifungal therapy with amphotericin B (52) and/or triazoles (41). The 71 pts received CAS for a mean duration of 43.5 days (range, 2–218) as single agent (22) or in combination with other antifungal agents (49). The mean maintenance dosage of CAS was 1.2 mg/kg (range, 0.4–2.9) or 34.8 mg/msqu (range, 16.3–57.5). In none of the pts, CAS was discontinued prematurely due to clinical or laboratory adverse events. Clinical adverse events were described in 35 children (49%), mostly fever (28), nausea and vomiting (18), diarrhea (8), and headache (5). Increases in hepatic or renal function parameters were frequent in these pts that received multiple other therapeutic compounds. Whereas at the end of treatment (EOT), mean GPT and GOT were slightly elevated (from 41 at baseline to 61 U/L at EOT; p=0.002 and from 29 to 80 U/L, p=0.001, respectively), mean serum creatinine, bilirubin, and alkaline phosphatase values were not different from baseline. Complete responses, partial responses, or stabilization were observed in 4/8/3 of 18 evaluable pts with proven, in 4/2/3 of 13 pts with probable, and in 3/8/2 of 15 pts with possible invasive fungal infection. Of 16 evaluable pts who received CAS empirically therapy, 10 successfully completed therapy. Overall survival was 74% at EOT and 67% at three months post EOT (65 and 60 evaluable pts, respectively).Conclusions: The data of this retrospective survey show that CAS displays acceptable safety and tolerance and may have useful antifungal efficacy for second line treatment of severely immunocompromised pediatric patients.

SIX MONTHS RESULTS OF ENTERIC-COATED MYCOPHENOLATE SODIUM (EC-MPS) IN DE NOVO HEART TRANSPLANT PATIENTS SHOWED EXCELLENT EFFICACY AND SAFETY.

O413 Aims: Enteric-coated mycophenolate sodium (EC-MPS, myfortic®) is a novel formulation designed to release MPA in the small intestine, and therefore to improve the GI tolerability of mycophenolic acid (MPA). EC-MPS 720mg b.i.d. has earlier been shown to be therapeutically equivalent to mycophenolate mofetil (MMF) 1000mg b.i.d. in de novo kidney recipients (M. Salvadori et al. Am J Transplant 2004; 4: 231-236). In this study the primary objective was to investigate the incidence of biopsy proven and treated acute rejection, graft loss or death of EC-MPS compared with MMF during the first six months of treatment in de novo heart transplant recipients. Secondary objectives were to investigate the overall safety and tolerability and to compare other defined variables of efficacy and safety at 6 and 12 months. Methods: In a single-blind, multicenter trial, a total of 154 de novo heart transplant patients were randomized to either EC-MPS 1080mg b.i.d. or MMF 1500 mg b.i.d. Male or female cardiac patients aged 18-65 undergoing primary heart transplantation treated with Neoral® and corticosteroids as basic immunosuppression were eligible. Six month data were previously presented: Baseline patient characteristics between groups were similar, 87% vs 80% males, 95% vs 96% Caucasians, mean age 53 vs 50 years, (donors: mean age 30 vs 34 years) in the EC-MPS and MMF groups, respectively. The donor sex distribution was statistically significant (32% vs 16% females). Results: The primary efficacy variable, i.e. the rate of treatment failure, defined as treated and biopsy proven acute rejections (BPAR), graft loss or death at 6 months was similar for the two treatments: The incidence rates of treatment failure considering follow up events were 50.0% for EC-MPS and 51.3% for MMF (difference -1.3, with 95% CI -17.1, 14.5) considered non-inferior to MMF based on 15% upper confidence limit; death: 3.8% vs 5.3% for EC-MPS and MMF, respectively. The overall safety profile was similar for both groups; mean serum creatinine values obtained throughout the study were comparable; mean values after 6 months were 125 umol/L (EC-MPS) and 130 umol/L (MMF) and almost unchanged from baseline values (EC-MPS: change -6; MMF: change +4). Conclusions: Previously reported 6-month results showed that EC-MPS was therapeutically similar to MMF in de novo heart transplant recipients showing excellent efficacy and safety; one year data will be presented.

