ABSTRACT
INTRODUCTION: Solid organ transplant patients are at heightened risk of several cancers compared to the general population. Secondary to a higher number of procedures and better survival after transplantation, cancer is a rising health concern in this situation. Limited data exist for lung cancer (LC) after renal transplantation. We report here the most important series of renal transplant recipients with lung cancer. METHODS: Retrospective study of all cases of LC diagnosed in three French Renal Transplant Units from 2003 to 2012. A control group consisted of non-transplant patients with LC matched with the cases for age (<30; 30-50; 50-65; >65 years), gender and diagnosis date. We recruited two controls for each case. RESULTS: Thirty patients (median age 60 years; range 29-85; male/female ratio 80/20%) with LC were analysed. LC incidence was 1.89/1000 person-years over the period 2008-2012. All patients were former or active smokers (median 30 pack-years). Transplanted patients had significantly more comorbidities, mainly cardiovascular disease. The median interval of time from kidney transplantation (KT) to diagnosis of LC was 7 years (range 0.5-47 years). LC was incidentally diagnosed in 40%. Most patients (70%) had advanced LC (stage III or IV) disease. Stage of LC at diagnosis was similar in cases and controls. Surgery and chemotherapy were proposed to the same proportion of patients. In cases, mortality was cancer related in 87% and median survival time after diagnosis was 24 months. Survival was not significantly different between the 2 groups. CONCLUSION: Despite frequent medical and radiological examinations, diagnosis of LC is usually made at an advanced stage and the overall prognosis remains poor.
Subject(s)
Kidney Transplantation , Lung Neoplasms/epidemiology , Lung Neoplasms/etiology , Transplant Recipients , Adult , Aged , Aged, 80 and over , Case-Control Studies , Combined Modality Therapy , Female , Humans , Incidence , Kaplan-Meier Estimate , Kidney Transplantation/adverse effects , Lung Neoplasms/diagnosis , Lung Neoplasms/therapy , Male , Middle Aged , Neoplasm Staging , Population Surveillance , Retrospective StudiesABSTRACT
High-dose intravenous immunoglobulin (IVIg) is commonly used during kidney transplantation. Its nephrotoxicity has been attributed to sucrose stabilizers. We evaluated the renal safety of newer formulations of sucrose-free IVIg. We retrospectively studied clinical and histological data from 75 kidney recipients receiving high-dose, sucrose-free IVIg courses. This group was compared with 75 matched kidney recipients not treated with IVIg. Sucrose-free IVIg treatment was not associated with any acute kidney injury episode at 3 months, but an increased frequency of tubular macrovacuoles (28% vs. 2.8%, P < 0.001) was observed. Among IVIg-treated patients, the presence of macrovacuoles at 3 months was associated with increased IF/TA scores at 3 months (1.7 ± 1 vs. 1 ± 1, P = 0.005) and was more often observed in kidneys with higher IF/TA scores on day 0 (0.6 ± 0.9 vs. 0.3 ± 0.8, P = 0.03) at 3 months. Finally, patients treated with amino-acid-stabilized formulations developed fewer macrovacuoles at 3 months (12% vs. 60%; P < 0.001) than those treated with carbohydrate-stabilized IVIg. Our study shows that high-dose, sucrose-free IVIg use in early kidney recipients is clinically well tolerated. Among sucrose-free IVIg, amino-acid-stabilized formulations are associated with less tubular toxicity than carbohydrate-stabilized IVIg.
