Pretransplant Biopsy of Marginal Kidneys: Is It Necessary?

INTRODUCTION: Pretransplant kidney biopsy from marginal donors is used to guide the decision of whether to accept or discard organs for transplantation; however, there is controversy about this procedure, and the need for a pretransplant biopsy is still a debate. We sought to determine if histologic evaluation before implantation of marginal kidneys would influence the outcome. METHODS: A retrospective observational cohort study of marginal donor transplants at Centro Hospitalar e Universitário de Coimbra was done. From 2009 to 2016, 650 marginal kidney transplants were analyzed. We evaluated long-term graft survival in a cohort of patients who received marginal kidneys. The recipients were divided into 2 groups based on whether a pretransplant donor biopsy was performed. Continuous variables were summarized by mean and standard deviation or median and range, as applicable. Categorical variables were summarized by relative and absolute frequencies. The survival analysis was obtained and plotted using the Kaplan-Meier method and compared with the log-rank test. RESULTS: The median age of recipients and donors were statistically different between both groups (P < .001), with the donors and the recipients being younger in the group without a pretransplant biopsy. The median cold ischemia time was higher in the biopsy group (P = .01). The survival analysis showed that graft survival didn't differ between the groups (P = .2). CONCLUSIONS: Selection of kidneys based on histological findings may not influence the graft survival and implies a higher cold ischemia time. More data are necessary to provide insight into which clinical, histologic, and biochemical parameters are necessary for decision making on kidney acceptance.

Post-Kidney-Transplant Diabetes: Evaluation of Risk Factors.

INTRODUCTION: Post-transplant diabetes mellitus is a complication of kidney transplantation with deleterious effects on graft and patient survival and is associated with higher mortality. The goal of this paper is to identify risk factors that contribute to its development so that it can be avoided. METHODS: We performed a retrospective analysis of 659 kidney transplants performed in adult patients between January 2013 and December 2017. We excluded patients with a previous diagnosis of diabetes mellitus and identified 61 patients with post-transplant diabetes mellitus (10.6%), then compared them to a control group of 61 patients who did not suffer from the disease, namely the kidney transplant pair or the patient submitted for transplant immediately after. DISCUSSION: A comparative analysis of the 2 groups revealed significant differences regarding the use of ß-blockers, fasting glucose on the fifth day post-transplant, kidney recipient age, and body mass index. Using multivariate logistic regression methods, 2 variables with an impact on post-transplant diabetes development were found: fasting glucose on the fifth day post-transplant (odds ratio 1.044, 95% confidence interval 1.010-1.079, P = .010) and body mass index (odds ratio 1.130, 95% confidence interval 1.009-1.264, P = .034). We did not find any differences for other potential risk factors. CONCLUSION: A high plasma glucose level on the fifth day after the transplant and a high body mass index in the setting of the transplant can potentially impact the transplant's outcomes, so it is important to identify these levels as soon as possible to take measures to prevent this disease.

A Rare Manifestation of Tuberculosis in a Renal Transplant Patient: A Case Report.

Cutaneous lesions in the presence of fever in patients undergoing immunosuppressive therapy are a diagnostic challenge and may represent manifestations of multiple diseases, such as fungal infections, nocardiosis, lymphoproliferative diseases, zoonosis, and tuberculosis. The authors report a case of a 66-year-old white man with chronic kidney disease since 2014 (chronic pyelonephritis) who had a renal transplant in the previous 6 months. Induction therapy was performed with thymoglobulin, and his current immunosuppression scheme included tacrolimus, mycophenolate mofetil, and prednisolone. The patient had no history of pulmonary tuberculosis. The patient presented with 2 cutaneous lesions, localized on the back and abdomen, that appeared to be firm, painful, subcutaneous, erythematous nodules with an approximately 5 cm diameter overlying an infected focus and purulent material inside. The patient also had a fever and fatigue. Blood analysis showed pancytopenia with an elevation of inflammatory markers and graft dysfunction. Tissue cultures and skin biopsy with histological analysis were performed. Histopathology of the lesion showed a nonspecific inflammatory infiltrate without granulomas, and acid-fast bacillus staining was negative. Nevertheless, serum QuantiFERON testing was positive. But polymerase chain reaction finally confirmed the presence of Mycobacterium tuberculosis, which confirmed the diagnosis of cutaneous tuberculosis. A chest computed tomography scan showed a lung pattern of miliary tuberculosis. The patient was treated with multidrug tuberculosis therapy, resulting in lesion clearance after 3 weeks. Tuberculosis is a serious infection, especially in high-risk patients, such as those in an immunocompromised state. The incidence of cutaneous tuberculosis is rare, but it should be considered in patients presenting with atypical skin lesions suggestive of an underlying infectious etiology.

