Pulmonary sarcomatoid carcinoma in a renal transplant recipient.

Sarcomatoid carcinomas (SC) are rare malignancies with concomitant occurrence of both carcinomatous and sarcomatous components. Although it may occur throughout the body, lungs are only very rarely involved. We present the first documented case of pulmonary SC (PSC) in a renal transplant recipient, and discuss clinical presentation, diagnostic procedures, treatment, and outcome.

Pain in the left ear as the presenting symptom of acute myocardial infarction in a renal transplant recipient.

Chest pain is the main presenting symptom in patients with acute myocardial infarction. However, many patients present with atypical symptoms, which may delay proper diagnosis and treatment. We present the first documented case of pain in the left ear as an atypical presentation of acute myocardial infarction 5 days after renal transplantation.

Renal transplantation in the Roma ethnicity-do all patients have equal chance for transplantation?

Racial and ethnic disparities exist in access to kidney transplantation worldwide. The Roma people are often socially deprived, uneducated, and unemployed. We investigated all dialysis centers in Croatia to determine number of Roma people on dialysis as well as their access and reasons for eventual failure to enter the waiting list. There are 9463 registered Roma people in Croatia, however, the estimated number reaches 40,000. Twenty-five Roma patients required renal replacement therapy, giving a prevalence of 830 per million people (pmp), compared with 959 pmp among the general population. Average age at the start of dialysis was 29 vs 67 years; waiting time to kidney transplantation was 48.9 vs 53.5 months; mean age at the time of transplantation was 33.18 vs 48.01 years in Roma versus the general population respectively. One patient received a kidney allograft from a living unrelated spousal donor, and all others from deceased individuals. Patients were followed for 51.5 months (range, 6-240). The most frequent post-transplant complications were urinary tract infections. One patient lost a graft due to severe acute rejection caused by noncompliance. Two young patients were also noncompliant with immunosuppressive medications. One patient died with a functioning graft at 20 years after transplantation due to cardiovascular disease. Among 14 Roma patients currently been treated with hemodialysis in Croatia, 10 are old with clinical contraindications for transplantation; 1 is on the waiting list; 1 left hospitalization for pretransplant evaluation twice; 1 refused evaluation; and 1 is currently being evaluated for the waiting list. The Roma people have excellent access to renal transplantation in Croatia. Many of them refuse evaluation. More efforts should be invested in their education to improve compliance and their post-transplant outcomes.

Muon-spin rotation measurements of an unusual vortex-glass phase in the layered superconductor Bi2.15Sr1.85CaCu2O8+δ.

Muon-spin rotation measurements, performed on the mixed state of the classic anisotropic superconductor Bi(2.15)Sr(1.85)CaCu(2)O(8+δ), obtain quantities directly related to two- and three-body correlations of vortices in space. A novel phase diagram emerges from such local probe measurements of the bulk, revealing an unusual glassy state at intermediate fields which appears to freeze continuously from the equilibrium vortex liquid but differs both from the lattice and the conventional high-field vortex glass state in its structure.

Epoetin theta: efficacy and safety of subcutaneous administration in anemic pre-dialysis patients in the maintenance phase in comparison to epoetin beta.

OBJECTIVE: To compare the efficacy and safety of epoetin theta and epoetin beta in anemic patients with chronic kidney disease (CKD) not yet receiving dialysis and previously on stable maintenance therapy with epoetin beta. METHODS: In this multicenter, randomized, controlled, double-blind, non-inferiority study, 288 patients were treated subcutaneously (s.c.) for 24 weeks with epoetin theta (n = 193) or epoetin beta (n = 95). The primary efficacy endpoint was change in hemoglobin (Hb) from a 2-week baseline period to end of treatment (12-week efficacy evaluation period [EEP], weeks 15-26). The non-inferiority limit was 1.0 g/dL (2-sided alpha = 0.05). Weekly doses of epoetin required to maintain Hb levels, dose changes, safety, tolerability, and immunogenicity were also evaluated. CLINICAL TRIAL REGISTRATION: EudraCT No. 2005-000142-37. RESULTS: Mean Hb values were comparable in both groups at baseline and during the 24-week treatment period. The estimated treatment difference between groups from baseline to EEP was 0.01 g/dL (95% confidence interval: -0.20, 0.22; p = 0.9207 (ANCOVA)), indicating that epoetin theta was non-inferior to epoetin beta. The weekly doses of epoetin theta or epoetin beta were nearly the same and the change from baseline to EEP in patients who switched to epoetin theta (36.6 to 30.0 IU/kg(BW)) was comparable to those continuing epoetin beta therapy (37.7 to 28.3 IU/kg(BW)). The profile and the frequency of adverse drug reactions (ADRs) were comparable in both groups (17.1% epoetin theta; 14.7% epoetin beta). The most common ADR was hypertension. No patient developed anti-erythropoietin antibodies. CONCLUSIONS: Epoetin theta (s.c.) has efficacy comparable with epoetin beta (s.c.) in pre-dialysis patients with renal anemia based on Hb changes from baseline to end of treatment (non-inferiority). The safety profile was also comparable. Patients could be switched from maintenance treatment with epoetin beta to epoetin theta without relevant dose changes.

