Long-term exposure to irinotecan reduces cell migration in glioma cells.

In spite of considerable research into the therapies for glioblastoma multiforme this tumour type remains very difficult to treat. As well as having a tendency to be inherently resistant to chemotherapy, glioblastoma multiforme also displays local invasion. Cell line studies have a continued and important role to play in understanding the mechanisms associated with both chemotherapy resistance and invasion. In the current study we have utilized the C6 glioma cell line to investigate the response to long-term, clinically relevant application of topoisomerase I and II inhibitors. Treatment with etoposide resulted in an increase in resistance to this topoisomerase II inhibitor. By contrast, the continuous exposure to a topoisomerase I inhibitor did not result in increased drug resistance, but was associated with a reduction in cell migration. This data supports further investigation of topoisomerase I inhibition as a means to inhibit glioma invasion without the development of parallel chemoresistance.

Fluid therapy in pediatric victims of the 2003 bam, Iran earthquake.

INTRODUCTION: On 26 December 2003, at 05:26 hours, an earthquake of magnitude 6.6 (Richter scale) caused a disaster in the Bam region of Southeastern Iran, which had a population of approximately 102,000. In this study, the clinical and laboratory features and therapeutic interventions in pediatric (three months to 14 years) crush victims were analyzed. Determination of the type and amount of fluid therapy for prevention of acute renal failure (ARF) was the main aim of this study. METHODS: The clinical and laboratory data and therapeutic interventions provided to 31 pediatric crush victims were collected. Early and vigorous fluid resuscitation was immediately performed. Resuscitation of the children from hypovolemic shock was initiated by interavenous (IV) administration of normal saline until the signs and symptoms of shock disappeared. For victims with crush injuries, an alkaline intravenous solution, up to 3 to 5 times more than maintenance doses was provided. In this study, there were two groups with decreasing severity of injury: (1) crush injury (CI), with or without ARF; and (2) non-crush injury (Non-CI). According to the above mentioned classification, there were 15 and 16 patients in group I and II, respectively. RESULTS: The mean time spent under the rubble was 2.2 +/-2.5 hours and 0.5 +/-0.5 hours in Groups I and II, respectively. Seventy-five percent of ARF patients (n = 8), were admitted to the hospital the day of the earthquake (Day 0) and the day after earthquake (Day 1). In non-ARF patients (n = 7), 85.7% of the victims were admitted on Day 0 and Day 1. In Group II (ARF and non-ARF), all patients were admitted within three days after the earthquake. Although ARF did not develop in any of the children without CI, it was observed in eight of 15 patients with CI. There was no significant difference between CI with ARF (n = 8) and CI without ARF (n = 7) patients, in terms of the admission date, time of admission, hospitalization duration, and time under the rubble (TUR). Admission SGOTs were significantly different between these two groups. The ratio of the amount of delivered IV fluid (DL) to expected (EX) was based on weight of children was the only fluid therapy parameter in which there was a statistically significant difference between ARF and non-ARF groups. It was 3.6 +/-0.99 in ARF and 4.8 +/-0.74 in Non-ARF group (p = 0.01). CONCLUSIONS: Early intravenous volume replacement may prevent both ARF and dialysis need that may develop on the basis of rhabdomyolysis. In adults, six liters or 12-14 liters of fluids for prophylaxis of ARF in crush syndrome, were suggested. In children, it seems that DL/EX ratio (delivered to expected ratio) is the best marker for evolution of IV fluid therapy in pediatric patients. In children with crush injuries, DL/EX ratio of >4.8 was sufficient for the prevention of ARF.

Feedback control of the neuromusculoskeletal system in a forward dynamics simulation of stair locomotion.

The aim of this study is to employ feedback control loops to provide a stable forward dynamics simulation of human movement under repeated position constraint conditions in the environment, particularly during stair climbing. A ten-degrees-of-freedom skeletal model containing 18 Hill-type musculotendon actuators per leg was employed to simulate the model in the sagittal plane. The postural tracking and obstacle avoidance were provided by the proportional-integral-derivative controller according to the modulation of the time rate change of the joint kinematics. The stability of the model was maintained by controlling the velocity of the body's centre of mass according to the desired centre of pressure during locomotion. The parameters of the proposed controller were determined by employing the iterative feedback tuning approach to minimize tracking errors during forward dynamics simulation. Simultaneously, an inverse-dynamics-based optimization was employed to compute a set of desired musculotendon forces in the closed-loop simulation to resolve muscle redundancy. Quantitative comparisons of the simulation results with the experimental measurements and the reference muscles' activities illustrate the accuracy and efficiency of the proposed method during the stable ascending simulation.