Subject(s)
Immunoglobulins, Intravenous/therapeutic use , Kidney Transplantation , Kidney/surgery , Renal Insufficiency/surgery , Adult , Aged , Biopsy , Carbohydrates , Female , Graft Rejection , Humans , Immunoglobulins, Intravenous/administration & dosage , Kidney/pathology , Male , Middle Aged , Retrospective Studies , Risk , SucroseABSTRACT
BACKGROUND: Prostate cancer (PCa) incidence is expected to increase in renal transplant recipients (RTR) with no clear nor contemporary data on management and oncological outcome. METHODS: We conducted a retrospective single center study of RTR diagnosed with PCa after transplantation between 2000 and 2013. Demographics, PCa characteristics, and treatment were assessed. For each RTR in radical prostatectomy (RP) subset, we included 4 non-organ transplant patients who underwent RP by the same surgeons, and compared pre-operative and post-operative oncological features, and biochemical recurrence (BCR) rate. RESULTS: Twenty-four RTR were included (PCa incidence 1.5%). Mean follow-up was 47 months. PCa was mostly localized (n=21, 87.5%) with treatments including RP (n=16, 76.2%), brachytherapy (n=3, 14.3%), radiation therapy (n=1, 4.7%), and active surveillance (n=1, 4.7%). No graft loss due to PCa treatment was reported. Nineteen RTR with localized PCa (90.5%) were free from BCR. Considering RP subset, no difference in PCa characteristics at diagnosis and BCR rate was found between RTR (n=16) and control patients (n=64). CONCLUSIONS: Localized PCa following renal transplantation was not associated with adverse features as compared with non-transplant patients. Standard treatments could be proposed to RTR with satisfying results both on oncological outcome and graft function.
Subject(s)
Kidney Transplantation/adverse effects , Postoperative Complications , Prostatic Neoplasms/etiology , Transplant Recipients , Aged , Follow-Up Studies , France/epidemiology , Humans , Incidence , Male , Middle Aged , Prognosis , Prostatic Neoplasms/diagnosis , Prostatic Neoplasms/epidemiology , Retrospective Studies , Survival Rate/trends , Time FactorsABSTRACT
After the first year post transplantation, prognostic mortality scores in kidney transplant recipients can be useful for personalizing medical management. We developed a new prognostic score based on 5 parameters and computable at 1-year post transplantation. The outcome was the time between the first anniversary of the transplantation and the patient's death with a functioning graft. Afterwards, we appraised the prognostic capacities of this score by estimating time-dependent Receiver Operating Characteristic (ROC) curves from two prospective and multicentric European cohorts: the DIVAT (Données Informatisées et VAlidées en Transplantation) cohort composed of patients transplanted between 2000 and 2012 in 6 French centers; and the STCS (Swiss Transplant Cohort Study) cohort composed of patients transplanted between 2008 and 2012 in 6 Swiss centers. We also compared the results with those of two existing scoring systems: one from Spain (Hernandez et al.) and one from the United States (the Recipient Risk Score, RRS, Baskin-Bey et al.). From the DIVAT validation cohort and for a prognostic time at 10 years, the new prognostic score (AUC = 0.78, 95%CI = [0.69, 0.85]) seemed to present significantly higher prognostic capacities than the scoring system proposed by Hernandez et al. (p = 0.04) and tended to perform better than the initial RRS (p = 0.10). By using the Swiss cohort, the RRS and the the new prognostic score had comparable prognostic capacities at 4 years (AUC = 0.77 and 0.76 respectively, p = 0.31). In addition to the current available scores related to the risk to return in dialysis, we recommend to further study the use of the score we propose or the RRS for a more efficient personalized follow-up of kidney transplant recipients.
Subject(s)
Kidney Transplantation/mortality , Cohort Studies , Decision Making , Europe , Humans , Prognosis , Survival AnalysisABSTRACT
BACKGROUND: Cystinosis is a rare lysosomal disorder leading to end stage renal disease in more than 90 % of patients before 20 years of age. Data about safety and efficiency of renal transplantation in patients with cystinosis is scarce. We evaluated long-term outcomes of renal transplantation in adult patients with cystinosis. METHODS: Data of renal transplantation (n = 31) in 30 adult patients with cystinosis in 5 French university transplant centers between 1980 and 2013 were retrospectively analyzed. A control cohort of 93 patients was matched for age, graft date, living/deceased donor status and transplant center. RESULTS: Median age at transplantation was 20.4 years (7-36.5). At transplantation, all patients with cystinosis had corneal cystine deposits, 3 had diabetes and 7 had hypothyroidism. Graft survival was better in patients with cystinosis than in control patients (p = 0.013). Multivariate analysis confirmed that cystinosis was an independent protective factor for graft survival (Hazard Ratio (HR) 0.11; CI95 [0.02-0.61]). Specific complications of cystinosis occurred during follow up: diabetes mellitus (n = 4), hypothyroidism (n = 1), liver involvement (n = 1), neurologic involvement (n = 2). Proportion of post-transplant diabetes mellitus (PTDM) was not statistically different in cystinosis group compared to control group: 4 (13.0 %) compared to 5 (5.0 %), respectively (p = 0.25), with no differences regarding calcineurin inhibitors and steroids treatments during follow-up. CONCLUSIONS: Renal transplantation appears to be safe with excellent long-term outcomes in patients with cystinosis. These patients may receive standard immunosuppressive regimens with steroids and calcineurin inhibitors.
