New-onset diabetes mellitus in cyclosporine-treated organ transplant patients in Taiwan: interim analysis (6 months) of postmarketing surveillance.

Posttransplant new-onset diabetes mellitus (NODM) is an important complication among patients receiving immunosuppressants. It has a considerable impact on chronic allograft dysfunction. Calcineurin inhibitors have been implicated in the development of posttransplant NODM. Since high-risk candidates also undergo transplantation, prevention and control of posttransplant NODM is important. A 3-year postmarketing surveillance study is currently underway in Taiwan to evaluate the incidence and risk factors leading to development of NODM among de novo and maintenance solid-organ transplant patients receiving cyclosporine (CsA)-based immunosuppressive therapy. Concomitant therapy consisted of basiliximab, mycophenolate mofetil or enteric-coated mycophenolate sodium, and corticosteroids. Diabetes was diagnosed according to the American Diabetes Association criteria. This 6-month protocol-defined interim analysis included 101 patients (84 de novo, 17 maintenance) who received renal (n = 77), liver (n = 13), or heart (n = 11) transplantation. At the end of 6 months, 8/101 (7.92%) patients experienced NODM. The mean time to NODM was 3.05 months. No significant difference was observed between NODM and non-NODM patients for risk factors: age, body mass index, blood pressure, gender, high-density lipoproteins/triglycerides hdl/tg, and anti-hepatitis C virus. The composite endpoint of biopsy-proven acute rejection, graft loss, or death was reached in four patients, with a mean time to event of 3.81 months. Infections were noted in 34 subjects but, no malignancies. Among 389 adverse events reported in 91 patients (90.1%), the majority were of mild to moderate severity. Two deaths were reported: heart transplant recipients with acute rejection and cytomegalovirus meningitis with respiratory failure. Long-term enrollment with follow-up evaluation of these NODM patients up to 3 years will help evaluate the NODM incidence rates and exact graft survival and overall survival rates of CsA-treated transplant patients in Taiwan.

Long-term outcomes of living kidney donors over the past 28 years in a single center in Taiwan.

BACKGROUND: The chronic shortage of kidneys for transplantation has increased the number of living donations, but demand remains high, which has created a long waiting list of end-stage kidney disease patients. Donors with decreased renal mass may suffer a higher risk of developing proteinuria, hypertension (HTN), and chronic renal disease (CKD) during long-term follow-up. METHODS: We retrospectively retrieved medical data of living kidney donors at our hospital over the past 28 years. RESULTS: There were 45 male and 60 female donors with a mean donation age of 46.34 ± 12.47 years (range = 20-70y). The mean follow-up duration was 4.67 ± 4.78 years. The serum creatinine (Cr) at donation was 0.93 ± 0.22 mg/dL, while the latest Cr was 1.26 ± 0.45 mg/dL (P < .001). The mean age at follow-up was 50.95 ± 14.57 years. At last follow-up, eight subjects (7.6%) displayed HTN requiring treatment, 10 (9.5%), proteinuria and 55.4%, an estimated glomerular filtration rate (eGFR) of less than 60 mL/min, including one with diabetic nephropathy at 10 years after donation who required long-term hemodialysis. Although gender did not correlate with occurrence of HTN, proteinuria, and CKD, the occurrence of CKD was associated with age at donation (P < .001, odds ratio [OR] = 1.076), and age at follow-up (P < .001, OR = 1.071). HTN donors were older (P = .036, OR = 1.057) with longer follow-up durations (P = .007, OR = 1.166) and had higher Cr values at donation (P = .044, OR = 94.4). Donors with proteinuria were not related to gender, follow-up duration, initial Cr, warm ischemic time, or duration of admission. eGFR was indeed worse after donation (P = .002). CONCLUSIONS: Our results indicated a significant proportion of living donors may develop CKD upon long-term follow-up. The factors affecting donor risk of CKD were baseline renal function, older age, and duration after kidney donation.

