[Show abstract][Hide abstract] ABSTRACT: In renal transplanted patients, lymphoceles and lymphorrhea are well-known lymphatic complications. Surgical damage of the lymphatics of the graft during the procurement and of the lymphatic around the iliac vessels of the recipients has been associated with development of lymphatic complications. However, lymphatic complications may be related to medical factors such as diabetes, obesity, blood coagulation abnormalities, anticoagulation prophylaxis, high dose of diuretics, delay in graft function and immunosuppressive drugs. Consistently, immunosuppression regimens based on the use of mTOR inhibitors, especially in association with steroids and immediately after transplantation, has been associated with a high risk to develop lymphocele or lymphorrhea. In addition, several studies have demonstrated the association between rejection episodes and lymphatic complications. However, before the discovery of reliable markers of lymphatic vessels, the pathogenic mechanisms underlining the development of lymphatic complications during rejection and the influence of mTOR inhibitors remained not fully understood. The recent findings on the lymphatic systems of either native or transplanted kidneys together with the advances achieved on lymphangiogenesis shared some lights on the pathogenesis of lymphatic complications after renal transplantation. In this review, we describe the surgical and medical causes of lymphatic complications focusing on the rejection and immunosuppressive drugs as causes of lymphatic complications.
[Show abstract][Hide abstract] ABSTRACT: Background:
Delayed graft function (DGF) is an early complication of kidney transplantation (KT) associated with increased risk of early loss of graft function. DGF increases using kidneys from extended criteria donors (ECD). NGAL is a 25KDa protein proposed as biomarker of acute kidney injury. The aim of this study was to investigate the role of NGAL as an early and accurate indicator of DGF and Tacrolimus (Tac) toxicity and as a mediator of tissue regeneration in KT from ECD.
We evaluated plasma levels of NGAL in 50 KT patients from ECD in the first 4 days after surgery or after Tac introduction.
Plasma levels of NGAL at day 1 were significantly higher in DGF group. In the non DGF group, NGAL discriminated between slow or immediate graft function and decreased more rapidly than serum creatinine. NGAL increased after Tac introduction, suggesting a role as marker of drug toxicity. In vitro, hypoxia and Tac induced NGAL release from tubular epithelial cells (TEC) favoring an autocrine loop that sustains proliferation and inhibits apoptosis (decrease of caspases and Bax/Bcl-2 ratio).
NGAL is an early and accurate biomarker of graft function in KT from ECD favoring TEC regeneration after ischemic and nephrotoxic injury.
PLoS ONE 06/2015; 10(6):e0129279. DOI:10.1371/journal.pone.0129279 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Encapsulating peritoneal sclerosis (EPS) is a serious complication in patients on peritoneal dialysis (PD) causing intestinal obstruction. Two different forms of EPS are reported: the classical one observed in patients on PD, and post-transplantation EPS (PostTx-EPS). The first-line therapy of classical and PostTx-EPS remains surgical treatment, but for both the complication rate and mortality are high. Recently, a few cases of EPS were successfully treated with inhibitors of mammalian target of rapamycin (mTORi). The aim of this study was to evaluate PostTx-EPS outcome in our patients, focusing on the potential benefit of mTORi treatment.
We performed a retrospective analysis on 1,048 kidney transplanted patients at our center between 11/2001 and 12/2011.
In the 226 patients treated with PD at any time before grafting, we found 10 cases of PostTx-EPS (prevalence 4.4 %). The mean age was 54.9 years (26-69), with a mean time on PD of 83.1 months (33-156). The interval between kidney transplant and EPS diagnosis was 10.5 months (4-18.9). Five of the ten patients were treated after the diagnosis with mTORi, with a favorable outcome in 4/5 cases. This result was substantially independent of surgical and steroid therapy, performed in 9/10 and 10/10 patients respectively.
EPS is a serious complication but susceptible to improvement if early diagnosed. mTORi represent a useful option for EPS treatment. We too suggest adopting an immunosuppressive protocol based on mTORi, mycophenolate mofetil and steroids in order to prevent PostTx-EPS in transplanted patients at high risk.
Journal of nephrology 01/2015; 28(2). DOI:10.1007/s40620-014-0168-7 · 1.45 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background
Kidney biopsy (KB) represents the criterion standard to obtain information on diagnosis and prognosis of renal allograft dysfunctions. However, it can be associated with bleeding complications (BCs). Bleeding time test (BTT), the best predictive indicator of post-biopsy BCs, is not a very reproducible test and is invasive. Therefore, the aim of this study was to evaluate whether the platelet function analyzer (PFA-100), a very reliable test to investigate primary hemostasis, could be useful in predicting the risk of bleeding complications in transplant patients undergoing KB.