NEW MARKER FOR THE EARLY DIAGNOSIS OF NEPHROPATHY ASSOCIATED WITH TYPE II DIABETES MELLITUS

In this study the relationship between values of serum cystatin C or serum creatinine and prognostic stages of type II diabetic nephropathy was determined. Blood samples from 87 patients with type II diabetes were obtained from Nephrology Department, Zagazig University Hospitals, Zagazig, Egypt. Patients were categorized into five stages as follows: stage I, stage II, stage IIIa, stage IIIb, and stage IV according to the concentration of albumin in their 24 hours urines. The values of both serum cystatin C and creatinine were measured. It was found that, the mean levels of serum cystatin C in stage IIIb, were significantly higher than those in stages I or II (p < 0.00001/ p < 0.0005 respectively). The mean values of serum cystatin C in stages III, and IV were also significantly higher than those in stage I (p < 0.00001). However, the mean values of serum creatinine in stage IIIa, were not significantly higher than those in stages I or II. The values of serum creatinine in stages III, and IV were significantly higher than those in stage I (p < 0.00001). The Receiver Operating Characteristic (ROC) plot indicated that, serum cystatin C may be superior to serum creatinine for detecting impaired glomerular filtration rate (GFR). It appears that the values of serum cystatin C may be of value in predicting prognostic stages of patients with type II diabetic nephropathy.

New aspects of posttransplant nephrotic syndrome: clinicopathologic correlations with outcomes

Although posttransplant nephrotic syndrome is frequent, its structural basis and prognosis have not been clearly defined. The biopsy findings of 54 patients with this disorder posttransplant, among 375 total renal transplant recipients engrafted during a 10-year period, were correlated with clinical follow-up data. The mean patient age was 41.7 ± 12.3 years, female/male ratio 22/32, and cadaveric/living-related donor ratio 37/17. The nephrotic syndrome developed 3 to 91 months posttransplant. At the onset the mean values of serum creatinine was 2.9 ± 1.8 mg/dL and proteinuria 4.5 ± 0.8 g/d. The index biopsy findings showed chronic allograft nephropathy (CAN) in 33; de novo glomerulonephritis (GN) in 6, recurrent GN in 9, and undetermined GN in 6 who had an unknown primary renal disease. Among 21 follow-up biopsies during a mean of 44.3 ± 28 months the CAN progressed but the GN remained the same. The treatment included augmented steroids alone (n = 1) or in combination with cyclophosphamide (n = 2) and with plasmapheresis (n = 1); angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) along (n = 5); calcium channel blockers (CCB) alone (n = 24); or the two types of drugs together (n = 22). Complete or partial remission was achieved in 8 and 5, respectively, but nephrotic syndrome recurred in 3 of these patients at 45.1 ± 18 months later. Sustained remission was more likely in cases of GN (minimal change disease and IgA nephropathy) and ACEI-ARB treatment (P < .01). Graft failure, which occurred in 35 patients, correlated strongly with serum creatinine at onset, being significantly greater in patients with CAN (P < .005). Both remission of the nephrotic syndrome and graft survival were greater among patients with GN as compared to those with CAN.