Diagnostic performance of serum cystatin C and serum creatinine in the prediction of chronic kidney disease in renal transplant recipients.

BACKGROUND: Chronic kidney disease (CKD) has adverse impacts on mortality and morbidity of renal transplant recipients. Serum cystatin C (sCysC) is a novel marker in predicting the CKD. We therefore compare sCysC and serum creatinine (sCr) with the aim of improving the detection of CKD in renal transplant recipients. METHODS: We enrolled 106 renal transplant recipients and estimated glomerular filtration rates (GFR) using the Cockcroft-Gault (GFR(CG)) and the abbreviated Modification of Diet in Renal Disease (GFR(aMDRD)) formulae. We defined CKD as the presence of structural or functional kidney damage, irrespective of the diagnosis. Comparisons of sCysC and sCr in detecting CKD were analyzed. RESULTS: sCysC correlates with sCr significantly (r = 0.87; P < .001). The receiver operating characteristic curve demonstrates that sCysC has a better specificity and area under the curve, but less sensitivity than sCr in predicting CKD in renal transplant recipients if GFR is estimated by GFR(CG). Additionally, if GFR was estimated by GFR(aMDRD), the role of sCysC or sCr in prediction of CKD was comparable. CONCLUSION: sCysC may be better than sCr to detect CKD in renal transplant recipients using the GFR(CG).

Tumor necrosis factor alpha promoter polymorphism in posttransplantation diabetes mellitus of renal transplant recipients.

Posttransplantation diabetes mellitus (PTDM) is a major complication in renal transplant recipients. Some studies have demonstrated that tumor necrosis factor alpha (TNF-α) expression and its genetic polymorphism are associated with diabetes mellitus. We investigated this association in Asian renal transplant recipients. Polymerase chain reaction-restriction-fragment length polymorphism was used to measure TNF-α G-238A and G-308A gene polymorphisms among 241 nonposttransplantation diabetic subjects and 73 PTDM patients. PTDM patients showed higher values of body weight and body mass index (BMI) than the non-PTDM group. However, no significant association was observed between TNF-α G-238A and TNF-α G-308A polymorphisms with PTDM incidence, gender, age at transplantation, follow-up duration, BMI, or type of immunosuppression.

High incidence of malignancy in polyomavirus-associated nephropathy in renal transplant recipients.

Human polyomaviruses (PV), including JC and BK virus, have been reported to cause polyomavirus-associated nephropathy (PVAN), in renal transplant patients. PV infection has been demonstrated to be associated with malignancies in animals; however, the association between malignancy and viral infections in humans is not clear. We retrospectively reviewed our 864 (M:F=502:362) kidney transplant patients over the past 25 years. We identified PVAN in 6 patients (0.69%), including BK nephropathy (n=5) and JC nephropathy (n=1). Three patients (50%) improved after reducing the immunosuppression, but 3 (50%) progressed to graft loss despite this reduction. Malignancy occurred in 5 out of the 6 patients (83%; P<.0001 compared with patients without PVAN), including transitional cell carcinoma (n=2), renal cell carcinoma (n=1), squamous cell carcinoma of skin (n=1) and Kaposi sarcoma (n=1). We concluded that kidney transplant patients with PVAN are at a significantly greater risk to develop malignancy. Whether this is due to a direct effect of PV infection or the result of overimmunosuppression remains to be determined in a future study.

A Salmonella infection complicated with suppurative thyroiditis and ruptured aortic mycotic aneurysm in a renal transplant recipient.

We report a renal transplant recipient who presented with fever and chills for 2 days. The blood and stool cultures revealed the growth of Salmonella enteriditis. A whole-body gallium scan played an important role in the subsequent diagnosis of suppurative thyroiditis. To our knowledge, this is the first report of acute S. enteriditis thyroiditis in a renal transplant recipient. Despite vigorous antibiotic use and a partial thyroidectomy, he experienced recurrent S. enteriditis infection, resulting in a ruptured thoracic mycotic aneurysm 1 month later. Finally the patient was successfully cured with aneurysm resection, in situ reconstruction of the thoracic aorta, and prolonged antibiotics.