Muscle-driven forward dynamics simulation for the study of differences in muscle function during stair ascent and descent.

The main scope of this study is to analyse muscle-driven forward dynamics simulation of stair locomotion to understand the functional differences of individual muscles during the movement. A static optimization was employed to minimize a performance criterion based on the muscle energy consumption to resolve muscle redundancy during forward dynamics simulation. The proposed method was employed to simulate a musculoskeletal system with ten degrees of freedom in the sagittal plane and containing 18 Hill-type musculotendon actuators per leg. Simulation results illustrated that simulated joint kinematics closely tracked experimental quantities with root-mean-squared errors less than 1 degree. In addition, estimated muscle activations have a good agreement with the salient features of the electromyographic recordings of the major muscles of the lower extremity. Distribution of mechanical power for individual muscles was estimated to elucidate the muscle's contribution to body support and forward progression during stair locomotion. The accuracy and relatively high computational performance of the proposed method make it suitable to generate subject-specific simulations of various activities for individuals with movement disorders in clinical studies.

Offspring-to-mother and husband-to-wife renal transplantation: a single-center experience.

BACKGROUND: It has been demonstrated that graft survival rates of offspring-to-mother and husband-to-wife renal transplants are equivalent to those of other living donors. Although the vast majority of these transplants proceed without incident, hyperacute rejection can result from an anamnestic reaction subsequent to the in utero exposure of the mother to human leukocyte antigen (HLA) of the fetus with sensitization developing during the pregnancy. PATIENTS AND METHODS: Among 1350 renal transplants performed at our center, 12 corresponded to offspring-to-mother (G1) and 9 were husband-to-wife transplantations (G2). All recipients were multiparous (2 to 5 children). We compared these patients with other multiparous women (n = 150) who received grafts from living unrelated donors (G3). RESULTS: Two subjects in G1 (16.6%), two in G2 (22.2%), and none in G3 developed hyperacute rejection, which led to graft loss. One, 3-, and 5-year patient and graft survival rates were different between the remaining patients. CONCLUSIONS: Our limited experience suggested that, for some women, pregnancy is in fact a sensitizing event. A pretransplantation cross-match testing negative result was by no means an absolute guarantee that an adverse anamnestic immunological event would not occur.

Impact of hepatitis B and hepatitis C virus infections on patients and allograft outcomes in renal transplant recipients: a single center study.

BACKGROUND: Hepatitis C virus (HCV) and hepatitis B virus (HBV) infections occur frequently among end-stage renal disease (ESRD) patients. We analyzed our data to address concern that these patients are at increased risk for mortality or allograft dysfunction after renal transplantation compared with noninfected patients. PATIENTS AND METHODS: We retrospectively compared outcomes and survivals among 1350 patients who received renal allografts from 1990 to 2006. RESULTS: Fourteen patients were positive for both hepatitis B surface antigen (HBsAg) and HCV antibody (anti-HCV; group 1); 23 were HBsAg-positive and anti-HCV-negative (group 2); 29 were HBsAg-negative and anti-HCV-positive (group 3); and 1284 were negative for both markers (group 4). With respect to mean serum creatinine, there were significant differences between groups 1 and 4 (P < .01), and groups 2 and 4 (P < .01), but no significant difference between groups 3 and 4. With respect to graft survival, there were significant differences between groups 1 and 4 (P < .01), and between groups 2 and 4 (P < .01). There was no significant difference for survival among groups. CONCLUSIONS: HBV or HCV infections are not a contraindication to kidney transplantation in Iranian patients; they had no effect on patient survival. However, allograft outcomes were worse among HBV- or HCV-infected patients.

Pregnancy after renal transplantation: ten-year single-center experience.