Varicella zoster infection in renal transplant recipients: prevalence, complications and outcome.

Varicella zoster virus (VZV) is an important pathogen after renal transplantation. In the present study, we examined the prevalence, clinical presentation and outcome of VZV infections in renal transplant recipients. Charts and medical records of adult renal allotransplant recipients were investigated to find patients with VZV infection. From December 1972 until July 2010, 1,139 patients received kidney allograft at our institution. VZV infection was diagnosed in 40 patients (3.51%). 28 patients (70%) had intensified immunosuppression prior to VZV infection occurrence. Median time of onset was 2.13 years after transplantation (range 9 days to 19.2 years). 35 patients developed VZV during the first post-transplant year (median 0.61 years). Four patients developed VZV infection more than 12 years after transplantation. 33 patients (82.5%) had dermatomal distribution, 5 (12.5%) disseminated herpes zoster (HZ), and 2 patients (5%) who were VZV IgG-negative before transplantation, developed chickenpox. Immunosuppression was reduced and patients received acyclovir. Cutaneous scarring was recorded in 7 cases (17.5%). Two patients developed post-herpetic neuralgia, which was accompanied by scarring and skin depigmentation in 1 of them. Five patients (12.5%) experienced relapse of HZ. Timely initiation of therapy may prevent development of complications and the visceral form of disease. Based on our experience with development of chickenpox, we suggest active immunization for all seronegative patients before organ transplantation.

Therapeutic plasma exchange in clinical practice: long-term single centre experience.

Therapeutic plasma exchange (TPE) is a powerful tool in the treatment of a whole host of diseases and there is hardly any organ for which TPE has not been shown to have some beneficial effects. In most instances, TPE is indicated only as a last resort treatment if all conservative measures have failed. However, there are lifethreatening conditions where TPE is the primary mode of acute treatment. Results from recent randomized prospective controlled trials caused a narrowing of the spectrum of indications for use of TPE, while advances in the various fields of medicine and technology have enabled wider clinical application of this procedure and generated several new indications. To define the current role of TPE, we retrospectively analysed changes in indications for TPE in our database, that contains information on all TPEs conducted during 27 years at University Hospital Centre Zagreb (a national referral centre for therapeutic apheresis, which covers approximately 90-95% of all TPEs performed in Croatia). The number of patients, including children and elderly people) who underwent this procedure and TPEs increased several-fold over 27 years of follow-up despite changes in the pattern of indications and the emergence of new, more selective therapeutic options (LDL-apheresis, immunoadsorption, etc.). With wider application of TPE, fear of its complications have diminished, which may be the reason for the more frequent treatment of very young children and very old patients. Our results derived from a large number of treatments indicate that TPE is a relatively safe method of treatment, providing it is carried out by experienced staff, and used for appropriate indications with all necessary precautions. Despite the development of more selective methods, TPE is still a widely applicable and useful procedure, possibly experiencing a renesance in this century.

Influence of long-term dialysis treatment on operative complications after renal transplantation.

BACKGROUND: We sought to assess the influence of long-term dialysis treatment on operative complications after kidney transplantation. METHODS: We identified and prospectively followed 2 groups of patients who underwent renal transplantation: group I were on dialysis <5 years and group II, >15 years. We compared the groups regarding mismatches, residual diuresis, operative and medical complications, as well as duration of hospitalization after transplantation. RESULTS: Groups I and II included 36 and 24 patients with 33.3% and 45.8% female of mean ages at transplantation of 49 (range, 9-73) and 45 (range, 27-56) years, respectively. Group I contained 9 seniors and 4 subjects <18 years. There were no significant differences in mean donor age, number of marginal donors, mismatches, postoperative bleeding, wound infections, urine leakage, or duration of hospitalization. However, the number of postoperative lymphoceles was significantly higher in group II: 5 (20.8%) versus 1 (2.7%) (P = .01). Graftectomy was performed in 2 group II patients including 1 primary graft nonfunction, and another for recurrent focal segmental glomerulosclerosis. CONCLUSION: Our results suggested that the duration of dialysis treatment was not a significant factor for postoperative complications and prolonged hospital stay, except for an increased risk of lymphocele formation.