Non-life-threatening leukopenia in a renal transplant recipient with acute overdose of mycophenolate mofetil.

Mycophenolate mofetil (MMF) is increasingly used as an immunosuppressant for organ transplantation and for treatment of autoimmune diseases. As yet, the experience with acute overdose of MMF in humans is limited. Herein we have reported a 40-year-old female kidney recipient with moderate leukopenia and lack of gastrointestinal toxicity following ingestion of 25 g MMF, which was confirmed by serum drug levels. We treated the patient with charcoal decontamination and oral cholestyramine. She recovered completely without sequelae.

Impact of variability of sirolimus trough level on chronic allograft nephropathy.

The efficacy of sirolimus is strictly dose-dependent; an inappropriate exposure may cause either rejection episodes or drug toxicity. The variability of sirolimus trough levels (C0) may also have an impact on renal allograft function. We prospectively evaluated the impact of the dose-normalized C0 of sirolimus and the intrapatient coefficient of variation (% CV) on renal allograft function at 6 months after the administration of sirolimus to kidney transplant recipients with chronic allograft nephropathy (CAN). We enrolled 51 recipients with CAN who were treated with sirolimus. The dose-normalized C0 of sirolimus was 3.8 +/- 1.9 ng/mL/mg. The intra- and interpatient variabilities of sirolimus C0 were 26.1% and 51.9%, respectively. Based on receiver operating characteristic analysis, patients were divided into 2 groups: group I, sirolimus % CV <22.9% (n = 36) versus group II, sirolimus % CV >22.9% (n = 15). Patients in group II experienced significantly greater risk for progressive deterioration of allograft function (group I vs group II: 11.1% vs 73.3%; P < .05). Multiple logistic regression analysis revealed that higher baseline serum creatinine, but not age, gender, or concomitant immunosuppressants, positively correlated with the sirolimus % CV. In conclusion, both higher baseline serum creatinine and higher intraindividual variability of sirolimus C0 impact the outcome of renal allograft function in CAN. Thus, we suggest that close monitoring of sirolimus C0 is necessary for recipients treated with sirolimus, especially for patients with CAN.

Early diagnosis of polyomavirus type BK infection in tailoring immunosuppression for kidney transplant patients: screening with urine qualitative polymerase chain reaction assay.

Polyomavirus type BK (BKV) nephropathy is increasingly a significant cause of graft dysfunction and even failure. Early diagnosis followed by reduction of immunosuppression has been associated with an improved prognosis. We screened 250 patients with the urine qualitative polymerase chain reaction (PCR) for BKV DNA. We followed with blood BKV PCR if the urine screen was positive and then reduced immunosuppression in viremic patients. One hundred ninety-nine patients (80%) had no viuria; 43 (17%) viuria; and 8 (3%) both viuria and viremia. Graft biopsy performed in three patients (1%) with viremia and impaired graft function all revealed BKV nephropathy. After 6 months of follow-up, seven out of eight viremic patients (88%) had negative repeat blood PCR and stabilized graft function. An early diagnosis of BKV infection with reduction of immunosuppression may reverse viremia and retard progression of BKV nephropathy. BKV screening by PCR assays should be considered in kidney transplant recipients, especially those with impaired graft function.

Predictors of renal function improvement following tacrolimus conversion in cyclosporine-treated kidney transplant recipients.

