Renal transplantation in patients with primary immunoglobulin A nephropathy

Background. Opinions on the clinical course and outcome of renal transplantation in patients with primary immunoglobulin A nephropathy (IgAN) have been controversial.
Methods. We conducted a retrospective single-centre study on 542 kidney transplant recipients over the period 1984–2001. Long-term outcome and factors affecting recurrence in recipients with primary IgAN were analysed.
Results. Seventy-five patients (13.8%) had biopsy-proven IgAN as the cause of renal failure, and their mean duration of follow-up after transplantation was 100 ± 5.8 months. Fourteen (18.7%) of the 75 patients had biopsy-proven recurrent IgAN, diagnosed at 67.7 ± 11 months after transplantation. The risk of recurrence was not associated with HLA DR4 or B35. Graft failure occurred in five (35.7%) of the 14 patients: three due to IgAN and two due to chronic rejection. Three (4.9%) of the 61 patients without recurrent IgAN had graft failure, all due to chronic rejection. Graft survival was similar between living-related and cadaveric/living-unrelated patients (12-year graft survival, 88 and 72%, respectively, P = 0.616). Renal allograft survival within the first 12 years was better in patients with primary IgAN compared with those with other primary diseases (80 vs 51%, P = 0.001). Thereafter, IgAN patients showed an inferior graft survival (74 vs 97% in non-IgAN patients, P = 0.001).
Conclusions. Our data suggested that around one-fifth of patients with primary IgAN developed recurrence by 5 years after transplantation. Recurrent IgA nephropathy in allografts runs an indolent course with favourable outcome in the first 12 years. However, the contribution of recurrent disease to graft loss becomes more significant on long-term follow up.

Histoplasmosis presenting as cellulitis 18 years after renal transplantation

A 49-year-old renal transplant patient, under an 18-year course of immunosuppressive therapy with prednisone and azathioprine and, more recently, prednisone plus mycophenolate sodium, developed a cutaneous-subcutaneous infection caused by Histoplasma capsulatum. The clinical presentation consisted of a slowly enlarging, erythematous and infiltrative 25 cm plaque in the major axis on the arm. There was no involvement of the lungs or any other organ. Cure was obtained with itraconazole treatment after 12 months. Histoplasmosis is an uncommon opportunistic infection among solid organ transplanted patients with incidence of 0% to 2.1% observed in a large number of cases. This report describes an atypical cutaneous clinical presentation of a potentially fatal disease in immunosuppressed patients.

Complete atrioventricular block during renal transplantation in a patient with Alport's syndrome: case report

CONTEXTO: A síndrome de Alport é responsável por aproximadamente 5% dos pacientes com insuficiência renal crônica. Nessa doença, anormalidades no sistema de condução cardíaco são mais freqüentes que na população em geral. OBJETIVO: Relatar caso de síndrome de Alport que desenvolveu bloqueio atrioventricular total durante um transplante renal. RELATO DE CASO: Paciente masculino, 21 anos de idade, com insuficiência renal crônica secundária à síndrome de Alport, foi submetido a transplante renal sob anestesia peridural. Durante o procedimento anestésico-cirúrgico apresentou bloqueio atrioventricular total, que foi tratado rapidamente, e com sucesso, usando-se um marcapasso transcutâneo. O bloqueio simpático extenso pode contribuir para o desenvolvimento de distúrbios no sistema de condução cardíaco, particularmente em pacientes com insuficiência renal crônica em esquema de diálise. Mesmo em pacientes com eletrocardiograma pré-operatório normal e sem distúrbios de condução, graus variáveis de bloqueio atrioventricular, incluindo bloqueio atrioventricular total, podem ocorrer. Nesse caso, o uso de marcapasso transcutâneo é tratamento rápido e efetivo na sala de operação até o final da cirurgia, quando o tratamento definitivo pode ser planejado.

