Urinary prostaglandin E2 and kallikrein-like activity excretion in renal transplant recipients

We investigated the relationship between urinary prostaglandin E2 (UPGE2), kallikrein (UKal), graft function and complications after renal transplantation in 11 patients. Grafts of 9 patients were from living-related donors (LRD), and other 2 patients were from a cadaveric donor (CAD). UPGE2 was measured by the radio immunoassay, and UKal was measured by the amidolytic method using Pro-Phe-Arg-MCA. The results were as follows. 1. In 5 of 6 patients from LRD without acute rejection episode (ARE), both UPGE2 and UKAL were within normal and/or slightly less than normal. UKal values of the other patient were high in his donor. 2. In 2 of 3 recipients from LRD who experienced ARE, UKal increased prior to ARE. UPGE2 also increased at the time of ARE, but it showed a periodic rise in the stable condition. 3. In 1 of 2 recipients from CAD, UKal exhibited a transient elevation at the time of acute tubular necrosis (ATN) and pyelonephritis while UPGE2 was low. In another recipient, UKal was almost within normal range at the time of ATN, and UPGE2 showed a periodic rise. 4. A significant correlation was seen between UKal, UPGE2 and UAld in the recipients from LRD without ARE (except 1 patient who showed high UKal values). However, the correlation was blurred inclusive of values in the patients who experienced ARE or other complications. There was no relationship between UKal, UPGE2, creatinine clearance, urine volume and urinary sodium. 5. Soybean trypsin inhibitor (STI) was used for the confirmation of specificity of the amidolytic method.(ABSTRACT TRUNCATED AT 250 WORDS)     

Tuberculosis in renal transplant recipients

BACKGROUND: Tuberculosis is an important cause of morbidity and mortality in renal transplant recipients, but there are insufficient data regarding the efficacy and complications of therapy and of INH prophylaxis. METHODS: This study is a retrospective review of the records of 880 renal transplant recipients in two centers in Turkey. RESULTS: Tuberculosis developed in 36 patients (4.1%) at posttransplant 3-111 months, of which 28 were successfully treated. Eight patients (22.2%) died of tuberculosis or complications of anti-tuberculosis therapy. Use of rifampin necessitated a mean of 2-fold increase in the cyclosporine dose, but no allograft rejection occurred due to inadequate cyclosporine levels. Hepatotoxicity developed in eight patients during treatment, two of whom died due to hepatic failure. No risk factor, including age, gender, renal dysfunction, hepatitis C, or past hepatitis B infection, was found to be associated with development of hepatic toxicity. A subgroup of 36 patients with a past history of or radiographic findings suggesting inactive tuberculosis, was considered to be at high risk for developing active disease, of whom 23 were given isoniazid (INH) prophylaxis. None versus 1 of 13 (7.7%) of cases with and without INH prophylaxis, respectively, developed active disease (P>0.05). None of the patients receiving INH had hepatic toxicity or needed modification of cyclosporine dose. CONCLUSIONS: These data show that tuberculosis has a high prevalence in transplant recipients, that it can effectively be treated using rifampin-containing antituberculosis drugs with a close follow-up of serum cyclosporine levels, and that INH prophylaxis is safe but more experience is needed to define the target population.     