Long-term follow-up of pediatric en bloc renal transplantation

We reviewed the outcomes of pediatric en bloc renal transplantation at two Canadian centers in the cyclosporine era. Between 1984 and 2002, 16 patients received pediatric en bloc renal transplants. Mean recipient age and weight were 45 ± 17 years and 72.2 ± 14.4 kg, respectively. En bloc kidneys were procured from donors aged 2.1 ± 0.8 years (range, 0.7 to 4.0), weighing an average of 14.3 ± 2.0 kg (range, 12 to 17). All en bloc kidneys were successfully transplanted without thrombosis. All patients received calcineurin inhibitors and corticosteroids. Only three patients received antibody-based induction therapy. Rejection episodes occurring in seven grafts were all successfully treated. Mean follow-up was 3.7 years (range 0.4 to 15.0). Mean serum creatinine values at 3 months and 1 and 3 years were 138.8 ± 54.5 μmol/L, 118.6 ± 38.1 μmol/L, and 95.1 ± 24.4 μmol/L, respectively. The mean creatinine value of five patients with at least 5 years follow-up was 96.8 ± 12.3 μmol/L. Three-year graft and patient survival rates were 94%. Two deaths with functioning grafts occurred secondary to cardiac and infectious etiologies. None of the grafts were lost independent of death. We conclude that en bloc transplantation has excellent short- and long-term results. Improving graft function after 3 years represented by reduced serum creatinine suggests that these kidneys have excellent renal reserve and growth potential.

Two-year results of multicenter phase III trials on the effect of the addition of sirolimus to Cyclosporine-based immunosuppressive regimens in renal transplantation

Randomized clinical trials conducted over 24 months and including nearly 1300 renal transplant patients compared the efficacy and safety of two dose levels of sirolimus versus azathioprine (United States) or placebo (Global) comparators administered with a cyclosporine (CsA) and prednisone (Pred) baseline regimen. Analysis of 24-month data revealed that patients in the 5 mg/d sirolimus groups experienced a significant delay in the onset and reduction in the incidence of acute rejection episodes compared with azathioprine (Aza) or placebo groups ( P = .02/ P = .001). Graft and patient survival rates and also the occurrence of transplant-related infections, lymphoproliferative disorders, or malignancies were similar among all treatment arms. Between 12 and 24 months, patients treated with 2 mg/d sirolimus displayed relatively stable mean serum creatinine values, namely 1.9–1.8 mg/dL for the US and 1.8–1.8 mg/dL for the Global ( P = NS) studies, which remained higher than those of the comparators. Both 5 mg/d groups showed an increase in mean serum creatinine during this interval, which was significantly higher than the value in both comparators at 24 months. Both sirolimus groups showed persistently elevated triglyceride levels compared with Aza-treated patients at month 24. The Global trial showed a less-pronounced difference in mean fasting triglyceride values compared with placebo. Data from both trials demonstrate that the addition of sirolimus to a CsA-Pred treatment regimen yielded a durable immunosuppressive effect associated with a progressive resolution of adverse side effects over time except for hyperlipidemia, which required continued countermeasure therapy.

Posterior urethral valves: prognostic factors.

To determine which variables besides bladder dysfunction can help to predict the outcome of renal function in boys with posterior urethral valves (PUV). All 40 patients with PUV in this retrospective study were diagnosed and began treatment in our hospital within the first 3 months of life, and have had >or= 5 years of follow-up. At the time of diagnosis, 33 were in renal insufficiency (RI) and seven had normal renal function (RF). At the time of the study 16 were in chronic renal failure (CRF) and 24 had normal RF. We compared their RF (initial and during follow-up), vesico-ureteric reflux (VUR), urinary tract infection (UTI), proteinuria, hypertension, renal echogenicity, final patient age and initial management. The mean serum creatinine values before and after initial treatment were worse in boys who developed CRF than in those who did not (P = 0.08); the mean glomerular filtrate rate (GFR) at 1 year old was 52 mL/min/1.73 m2 in the former and 102 in the latter (P < 0.001). Proteinuria was present during the follow-up in 79% of patients in CRF and in only 17% of those with normal RF. All patients who developed CRF had echogenic renal changes while only 53% of the others had (P < 0.01). Other variables showed no statistically significant differences (VUR, UTI, hypertension and final patient age). Of 33 patients in RI at diagnosis, nine were treated by valve ablation and 24 by temporary pyelo-ureterostomy. The initial mean serum creatinine value was worse in the latter than in the former (20.8 vs 13.0 mg/L). However, at 1 year old the mean GFR was better in the latter than in the former (P < 0.05). These GFR differences persisted during the first years of life but had disappeared by the fifth. The most significant prognostic factor for the future development of CRF is the GFR at 1 year old. The onset of proteinuria during the follow-up is associated with a worse prognosis. Echogenic renal changes may help to identify those dysplastic kidneys that will develop RI. Neonatal boys in RI who underwent pyelo-ureterostomy had better RF during the first years of life than those who underwent valve ablation.