The objective of this study was to evaluate the relationship between variability of cyclosporine (CsA) absorption and tacrolimus (TAC) conversion seeking factors that predict improvement in allograft function after TAC conversion. We performed a retrospective study of 44 adult kidney transplant recipients undergoing conversion from CsA to TAC-based immunosuppression. Before TAC conversion, patients had complete, consecutive, 6 monthly C2 levels and a follow-up duration beyond 6 months after TAC conversion. The patients were divided into 2 groups: one (n=23) with low variability of CsA absorption and one (n=21) with high variability of CsA absorption. At TAC conversion, the estimated glomerular filtration rate (eGFR) was similar in both patient groups. Six months after TAC conversion, eGFR improved in both groups. Stepwise regression analysis revealed the DeltaSCr6 (change in serum creatinine level at 6 months) to be independently associated with the preconversion serum creatinine (SCr; P<.0001) and the percent coefficient of variation (%CV) of SCr (P=.0034). DeltaSCr6 was inversely associated with posttransplantation years (P=.0033), and 6-month TAC blood levels (P=.0053). The DeltaSCr6 was not associated with variability of oral CsA absorption. The cutoff value of baseline SCr at TAC conversion differentiated an increase in or reduction of SCr to be about 1.0 mg/dL. Our study of CsA-treated kidney transplant recipients who underwent TAC conversion showed that a preconversion SCr>1.0 mg/dL, a high variability of SCr, and early TAC conversion predicted greater short-term benefit on graft function.

Lack of hepatotoxicity upon sirolimus addition to a calcineurin inhibitor-based regimen in hepatitis virus-positive renal transplant recipients.

BACKGROUND: We retrospectively analyzed the impact of sirolimus addition (SRL) with a 25% dosing reduction in calcineurin inhibitors on liver function among patients with or without hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. METHODS: Forty-eight renal transplant recipients (HBsAg-positive, n = 5; anti-HCV-positive, n = 7) with allograft dysfunction (serum creatinine: mean 2.7, median 2.0 mg/dL) and normal liver function were enrolled. The duration of the SRL add-on therapy was 8.0 +/- 3.6 months. SRL trough levels were maintained within 6.5 +/- 3.7 ng/mL. The trough levels of tacrolimus and the 2-hour cyclosporine postdose levels were tapered to 4.6 +/- 1.9 ng/mL (24.6% reduction) and 650 +/- 170 ng/mL (24.3% reduction), respectively. SRL-related hepatitis was defined as a rise in liver transferase or alkaline phosphatase or bilirubin over twice the upper limit of normal. Thirty-six HBsAg-negative and anti-HCV-negative patients served as the controls. RESULTS: Hepatotoxicity developed in 6 (12.5%) of the 48 patients and in 3 (8.3%) of 36 control subjects. One (20.0%) of five HBsAg-positive patients (P = .959) and two (28.6%) of seven anti-HCV-positive patients (P = .496) developed hepatotoxicity, respectively. Three (25.0%) of the 12 HBsAg-positive or anti-HCV-positive patients developed hepatotoxicity (P = .420). CONCLUSIONS: Patients with seropositivity of HBsAg or anti-HCV had an insignificantly higher percentage of hepatitis. Use of SRL in the HBV/HCV patients is not contraindicated, but needs monitoring for HBV/HCV activation.

Effect of pentoxifylline on graft function of renal transplant recipients complicated with chronic allograft nephropathy.