Pregnancy in renal transplant recipients

Fertility is restored after renal transplantation when good function is achieved. Our aim was to describe the gestations of our transplanted patients, analyzing outcomes and complications as well as long-term evolution of renal function. From 1976 to 2004, 43 gestations occurred in 35 renal transplanted women: their mean age was 31.7 +/- 4.06 years, with a mean time from the transplant to pregnancy of 4.32 years (0.4-13). At conception, all showed normal renal function (SCr 1.05 +/- 0.2 mg/dL). There were 19 abortions (43.8%), 9 of them spontaneous (21%) and 10 therapeutic (six cases for noncompliance with described criteria of European Best Practice Guidelines for Renal Transplantation, especially pregnancy less than 6 months after transplantation). Excluding these six cases of therapeutic abortions, 24 successful pregnancies occurred in 37 women (65.7%), although eight (29.1%) had premature delivery with live fetuses. Arterial hypertension was the most frequently complication (64%). Preeclampsia occurred in nine (37.5%) pregnancies, with proteinuria in five and only two with mild renal function deterioration. The majority of patients received cyclosporine (n = 20) or tacrolimus (n = 19). Since 1996, mycophenolate mofetil and sirolimus were stopped before conception. Birth weight was lower than 2500 g in 33.3% of pregnancies. Every newborn baby was healthy. Afterward, of the 24 patients with successfully pregnancy, 21 (87.5%) have functioning renal transplants at 53.2 months. After delivery, all currently show good renal function (SCr 1.16 +/- 0.35 mg/dL, CrCl 91 +/- 28.45 mL/m). In conclusion, pregnancy in our renal transplant women shows a success rate of 65.6%. However, complications related to arterial hypertension such as preeclampsia are frequent. The incidence of spontaneous abortions was similar to other series (21%). Long-term graft survival does not seem to be negatively affected by pregnancy.     

Infection in renal transplant recipients

Renal transplant recipients are susceptible to infection by a wide array of pathogens. Impaired inflammatory responses due to immunosuppressive therapies suppress clinical and radiologic findings engendered by microbial invasion. As a result, patients are often minimally symptomatic and evaluation and diagnosis are delayed. Specific microbiologic diagnosis is essential both for the optimization of antimicrobial therapy and to avoid unnecessary drug toxicities. Differential diagnosis is guided by knowledge of organisms commonly involved in infection in immunocompromised hosts and understanding of the limitations of prophylactic strategies. The risk of infection in the organ transplant recipient is determined by the interaction between the individual's epidemiologic exposures and net state of immunosuppression. Epidemiology includes environmental exposures in the community and hospital, organisms derived from donor tissues and latent infections activated in the host during immune suppression. The net state of immune suppression is determined by the interaction of all factors contributing to infectious risk. Routine antimicrobial prophylaxis is aimed at common infections and unique risk factors in individual patient groups. This includes trimethoprim-sulfamethoxazole (for Pneumocystis, Toxoplasma, most Nocardia and Listeria, common urinary pathogens), perioperative (eg, anti-fungal prophylaxis for pancreas transplants), or antiviral (for herpesviruses in high risk recipients).     

Cancers in renal transplant recipients

Data regarding posttransplant cancers are reviewed from the Cincinnati Transplant Tumor Registry (CTTR) and from the literature. The CTTR has data on 9,688 types of cancer that developed in 9,032 renal allograft recipients. The predominant tumors are lymphomas and lymphoproliferations (PTLD), carcinomas of the skin and lips, carcinomas of the vulva and perineum, in situ carcinomas of the cervix of the uterus, Kaposi's sarcoma (KS), hepatocellular carcinomas, renal carcinomas, and various sarcomas (excluding KS). Prominent features of the PTLD cases are their high incidence, frequent involvement of extranodal sites, a marked predilection for the brain, and frequent involvement of the allograft by tumor. Skin cancers also present unusual features, a remarkable high frequency of KS, reversal of the ratio of basal cell carcinomas to squamous cell carcinomas that is seen in the general population, the young age of the patients, the high incidence of multiple tumors (in 44% of patients), and the aggressive behavior of some squamous cell carcinomas. Cancers of the vulva and perineum occur at a much younger age than in the general population and are preceded by a history of condyloma acuminatum in over 57% of cases. Reduction or cessation of immunosuppressive therapy is of value in some patients with PTLD or KS but carries the risk of allograft rejection.     