Subject(s)
Cystinosis/complications , Kidney Failure, Chronic/surgery , Kidney Transplantation , Adolescent , Adult , Child , Cystinosis/physiopathology , Humans , Kidney Failure, Chronic/etiology , Treatment Outcome , Young AdultABSTRACT
Although cold ischemia time has been widely studied in renal transplantation area, there is no consensus on its precise relationship with the transplantation outcomes. To study this, we sampled data from 3839 adult recipients of a first heart-beating deceased donor kidney transplanted between 2000 and 2011 within the French observational multicentric prospective DIVAT cohort. A Cox model was used to assess the relationship between cold ischemia time and death-censored graft survival or patient survival by using piecewise log-linear function. There was a significant proportional increase in the risk of graft failure for each additional hour of cold ischemia time (hazard ratio, 1.013). As an example, a patient who received a kidney with a cold ischemia time of 30 h presented a risk of graft failure near 40% higher than a patient with a cold ischemia time of 6 h. Moreover, we found that the risk of death also proportionally increased for each additional hour of cold ischemia time (hazard ratio, 1.018). Thus, every additional hour of cold ischemia time must be taken into account in order to increase graft and patient survival. These findings are of practical clinical interest, as cold ischemia time is among one of the main modifiable pre-transplantation risk factors that can be minimized by improved management of the peri-transplantation period.
Subject(s)
Cold Ischemia/adverse effects , Kidney Transplantation/adverse effects , Adult , Aged , Cohort Studies , Female , France/epidemiology , Graft Survival , Humans , Kidney Transplantation/mortality , Male , Middle Aged , Proportional Hazards Models , Prospective Studies , Risk Factors , Survival Analysis , Time Factors , Treatment FailureABSTRACT
Delayed graft function (DGF) is a common complication in kidney transplantation and is known to be correlated with short- and long-term graft outcomes. Here we explored the possibility of developing a simple tool that could predict with good confidence the occurrence of DGF and could be helpful in current clinical practice. We built a score, tentatively called DGFS, from a French multicenter and prospective cohort of 1844 adult recipients of deceased donor kidneys collected since 2007, and computerized in the Données Informatisées et VAlidées en Transplantation databank. Only five explicative variables (cold ischemia time, donor age, donor serum creatinine, recipient body mass index, and induction therapy) contributed significantly to the DGF prediction. These were associated with a good predictive capacity (area under the ROC curve at 0.73). The DGFS calculation is facilitated by an application available on smartphones, tablets, or computers at www.divat.fr/en/online-calculators/dgfs. The DGFS should allow the simple classification of patients according to their DGF risk at the time of transplantation, and thus allow tailored-specific management or therapeutic strategies.