Staphylococcus Infection-Associated Glomerulonephritis in a Kidney Transplant Patient: Case Report.

BACKGROUND: Staphylococcus infection-associated glomerulonephritis is a rare cause of graft dysfunction in kidney transplant. Suspicion should be high in the setting of elevation of serum creatinine, active urinary sediment, with or without hypocomplementemia, and simultaneous Staphylococcus aureus infection. A kidney biopsy is usually diagnostic. CASE REPORT: A 56-year-old man, who received a kidney transplant in 1998, with basal serum creatinine of 1.2 mg/dL and normal urinary sediment, was admitted to our kidney transplantation unit with graft dysfunction and a urinary tract infection caused by S aureus with septicemia, treated with antibiotics, in the context of recently intensified immunosuppression for a primary immune thrombocytopenia diagnosed 3 weeks earlier. After antibiotic treatment, the patient persisted with graft dysfunction, edema, and hypertension, with a S aureus isolation in the urine culture, active urinary sediment, and low C3. A kidney biopsy was performed, showing diffuse proliferative endocapillary and mesangial glomerulonephritis, with IgA(++) and C3(++) mesangial and endocapillary deposits in immunofluorescence. The patient was treated symptomatically and maintained his regular immunosuppression. At the last follow-up, his serum creatinine value was stable at 2.5 mg/dL. CONCLUSIONS: The onset of a nephritic syndrome with a simultaneous S aureus infection should lead to suspicion of this uncommon entity, confirmed histologically. Despite its association with poor graft survival, our patient's graft survival remained stable.

Long-Term Outcomes of Kidney Transplantation From Expanded-Criteria Deceased Donors: A Single-Center Experience.

BACKGROUND: Organ shortage has prompted the use of expanded-criteria donors (ECDs). Our objective was to compare long-term outcomes of kidney transplants from ECDs with those from concurrent standard-criteria donors (SCDs). In addition, we evaluated variables associated with graft survival in both groups. METHODS: We retrospectively reviewed all 617 deceased-donor kidney transplantations performed from 2005 to 2009 in our department. The population was divided according to donor status into ECD or SCD. Patients were followed until 5 years after transplantation, death, graft failure, or loss to follow-up. RESULTS: We transplanted 150 deceased-donor kidneys from ECDs and 467 from SCDs. ECD were older, more frequently women, had a lower pre-retrieval glomerular filtration rate, and more frequently died due to cerebrovascular accident. ECD recipients were older, presented a lower proportion of black race, more frequently were on hemodialysis, and presented a higher rate of first kidney transplants. Mean glomerular filtration rate was consistently lower in the ECD group. Patient and graft survivals were lower in the ECD group, but statistical significance was present only in graft survival censored for death with a functioning graft at 3 years and graft survival noncensored for death with a functioning graft at 5 years. Younger recipient ages, longer time on dialysis, acute rejection episodes, and glomerular filtration rate at 1 year after transplantation were independent risk factors for lower graft survival. CONCLUSIONS: Transplantation with the use of ECD kidneys provide quite satisfactory patient and graft survival rates despite their poorer long-term outcomes.

Early Rehospitalization Post-Kidney Transplant Due to Infectious Complications: Can We Predict the Patients at Risk?