肾移植后高同型半胱氨酸血症的发生率及其与心脑血管疾病风险因素的关系

目的 心脑血管并发症是肾移植受者(renal transplantation recipients,RTRs)的重要死亡原因,近来证实同型半胱氨酸与脑卒中有密切关系,本研究旨在探讨肾移植受者高同型半胱氨酸的发生率及其与传统心脑血管疾病风险因素的关系.方法 测定120例连续随访肾移植受者的同型半胱氨酸水平,其中男82例,平均年龄(42.5±8.7)岁;女38例,平均年龄(40.2±3.4)岁.同时监测空腹血糖、总胆固醇、甘油三酯、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇、脂蛋白a、尿酸、肌酐、C反应蛋白的数值.结果 高同型半胱氨酸血症的总体发生率为95％,其中男性97.6％,女性89.5％,男女之间无显著差异(P＞0.05);高同型半胱氨酸血症组中脂蛋白a、尿酸、肌酐显著高于正常同型半胱氨酸组,分别为(305±132)mg/L、(406±34.6)μmol/L、(135±14)μmol/L和(221±129)mg/L、(320±51.1)μmol/L、(127±38.2) μmol/L(P＜0.05).Pearson相关分析结果显示,同型半胱氨酸与同时期的肌酐(r=0.832,P=0.013)、尿酸(r=0.263,P=0.005)、脂蛋白a(r=0.754,P=0.003)呈正相关,与总胆固醇(r=-0.197,P=0.036)呈负相关.结论 肾移植受者的高同型半胱氨酸血症发生率高,尤其是男性肾移植受者,与影响移植后心脑血管疾病的传统风险因素并存,可能增加肾移植受者发生心脑血管疾病的风险,提示应在肾移植受者中筛查同型半胱氨酸,及对高同型胱氨酸血症患者进行降同型半胱氨酸治疗的必要性.     

Pregnancy in renal transplant recipients

Most women of childbearing age who receive a renal transplant have a return of normal menses and have the ability to become pregnant. Most studies indicate that pregnancy does not adversely affect the transplant kidney's survival as long as renal function is good and serum creatinine is stable before pregnancy. The experience with immunosuppressive drugs has been surprisingly reassuring with no increase in congenital anomalies with cyclosporine, prednisone, and azathioprine. There is little experience with newer drugs. Pregnant transplant recipients need to be monitored for opportunistic infections, which may adversely affect the fetus, including herpes, toxoplasmosis, and CMV. Hypertension, urinary tract infections, and anemia are other common problems in pregnant transplant recipients. Despite a high frequency of premature births, over 80% of pregnancies result in surviving infants.     

Nocardiosis in tropical renal transplant recipients

BACKGROUND: The epidemiology of nocardiosis in the tropics among renal transplant recipients has not been reported. METHODS: An evaluation of nocardiosis for 30 yr in one of the large transplant centres in South Asian region. RESULTS: Of the 1968 patients who received primary renal allografts at Christian Medical College & Hospital, 27 patients developed nocardiosis over 30 yr. Early nocardiosis (2 yr). Seventeen patients (63%) had two or more associated post-transplant infections, of whom 10 had tuberculosis. Mortality in these patients was associated with chronic liver disease. CONCLUSIONS: Nocardiosis manifests earlier (<2 yr) in CsA treated patients who have chronic liver disease. Among renal transplant recipients of the tropics nocardiosis is a marker of a high susceptibility to tuberculosis and other infections, the association with tuberculosis is stronger in those developing early nocardiosis (<2 yr). Chronic liver disease is a risk factor for death in patients with nocardiosis especially when associated with tuberculosis. This report constitutes the largest single centre experience among renal transplant recipients.     