Subject(s)
Decision Support Techniques , Delayed Graft Function/diagnosis , Kidney Transplantation/adverse effects , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , Antilymphocyte Serum/administration & dosage , Area Under Curve , Body Mass Index , Cadaver , Child , Child, Preschool , Cohort Studies , Cold Ischemia/adverse effects , Creatinine/blood , Delayed Graft Function/etiology , Delayed Graft Function/therapy , Female , Humans , Immunosuppressive Agents/administration & dosage , Induction Chemotherapy , Infant , Male , Middle Aged , Mobile Applications , Predictive Value of Tests , Prospective Studies , ROC Curve , Risk Factors , Smartphone , Tissue Donors , Young AdultABSTRACT
Post-transplant lymphoproliferative disorder (PTLD) is an uncontrolled proliferation of transformed lymphocytes fostered by immunosuppression. In addition to chemotherapy, treatment of PTLD includes a reduction of maintenance immunosuppression. Patients with PTLD have an increased risk of graft loss, suggesting that reduced immunosuppression strategy needs to be optimized with regard to graft outcome. Here we retrospectively reviewed 101 cases involving PTLD to identify the risks associated with graft loss. During a median follow-up of 70 months, 39 patients died and 21 lost their graft. Multivariate analysis found that an eGFR under 30 ml/min per 1.73 m(2) at PTLD diagnosis, a biopsy-proven acute rejection episode following reduction of immunosuppression, and the absence of calcineurin inhibition in maintenance immunosuppression are independent risk factors for allograft loss. Neither the type of PTLD nor the chemotherapy regimen was predictive of allograft failure. Histological analysis of graft biopsies showed that maintaining calcineurin inhibition after the diagnosis of PTLD reduced the risk of developing de novo anti-HLA antibodies and humoral rejection. Remarkably, calcineurin inhibitor maintenance was neither associated with higher mortality nor with worse progression-free survival. Thus, maintaining calcineurin inhibition at a reduced dose after the diagnosis of PTLD seems safe and may improve renal graft outcome, possibly through better control of the recipient's humoral immune response.
Subject(s)
Calcineurin Inhibitors , Calcineurin/physiology , Graft Survival/drug effects , Kidney Transplantation/mortality , Lymphoproliferative Disorders/drug therapy , Postoperative Complications/drug therapy , Adolescent , Adult , Aged , Child , Child, Preschool , Female , France/epidemiology , Graft Rejection/pathology , Graft Rejection/prevention & control , Humans , Immunosuppression Therapy , Infant , Kidney/pathology , Lymphoproliferative Disorders/mortality , Male , Middle Aged , Postoperative Complications/mortality , Retrospective Studies , Risk Factors , Young AdultABSTRACT
BACKGROUND AND OBJECTIVES: Contradictory results are reported concerning the influence of anemia on patient and graft survival after renal transplantation. Assuming that level of renal function and anemia are strongly correlated, posttransplantation anemia (PTA) may have a different impact depending on the stage of chronic kidney disease (CKD). METHODS: This study is a retrospective multicenter analysis using the DIVAT French database. The prevalence, risk factors, and influence of 12-month PTA (World Health Organization's definition) on patient and graft survival were analyzed according to CKD stage (Modification of Diet in Renal Disease equation). RESULTS: The prevalence of 12-month PTA in our cohort of 4217 patients was 41.1%. Multivariate analysis demonstrated that worse renal function, donor age, period of transplantation, induction therapy, and mTOR inhibitors were significant risk factors for PTA. Posttransplantation anemia was a significant risk factor for all-cause mortality in CKD stages 1 to 2T (hazard ratio, 2.39; 95% confidence interval, 1.99-4.40) and 3T (hazard ratio, 1.52; 95% confidence interval, 1.08-2.15) and for cardiovascular mortality only on CKD stages 1T and 2T. In renal transplant recipients with CKD stages 4 to 5T, patient and graft survival were similar in patients with versus without anemia. Graft survival was not influenced by PTA, whatever the CKD stage. CONCLUSIONS: Posttransplantation anemia is associated with decreased patient survival only in CKD stages 1T, 2T, and 3T. Posttransplantation anemia has no influence on graft survival regardless of CKD stage.
Subject(s)
Anemia/mortality , Graft Survival , Kidney Transplantation/mortality , Postoperative Complications/mortality , Renal Insufficiency, Chronic/surgery , Adult , Aged , Anemia/epidemiology , Cohort Studies , Female , Hemoglobins/analysis , Humans , Male , Middle Aged , Postoperative Complications/epidemiology , Retrospective StudiesABSTRACT
Compared to dialysis, kidney transplantation appears to be the best treatment for chronic kidney failure, even for older aged patients. Nevertheless, the individual benefit of transplanting elderly patients has to be balanced against the corresponding increase in the number of patients awaiting grafts. We analyzed the excess mortality related to kidney transplant recipients by taking into account the expected mortality of the general population (additive regression model for relative survival). We applied this method to a cohort of patients who received a first deceased-donor kidney transplant between 1998 and 2009 in France (DIVAT, n = 3641). Overall 10-year mortality was 13%. As expected, recipient age was the main risk factor associated with overall mortality. In contrast, recipient age was no longer significantly associated with the excess of mortality related to kidney transplant status by subtracting the expected mortality of the general population. Delayed graft function (DGF), pretransplantation immunization, and past history of diabetes appeared as the main risk factors of this higher mortality rate. Our results constitute a strong argument in favor of kidney transplantation, regardless of the patient's age. Preventing DGF may be more effective for decreasing the risk of death specifically attributable to the disease.