Quantified power Doppler as a predictor of delayed graft function after renal transplantation

No safe ultrasound (US) parameters have been established to differentiate the causes of graft dysfunction.To define US parameters and identify the predictors of normal graft evolution, delayed graft function (DGF), and rejection at the early period after kidney transplantation.Between June 2012 and August 2013, 79 renal transplant recipients underwent US examination 1-3 days posttransplantation. Resistive index (RI), power Doppler (PD), and RI + PD (quantified PD) were assessed. Patients were allocated into three groups: normal graft evolution, DGF, and rejection.Resistive index of upper and middle segments and PD were higher in the DGF group than in the normal group. ROC curve analysis revealed that RI + PD was the index that best correlated with DGF (cutoff = 0.84). In the high RI + PD group, time to renal function recovery (6.33 +/- A 6.5 days) and number of dialysis sessions (2.81 +/- A 2.8) were greater than in the low RI + PD group (2.11 +/- A 5.3 days and 0.69 +/- A 1.5 sessions, respectively), p = 0.0001. Multivariate analysis showed that high donor final creatinine with a relative risk (RR) of 19.7 (2.01-184.7, p = 0.009) and older donor age (RR = 1.17 (1.04-1.32), p = 0.007) correlated with risk DGF.Quantified PD (RI + PD) was the best DGF predictor. PD quantification has not been previously reported .

Do anticoagulant and antiplatelet agents prevent acute graft thrombosis in renal transplantation? A meta-analysis of case series studies

Introduction & Objectives: Thrombosis of the renal allograft is expected to occur in 1–6% of kidney transplants, and graft loss is expected in almost all cases. Anticoagulant and anti-platelet agents could serve as an adjunctive preventive measure, but sound evidence of benefits are still lacking, in this setting. We therefore assessed the efficacy and safety of anticoagulant and anti-platelet agents, in reducing the rate of renal allograft thrombosis. Methods: A review of the literature was carried out in major databases (MEDLINE, EMBASE and LILACS), with a comprehensive search strategy, to locate all available case series studies of anticoagulant and/or anti-platelet prophylaxis of thrombosis in renal transplantation. The date of the last search was 11 August 2014. We pooled all case series in a proportional meta-analysis. Statistical significance was achieved if the 95% confidence intervals obtained for each intervention did not overlap. Results: Our search strategy retrieved 7160 titles, from which 21 case series were chosen for analysis. A total of 3246 patients were identified (1718 treated with antiplatelet and/or anticoagulant agents, and 1528 non-treated control subjects). Allograft thrombosis occurred in 7.24% (95% CI 3.45 to 12.27%) of the patients receiving no intervention, compared to 3.38% (95% CI 1.45 to 6.1%), 1.2% (95% CI 0.6 to 2.1%) and 0.47% (95% CI 0.001 to 1.79%), in the anticoagulant, aspirin, and aspirin + anticoagulant groups, respectively. Bleeding complication rates were 28.0% (95% CI 15.4 to 42.7%) for anticoagulants, compared to 12.13% (95% CI 0.8 to 33.93%) for aspirin + anticoagulant, 0.31% (95% CI 0.0001 to 1.32%) for aspirin, and 6.1% (95% CI 2.2 to 11.7%) for the control group. Conclusions: Aspirin is more effective in reducing allograft thrombosis, after kidney transplantation, whether alone or in association with an anticoagulant, when compared to no drug prophylaxis, and without higher haemorrhagic complication rates. Anticoagulants, when used alone, do not show a beneficial effect on thrombosis rates, additionally yielding higher bleeding rates.

The impact of pretransplant donor-specific antibodies on graft outcome in renal transplantation: a six-year follow-up study

OBJECTIVE: The significance of pretransplant, donor-specific antibodies on long-term patient outcomes is a subject of debate. This study evaluated the impact and the presence or absence of donor-specific antibodies after kidney transplantation on short-and long-term graft outcomes. METHODS: We analyzed the frequency and dynamics of pretransplant donor-specific antibodies following renal transplantation from a randomized trial that was conducted from 2002 to 2004 and correlated these findings with patient outcomes through 2009. Transplants were performed against a complement-dependent T-and B-negative crossmatch. Pre- and posttransplant sera were available from 94 of the 118 patients (80%). Antibodies were detected using a solid-phase (Luminex (R)), single-bead assay, and all tests were performed simultaneously. RESULTS: Sixteen patients exhibited pretransplant donor-specific antibodies, but only 3 of these patients (19%) developed antibody-mediated rejection and 2 of them experienced early graft losses. Excluding these 2 losses, 6 of 14 patients exhibited donor-specific antibodies at the final follow-up exam, whereas 8 of these patients (57%) exhibited complete clearance of the donor-specific antibodies. Five other patients developed "de novo'' posttransplant donor-specific antibodies. Death-censored graft survival was similar in patients with pretransplant donor-specific and non-donor-specific antibodies after a mean follow-up period of 70 months. CONCLUSION: Pretransplant donor-specific antibodies with a negative complement-dependent cytotoxicity crossmatch are associated with a risk for the development of antibody-mediated rejection, although survival rates are similar when patients transpose the first months after receiving the graft. Our data also suggest that early posttransplant donor-specific antibody monitoring should increase knowledge of antibody dynamics and their impact on long-term graft outcome.