Epoetin theta: efficacy and safety of IV administration in anaemic haemodialysis patients in the maintenance phase in comparison to epoetin beta.

OBJECTIVE: To compare the efficacy and safety of epoetin theta and epoetin beta in anaemic patients with chronic kidney disease, undergoing haemodialysis and previously on stable maintenance therapy with epoetin beta. METHODS: In this multicentre, randomised, controlled, double-blind study 270 haemodialysis patients were treated intravenously (i.v.) for 24 weeks with either epoetin theta (n = 180) or epoetin beta (n = 90). The primary efficacy endpoint was the change in haemoglobin (Hb) from baseline to end of treatment (efficacy evaluation period, EEP, weeks 15-26). Hb levels, weekly doses of epoetin theta or epoetin beta required to maintain Hb levels, dose changes, safety, tolerability and immunogenicity were evaluated. CLINICAL TRIAL REGISTRATION: EudraCT No. 2005-000143-28. RESULTS: Mean Hb values were similar in both treatment groups at baseline and during the 24-weeks treatment period. The estimated treatment difference between epoetin theta and epoetin beta from baseline to EEP was -0.01 g/dL (95% confidence interval: -0.24, 0.21), p = 0.9021, indicating that the difference between both groups was not statistically significant. The weekly doses of epoetin theta or epoetin beta required to maintain Hb levels were nearly the same. The changes from baseline to EEP in patients who switched to treatment with epoetin theta (95.5-99.7 IU/kg(BW)) were smaller than in patients staying on their epoetin beta therapy (89.0-98.0 IU/kg(BW)). The profile and the frequency of adverse drug reactions (ADRs) were similar in both treatment groups (21.7% epoetin theta; 22.2% epoetin beta). The most common ADRs were hypertension, headache and arteriovenous fistula thrombosis. None of the patients developed anti-erythropoietin antibodies. CONCLUSIONS: Epoetin theta (i.v.) has a similar efficacy compared to epoetin beta (i.v.) in haemodialysis patients based on Hb changes from baseline to end of treatment (non-inferiority). The safety profile was similar in both groups. Patients could be switched from maintenance treatment with epoetin beta to epoetin theta without relevant dose changes.

Appendiceal carcinoid and mucinous cystadenoma in renal transplant recipients: case reports.

There is an increased incidence of tumors among renal transplant patients, which are associated with immunosuppression. Carcinoids are rare neuroendocrine tumors that arise from the enterochromaffin cells. Although appendiceal carcinoid tumors are the commonest malignant neoplasms affecting the appendix, and mucinous cystadenoma is the commonest benign appendiceal neoplasm, they have not been reported in immunosuppressed patients. We present two renal transplant recipients who developed combined appendiceal carcinoid and mucinous cystadenoma.

Bone density in renal transplant recipients and in patients with chronic kidney disease: a follow-up study in children and adolescents.

AIMS: Disturbances in mineral and bone metabolism are common in patients with chronic kidney disease. The purpose of this follow-up study was to compare the change of bone mineral density in patients with chronic kidney disease to those who have received the renal transplant. METHODS: The study included 47 children and adolescents: 16 with mild to moderate kidney disease, 14 on dialysis and 17 patients with renal transplant. At the baseline and follow-up visits, regular biochemistry, anthropometry and bone mineral density were measured. To minimize the effect of skeletal size, bone mineral apparent density (BMAD; g/cm3) was calculated. RESULTS: The mean height was below one standard deviation from reference values in patients on dialysis and in those with renal transplant. After correction for age, baseline and follow-up BMAD did not differ significantly between patients after transplantation and those with chronic kidney disease. The increase of BMAD between two measurements (mean period 16.0 +/- 4.4 months) was not significantly higher in patients with kidney transplant compared to those with chronic kidney disease. The significant predictors of BMAD were PTH in patients with chronic kidney disease and duration of steroid therapy in patients with renal transplant. CONCLUSIONS: The results showed that bone density in children and adolescents, even several years after kidney transplantation, did not significantly change over time comparing to patients with chronic kidney disease. Hyperparathyroidism and steroid therapy were the most important risk factors for the slow increase of bone density.