There has been an increase in the number of pregnancies among renal transplant recipients. Our experience included 61 pregnancies in 53 patients from January 1997 to April 2007, with 6 patients having multiple pregnancies. Patients were studied for clinical, obstetrical, and perinatal outcomes. The mean patient age was 24.5 years (range, 19-38). They all received living donor kidneys. The mean transplantation-pregnancy interval was 2.7 years (range, 1.7-5.3 years). Immunosuppressive drugs consisted of cyclosporine (CsA), mycophenolate mofetil (MMF), and prednisolone (pred) in 38 patients (72%); CsA, azathioprine (AZA), plus pred were used in 15 patients (28%). Pregnancy complications were chronic hypertension in 21 patients (40%), anemia in 28 (52.6%), and urinary tract infection in 18 (34%). Twelve patients (22.6%) received blood transfusions. Pre-eclampsia was diagnosed in 14 cases (26.4%) and renal dysfunction in 11 (20.7%) with pre-eclampsia assumed to be the main cause. Three patients (5.6%) had graft losses as a result of hemorrhagic shock, sepsis, and eclampsia. Premature rupture of membranes occurred in 6 cases (11.3%), and preterm delivery occurred in 14 cases (26.4%). Eleven (20.7%) newborns were small for gestational age. One club foot and one large facial hemangioma occurred in 2 infants, respectively. One case of neonatal death was registered as a result of excessive prematurity. One mother died due to sepsis. Cesarean section was performed in 24 patients (45.2%), the main indications being related to hypertension and fetal distress. There were no significant differences between MMF-treated and AZA-treated patients with respect to clinical, obstetrical, and perinatal outcomes. This group of patients was characterized by a wide range of antenatal and perinatal problems that must be managed in specialized tertiary units to achieve the best results. MMF may be as safe as AZA in pregnancy.

Impact of donor/recipient body weight mismatch on allograft outcome in renal transplant recipients.

BACKGROUND: There have been conflicting reports that kidneys from small donors may be at risk for graft loss if they are transplanted into large recipients. The aim of this work was to examine the impact of donor/recipient body weight ratio (D/RBWR) on allograft outcome. PATIENTS AND METHODS: Two hundred and seventeen kidney transplant recipients from living unrelated donor with 5-year follow-up underwent immunosuppression with cyclosporine, mycophenolate mofetil (or azathioprine), and prednisolone. According to the D/RBWR, the patients were divided into 3 groups: low (less than 0.8; G1), medium (0.81-1.1; G2), and high (more than 1.1; G3). We recorded 1-, 3-, and 5-year graft survivals, episodes of acute rejection, and mean serum creatinine values. RESULTS: Among the patients, 126 (58%) were female and the overall mean age was 41.62 years. There were no significant differences in 1-, 3-, and 5-year allograft survivals between the groups. CONCLUSION: We concluded that low D/RBWR had no effect on short- or long-term renal allograft survival.

Renal transplantation in patients with lupus nephritis: a single-center experience.

BACKGROUND: Few data are available about the long-term outcome of renal transplantation in patients with systemic lupus erythematosus (SLE). METHODS: We retrospectively studied all lupus nephritis patients who received kidney allografts in our center between June 1989 and 2006. Patient and allograft outcomes were compared with those of 60 controls. RESULTS: Mean follow-up after renal transplantation was 87 +/- 39 months for patients with lupus and 88 +/- 54 months for controls. Actuarial 10-year patient (83% vs 85%; P = .62) and death-censored graft survival rates (73% vs 69%; P = .36) were not significantly different between lupus patients and controls. Intravascular thrombotic events occurred in 4 patients with SLE (17.4%) and 3 controls (5%; P < .05). Recurrence of lupus nephritis was documented in 1 renal allograft (4.3%). CONCLUSION: Long-term patient and graft survivals were similar in SLE and non-SLE renal transplant recipients. The risk for thrombotic complications was greater among SLE patients.

Anemia among long-term renal transplant recipients.