INTRODUCTION: Rehospitalization early post-kidney transplant is common and has a negative impact in morbidity, graft survival, and health costs. Infection is one the most common causes, and identifying the risk factors for early readmission due to infectious complications may guide a preventive program and improve outcome. The aim of this study was to evaluate the incidence, characterize the population, and identify the risk factors associated with early readmission for infectious complications post-kidney transplantation. METHODS: We performed a retrospective cohort study of all the kidney transplants performed during 2015. The primary outcome was readmission in the first 3 months post-transplant due to infectious causes defined by clinical and laboratory parameters. RESULTS: We evaluated 141 kidney transplants; 71% of subjects were men, with an overall mean age of 50.8 ± 15.4 years. Prior to transplant, 98% of the patients were dialysis dependent and 2% underwent pre-emptive living donor kidney transplant. The global readmission rate was 49%, of which 65% were for infectious complications. The most frequent infection was urinary tract infection (n = 28, 62%) and the most common agent detected by blood and urine cultures was Klebsiella pneumonia (n = 18, 40%). The risk factors significantly associated with readmission were higher body mass index (P = .03), diabetes mellitus (P = .02), older donor (P = .007), and longer cold ischemia time (P = .04). There were 3 graft losses, but none due to infectious complications. CONCLUSION: There was a high incidence of early rehospitalization due to infectious complications, especially urinary tract infections to nosocomial agents. The risk factors identified were similar to other series.

Fibrogenesis in Kidney Transplant: Dysfunction Progress Biomarkers.

INTRODUCTION: Fibrogenesis markers, such as alpha-actin (AA), CD163 (macrophages), and E-cadherin, have been studied as chronic kidney allograft injury (CAI) predictors, a major cause of allograft failure. OBJECTIVE: Investigate the value of these markers in predicting CAI and initiation of dialysis. MATERIALS AND METHODS: Retrospective analysis of 26 kidney allograft biopsies (from 22 patients with CAI) during 2 years, evaluating intensity and percentage of marked cells on glomeruli and tubulointerstitial compartment. At the time of the biopsy, patients were 45.5 ± 15.8 years and 4.2 years after transplant, and they had a mean glomerular filtration rate (GFR) of 25.8 ± 9.9 mL/min. From an average of 8.5 glomeruli per biopsy, there was ≤25% sclerosis in 17 cases, 26% to 50% in 5, and >50% in 4. Interstitial fibrosis or tubular atrophy affected ≤25% of cortical area in 14 cases, 26% to 50% in 8, and >50% in 2. Twelve patients started dialysis 5.8 ± 4.7 years after transplant, with an average GFR 20.9 mL/min at the time of the biopsy. RESULTS: There was a higher intensity and percentage of CD163-marked cells in the tubulointerstitial compartment in advanced interstitial fibrosis. We found an association between intensity of AA in the tubulointerstitial compartment and initiation of dialysis (P = .003) and a negative correlation between intensity of E-cadherin loss and GFR (r = -0.56, P = .012). CONCLUSIONS: In our study, intensity of tubulointerstitial AA was shown to be a predictor of initiation of dialysis, and E-cadherin loss intensity was associated to CAI progression. However, prospective and larger studies are needed to evaluate the predictive value of these markers.

Nephrotic Range Proteinuria in Renal Transplantation: Clinical and Histologic Correlates in a 10-year Retrospective Study.

INTRODUCTION: There is a high incidence of nephrotic proteinuria in renal transplant recipients, which is an accurate predictor of graft loss. Despite this, its histologic correlates and prognostic implications are still not well characterized. We assessed the clinical and histological correlates of kidney transplantation patients with nephrotic range proteinuria. METHODS: We have retrospectively analyzed clinical and histological data from 50 kidney transplantation biopsy specimens from 44 renal transplant recipients with nephrotic range proteinuria between 2006 and 2015. The median follow-up time was 93 months (range, 14 months to 190 months). RESULTS: The mean age of the patients was 45.2 ± 13.7 years and our cohort included 86% recipients of deceased-donor grafts. The maintenance immunosuppressive regimen included calcineurin inhibitors in 68% and mammalian target of rapamycin inhibitors in 32% of patients. The average proteinuria was 6.9 ± 3.8 g/d and 52% of patients presented with nephrotic syndrome. The main histological findings were transplant glomerulopathy (22%), de novo glomerular disease (22%), and recurrence of primary disease (22%). Tubular atrophy and interstitial fibrosis was present in 78% of the biopsy specimens. Thirty-one patients (62%) lost the graft at follow-up. There was no statistically significant difference between the histologic diagnosis nor the proteinuria levels and the outcome of the graft. CONCLUSIONS: The main causes of nephrotic range proteinuria in patients undergoing biopsy were transplant glomerulopathy, recurrence of the underlying disease, and de novo glomerulonephritis. Nephrotic range proteinuria was related to a high rate of graft loss.