Thymoglobulin, sirolimus, and reduced-dose cyclosporine provides excellent rejection prophylaxis for pancreas transplantation.

We investigated a novel immunosuppressive protocol including thymoglobulin induction in combination with sirolimus and corticosteroids, followed by introduction of markedly reduced exposures to cyclosporine to prevent pancreas-transplant rejection. A 7-day course of thymoglobulin (1.5 mg/kg per day) was begun on postoperative day (POD) 0, together with 15 mg of sirolimus on POD 1, and followed by 5 mg per day, targeting these doses to achieve a trough of 10 to 20 ng/mL. When the serum creatinine was below 2.5 mg/dL, cyclosporine was introduced at 50 mg twice daily with dose adjustment to maintain a trough concentration of 100 to 125 ng/mL. The 18 patients included 14 simultaneous pancreas-kidney and 4 pancreas-after-kidney transplant recipients. Two patients were African-American, three patients had a pretransplant panel reactive antibody greater than 20%, and the human leukocyte antigen (HLA) mismatch was 4.5+/-1 (mean+/-standard deviation). With a mean follow-up of 13.6+/-4.7 months, patient, kidney, and pancreas graft survivals are 100%, 100%, and 94%, respectively. A single pancreas graft was lost to thrombosis. There were no acute rejection episodes and no opportunistic infections. Mean hospital stay was 9+/-3 days. At 3 months posttransplantation, the mean value of serum creatinine was 1.2+/-0.3 mg/dL, fasting glucose was 88+/-15 mg/dL, and sirolimus dose at month 3 was 6.3+/-3 mg per day and at month 12 2.7+/-1 mg per day. The average total daily cyclosporine A dose at month 3 was 208+/-62 mg per day and 133+/-13 mg per day at 1 year. This immunosuppressive regimen provided excellent prophylaxis against acute rejection with no opportunistic infections. We believe that careful monitoring of sirolimus and cyclosporine levels was critical to success of this protocol.

Successful Long-Term Outcomes Using Pediatric En Bloc Kidneys for Transplantation

The objective of our study was to determine whether acceptable long-term graft survival and function can be achieved using pediatric en bloc renal transplants by employing specific immunologic and selection strategies. A retrospective analysis of pediatric en bloc kidney transplants at a single institution was performed. A Kaplan-Meier analysis was used to evaluate graft survival. Fifty-seven adult recipients with at least a 1-year follow-up period were successfully transplanted using pediatric en bloc kidneys between 1993 and 1998. Complete data regarding immunosuppression were available for 53 patients. All patients had a cyclosporine (CsA)- or tacrolimus (TAC)-based regimen with either azathioprine (Aza) or mycophenolate mofetil (MMF) and corticosteroids. All but two received induction with OKT3. One-, 3-, 4-, 5- and 7-year graft survival was calculated to be 88%, 86%, 83%, 68% and 68%, respectively. The mean serum creatinine value at 3 years was 1.0+/-0.4 mg/dL. Thirteen patients (23%) had biopsy-proven rejection. Ten of 19 (53%) patients treated with CsA/Aza had rejection, whereas 2/15 (13%) on CsA/MMF and 1/19 (5%) of patients on TAC/MMF had rejection. Nine patients (16%) had surgical complications. Excellent long-term results can be achieved in pediatric en bloc kidney transplantation using OKT3, TAC and MMF in carefully selected adult recipients.