BACKGROUND: Chronic allograft nephropathy (CAN) is characterized by a progressive deterioration of renal function with various degrees ofproteinuria. Currently, there is no effective treatment despite the introduction of new generations of immunosuppressants. Pentoxifylline (PTX) is a phosphodiesterase inhibitor that possesses antiproteinuric effect and has been proved to be effective in treating several glomerular diseases. The purpose of the current study was to examine the effect of PTX on renal transplant patients with established CAN. MATERIALS AND METHODS: Renal transplant recipients with biopsyproven CAN were recruited for the study. All the patients had been on angiotensin-converting enzyme inhibitor or angiotensin receptor blocker for more than 1 year and were on a triple immunosuppressive regimen including corticosteroid, calcineurine inhibitor and mycophenolate mofetil. PTX in a dose of 1,200 mg/day was administered for at least 6 months. The following parameters were assessed at baseline, the 3rd and the 6th month post treatment: systolic and diastolic blood pressure, number of anti-hypertension drugs, serum creatinine (sCr),estimated glomerular filtration rate (eGFR), 24-hour urinary protein excretion (U/P), urinary N-acetylglucosaminidase (NAG) and intracytoplasmic Thl/Th2 cytokines production of peripheral blood CD4+ cells. RESULTS: A total of 17 (11 male and 6 female) patients were enrolled in the study. The mean duration of follow-up post transplant was 10.6+/- 4.4 years. The baseline data of sCr, eGFR and U/P were 1.83+/-0.46 mg/dl, 38+/-8 ml/min and 2.65+/-2.15 g/day, respectively. Corresponding values at the 3rd and 6th month post treatment were 1.90+/-0.43 mg/dl (p = NS), 33+/-7 ml/min (p=NS), 2.13 +/-1.13 g/day (p < 0.05) and 2.03+/-0.64 mg/dl (p < 0.05), 32+/-10 ml/min (p < 0.05), 2.74 +/-0.93 g/day (p = NS), respectively. When individual data were analyzed, five cases (29.4%) showed a U/P significant reduction of more than 50% of baseline value, while in 10 cases (58.8%) the graft function remained either stable (9 cases) or improved (1 case) at the end of treatment. Urinary NAG was elevated at the 3rd month, but stabilized thereafter. The Thl/Th2 intracytoplasmic cytokine pattern of peripheral blood CD4+ cells showed a significant decrease of cells bearing TNF-alpha (15.0+/-14.4% vs 14.2+/-17.0%, p < 0.05) and cells bearing IL-10 (1.60 +/-1.23% vs 0.90+/-0.66%, p < 0.05) at the 3rd month. CONCLUSION: In this pilot study, PTX seemed to be temporarily effective in reducing proteinuria. The graft function was stabilized in more than half of patients at the end of follow-up.

Mycobacterium tuberculosis infection following renal transplantation in Taiwan.

BACKGROUND: Tuberculosis (TB) is one of the major causes of morbidity and mortality worldwide. Post-transplant (post-Tx) TB is a problem in successful long-term outcome of renal transplantation recipients. It is a life-threatening opportunistic infection that is frequently encountered, but the diagnosis is often delayed. With the emergence of newer potent immunosuppressive regimens and an increased incidence of TB in the general population, post-Tx TB among transplant recipients can be anticipated. Our objective was to describe the pattern and risk factors of TB infection, and the prognosis in an endemic area. METHODS: This study was a retrospective review of the records of 756 renal transplant recipients in our hospital during the period from January 1983 to December 2003. The demographic data, transplant characteristics, clinical manifestations, diagnostic criteria, treatment protocol, and long-term outcome of this cohort of patients were analyzed. RESULTS: Thirty-one episodes developed into TB in 29 patients (3.8%) with a mean age of 45.5 (range: 24.2-66.2) years and a mean post-Tx period of 57.9 (range: 1.2-145.2) months. The forms of the diseases were pulmonary in 22/31 (71%), disseminated in 1/31 (3%), miliary in 1/31 (3%), and extrapulmonary in 7/31 (23%). All patients initially received 4-drug combination therapy, and then dosage was adjusted based on clinical condition. Because of drug interaction, a mean 2-fold increase in the dose of calcineurium inhibitor, but no change in steroid, was required. Twenty-two patients (71%) had an elevated creatinine (Cr) level, and 6 (19%) patients did not recover owing to tissue-proof acute rejection (3 cases) and chronic allograft nephropathy (3 cases), respectively, after treatment. The serum Cr level on diagnosis of TB was 1.9+/-0.7 mg/dL; it then deteriorated to 2.4+/-1.5 mg/dL (P=0.134). Hepatotoxicity developed in 11 patients (35.5%) during treatment. Twenty-five patients were successfully treated, 2 patients remain under treatment, and 4 (12.9%) died. Based on univariate analysis, we found the post-Tx TB risk factors were diabetes and more than 3 episodes of rejection, modalities for acute rejection (high-dose steroid and anti-lymphocyte globulin), and maintenance therapy with steroid. CONCLUSION: Post-Tx TB is a serious problem worldwide, and a high index of suspicion is warranted to ensure early diagnosis and prompt initiation of treatment for TB among renal transplant patients. The use of optimal immunosuppressive agents to minimize acute rejection seems reasonable to prevent TB infection in endemic areas like Taiwan. More than 9 months of treatment may be necessary to prevent recurrence.