Polyomavirus Nephropathy: Ten-Year Experience.

BACKGROUND: Polyomavirus nephropathy (BKVN) is an important cause of chronic allograft dysfunction (CAD). Recipient determinants (male sex, white race, and older age), deceased donation, high-dose immunosuppression, diabetes, delayed graft function (DGF), cytomegalovirus infection, and acute rejection (AR) are risk factors. Reducing immunosuppression is the best strategy in BKVN. The objective of our study was to evaluate CAD progression after therapeutic strategies in BKVN and risk factors for graft loss (GL). METHODS: Retrospective analysis of 23 biopsies, from patients with CAD and histological evidence of BKVN, conducted over a period of 10 years. Glomerular filtration rate was <30 mL/min in 16 patients at the time of the BKVN diagnosis. RESULTS: BKVN was histologically diagnosed in 23 recipients (19 men, 4 women). All patients were white, with age of 51.2 ± 12.1 years (6 patients, age >60 years), and 22 had a deceased donor. Diabetes affected 4 patients, DGF occurred in 3, cytomegalovirus infection in 2, and AR in 15. All patients were medicated with calcineurin inhibitors (CNI) (95.7% tacrolimus) and corticoids, and 16 also received an antimetabolite. One year after antimetabolite reduction/discontinuation and/or CNI reduction/switching and/or antiviral agents, graft function was decreased in 11 patients, increased/stabilized in 10, and unknown in 2. GL occurred in 9 patients. Older age (hazard ratio, 1.76; 95% confidence interval, 0.94-3.28) and DGF (hazard ratio, 2.60; 95% confidence interval, 0.54-12.64) were the main risk factors for GL. The lower GFR at the time of the BKVN diagnosis was associated with an increased risk of initiation of dialysis. CONCLUSIONS: GL occurred in 39.1% of patients with BKVN and DGF; older age and lower GFR at the time of diagnosis were important risk factors. Early diagnosis of BKVN is essential to prevent GL.

Surgical Complications in Early Post-transplant Kidney Recipients.

BACKGROUND: The purpose of this study was to determine the incidence of early surgical complications of kidney transplantation in our institution and its association with donor and recipient factors, as well as patient and transplant outcome. METHODS: A retrospective cohort study of all kidney transplants performed during 2015 was made. We evaluated the incidence of surgical complications and the outcome of patients and grafts at a 3-month follow-up interval. RESULTS: During the study period, 141 kidney transplants occurred. Seventeen patients had surgical complications (6 urologic, 6 vascular, and 5 other complications). Five patients lost the graft during the follow-up. Older age was associated with other surgical complications (P = .023), and graft loss was associated with the existence of surgical complications, namely, vascular complications (P <.001). For both surgical complications in general and urologic complications, a statistically significant relationship was found with patient weight (P = .003 and P = .034, respectively). The correlation between body mass index (BMI) and surgical complications was not statistically significant. CONCLUSIONS: Our study reveals that older and heavier patients have a higher risk of surgical complications and that vascular complications are associated with graft loss. A statistically significant relationship was not found between BMI and surgical complications, which could indicate that BMI is not the ideal obesity marker. The incidence of surgical complications found in our study is similar to the literature. The selection of transplant recipients is a difficult task, and the possibility of additional surgical complications in older and overweight patients should be taken into account.

What Can We Do When All Collapses? Fatal Outcome of Collapsing Glomerulopathy and Systemic Lupus Erythematosus With Diffuse Alveolar Hemorrhage: Case Report.