Subject(s)
Kidney Transplantation/mortality , Kidney Transplantation/methods , Renal Insufficiency/mortality , Renal Insufficiency/therapy , Adult , Age Factors , Aged , Cohort Studies , Data Interpretation, Statistical , Delayed Graft Function , Female , France , Humans , Male , Middle Aged , Proportional Hazards Models , Regression Analysis , Risk Factors , Survival Analysis , Time Factors , Treatment OutcomeABSTRACT
Kidney transplant recipients usually have low vitamin D levels, especially in the early posttransplantation period, but the association between vitamin D status with renal outcomes is not well described in this population. Here, we studied a prospective cohort of 634 kidney recipients who underwent transplantation at a single institution between January 2005 and June 2010. In this cohort, low 25-hydroxyvitamin D concentrations 3 months after transplantation did not predict early death or graft loss but were independently associated with lower measured GFR at 12 months (P=0.001) and higher risk for interstitial fibrosis and tubular atrophy (P=0.01). In contrast, levels of calcium, phosphorus, calcitriol, parathyroid hormone, or fibroblast growth factor-23 were not consistently associated with any of the studied outcomes. In conclusion, low 25-hydroxyvitamin D concentration measured 3 months after transplantation is an independent risk factor for interstitial fibrosis progression and is associated with a lower GFR 1 year after transplantation.
Subject(s)
Kidney Transplantation , Vitamin D/analogs & derivatives , Adult , Aged , Cohort Studies , Female , Fibrosis , Glomerular Filtration Rate , Humans , Kidney/pathology , Kidney Transplantation/mortality , Kidney Tubules/pathology , Male , Middle Aged , Prospective Studies , Transplantation, Homologous , Treatment Outcome , Vitamin D/bloodABSTRACT
One of the most significant advances in medicine during the last 50 years is the development of organ transplantation. In the context of chronic kidney diseases, renal transplantation offers patients a better clinical outcome than other treatment options. However, the benefits of organ transplantation have not been maximized due to an inadequate supply of organs for transplantation. Despite the establishment of elaborate legal rules for organs procurement, both on deceased and living donors in numerous countries, ethical concerns remain. Most of them are consequences of the strategies implemented or proposed to address the so-called organ shortage. The involvement of society in these complex problems is crucial as numerous questions emerge: could actual state of organ procurement change? Is it possible and/or realistic to increase the number of organs, with respects to living donors or deceased persons? Is the shortage an indicator to limit the use of kidney transplantation? How do we maintain efficiency and justice, in this context.
Subject(s)
Kidney Transplantation/ethics , Tissue Donors/ethics , Tissue Donors/supply & distribution , Tissue and Organ Procurement/ethics , Death , Humans , Presumed Consent/ethics , Waiting ListsABSTRACT
BACKGROUND: Old studies reported a worse outcome for second transplant recipient (STR) than for first transplant recipient (FTR) mainly due to non-comparable populations with numbers confounding factors. More recent analysis, based on improved methodology by using multivariate regressions, challenged this generally accepted idea: the poor prognosis for STR is still under debate. METHODOLOGY: To assess the long-term patient-and-graft survival of STR compared to FTR, we performed an observational study based on the French DIVAT prospective cohort between 1996 and 2010 (N = 3103 including 641 STR). All patients were treated with a CNI, an mTOR inhibitor or belatacept in addition to steroids and mycophenolate mofetil for maintenance therapy. Patient-and-graft survival and acute rejection episode (ARE) were analyzed using Cox models adjusted for all potential confounding factors such as pre-transplant anti-HLA immunization. RESULTS: We showed that STR have a higher risk of graft failure than FTR (HR = 2.18, p = 0.0013) but that this excess risk was observed after few years of transplantation. There was no significant difference between STR and FTR in the occurrence of either overall ARE (HR = 1.01, p = 0.9675) or steroid-resistant ARE (HR = 1.27, p = 0.4087). CONCLUSIONS: The risk of graft failure following second transplantation remained consistently higher than that observed in first transplantation after adjusting for confounding factors. The rarely performed time-dependent statistical modeling may explain the heterogeneous conclusions of the literature concerning second transplantation outcomes. In clinical practice, physicians should not consider STR and FTR equally.
