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BACKGROUND In the developed world, kidney transplantation (KT) in patients with human immunodeficiency virus (HIV) infection is well established. Developing countries concentrate 90% of the people living with HIV, but their experience is underreported. Regional differences may affect outcomes. OBJECTIVES We compared the 3-year outcomes of patients with HIV infection receiving a KT in two different countries, in terms of incomes and development. METHODS This was an observational, retrospective, double-center study, including all HIV-infected patients >18 years old undergoing KT. RESULTS Between 2005 and 2015, 54 KTs were performed (39 in a Brazilian center, and 15 in a Spanish center). Brazilians had less hepatitis C virus co-infection (5% vs 27%, P=.024). Median cold ischemia time was higher in Brazil (25 vs 18 hours, P=.001). Biopsy-proven acute rejection (AR) was higher in Brazil (33% vs 13%, P=.187), as were the number of AR episodes (22 vs 4, P=.063). Patient survival at 3 years was 91.3% in Brazil and 100% in Spain; P=.663. All three cases of death in Brazil were a result of bacterial infections within the first year post transplant. At 3 years, survival free from immunosuppressive changes was lower in Brazil (56% vs 90.9%, P=.036). Raltegravir-based treatment to avoid interaction with calcineurin inhibitor was more prevalent in Spain (80% vs 3%; P

Candida peritonitis is a potentially life-threatening infection after abdominal transplantation, although there is scant information regarding its incidence and outcome. We analysed the incidence rate and outcome of Candida peritonitis in 717 liver or pancreas transplant recipients. Five cases of Candida peritonitis were diagnosed, representing the second most frequent cause of invasive fungal infection in the cohort. The incidence rate of Candida peritonitis during the first 30 days after transplantation was 6.5 cases/10 000 transplant days in pancreas recipients and 1.2 cases/10 000 transplant days in liver recipients (P = 0.035). Four of the five patients received an echinocandin in combination with other antifungal. All patients were alive and with good graft function at 1-year follow-up. In our series, Candida peritonitis in liver and pancreas transplant recipients was not uncommon and had a good prognosis.

Antiretroviral therapy has been immensely successful in reducing the incidence of opportunistic infections and death after HIV infection. This has resulted in heightened interest in noninfectious comorbidities including kidney disease. Although HIV-associated nephropathy, the most ominous kidney disease related to the direct effects of HIV, may be prevented and treated with antiretrovirals, kidney disease remains an important issue in this population. In addition to the common risk factors for kidney disease of diabetes mellitus and hypertension, HIV-infected individuals have a high prevalence of other risk factors, including hepatitis C and exposure to antiretrovirals and other medications. Therefore, the differential diagnosis is vast. Early identification (through efficient screening) and prompt treatment of kidney disease in HIV-infected individuals are critical to lead to better outcomes. This review focuses on clinical and epidemiological issues, treatment strategies (including dialysis and kidney transplantation), and recent advances among kidney disease in the HIV population.

The aim of the present study was to determine the clinical characteristics, frequency of opportunistic infections (OI) in HCV-positive kidney recipients, and to evaluate HCV replication as a risk factor for developing an OI. We conducted a retrospective study of all kidney recipients from 2003 to 2014. A total of 1203 kidney transplants were performed during the study period. Opportunistic infections were recorded in 251 patients (21%) and nucleic acid amplification testing (NAAT) positivity in 75 (6%). Patients who are HCV NAAT positive were more likely to present an OI than those who are HCV NAAT negative (45% vs 20%, P < 0.001). Multivariate analysis showed the factors that were independently associated with the development of OI to be acute rejection, graft loss, post-transplantation hemodialysis, and HCV replication. Liver cirrhosis after transplantation could not be considered a risk factor to develop OI. To conclude, a high index of suspicion of OI must be maintained in the case of kidney recipients with HCV replication. Active surveillance of cytomegalovirus infection and other prophylactic strategies against OI should be considered after 6 month post-transplantation. Prompt initiation of DAA therapies may be a useful option aiming to decrease the incidence of OI after transplantation.