Posttransplant lymphoproliferative disorder in the wall of a lymphocele: a case report.

Posttransplant lymphoproliferative disorder (PTLD) is a well-known complication of renal transplantation with increased incidence after introduction of more powerful immunosuppressive drugs. Presenting symptoms are nonspecific; some patients may be entirely asymptomatic. Herein we have reported a case of PTLD arising in the lymphocele wall presenting with B-symptoms and deterioration of graft function. A 62-year-old-female with end-stage renal disease secondary to Balkan endemic nephropathy and positive Epstein-Barr virus (EBV) serology before transplantation received a renal transplant from a deceased donor. Six months after transplantation she was admitted to the hospital with a 1-week history of malaise, weight loss, anorexia, night sweats, and febrile episodes. Multisliced computed tomography demonstrated a cystic structure at the renal hilus. Graft function deteriorated, so the patient underwent puncture of the lymphocele. Urgent graftectomy was necessary to stop the bleeding. Pathohistology demonstrated EBV-positive, CD20-positive PTLD. The patient received 6 cycles of chemotherapy and continued on hemodialysis. We concluded that a high index of suspicion for PTLD should be maintained when evaluating lymphoceles arising in the later posttransplantation period. Irrespective of their imaging features, biopsy should be performed to exclude PTLD.

Clinical features of Kaposi's sarcoma in Croatian renal transplant recipients.

AIM: To investigate the prevalence, clinical manifestations and outcome of Kaposi's sarcoma in Croatian renal transplant recipients. METHODS: The Department database was retrospectively analysed according to clinical presentation, immunosuppressive protocol, treatment, and outcome of patients with Kaposi's sarcoma. RESULTS: Kaposi's sarcoma occurred in four male patients (0.67% of all renal transplant recipients), with the onset of clinical presentation at 4 to 18 months of transplantation. HLA-B35 was present in all patients, whereas HLA-A2, -DR3 and -DR5 were present in three patients each. In all patients, the disease manifested with purple or bluish papules on the skin, without visceral organ or lymph node involvement. Immunosuppression was rapidly reduced in the first patient who rejected the graft. Three patients achieved complete remission upon reduction of immunosuppressive therapy and local irradiation, with preserved renal function. CONCLUSION: Kaposi's sarcoma is rare in Croatian renal transplant recipients. It tends to occur in male patients, soon after transplantation and is associated with HLA-B35. Reduction of immunosuppression is recommended as the first choice method in patients with skin-limited disease, accompanied by radiotherapy in resistant cases.

Outcome after renal transplantation in a "senior" program: the Croatian experience.

BACKGROUND: The Eurotransplant "senior" program allocates kidneys from elderly donors to patients >65 years old. It aims to increase the number of renal transplantations. Kidneys are allocated locally without human leukocyte antigen (HLA) matching to decrease the cold ischemia time. Croatia has introduced its own "senior" program based on HLA matching. We compared results with those from Eurotransplant. METHODS: We identified and prospectively followed all patients aged of >or=65 years who underwent a first renal transplantation. We recorded their HLA matching, cold ischemia time, renal function, surgical and medical complications, and duration of hospitalization. RESULTS: Through October 2007, 22 elderly patients received an allograft from donors who were >65 years old. There were 8 female and 14 male patients of mean age at transplantation of 67.4 years. Mean donor age was 66 years. The number of HLA mismatches ranged from 1 to 5, and cold ischemia time from 7 to 15 hours. One-year patient survival was 95.4%, and graft survival was 81.8%. Delayed graft function, defined as the need for dialysis for >7 days after transplantation, occurred in 63.6% of patients. Older recipients required prolonged hospitalization after transplantation (45 days; range, 16-131). Frequent posttransplant complications included posttransplant diabetes mellitus in 1 patient, delayed wound healing in 5 patients, and lymphocoel in 2 patients. Maligancies occurred in 3 patients, neoplasm of the native kidney, posttransplant lymphoproliferative disease, and skin cancer. One patient experienced acute rejection that was successfully treated with steroids. Seventeen patients experienced 20 viral infections. There was only 1 serious infection (pulmonary tuberculosis). The major problems were cardiovascular complications which occurred in 40.9% of patients.

Picovoltmeter for probing vortex dynamics in a single weak-pinning Corbino channel.

We have developed a picovoltmeter using a Nb dc superconducting quantum interference device for measuring the flux-flow voltage from a small number of vortices moving through a submicron weak-pinning superconducting channel. We have applied this picovoltmeter to measure the vortex response in a single channel arranged in a circle on a Corbino disk geometry. The circular channel allows the vortices to follow closed orbits without encountering any sample edges, thus eliminating the influence of entry barriers.