Early experience with enteric-coated mycophenolate sodium in de novo kidney transplant recipients.

INTRODUCTION: We sought to evaluate the efficacy of enteric-coated mycophenolate sodium (EC-MPS) and the gastrointestinal (GI) adverse events in de novo kidney transplant recipients. METHODS: This noncontrolled, retrospective review includes 22 de novo kidney transplant recipients. All patients received a standard course of basiliximab and were maintained on triple-drug therapy with EC-MPS, cyclosporine microemulsion (CsA), and prednisolone. The follow-up lasted 7.9 +/- 1.2 months. The incidence of GI adverse effects were compared with those of historical mycophenolate mofetil (MMF) studies. RESULTS: The serum creatinine was maintained within 1.4 +/- 0.7 mg/dL. The 2-hour CsA postdose level was 1080 +/- 327 ng/mL initially and gradually tapered to 851 +/- 435 ng/mL. The daily EC-MPS dose was 1404 +/- 180 mg initially and gradually tapered to 1098 +/- 288 mg. The GI adverse effects at the daily dose of EC-MPS 1422 +/- 126 mg included dyspepsia 27%, acid regurgitation 18.2%, epigastralgia 9%, nausea 9%, vomiting 4.5%, and poor appetite 4.5%. In comparison those from historical MMF 2 g/d studies included dyspepsia 3.1% to 40%, epigastralgia 10%, nausea 3.7% to 34%, and vomiting 0.6% to 10.7%. CONCLUSION: Immunosuppression with CsA, EC-MPS, and steroids maintains stable graft functions. Minimal dose reduction of EC-MPS decreases GI adverse events but without significance. EC-MPC and MMF have respective GI side effects; they can be used alternatively in patients with individual GI intolerance.

Lethal cytomegalovirus ischemic colitis presenting with fever of unknown origin.

We report a fatal case of cytomegalovirus (CMV) ischemic colitis in a renal transplant recipient. The disease was manifested with fever of unknown origin for 27 days followed by progressive right lower abdominal pain. The clinical condition deteriorated rapidly with development of disseminated intravascular coagulopathy and internal bleeding despite right hemicolectomy and antiviral therapy. The patient died 11 days after the onset of abdominal pain. We conclude that the possibility of CMV ischemic colitis should be suspected if a patient presents with fever and abdominal pain in the early months after transplantation, and that early viral detection by CMV polymerase chain reaction can be lifesaving.

Sirolimus addition is beneficial for renal allograft dysfunction due to simultaneous acute rejection episode and calcineurin inhibitor nephrotoxicity.

We report a diabetic renal transplant recipient who experienced an episode of acute allograft rejection in the 6th month posttransplant when there was an attempt at steroid withdrawal. The acute rejection was steroid resistant. Furthermore calcineurin inhibitor nephrotoxicity was exacerbated by rescue therapy with tacrolimus conversion. The allograft dysfunction ultimately stabilized upon institution of sirolimus and minimization of tacrolimus.

Lamivudine is effective for the treatment of reactivation of hepatitis B virus and fulminant hepatic failure in renal transplant recipients.