The aim was to evaluate feasibility and safety of calcineurin inhibitor-free immunosuppression in high-risk donor kidney transplantation with sequential sirolimus introduction. Kidney transplant patients (n=76) with a donor aged >60 years, donor with acute renal failure, or a nonheartbeating donor were included. Immunosuppression consisted of antithymocyte globulin or basiliximab, mycophenolate mofetil, prednisone, and sequential introduction of sirolimus. One-year patient survival was 96.2% and 95.8%; graft survival was 94.2% and 91.7%; acute rejection rates were 21.2% and 12.4%; delayed graft function was 21.2% and 66.7%; and creatinine clearance was 58+/-20 mL/min and 56+/-21 mL/min for the brain-dead donor group and the nonheartbeating donor group, respectively. Most adverse events were infections, but also three lymphoceles, three urinary fistulas, three wound seromas. Sequential sirolimus introduction in high-risk donor kidney transplantation was found to lead to good patient and graft survival and incidence of acute rejection and delayed graft function.

The aim of the study was to evaluate the efficacy and safety of percutaneous renal artery embolisation of non-functioning renal allografts in patients with graft intolerance syndrome (GIS). Transcatheter artery embolisation was performed in 30 kidney transplant recipients with GIS. The duration of graft function had been 60+/-45 months. Infectious disease was ruled out in all patients. Embolisation consisted of the injection of polyvinyl alcohol microspheres followed by the insertion of a stainless steel coil in the renal artery branches. Symptoms of GIS included: fever-graft pain (44%, n=13), fever-hematuria-pain (20%, n=6), fever-hematuria (13%, n=4) and fever alone (23%, n=7). Latency time between graft failure and embolisation was 184+/-227 (17-1181) days. Embolisation was clinically successful with the prolonged disappearance of GIS in 24 patients (80%). Six patients showed initial clinical improvement, but GIS reappeared at 40+/-18 days, and graft nephrectomy was required. There were no major complications associated with embolisation and no deaths. Perirenal collateral supply was a risk factor for the reappearance of GIS. Renal vascular embolisation is a simple, safe and effective technique for treating renal allograft intolerance syndrome and could be a feasible alternative for the first-line treatment.

Uremic tumoral calcinosis is an uncommon, benign condition characterized by slow-growing calcified periarticular soft tissue masses of varying size. We describe two patients with chronic renal failure on hemodialysis presenting uremic tumoral calcinosis, one in the fifth toe of the right foot and the other in the dorsum of the left foot between the first and second metatarsals. Excision of the calcic masses and parathyroidectomy were successfully performed in both patients. These cases are unusual in their rapid onset, mimicking acute infection. Differential diagnosis, radiological features and therapy are discussed.

Methods We analyzed all PRA-negative patients who received a first kidney transplant from an HLA-identical living donor. The patients received no antibody induction. An intraoperative bolus of 500 mg of methylprednisolone was administered. Then, steroid therapy was withdrawn within one week. Tacrolimus and mycophenolate treatment were started 3 days before transplantation with tacrolimus target levels of 4 to 8 ng/mL. In the absence of rejection, tacrolimus was withdrawn between 3 and 12 months post-transplant to reach mycophenolate mofetil monotherapy of 2 g/day or equivalent. Results Six patients were treated with the above protocol. At last follow-up, graft and patient survival were 100%. MDRD glomerular filtration rates were 54, 60, and 62 mL/min at 3 months, 12 months and last follow-up, respectively. None of the patients developed PRA post-transplant. One episode of acute rejection Banff IA occurred 9 years after transplantation due to non-adherence with good outcome after treatment. The mean number of concomitant drugs given with mycophenolate was 2.6. Four patients needed antihypertensive drugs. Conclusion Steroid-free de novo treatment and calcineurin-inhibitor weaning with mycophenolate monotherapy is feasible in first HLA-identical kidney transplantation from a living sibling. Although recipients of a first HLA-identical living-donor kidney transplant seem to need less immunosuppression, there are no guideline recommendations for these patients, and few prospective trials are available.