Octogenarians on hemodialysis: a prospective study.

Octogenarians represent the fastest growing group of patients on hemodialysis. These patients were previously treated with conservative measures, while they were believed to have too poor prognosis on renal replacement therapy. We investigated clinical characteristics and outcome of patients prospectively after at least 2 years of follow-up. Six male and six female patients who were older than 80 years at the start of hemodialysis were followed up. Their clinical characteristics, comorbidities, etiology of renal disease, nutritional status, complications, vascular access, hospitalizations, compliance and outcome were recorded. The primary renal disease was unknown in 42.8% of patients. All patients had one or more comorbid conditions. Dialysis was initiated in an emergency situation in 64.3%. Vascular access was long-term hemodialysis catheter in 71.4%. Only 14.2% of them received erythropoietin. There were no major bleedings with reduced doses of heparin. The most common complications were catheter-related ones (infections, ruptures). All patients together required seven hospitalizations per year (0.58 per patient). The octogenarians tended to be underdialyzed with the mean adequacy of dialysis (Kt/V) 0.92. The 1-year survival was 71.4%, and 2-year survival was 50%, i.e., they had good survival on hemodialysis. Most of them died from causes that were not related to the uremia. Their treatment requires a careful planning of renal service expansion while more octogenarians who need renal replacement treatment may be expected.

Anderson-Fabry disease in kidneys from deceased donor.

Anderson-Fabry disease (AFD) is a rare, X-linked lysosomal storage disease that leads to progressive intracellular accumulation of globotriaosylceramide in visceral organs and the vascular endothelium. We report two patients with end-stage renal disease who received renal allograft from deceased female donor who died from heart failure. A 62-year-old women received a renal allograft in July 2006. Except for low-range proteinuria, renal function was normal until 6 months after transplantation when serum creatinine increased from 120 to 150 micromol/L. A renal biopsy was performed. Based on the specific pathological finding, AFD in donor was suspected. In order to prove the diagnosis, the other recipient also underwent renal biopsy 3 months later. This was 45-year-old female with stable graft function and nonnephrotic proteinuria. Light microscopic findings included a 'foamy' appearance of affected cells with swelling and vacuolization of podocytes. Electron microscopic finding show mesangial cells and podocytes filled with dense lysosomal granules appearing as myelin figures and 'zebra bodies'. Changes were less intensive than in the biopsy of the first recipient. The donor was 54-year-old Italian women who died on the Adriatic coast after heart attack. This is the first case of AFD found in a kidney allograft from deceased donor.

Renal transplantation in patients with Balkan endemic nephropathy.

BACKGROUND: Balkan endemic nephropathy (BEN) is a chronic tubulointerstitial disease prevalent in Croatia, Romania, Bulgaria, Bosnia and Herzegovina, and Serbia. In addition to renal disease, an increased incidence of upper urothelial carcinomas (UUCs) has been observed in the foci of BEN. Carcinoma may occur alone or in combination with BEN. Immunosuppression is associated with an increased risk for development of different malignancies. There are no data in the literature about the outcome of patients with BEN after transplantation. METHODS: We performed a retrospective evaluation of the database and review of the charts and pathology reports of 601 renal transplant recipients treated at our institution. RESULTS: From January 1995 to December 2004, kidney transplantations were performed in nine patients with BEN. One-year graft survival was 100%. A man, who was transplanted in 1997 died 2 years after transplantation with a functioning graft due to disseminated cancer from the pelvis of his own kidney. A female patient developed UCC 2 years after transplantation. They were both treated with a bolus of methylprednisolone before transplantation, because of four HLA-mismatches. A male patient developed UCC in the native and transplanted kidneys. He underwent a native nephroureterectomy with partial nephroureterectomy of transplanted kidney. His graft function was preserved with decreased immunosuppression. Three years later a urinary bladder carcinoma was discovered on a regularly performed multislice computed tomography. One patient developed a skin malignancy. Other patients have had uneventful posttransplantation courses with excellent graft function. Thus, 33.3% of patients with BEN developed UUC, compared with a 0.67% prevalence of urinary tract tumors among transplanted patients with other causes of end-stage renal disease. CONCLUSION: Patients with BEN are at increased risk for the development of UCC after transplantation. Regular screening for early detection of malignancy is mandatory. Longer follow-up and results from other transplant centers are needed to further investigate the relationship between BEN and UCC after renal transplantation.