Lamivudine is a potent inhibitor of hepatitis B virus (HBV) replication. The aim of this study is to elucidate the effectiveness of lamivudine for the treatment of HBV reactivation with or without fulminant hepatic failure in renal transplant recipients. Forty-two renal transplant recipients (30 men, 12 women) were enrolled onto this study. Eight patients presented with HBV reactivation without fulminant hepatic failure and were administered lamivudine (group I), 5 patients presented with HBV and hepatic failure and were administered lamivudine (group II), 5 patients presented with HBV and hepatic failure but were not administered lamivudine (group III), and 24 patients were asymptomatic HBV carriers who were not administered lamivudine (group IV). Lamivudine was administered at a dose of 100 or 150 mg once daily. A greater prevalence of recent use of a combination of antilymphocyte immunoglobulin (ALG) and methylprednisolone (MP) occurred in patients with hepatic failure (groups II and III) than those without hepatic failure (30% versus 6.3%; P = 0.043). However, there was no significant difference in the incidence of MP use alone (20% versus 25%; P = 0.746). Mortality rates for groups I, II, and III were significantly different (12.5%, 40%, 100%; P = 0.008). One patient in group I died of sepsis without evidence of HBV DNA, even in the terminal event. In group II, 3 of 5 patients (60%) were rescued by lamivudine therapy. In group III, without lamivudine treatment, there was a 100% mortality rate despite intensive plasmapheresis. HBV DNA was not detectable after lamivudine treatment in 7 of 8 patients in group I and 3 of 5 patients in group II. Creatinine levels did not change significantly during lamivudine treatment. Hepatitis B surface antigen and hepatitis B e antigen seroconversion rates after lamivudine treatment were 7.7% and 37.5%, respectively. We conclude that ALG is a potent trigger of HBV-related fulminant hepatic failure in renal transplant recipients, whereas lamivudine is an effective and lifesaving treatment. Prompt use of lamivudine is recommended in renal transplant recipients with evidence of HBV reactivation to prevent catastrophic fulminant hepatic failure.

Evaluation of the severity of traumatic rhabdomyolysis using technetium-99m pyrophosphate scintigraphy.

A quantitative scoring method was designed to assess the extent of muscle damage. Technetium-99m pyrophosphate (99mTc-PYP) scintigraphy was performed for 9 patients experiencing crush injury in the Chichi (Taiwan) earthquake. The magnitude of muscle uptake of 99mTc-PYP was graded as follows: grade 0, less than bone radioactivity (BRA); grade 1, equal to BRA; grade 2, higher than BRA; or grade 3, greatly higher than BRA. The area of muscle injury was estimated according to the rule of nines. The sum of the muscle injury size multiplied by its corresponding grading was defined as the anterior or posterior score according to the anterior or posterior images. Each image was interpreted by two physicians and average anterior and posterior scores were calculated. The muscle score was defined as the geometric mean of the average anterior and posterior scores. Significant correlations were obtained between the muscle score and duration of time trapped (r = 0.868, p < 0.01), peak serum creatine kinase level (r = 0.866, p < 0.01), peak serum phosphorus level (r = 0.877, p < 0.01) and number of hospital days (r = 0.875, p < 0.01). A negative correlation between the muscle score and blood pH (r = -0.706, p < 0.01) was also observed. We concluded that this scoring method may be used as an adjunct for evaluating the locations of trauma and the severity of crush syndrome, and for predicting the duration of hospital stay.

A regulatory region rearranged BK virus is associated with tubulointerstitial nephritis in a rejected renal allograft.

A renal allograft transplant patient with high serum creatinine presented clinical symptoms of rejection. Sections of renal biopsy tissue showed mononuclear leukocyte infiltration in the tubulointerstitium and nuclear enlargement with inclusions in the tubular epithelium. The morphological characteristics resembled polyomavirus-induced interstitial nephritis. Electron microscopy of the nuclear inclusions showed paracrystalline arrays of naked viral particles with a diameter of 45 nm. Molecular studies revealed that a new variant of BK virus (BKV) with rearrangement at the regulatory region was involved in the nephritis. The BKV regulatory region contained a tandem repeat from the P-block to the Q-block causing duplication of several important transcriptional elements or transcriptional factor binding motifs. This is the first report to show a naturally occurring BKV variant with regulatory region rearrangement associated with tubulointerstitial nephritis.