The prognosis of human immunodeficiency virus (HIV) infection has improved in recent years with the introduction of antiretroviral treatment. While the frequency of AIDS-defining events has decreased as a cause of death, mortality from non-AIDS-related events including end-stage renal diseases has increased. The etiology of chronic kidney disease is multifactorial: immune-mediated glomerulonephritis, HIV-associated nephropathy, thrombotic microangiopathies, and so on. HIV infection is no longer a contraindication to transplantation and is becoming standard therapy in most developed countries. The HIV criteria used to select patients for renal transplantation are similar in Europe and North America. Current criteria state that prior opportunistic infections are not a strict exclusion criterion, but patients must have a CD4+ count above 200 cells/mm(3) and a HIV-1 RNA viral load suppressible with treatment. In recent years, more than 200 renal transplants have been performed in HIV-infected patients worldwide, and mid-term patient and graft survival rates have been similar to that of HIV-negative patients. The main issues in post-transplant period are pharmacokinetic interactions between antiretrovirals and immunosuppressants, a high rate of acute rejection, the management of hepatitis C virus coinfection, and the high cardiovascular risk after transplantation. More studies are needed to determine the most appropriate antiretroviral and immunosuppressive regimens and the long-term outcome of HIV infection and kidney graft.

Background: HMG-CoA reductase inhibitors (statins) have effects beyond lipid lowering, including immunomodulatory and anti-inflammatory properties. Statins are frequently combined with immunosuppressive agents in transplant recipients to modulate the hyperlipidemic side effects of the immunosuppressants. However, the role of statins in the immunosuppressive response that is achieved in individual patients remains to be assessed. Objective: The aim of this study was to evaluate the immunomodulatory effect of atorvastatin given alone and in combined treatment with tacrolimus and mycophenolate mofetil. Study Design: Two patient groups were studied: renal transplant recipients receiving tacrolimus and mycophenolate mofetil therapy, and hypercholesterolemic patients (the control group). Fasting blood samples were taken from participants before and 1 month after atorvastatin treatment was started to study a small battery of biomarkers that are able to reflect the range of the effects of immunosuppressive therapy and atorvastatin. Setting: All patients in the study were enrolled at the Hospital Clinic of Barcelona. Patients: All patients enrolled in the study were candidates for treatment with atorvastatin because of high cholesterol levels. One group consisted of 25 stable renal transplant recipients with low-density lipoprotein (LDL) cholesterol levels above 100mg/dL after 3 months of therapeutic lifestyle changes, according to the guidelines of the National Kidney Foundation —Kidney Disease Outcomes Quality Initiative. The other group included 25 hypercholesterolemic patients with LDL cholesterol levels above target values for the patients’ overall risk, as derived from the National Cholesterol Education Program Adult Treatment Panel III criteria. Intervention: Atorvastatin (Lipitor®) treatment was started at a fixed dose of 20 mg daily. Main Outcome Measure: The studied biomarkers were lymphocyte proliferation, intracellular adenosine triphosphate (ATP) synthesis in CD4+ T cells, intralymphocytary cytokine expression (interleukin [IL]-2, interferon [IFN]-γ), soluble cytokine production (IL-2, IFN-γ, IL-10, IL-17, and transforming growth factor-β) and regulatory T (Treg) cells. Results: Atorvastatin proved to be an immunomodulatory agent, significantly decreasing lymphocyte proliferation by 15% (p = 0.001), increasing ATP levels by 16% (p = 0.0004), and showing a trend toward increasing Treg cells in hypercholesterolemic patients (p = 0.09). In the renal transplant recipients, atorvastatin therapy did not modify any of the biomarkers of immunosuppression that were studied. Conclusion: Atorvastatin showed immunoregulatory effects on T cells in hypercholesterolemic patients. These effects were absent in renal transplant recipients, suggesting that the beneficial effects of atorvastatin in this patient group do not relate to immunoregulation. Therefore, statin treatment cannot be considered as a means to reduce the dose of immunosuppressive agents.