We carried out a retrospective analysis of PFA-100 collagen-epinephrine (C-EPI) and collagen–adenosine diphosphate (C-ADP) closure times in 119 patients undergoing KB in our center. Data regarding BTT, age, sex, blood pressure, number of renal allograft punctures for each biopsy procedure, thromboplastin time, prothrombin time, complete blood count, and prophylactic therapy with desmopressin were also collected. Major (need for blood transfusion) or minor (no need for any intervention) BCs (hematoma and hematuria) were recorded.
Indications for KB were: delayed graft function (n = 23), allograft dysfunction (n = 40), proteinuria (n = 27), allograft dysfunction plus proteinuria (n = 19), and protocol biopsy (n = 10). Nine of the 119 patients (7.5%) developed minor BCs (6 macrohematuria, 3 hematoma), major BCs did not develop. No significant differences were found in any of the clinical and laboratory data, including BTT and PFA-100 (C-EPI and C-ADP) between patients who developed BCs compared with those who did not. In addition, there was no correlation between PFA-100 test (C-EPI and C-ADP) values and BTT data [R2 = 0.002; P = .6].
The PFA-100 test was not useful in predicting the risk of BCs in kidney transplant patients undergoing renal allograft biopsy.
[Show abstract][Hide abstract] ABSTRACT: Pneumotoxic drugs like amiodarone and m-TOR inhibitors (m-TORi) may be administered contemporaneously in therapy for patients who had renal transplants. We present a case of amiodarone pulmonary toxicity (APT) in a patient treated with amiodarone and everolimus. A 57-year-old Caucasian male, under treatment with both everolimus (for 3 years) and amiodarone (for 2 months), presented with fever, dyspnoea and a negative chest X-ray after his second kidney transplant with suboptimal serum creatinine (3 mg/dl). A non-contrastive high-resolution CT scan showed bilateral interstitial lung disease with an associated reduction in carbon monoxide diffusing capacity. Bronchoalveolar lavage (BAL) was negative for an infection, but BAL cytology was suitable for APT (50% of 'foamy' macrophages). A complete recovery was achieved after amiodarone interruption and an oral steroid therapy increase. Everolimus was continued. His kidney function remained unchanged in the upcoming months. In conclusion, we suggest a possible synergistic effect between m-TORi and amiodarone. Furthermore, we propose a diagnostic algorithm that can be used as a surveillance tool to identify a potential initial lung damage in patients treated with 1 or more pneumotoxic drugs.
[Show abstract][Hide abstract] ABSTRACT: The Oxford Classification of IgA Nephropathy (IgAN) identified mesangial hypercellularity (M), endocapillary proliferation (E), segmental glomerulosclerosis (S), and tubular atrophy/interstitial fibrosis (T) as independent predictors of outcome. Whether it applies to individuals excluded from the original study and how therapy influences the predictive value of pathology remain uncertain. The VALIGA study examined 1147 patients from 13 European countries that encompassed the whole spectrum of IgAN. Over a median follow-up of 4.7 years, 86% received renin–angiotensin system blockade and 42% glucocorticoid/immunosuppressive drugs. M, S, and T lesions independently predicted the loss of estimated glomerular filtration rate (eGFR) and a lower renal survival. Their value was also assessed in patients not represented in the Oxford cohort. In individuals with eGFR less than 30 ml/min per 1.73 m2, the M and T lesions independently predicted a poor survival. In those with proteinuria under 0.5 g/day, both M and E lesions were associated with a rise in proteinuria to 1 or 2 g/day or more. The addition of M, S, and T lesions to clinical variables significantly enhanced the ability to predict progression only in those who did not receive immunosuppression (net reclassification index 11.5%). The VALIGA study provides a validation of the Oxford classification in a large European cohort of IgAN patients across the whole spectrum of the disease. The independent predictive value of pathology MEST score is reduced by glucocorticoid/immunosuppressive therapy.
Keywords: glomerular diseases; IgA nephropathy; progression of chronic renal failure; proteinuria; renal pathology; risk factors
[Show abstract][Hide abstract] ABSTRACT: Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a rare disease caused by thymidine phosphorylase deficiency which leads to toxic accumulations of thymidine (dThd) and deoxyuridine (dUrd). It lacks an established treatment and the prognosis is traditionally poor. We report a case of a young female patient with normal renal function and MNGIE treated by peritoneal dialysis (PD) and allogeneic bone marrow transplantation (BMT). PD was effective in reducing dThd and dUrd plasma levels and in improving clinical symptoms. To our knowledge, this is the first report on the beneficial effects of PD regarding MNGIE neurological symptoms. PD, therefore, should be considered especially in medically compromised patients as a supportive treatment to improve clinical conditions before BMT.