BACKGROUND: The effects of anemia on cardiovascular disease among the end-stage renal disease (ESRD) population suggest that it may be one of the major factors explaining this complication among kidney transplant recipients. Systematic investigation into the prevalence of posttransplantation anemia (PTA) is therefore of critical importance. MATERIALS AND METHODS: This cross-sectional study of data from 650 patients followed at a single outpatient transplant clinic utilized the guidelines of the American Society of Transplantation to define anemia as a hemoglobin (Hb) < or =130 g/L in men or < or =120 g/L in women. RESULTS: Among the 39% of patients who were anemic, the prevalence was greater in women than in men. Serum Hb concentrations significantly correlated with the glomerular filtration rate (GFR), serum transferrin, the use of angiotensin converting enzyme inhibitors and mycophenolate mofetil therapy. Upon multivariate analysis, the GFR, serum transferrin, potential nutritional markers, chronic inflammation, and iron deficiency were independently and significantly associated with the presence of anemia. Erythropoietin was administered to 15 (5.7%) anemic patients. CONCLUSIONS: PTA is a prevalent, undertreated condition. Based on our results, we suggest that protein/energy malnutrition and/or chronic inflammation were independently associated with anemia.

Renal transplantation in elderly recipients: a single-center experience.

BACKGROUND: Chronic renal failure is a disease of the elderly, who are the fastest growing population of dialysis patients and those waiting for kidney transplantation. The objective of this study was to analyze the results of the renal transplantation among recipients older than 60 years. METHODS: All renal transplant recipients older than 60 years at the time of transplantation were included in the study, which analyzed patient and graft outcomes. RESULTS: Among 1400 renal transplantations 80 patients were at least 60 years old, including 44 (55%) men and an overall mean age 67.3 +/- 5.95 (range = 60 to 72). One-, 3-, 5-, and 10-year patient survivals were 92.25%, 87.79%, 73.56%, and 64.32%, respectively. One-, 3-, 5-, and ten 10-year death-censored graft survivals were 92.11%, 87.71%, 72.32%, and 62.12%. The most common complications were cardiovascular and infectious. CONCLUSIONS: Our single-center results confirmed that transplantation is a good option for renal replacement therapy among patients older than 60 years.

BK polyoma virus nephropathy among Iranian renal transplant recipients.

BACKGROUND: BK virus nephropathy (BKVN) is recognized as a cause of graft loss in renal transplant patients. The disorder may be related to the introduction of new, potent immunosuppressive regimens. We sought to assess the prevalence, outcome, and clinical characteristics of BKVN. MATERIALS AND METHODS: We retrospectively analyzed 160 specimens from episode biopsies. BKVN was diagnosed by light microscopic examination and positive immunohistochemical staining. RESULTS: Among 160 patients, 21 (13.1%) were diagnosed as BKVN. The mean interval between biopsy and transplantation was 13.6 +/- 10.67 months. There were no significant differences between BKVN patients and non-BKVN patients with respect to age, sex, interval between diagnosis and transplantation, cyclosporine blood level, and azathioprine versus mycophenolate mofetil immunosuppression. Graft loss occurred in 57.1% of BKVN versus 12.2% of non-BKVN subjects (P = .005). There was a significant difference between antilymphocyte globulin (ALG)- and non-ALG-treated groups with respect to the incidence of BKVN (6.6% in non-ALG versus 19% in ALG groups; P < .01). BKVN was diagnosed by immunohistochemistry in 61% of specimens with acute rejection according to light microscopic evaluation. CONCLUSIONS: This is the first report of BKVN in Iranian renal allograft recipients. In our hospital, the prevalence of BKVN was higher than that previously reported for non-Iranian recipients. BKVN had a negative impact on graft survival.

Do mechanical fluid laws dictate the branching pattern of the renal artery?