INTRODUCTION: Collapsing glomerulopathy (CG) is a rare form of glomerular injury. Although commonly associated with human immunodeficiency virus (HIV) infection, it can occur in association with systemic lupus erythematosus (SLE). CASE REPORT: We present the case of a 50-year-old man, with chronic kidney disease secondary to focal and segmental glomerulosclerosis, who received a cadaveric kidney transplant in 2007. There were no relevant intercurrences until May 2015, when he presented with nephrotic range proteinuria (± 4 g/d). A graft biopsy was performed and it did not show any significant pathological changes. In September, he developed a full nephrotic syndrome (proteinuria 19 g/d) and a graft biopsy was repeated. CG features were evident with a rich immunofluorescence. Antinuclear antibodies (ANA) and anti-double-stranded DNA (anti-dsDNA) antibodies were positive; the remaining immunologic study was normal. Viral markers for HIV, hepatitis C virus (HCV), and hepatitis B virus (HBV) were negative. The patient was treated with corticosteroid pulses and plasmapheresis (seven treatments). A rapid deterioration of kidney function was seen and he became dialysis dependent. He was discharged with a low-dose immunosuppressive treatment. In October, he was hospitalized with diffuse alveolar hemorrhage (DAH). The auto-immune study was repeated, revealing complement consumption and positive titers of ANA and Anti-dsDNA antibodies. Anti-neutrophil cytoplasmic antibodies (ANCAs) and antiglomerular basement membrane antibody (anti-GBM) were negative. Treatment with intravenous corticosteroids, plasmapheresis, and human immunoglobulin was ineffective and the outcome was fatal. CONCLUSION: This case report highlights the possible association of CG and SLE. To our knowledge, it is the first case of SLE presenting with CG and DAH, with the singularity of occurring in a kidney transplant recipient receiving immunosuppression.

Kidney transplantation: which variables should be improved?

INTRODUCTION: Several factors have an impact on allograft survival but many are still controversial. In this study we investigated the effect of multiple factors on early renal graft function as an effort to find new tools to improve. MATERIAL AND METHODS: This was a transversal study of 64 patients who underwent kidney transplantation during the first semester of 2013. Demographic, clinical, and laboratory data were collected and analyzed. We used SPSS 20.0. Univariate analysis through nonparametric tests and multivariate analysis through linear regression were made. RESULTS: Regarding the donor, age (ß = 1.581; P = .003) and stroke as cause of death (P = .044) were associated with a higher creatinine level. Concerning the recipient, age (ß = 0.963; P = .001) as well as the difference between the candidate and the donor (ß = 1.203; P = .000), black race (P = .032/.000), male gender (P = .027/.046), vasculopathic end-stage renal disease (ESRD; P = .050), hemodialysis (HD) modality (P = .001/.033), HD session before surgery (P = .005), body mass index (BMI) >25 kg/m(2) (P = .043), hypoalbuminemia (ß = -0.280/-0.076; P = .029/.046), and anemia (ß = -0.361; P = .032) were also associated with a higher creatinine level. Living donor transplant (P = .000/.043), instant diuresis (P = .000/.021), and post-transplantation higher blood pressure (BP; systolic BP [SBP] ß = -0.452; P = .021 and diastolic BP [DBP] ß = -0.318; P = .033) were associate with lower creatinine values. Overall, 87.6% of the renal function markers after the first semester were explained by the multiple factors above mentioned. CONCLUSIONS: Our findings are of practical clinical interest because nutritional status, hemoglobin, albumin, and BP are some of the objective measurable and modifiable parameters of which management may improve renal graft function.

New Recipes With Known Ingredients: Combined Therapy of Everolimus and Low-dose Tacrolimus in De Novo Renal Allograft Recipients.

BACKGROUND: Calcineurin inhibitors (CNIs) are the cornerstones of immunosuppressive management in renal allograft recipients even though their nephrotoxicity may contribute to a reduced long-term graft survival. This has created a great interest in improving immunosuppressive strategies in the early post-transplantation period. Proliferation signal inhibitors (PSIs), such as everolimus, are promising alternatives, although their side effects may have a drawback in de novo renal transplant recipients, for instance, delaying renal function in the presence of renal ischemia/acute tubular necrosis and predisposing to lymphocele development. STUDY AND METHODS: A retrospective study was developed to compare the combined therapy of low-dose tacrolimus and everolimus (study group) with mycophenolate mofetil/mycophenolic acid and standard-dose tacrolimus (control group) in the first 3 months post-transplantation. The study's end-points concerned renal graft function, proteinuria, incidence of biopsy-proven acute rejection, surgical complication rates, and incidence of new-onset diabetes after renal transplantation. RESULTS: There was no more delayed graft function in the study group and graft function distribution was similar between groups. Median serum creatinine and eGFR were comparable as well as proteinuria levels. Generally, adverse events were rare in both groups and there were no significant statistical differences between them in terms of biopsy-proven acute rejection, surgical complication, and new-onset diabetes after renal transplantation rates. CONCLUSION: Despite the slightly lower tendency for serum creatinine in the study group, renal allograft function wasn't statistically different between groups. Moreover, there weren't more metabolic or surgical complications in the study group. Everolimus may be a choice in tacrolimus-sparing strategies, but a larger study and a longer follow-up are still required.