Journal of nephrology 03/2014; 28(1). DOI:10.1007/s40620-014-0069-9 · 1.45 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Epstein-Barr virus (EBV) is a γ-herpes virus, responsible for infectious mononucleosis in immunocompetent hosts. Cellular immunity appears rapidly during EBV primary infection, keeping it silent despite long-life persistence in B lymphocytes. Defects of the EBV-specific cellular immunity are supposed to be the basis of post-transplantation lymphoproliferative disorders, promoted by high levels of immunosuppression. We retrospectively reviewed 197 solid organ transplant recipients to investigate EBV-specific lymphocyte responsiveness using Enzyme-linked ImmunoSpot assay (EliSpot), which assesses the EBV-specific interferon (IFN)-γ producing peripheral blood mononuclear cells, and kinetics of EBV infection/reactivation post-transplantation using quantitative real-time polymerase chain reaction (PCR) on whole blood. Overall, 102 of the 197 patients (51.8%) showed EBV responsiveness at the EBV-EliSpot assay: 68 (66.6%) showed a persistently positive EBV response in 3 or more determinations and 34 (33.3%) had transient episodes of nonresponsiveness. Ninety-five (48.2%) patients were persistently EBV nonresponders. EBV-DNAemia data were available for 58 patients: 27.6% presented at least one episode of EBV-DNA occurrence. No differences were found in EBV-EliSpot response stratification between the groups of patients who experienced episodes of EBV reactivation and those without EBV-DNAemia. However, EBV DNAemia peak values tended to be higher in the first year post-transplantation in the group of patients with a persistent positive EBV-specific immune response. EBV viral load quantitation in blood and EliSpot EBV-specific immune response determination may represent a powerful tool for monitoring solid organ transplant recipients, guiding immunosuppression modulation in patients with active EBV replication.
[Show abstract][Hide abstract] ABSTRACT: Atypical hemolytic uremic syndrome (aHUS), which can recur after renal transplantation, is associated with poor graft outcomes. The underlying genetic defect, namely, mutations in genes coding for the complement factor H, I (CFI), or membrane cofactor protein, greatly impacts the risk of aHUS recurrence. We report here the case of a patient with chronic renal failure due to aHUS in which screening for complement mutations, performed before wait-listing for kidney transplantation, showed a never described previously heterozygous mutation in the exon II of the CFI gene. Specifically, this mutation leads to a substitution of cytosine for guanosine at nucleotide 148, resulting in the change at amino acid 50 from arginine to proline. Subsequently, he received a renal allograft from deceased donor. Good graft function was established immediately, without clinical features of aHUS. Due to a lack of data on this mutation, we avoided prophylactic treatment for aHUS but closely monitored biochemical markers of aHUS to treat a possible recurrence. Immunosuppressive treatment was based on basiliximab, tacrolimus, steroids, and mycophenolic acid. At the time of discharge the serum creatinine was 1.4 mg/dL. Ten months after transplantation the patient is doing well without evidence of aHUS. Our case suggested that a heterozygous mutation in exon II of the CFI gene was not associated with a risk of early post-transplant aHUs recurrence adding new knowledge on complement mutations implicated in aHUS post-transplant recurrences.
[Show abstract][Hide abstract] ABSTRACT: Recurrent or "de novo" AA amyloidosis in the renal allograft is rarely described. We describe a case of severe nephrotic syndrome in a recipient of a kidney graft with a previous diagnosis of polycystic nephropathy caused by AA amyloidosis diagnosed only after the renal transplantation. The disease was possibly a tumor necrosis factor receptor-associated periodic syndrome (TRAPS). TRAPS is a rare hereditary inflammatory disease never reported to the best of our knowledge, as a de novo diagnosis in the transplantation setting. Biopsy of the renal graft, indicated for the onset of heavy proteinuria, and genetic investigation provided the clues for diagnosis.
[Show abstract][Hide abstract] ABSTRACT: Introduction:
Forgotten indwelling ureteral stents can cause significant urological complications. Only few cases are reported after kidney transplantation.
Materials and methods:
We present a case of a 39-year-old woman, transplanted in 1993 and referred to our Transplant Center 8 years later, because of a serious urinary tract infection with renal function impairment. Abdominal CT scan showed pyelonephritis and hydronephrosis in the transplanted kidney and the presence of a calcific ureteral stent, which had been forgotten in situ for 8 years. The stent was removed, but it was impossible to replace it with a new stent both retrogradely and anterogradely, because of a tight obstruction of the mid ureter. So a uretero-ureteral anastomosis with up urinary tract was performed.
No intra- or post-operative complications occurred. At 9 years' follow-up, the patient shows an optimal renal function, with no urinary tract infection.
A forgotten ureteral stent in a transplanted kidney can cause a lot of complications and can lead to graft loss. The prosthesis may cause an irreversible ureteral damage, so, as in our experience, forgetting a ureteral stent can result in a complex surgery.