INTRODUCTION: Anatomy of the renal artery is an important issue in the renal transplantation era. Multi-detector computed tomography angiography (MDCTA) is an accurate modality for the preoperative assessment of live renal donors, and it provides excellent details of donor arterial anatomy. We studied the relationship between the angle of emergence of the renal artery from the aorta and its branching pattern. METHODS: In this study, the MDCTA images obtained from the 138 kidneys of 77 potential renal transplant donors were studied. The courses of the right and left renal arteries from the aorta to the kidney hilus were delineated. The branching angle of the renal artery from the aorta (beta, angle) and the length of the renal artery from the aorta until its first division were measured (Delta, distance). The renal artery deviation from the perpendicular plane of the aorta (D, factor of deviation) was calculated by the following formula: D = (1 - sin [beta]). The cosine of this angle (cos [beta]) was also calculated. Statistical analyses were performed with Pearson correlation tests. The P value was set at .05. RESULTS: The mean age of patients was 28.7 +/- 4.3 with a male to female ratio of 63:14. The mean Delta distance and small de, Cyrillic diameter were 34.37 +/- 10.68 mm (range, 10-58) and 6.13 +/- 1.37 mm (range, 2.8-9.9), respectively. The mean beta angle, factor of deviation, and cos (beta) were 62.19 degrees +/- 16.44, 0.15 +/- 0.14, and 0.45 +/- 0.25, respectively. Significant negative correlations were found between the beta angle, and Delta distance (r = -0.308; P < .001), and small de, Cyrillic diameter (r = -0.303; P = .003). Factor of deviation and cos (beta) were directly associated Delta distance and small de, Cyrillic diameter. CONCLUSION: These findings indicated that with the main renal artery axis deviating from the perpendicular plane of the aorta or with a smaller branching angle, this artery had a greater diameter and underwent late branching. This study suggested that the renal artery diameter and branching pattern might be determined by the mechanical fluid laws.

Effect of prophylaxis with low-dose anti-thymocyte globulin on prevention of acute kidney allograft rejection.

INTRODUCTION: During kidney transplantation, the first contact between the recipient's immune system and the donor organ takes place immediately following the arterial anastomosis. The aim of this study was to evaluate the efficacy of a single, low-dose anti-thymocyte globulin (ATG) prophylaxis in the reduction of early acute rejection in renal allograft recipients. METHODS: In a randomized, controlled clinical trial, we studied the rate of acute rejection within the first month of kidney transplantation in patients who had received their transplant at a single center between the years 2004 and 2007. The patients were divided into 2 groups: group 1 (n = 37) received cyclosporine, mycophenolate mofetil or azathioprine, and prednisolone; group 2 (n = 31) received the above-mentioned agents plus a single ATG bolus (Thymoglobulin; SangStat, Lyon, France; 4-5 mg/kg) the night before the transplantation ( approximately 12 hours before the operation). Blood urea and serum creatinine levels were measured regularly in the posttransplantation period. Acute allograft rejection was justified clinically and/or pathologically. Statistical analysis was performed by SPSS 13.0 using Student t test and Fisher exact test. A P value < or = .05 was considered to indicate statistical significance. RESULTS: There were no significant differences regarding the age and gender ratio between the 2 groups. Acute allograft rejection was found in 32.4% (n = 12) of group 1 patients, and was reduced to 12.9% (n = 4) in group 2 (P = .05). Hence, the first-month acute rejection episodes decreased by approximately 60% with ATG prophylaxis in renal transplant recipients. CONCLUSION: Prophylactic administration of a single and low-dose ATG the night before kidney transplantation could reduce the risk of acute allograft rejection in renal transplant recipients. However, further studies with a greater number of patients should be conducted to confirm these results.

Transplantation of a kidney with a renal cell carcinoma after living donation: a case report.

Transmission of cancer is a serious risk in organ transplantation. We present a case of renal cell carcinoma (RCC) in a kidney obtained from a living donor. A 48-year-old mother was evaluated for donation to her 12-year-old daughter. Donor renal ultrasound, intravenous pyelography, and angiography were normal. A 5 x 5 mm nodule found on the surface of the kidney during harvesting was totally excised before transplantation. The histology revealed RCC with free margins at 2 weeks after transplantation. The immunosuppressive drugs consisted of cyclosporine, mycophenolate mofetil, and prednisolone. The graft function remained stable. Donor and recipient are without evidence of tumor recurrence at 15 months after transplantation. This experience indicated that donor kidneys with small, incidental RCC may be managed with excision and transplantation, without tumor recurrence in recipients who are informed of the potential risks of recurrence and metastases.

Serum T-lymphocyte cytokines cannot predict early acute rejection in renal transplantation.