Background. The contribution of mammalian target of rapamycin (mTOR) inhibitors to proteinuria is controversial. The aim was to analyse proteinuria in suboptimal kidney calcineurin inhibitor-(CNI) free de novo immunosuppression. Methods. All patients from our centre with donors >60 years and CNI-free treatment were included (n ¼ 108). Patients were divided into two groups: (i) SRL group: sirolimus (SRL) þ prednisone þ mycophenolate mofetil (MMF) þ antiCD25; (ii) MMF group: prednisone þ MMF w/ or w/o antiCD25 (n ¼ 75). Follow-up was 12 months. Results. Donors were slightly younger in the SRL group (68 vs 71 years; P < 0.05), receptor age (67 vs 65 years) was not significantly different. Patient survival in the MMF group was 88 vs 94% in the SRL group, however, these differences did not reach statistical significance. One-year graft survival censored for death was 83% in the MMF group and 94% in the SRL group. Acute rejection rate was 45% in the MMF and 15% in the SRL group (P < 0.01). The incidence of CNI introduction was higher in the MMF-group (35 vs 5; P < 0.05). The intention-to-treat analysis revealed significant differences of proteinuria [SRL vs MMF at 12 months: 461 (163–6988) vs 270 (53–3029) mg/day], which did not exist in the on-therapy (OT) analysis [SRL vs MMF at 12 months: 357 (199–1428) vs 279 (53–3029) mg/day]. New onset nephrotic range proteinuria seemed to occur slightly more frequently in SRL patients (3/33 vs 1/75; P ¼ 0.049), however, all four cases occurred in a context of recurrent disease, or previous drug-independent damage or non-adherence. All of these patients were converted to CNI. Conclusion. SRL-based compared with MMF-based treatment in kidney transplantation with advanced age donors is associated with an acceptable outcome, however, with increased proteinuria in the intentionto-treat analysis. A large subgroup of the patients in the MMF group experienced acute rejection and required conversion to CNI.

Chronic hemodialysis patients show a high incidence and prevalence of cardiovascular disease of multifactorial etiology and an association between dyslipidemia and accelerated atherosclerosis. We analyzed characteristics of dyslipidemia in 1824 hemodialysis patients (59% men; mean age 65 ± 15 years) in Catalonia and identified risk factors by logistic regression. Prevalence of dyslipidemia was high (63%). Most frequent lipid alterations were decreased HDL cholesterol (40%), hypertriglyceridemia (31%) and hypercholesterolemia (19%). Total cholesterol/HDL ratio was elevated in 23%. Body mass index (OR 1.08; 95% CI 1.05–1.11), diabetes mellitus (1.4; 1.09–1.79), ischemic heart disease (1.38, 1.08–1.75) and stroke (1.30; 1.0–1.69) were independent factors associated with dyslipidemia. Lengthy time (>7 years) on dialysis (0.77; 0.59–0.99) and female sex (0.78; 0.64–0.96) were independent protective factors. A significant reduction in the risk of developing dyslipidemia was observed after the age of 50. Lipid-lowering drug use was low (19%), with statins being the most frequent (83%). The percentage of patients reaching target LDL levels according to individual cardiovascular risk (ATPIII) was unsatisfactory, particularly in high risk patients (52%). In light of the high prevalence of dyslipidemia and low adherence to target LDL goals, we conclude that strict control of dyslipidemia should be included in cardiovascular risk prevention strategies for chronic hemodialysis patients.

Background: Muromonab-CD3 is a murine monoclonal antibody (MoAb) that is used in the prophylaxis and treatment of acute graft rejection. Activation of coagulation and fibrinolysis following anti-CD3 administration have been reported in some patients to lead to irreversible intragraft thrombosis. Design and methods: We have studied the effect of muromonab-CD3 infusion on platelets using flow cytometry in six patients who received three daily doses of muromonab-CD3 as prophylaxis of rejection before receiving a living donor renal transplant. Samples were collected before, 15 and 60 min after muromonab-CD3 infusion. Immunolabeling of platelets was performed in whole blood using dual-color analysis. The following conjugated MoAb were used: anti-CD41a, -CD36, -CD42b, -CD62P, -CD63, -factor V/Va and nonspecific Ig. Samples were analyzed with a FACScan flow cytometer (Becton Dickinson, Mountain View, CA, USA). Results: After muromonab-CD3 infusion, an increase in the binding of MoAb anti-factor V/Va to platelets was seen, which was only statistically significant (2.2% vs. 12.8%, P=.04) after 15 min of the second dose. No significant changes were seen in the other MoAbs studied. No thrombotic complications were observed after transplantation. Interpretation and conclusion: In uremic patients receiving muromonab-CD3 infusion as prophylaxis of graft rejection, an increase in the binding of anti-factor V/Va, denoting an increased exposure of anionic phospholipids in platelets, was seen. This increase in platelet procoagulant activity might contribute to the appearance of thromboses within renal graft seen in some patients who received muromonab-CD3.