[Show abstract][Hide abstract] ABSTRACT: The phosphodiesterase type 5 (PDE5) inhibitors are generally well tolerated and effective for treating erectile dysfunction (ED), including in patients with significant comorbidity. Because of this benign safety profile, investigators have used PDE5 inhibitors to treat patients with ED and severe renal disease or those who have received renal transplants.
To assess safety and efficacy of PDE5 inhibitors in patients receiving dialysis or renal transplants.
Erectile function as assessed by the International Index of Erectile Function (IIEF) and Global Assessment Questions; adverse events (AEs).
We reviewed published studies of PDE5 inhibitors in patients receiving dialysis or renal transplants.
In double-blind, placebo-controlled studies in patients receiving dialysis or renal transplants, sildenafil significantly improved erectile function as assessed by the IIEF, and 75–85% of patients reported improved erectile function on Global Assessment Questions; efficacy was more variable in less well-controlled studies. In >260 patients undergoing dialysis who received sildenafil in clinical studies, there were only six reported discontinuations because of AEs (headache [N = 3], headache and nausea [N = 1], gastrointestinal [N = 1], and symptomatic blood pressure decrease [N = 1]). In approximately 400 patients with renal transplants who received sildenafil, only three patients discontinued because of AEs. Vardenafil improved IIEF scores of up to 82% of renal transplant recipients in randomized, controlled studies (N = 59, total), with no reported discontinuations because of AEs. Limited data also suggest benefit with tadalafil.
ED is common in patients undergoing renal dialysis or postrenal transplant and substantially affects patient quality of life. Sildenafil and vardenafil appear to be efficacious and well tolerated in patients receiving renal dialysis or transplant. Lasaponara F, Sedigh O, Pasquale G, Bosio A, Rolle L, Ceruti C, Timpano M, Negro CLA, Paradiso M, Abbona A, Segoloni GP, and Fontana D. Phosphodiesterase type 5 inhibitor treatment for erectile dysfunction in patients with end-stage renal disease receiving dialysis or after renal transplantation. J Sex Med 2013;10:2798–2814.
Journal of Sexual Medicine 01/2013; 10(11). DOI:10.1111/jsm.12038 · 3.15 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Comparative analysis of the different subsets of CD4+ T-lymphocytes may provide hints on the immunologic mechanisms operating in the long-term fate of a kidney transplant.We analyzed peripheral regulatory CD4+ T cells (Tregs) and CD4+ cytotoxic T lymphocytes (CTLs) in antibody-mediated chronic rejection (AMCR), in middle-term kidney transplants (2-4years, MTKT) with good graft function and rejection-free history, in long-term kidney transplants (>15years, LTKT) and in normal healthy subjects (NHS).Transplant groups with good prognosis (MTKT and LTKT) displayed a significant lower amount of CD4+CD25high T lymphocytes than NHS, with a trend of a higher percentage in AMCR than in MTKT and LTKT. However, CD4+CD25high Foxp3+ cells were significantly higher in LTKT and MTKT than AMCR. Characterization of CD4+CD25high T cells showed a marked increase of intracellular CTLA-4 in the AMCR group in respect to the other transplant groups, while the expression of the surface molecule seemed to follow a reverse trend. In addition, CD27, a costimulatory receptor involved in long-term T cell survival and prevention of immune tolerance, is significantly reduced in CD4+CD25high and CD4+Foxp3+ T cells in the LTKT in respect to the other transplant groups. CD4+CD25highCD45RO+ and CD4+Foxp3+CD45RO+ regulatory T cells with memory function were increased in LTKT compared to NHS and for the latter also in AMCR group.Finally, CD4+CTLs that were quantified on the basis of granzyme A expression, were more represented in AMCR patients in comparison to the other groups. Strikingly, CD27 in the CD4+CTLs was suppressed in LTKT and MTKT and markedly expressed in AMCR group. No significant differences in the expression of CD28 were observed among different groups.In conclusion, different profiles of Tregs and CD4+CTL populations correlate with different long-term conditions of kidney-transplanted patients, suggesting their role in the development of immunologic events in kidney transplantation.
[Show abstract][Hide abstract] ABSTRACT: The recognition of antibody-mediated rejection as an important factor in the reduction of long-term renal graft survival represents a new challenge to the immunosuppressive strategies of recent years, which have been quite successful in reducing the acute rejection rates as well as the side effects of pharmacological immunosuppression. The search for an effective treatment of chronic anti-donor antibody disease has been pursued mostly through limited single-center experiences and therefore in a dispersed fashion, without leading to the definition of a consolidated approach. The most frequently used pharmacological approaches stem from the experience of antibody-mediated acute rejection. In this review we will critically analyze the results reported so far of various intervention strategies and we will discuss future pharmacological novelties targeting the humoral immune response.
Giornale italiano di nefrologia: organo ufficiale della Societa italiana di nefrologia 11/2012; 29(5):579-91.