Invasive Fungal Infections After Kidney Transplantation: A Single-center Experience.

INTRODUCTION: Invasive fungal infections (IFI) affecting transplant recipients are associated with increased mortality and graft dysfunction. OBJECTIVE: Describe the frequency, clinical features, and outcomes of IFI (except pneumocystis infection) in kidney transplant recipients. METHOD: Single-center descriptive study including every kidney transplant recipient with a culture-proven or probable IFI between 2003 and 2013, according to the EORTC-MSG criteria. RESULTS: We identified 45 IFI. There were 13 cases of invasive candidiasis (C. albicans: 6 and non-C. albicans candidial spp.: 7), 11 cases of pulmonary aspergillosis (A. fumigatus: 9 and A. flavus: 2); 11 cases of subcutaneous mycosis (Alternaria spp.: 9, Paecilomyces spp.: 1, and Pseudallescheria spp.: 1); 7 cases of cryptococcosis; 2 cases of pneumonia by non-Aspergillus molds (Mucor spp.: 1 and Cunninghamella spp.: 1); and 1 case of Geotrichum capitatum pneumonia. All patients were recipients from deceased donors. Six cases occurred in the first 3 months post-transplant, 15 cases between the third and twelfth months, and 21 cases after the twelfth month. Treatment options were fluconazole for Candida infections, voriconazole or caspofungin for aspergillosis, liposomal amphotericin for cryptococcosis, and itraconazole plus excision or cryotherapy for subcutaneous mycosis. Fifteen patients died (33%). Mortality rates were 15% for invasive candidiasis, 45% for aspergillosis, 71% for cryptococcosis, 100% for non-Aspergillus molds and G. capitatum pneumonia, and 0% for subcutaneous mycosis. Six patients who survived (14%) started regular hemodialysis. CONCLUSION: IFI still have a high mortality and morbidity in kidney transplant recipients, as verified in this report. We reinforce the need for a high index of suspicion and prompt treatment.

Malignancy in Kidney Transplantation: A 25-Year Single-center Experience in Portugal.

It is known that the incidence of malignancy in transplant recipients is higher than in the general population, with a more aggressive behavior and a worse outcome. In fact, malignancy is the third most common cause of death among kidney transplant (KT) recipients, after cardiovascular events and infections. The aim of this study was to investigate the incidence and characteristics of malignancies after KT in a single center. A total of 2353 patients who underwent KT between 1987 and 2012 were retrospectively studied. The results were compared with a group without cancer. During the follow-up period leading to August 2014, which included a median duration of 126.3 ± 81.8 months, 223 malignancies (9.4%) were diagnosed, which were the cause of death in 59 patients. Patients with cancer were older, had a longer duration of graft function, and had more episodes of acute rejection (AR), and a higher number of patients were treated with azathioprine and cyclosporine as initial immunosuppressive regime (P = .001). The most frequent malignancy was skin cancer (28.7%), followed by malignant lymphoma (12.1%) and kidney cancer (10.8%). The mean age of patients at diagnosis was 58.0 ± 11.1 years. The average time for development of a cancer was 7.5 ± 5.8 years, with 43.2% detected between 1 and 5 years. Patient survival was significantly lower among subjects with cancer, and censored graft survival was significantly higher in this group (P = .001). Multivariate logistic regression analysis showed that recipients' age and acute rejection episode are risk factors for development of post-kidney transplantation malignancy.