Despite numerous studies, the precise role of Th1/Th2 cytokines in acute renal allograft rejection remains unclear. To provide insight into the role of cytokines in acute allograft rejection, we measured serum T-cell cytokine concentrations for correlation with clinical events after renal transplantation in adults. Serum Th1 (interleukin-2 [IL-2] and interferon-gamma [IFN gamma] and Th2 (IL-4, IL-10) cytokine concentrations were measured in 60 consecutive living donor kidney transplant recipients namely, 40 males, overall mean age 38.82 years), on the day before as well as 7 and 14 days posttransplantation using ELISA. Patients were stratified based upon acute rejection episode (ARE) in the first month after transplantation. Immunosuppression consisted of cyclosporine, mycophenolate mofetil, and prednisolone. ARE was diagnosed based on an increased plasma creatinine of more than 50%, sonographic analysis, radioisotope scan, pathologic findings, or measured cyclosporine blood levels. Twelve ARE were diagnosed among patients (20%). There was no significant difference between the 2 groups with respect to the mean serum concentration values of IL-2, IL-10, IL-4, and IFN gamma on the day before or 7 or 14 days after transplantation. This study showed that there was no correlation between the Th1/Th2 serum cytokine profiles and early ARE in living donor kidney transplantation.

Seroprevalence of human herpes virus-8 in renal transplant recipients: a single center study from Iran.

The long-term risk of malignancy among renal transplant patients is approximately 100 times that of the general population. Unlike North America and many European countries, Kaposi's sarcoma is the most common cancer after renal transplantation in most series reported from the Middle East. Human herpes virus-8 (HHV-8) has a major role in the pathogenesis of Kaposi's sarcoma. The risk of posttransplantation Kaposi's sarcoma is 23% to 28% among seropositive patients compared with 0.7% among seronegative patients. This study was conducted to investigate the seroprevalence of HHV-8 among our transplant recipients. The sera from 100 renal transplant recipients were examined by indirect immunofluorescence against latent nuclear antigen. Sixty of 100 patients were males. The overall mean age was 41.1 years (range, 17-74 years) with 17 patients older than 55 years. The mean transplantation duration was 41.6 months. Twenty-five percent of patients were seropositive for HHV-8. There was statistically significant seropositivity for HHV-8 among recipients older than 55 years (P=.02). Eight of 17 patients older than 55 years were seropositive (47%), whereas 17/83 patients younger than 55 years were seropositive (20%). There were no significant differences for HHV-8 seropositivity regarding sex, transplantation duration, and immunosuppressive regimen, including dose of immunosuppressive drugs and cyclosporine blood levels. In this study, we showed seropositivity for HHV-8 among a significant percentage of our renal transplant recipients, a finding which may render them at risk to develop Kaposi's sarcoma. Seropositive and seronegative patients were followed for 16 months. One HHV-8 seropositive patient (1/25) developed Kaposi's sarcoma.

Tuberculosis in Iranian kidney transplant recipients: a single-center experience.

INTRODUCTION: Renal transplantation recipients are at a high risk of developing tuberculosis (TB) following transplantation, especially in developing countries, with high incidences of morbidity and mortality. In this report, we examined the risk factors and impact of TB on the outcome of kidney transplantation. PATIENTS AND METHODS: Among 1350 living donor Iranian kidney transplantations, 52 (3.9%) had TB diagnosed in various organs. Of these, 7 (13.5%) had TB pretransplantation and 40 (76.9%) were men. The overall mean age was 32.6 +/- 10.5 years. RESULTS: The interval between transplantation and diagnosis was 54.6 +/- 48.23 (range 4 to 140) months. In 34 (65.6%) patients TB was diagnosed after the first year posttransplantation. Pleuro/pulmonary TB was the most common form (68%). All posttransplant TB patients received a quadriple antituberculosis therapy; pyrazinamide, rifampicin, ethambutol, and isoniazide). Hepatotoxicity was seen in 16 (30%) patients, including 12 mild cases with normalization after temporary withdrawal of isoniazide and rifampicin, and four were severe, but mortality was not attributable to hepatocellular failure. Twelve patients (23%) died. Chronic allograft dysfunction occurred in 34 (65%) patients, 19 (37%) with graft loss. Pre-TB patients showed comparable posttransplant courses. CONCLUSION: TB is a common infection among renal transplant recipients in developing countries. The peak incidence is after the first year of transplantation and mortality is considerable. Hepatoxicity is a considerable risk of treatment, possibly as a result of additive toxic effects of immunosuppressive drugs. Chronic allograft nephropathy is a serious complication that has a negative impact on the graft survival.