Tacrolimus-associated hypomagnesemia in renal transplant recipients

BACKGROUND: Since hypomagnesemia occurs frequently in tacrolimus treated patients, we studied the correlation between renal magnesium wasting and tacrolimus blood levels in renal transplant patients. METHODS: Serum magnesium, fractional excretion of magnesium (FEMg), and 24-hour urinary excretion of magnesium were measured in 41 transplant patients and 10 healthy volunteers for correlation with tacrolimus level. RESULTS: Of tacrolimus-treated patients, 43% displayed hypomagnesemia. FEMg (7.42+/-3.59% versus 1.88+/-0.43%) and 24-hour urinary excretion (112.36+/-51.43 mg/dL versus 6.7+/-2.79 mg/dL) were significantly higher among tacrolimus-treated patients than controls. Magnesium replacement did not influence FEMg or 24-hour urinary magnesium excretion. Tacrolimus level was the best predictor of 24-hour urinary magnesium excretion and FEMg. Serum magnesium levels correlated inversely with tacrolimus concentrations and creatinine clearance. CONCLUSION: Hypomagnesemia in renal transplant recipients results from renal magnesium wasting. Tacrolimus levels and renal function impact on the excess renal magnesium excretion. Studies of longer duration are warranted to assess the long-term effects of this early posttransplant hypomagnesemia.     

Anemia in pediatric renal transplant recipients

The aim of this study was to establish the prevalence of anemia in stable pediatric renal transplant recipients and to examine the association of anemia with renal function, immunosuppressants, angiotensin converting enzyme inhibitors, and growth, as well as iron, vitamin B₁₂, and folate stores. This is a cross-sectional study of the 50 renal transplant recipients currently followed at our center. Patient data were collected regarding hematological parameters, growth, medications, renal function, underlying renal disease, delayed graft function, episodes of rejection, and iron or erythropoietin therapy post transplantation. The mean hemoglobin level (Hb) was 110 g/l and the overall prevalence of anemia was 60%, including 30% who were severely anemic (Hb<100 g/l). There was a high rate of iron deficiency (34%) and serum iron was the parameter of iron metabolism most closely associated with anemia. Hb in patients with low serum iron was 90.7 g/l versus 114.4 g/l in those with normal serum iron (P<0.01). Both univariate and multiple linear regression determined tacrolimus dose and creatinine clearance to be significant factors associated with anemia. Tacrolimus dose correlated with a 10 g/l reduction in Hb for every increase of tacrolimus dose of 0.054 mg/kg per day (P=0.001). The dose of mycophenolate was positively correlated with Hb, but this was likely to be confounded by our practice of dose reduction in the setting of anemia. Angiotensin converting enzyme inhibitor use was not associated with anemia. Severely anemic patients tended to be shorter, with a mean Z-score for height of –1.8 compared with –0.9 for those with normal Hb (P=0.02). Anemia is a significant and common problem in pediatric renal transplant patients. Deteriorating renal function is an important cause, but other factors like iron deficiency and immunosuppression are involved. Definition of iron deficiency is difficult and serum iron may be a valuable indicator. Medication doses, nutritional status, need for erythropoietin and iron, as well as poor graft function and growth require systematic scrutiny in the care of the anemic renal transplant recipient.     

Skin infections in renal transplant recipients

BACKGROUND: Skin infection is a frequent complication in renal transplant recipients. The purpose of the study was to acquire long-term, period-specific incidence data on the most commonly occurring skin infections in renal transplant recipients. METHODS: A retrospective analysis was performed using medical records of 134 patients, covering a period between 10 and 29 yr. Cumulative incidences of the skin infections were calculated by counting the infections per patient for different time periods and were expressed as a percentage of the total group of patients. The incidence of the skin infections was determined for different post-transplant time periods. RESULTS: A total of 340 skin infections in 105 out of 134 patients were recorded. Some infections, such as candidal infection, herpes simplex infection, and impetigo were most prominent during the first post-transplant year and did not affect many new patients after the first year. Other infections, such as dermatomycoses, herpes zoster, and folliculitis were also affecting a substantial number of new patients after the first post-transplant year. CONCLUSIONS: This study confirms that skin infections among renal transplant recipients are very common and that the spectrum of skin infections differs according to the post-transplant time period.