Malakoplakia after renal transplantation in the current era of immunosuppressive therapy: case report and literature review

Malakoplakia is a rare chronic granulomatous disease of unknown cause. It is thought to be caused by an acquired bactericidal defect of macrophages. Malakoplakia is associated with chronic infections and immunosuppression. Although it occurs mainly in the urinary tract, it has already been reported in almost every organ system. The isolation of bacteria, especially Escherichia coli, is common in malakoplakia patients. Here, we present a case of primary cutaneous malakoplakia in a kidney transplant recipient who had been taking prednisone, tacrolimus, and mycophenolate. Culture of a lesion grew Burkholderia cepacia complex. Treatment with high doses of trimethoprim-sulfamethoxazole was successful. We also present a systematic review of the literature, identifying 4 previously reported cases of malakoplakia after renal transplantation under similar immunosuppressive therapy, most occurring in the urinary tract or perineum and following benign courses to cure. Data in the literature suggest that malakoplakia has become even rarer since changes were made in the immunosuppressive therapy employed after kidney transplantation.

Which patients are more likely to benefit from renal transplantation?

Background: We evaluated whether the advantages conferred by renal transplantation encompass all individuals or whether they favor more specific groups of patients. Methods: One thousand and fifty-eight patients on the transplant waiting list and 270 receiving renal transplant were studied. End points were the composite incidence of CV events and death. Patients were followed up from date of placement on the list until transplantation, CV event, or death (dialysis patients), or from the date of transplantation, CV event, return to dialysis, or death (transplant patients). Results: Younger patients with no comorbidities had a lower incidence of CV events and death independently of the treatment modality (log-rank = 0.0001). Renal transplantation was associated with better prognosis only in high-risk patients (p = 0.003). Conclusions: Age and comorbidities influenced the prevalence of CV complications and death independently of the treatment modality. A positive effect of renal transplantation was documented only in high-risk patients. These findings suggest that age and comorbidities should be considered indication for early transplantation even considering that, as a group, such patients have a shorter survival compared with low-risk individuals.

Preserving the B-Cell Compartment Favors Operational Tolerance in Human Renal Transplantation

Transplanted individuals in operational tolerance (OT) maintain long-term stable graft function after completely stopping immunosuppression. Understanding the mechanisms involved in OT can provide valuable information about pathways to human transplantation tolerance. Here we report that operationally tolerant individuals display quantitative and functional preservation of the B-c ell compartment in renal transplantation. OT exhibited normal numbers of circulating total B cells, naive, memory and regulatory B cells (Bregs) as well as preserved B-cell receptor repertoire, similar to healthy individuals. In addition, OT also displayed conserved capacity to activate the cluster of differentiation 40 (CD40)/signal transducer and activator of transcription 3 (STAT3) signaling pathway in Bregs, in contrast, with chronic rejection. Rather than expansion or higher activation, we show that the preservation of the B-cell compartment favors OT. Online address: http://www.molmed.org doi: 10.2119/molmed.2011.00281

The role of myocardial scintigraphy in the assessment of cardiovascular risk in patients with end-stage chronic kidney disease on the waiting list for renal transplantation

The usefulness of stress myocardial perfusion scintigraphy for cardiovascular (CV) risk stratification in chronic kidney disease remains controversial. We tested the hypothesis that different clinical risk profiles influence the test. We assessed the prognostic value of myocardial scintigraphy in 892 consecutive renal transplant candidates classified into four risk groups: very high (aged epsilon 50 years, diabetes and CV disease), high (two factors), intermediate (one factor) and low (no factor). The incidence of CV events and death was 20 and 18, respectively (median follow-up 22 months). Altered stress testing was associated with an increased probability of cardiovascular events only in intermediate-risk (one risk factor) patients [30.3 versus 10, hazard ratio (HR) 2.37, confidence interval (CI) 1.693.33, P 0.0001]. Low-risk patients did well regardless of scan results. In patients with two or three risk factors, an altered stress test did not add to the already increased CV risk. Myocardial scintigraphy was related to overall mortality only in intermediate-risk patients (HR 2.8, CI 1.55.1, P 0.007). CV risk stratification based on myocardial stress testing is useful only in patients with just one risk factor. Screening may avoid unnecessary testing in 60 of patients, help stratifying for risk of events and provide an explanation for the inconsistent performance of myocardial scintigraphy.