Low-dose versus high-dose cyclosporine induction protocols in renal transplantation.

BACKGROUND: Current immunosuppressive therapies are effective to prevent acute rejection episodes (ARE) and graft loss following renal transplantation. Newer agents now make it possible to develop equally efficacious but better tolerated, less toxic strategies. We compared the efficacy of early low- versus high-dose cyclosporine (CsA) induction therapy in living donor renal transplantation. METHODS: In this single-center study, 90 consecutive recipients of living donor kidney transplants between November 2002 to October 2003 including 51 females and mean average age of 48.23 years were treated with either CsA (5 mg/kg/d) plus mycophenolae mofetil (MMF; 30 mg/kg/d) and prednisolone (1 mg/kg/d; group 1; n=42); or CsA (8 mg/kg/d) plus MMF (30 mg/kg/d) and prednisolone (1 mg/kg/d; group 2; n=48). The 2 groups were matched with respect to age, sex, underlying renal diseases, pretransplantation dialysis period, number of transplantations, and panel-reactive antibody tests. CsA dose tapering was initiated in the 2 group 3 months after transplantation. At the end of the first year, the CsA dose was 3.5 +/- 0.65 mg/kg in group 1 and 3.4 +/- 0.34 mg/kg in group 2. Prednisolone was tapered within the first 2 months, reaching 10 mg/d in all patients. The MMF dose remained unchanged. The 2 groups were compared with respect to ARE, patient and graft survivals, and clinical outcomes within 2 years after transplantation. RESULTS: There were no significant differences between the 2 groups with respect to clinical outcomes, including 2-year patient survival (97.62% vs 97.92%; P=.76), 2-year graft survival (80.32% vs 80.41%; P=.82), ARE (47.61% vs 52.08%; P=.09), or length of immediate postsurgical hospital stay, number of readmissions, total hospitalization days, posttransplantation diabetes mellitus, and infectious, cardiovascular, gastrointestinal, and hematologic complications. There was more hypertension (67.5% vs 50.23%; P=.007), hypertriglyceridemia (45.5% vs 32.64%; P=.005), and elevated liver enzymes in group 2 (12.5% vs 7.14%; P=.018). CONCLUSIONS: Compared with 8 mg/kg CsA induction therapy, the lower doses of CsA were effective, well tolerated, and safe with relatively fewer side effects.

Antineutrophil cytoplasmic antibody-associated glomerulonephritis in chronic graft-versus-host disease after allogenic hematopoietic stem cell transplantation.

Graft-versus-host disease (GVHD) is one of the most frequent complications that occur after hematopoietic stem cell transplantation (HSCT). Recently, renal involvement, including membranous nephropathy, focal segmental glomerulosclerosis, and minimal change disease, has been described as a manifestation of chronic GVHD. This case report describes a patient who developed antineutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis after HSCT. Following preparation with chemotherapy, a 29-year-old man with chronic myeloid leukemia underwent allogenic peripheral blood stem cell (PBSC) transplantation, after which first acute and then chronic GVHD developed. Treatment with prednisone resulted in improvement in the patient's GVHD. After the termination of steroid therapy and about 10 months after PBSC transplantation, nephritic syndrome appeared and the patient's serum creatinine value increased to 1.7 mg/dL. Laboratory evaluation revealed perinuclear antineutrophilic cytoplasmic antibody (p-ANCA) in the serum. Histological examination of renal biopsy tissue showed focal segmental proliferative glomerulonephritis with glomerulosclerosis in 20% of available glomeruli, large cellular crescents in 6% of glomeruli, and no staining of immunoglobulins or complement along the capillary walls. Electron microscopy revealed no immune deposits. After treatment with prednisone 60 mg/d, diltiazem 120 mg/d, and enalapril 10 mg/d, the proteinuria gradually decreased, and p-ANCA was undetectable. These findings suggest that in this patient the ANCA-associated glomerulonephritis was associated with renal involvement that occurred during the course of chronic GVHD.