Dialysis and Renal Transplantation in HIV-Infected Patients: a European Survey

OBJECTIVES:: To determine prevalence and characteristics of end-stage renal diseases (ESRD) [dialysis and renal transplantation (RT)] among European HIV-infected patients. METHODS:: Cross-sectional multicenter survey of EuroSIDA clinics during 2008. RESULTS:: Prevalence of ESRD was 0.5%. Of 122 patients with ESRD 96 were on dialysis and 26 had received a RT. Median age was 47 years, 73% were males and 43% were black. Median duration of HIV infection was 11 years. Thirty-three percent had prior AIDS; 91% were receiving antiretrovirals; and 88% had undetectable viral load. Median CD4T-cell count was 341 cells per cubic millimetre; 20.5% had hepatitis C coinfection. Most frequent causes of ESRD were HIV-associated nephropathy (46%) and other glomerulonephritis (28%). Hemodialysis (93%) was the most common dialysis modality; 34% of patients were on the RT waiting list. A poor HIV control was the reason for exclusion from RT waiting list in 22.4% of cases. All the RT recipients were all alive at the time of the survey. Acute rejection was reported in 8 patients (30%). Functioning graft was present in 21 (80%). CONCLUSIONS:: This is the first multinational cross-sectional study of ESRD among European HIV population. Low prevalence of ESRD was found. Two-thirds of patients were excluded from RT for non-HIV/AIDS-related pathologies. Most patients had a functioning graft despite a high acute rejection rate.

[Renal transplantation - new developments]

Renal transplantation has become an established option for renal replacement therapy in many patients with end stage renal disease. Living donation is a possibility for timely transplantation, hampered in 20 % of all possible donors and recipients byincompatible blood groups. AB0-incompatible renal transplantation overcomes this hurdle with acceptable allograft survival compared to conventional living-donor renal transplantation. During the last 10 years, the number of patients awaiting renal transplantation older than 65 years has nearly doubled. The decision to transplant those patients and their medical treatment is a growing challenge in transplantation. On the other hand donor age is increasing with potential negative consequences for long-term outcome of organ function. Antibody-mediated humoral rejection have been identified lately as an important cause for allograft failure during long-term follow up of renal transplant patients. New immunological methods to detect donor-specific antibodies, like solid-phase assays (Luminex®), have increased the knowledge and understanding of humoral rejection processes. This will lead hopefully to modified immunosuppressive strategies to minimize organ failure due to chronic rejection.

Six-year follow-up of azathioprine and mycophenolate mofetil use during the first 6 months of renal transplantation

Long-term follow-up examination to test whether therapy with mycophenolate mofetil (MMF) or azathioprine (AZA) during the first year translates into different graft or patient survival and graft function is important. Therefore, 6-year follow-up data of a group of 80 consecutive renal transplant recipients were analyzed. The first group of 40 patients was treated with AZA, cyclosporine and prednisone and the second group with MMF, cyclosporine and prednisone for the first 6 months. Graft failure rates were compared during follow-up. Creatinine, inverse slope of creatinine (delta/creatinine) and 24-hour proteinuria at 6 years post transplantation were compared. The Kaplan-Meier analyses for death-censored and non-censored graft failure showed no difference between the groups. Creatinine values at 6 years for the AZA Group were 139 +/- 36 micromol/l (95% CI 125.9-151.2 micromol/l) and for the MMF Group 149 +/- 52 micromol/l (95% CI 133.9-164.9 micromol/l). Delta/creatinine and 24-hour proteinuria at 6 years did not differ between the two groups. We conclude that an initial 6-month treatment with MMF as opposed to AZA reduced the early rejection rate, but did not result in superior long-term graft function or survival after 6 years of follow-up observation.