Subject(s)
Graft Rejection/epidemiology , Graft Survival/physiology , Kidney Transplantation/adverse effects , Cohort Studies , France/epidemiology , Humans , Kidney Transplantation/mortality , Proportional Hazards Models , Reoperation , Survival Analysis , Time Factors , Treatment OutcomeABSTRACT
The aim of this study was to analyze the clinical and immunological features of the 56 still alive patients at our institution harboring a functional first renal transplant since more than 30 years. The mean post-transplant graft survival in all patients was 35.4 ± 3.1 years, the mean serum creatinine concentration was 128.7 ± 7 µmol/l, and the mean urinary protein concentration was 0.6 ± 0.5 g/l. Fifty-one percent of the patients had experienced cancer involving the skin (46.1%) and/or other tissues (28%). Hepatocarcinoma was diagnosed in 11% of the patients with chronic viral hepatitis B and/or C (48%). The 5-year patient survival rate (considered after the 30th transplantation anniversary) was 27% in patients presenting a tumor versus 87% in those tumor-free (P < 0.0001). The thymic output, the proportions of the memory and naïve T cell subsets, and the frequencies of EBV- and CMV-reactive, IFN-γ-producing T cells did not differ from those observed in more recently transplanted patients. These results suggest that the impact of chronic immunosuppression on some immune functions does not worsen over time and that the observed high prevalence of cancer in these patients may be related to the synergistic effects of decreased immunosurveillance and the time required for carcinogenesis.
Subject(s)
Kidney Transplantation/physiology , Adolescent , Adult , B-Lymphocyte Subsets/immunology , Cohort Studies , Creatinine/blood , Cytomegalovirus/immunology , Female , Graft Survival , Herpesvirus 4, Human/immunology , Humans , Immunosuppression Therapy/adverse effects , Kidney Transplantation/immunology , Kidney Transplantation/mortality , Kidney Transplantation/pathology , Male , Middle Aged , Neoplasms/etiology , Neoplasms/mortality , Paris/epidemiology , Survival Rate , T-Lymphocyte Subsets/immunology , Time Factors , Young AdultABSTRACT
Knowledge of the very long-term consequences of kidney donors has not been previously reported extensively. The 398 persons who had donated a kidney between 1952 and 2008 at Necker hospital were contacted. Among the 310 donors who were located, the survival probabilities for this population were similar to those of the general population and end stage renal disease incidence was 581 per million population per year. All located donors still alive were asked to complete a medico-psychosocial questionnaire and give samples for serum creatinine and urinary albumin assays. Among the 204 donors who responded to the questionnaire, mean eGFR was 64.4±14.6ml/min per 1.73m(2) and mean microalbuminuria was 27.0±83mg/g. Most donors never regretted the donation and consider that it has no impact on their professional or social lives. Among the 59 donors who gave a kidney more than 30years ago (mean 40.2years, range 30-48years) had a mean eGFR of 67.5±17.4µmol/l, a mean microalbuminuria level of 44.8±123.2mg/g and none was dialyzed. In conclusion, living kidney donation does not impact survival, kidney function, medical condition or psychological or social status over the very long-term.
Subject(s)
Kidney Transplantation , Living Donors , Adult , Aged , Albuminuria/urine , Female , Follow-Up Studies , Glomerular Filtration Rate , Humans , Kidney/physiology , Kidney Transplantation/mortality , Living Donors/psychology , Male , Middle Aged , Risk FactorsABSTRACT
BACKGROUND: Chronic allograft injury, the primary cause of late allograft failure in renal transplantation, can be diagnosed early at a preclinical stage by histopathological changes such as interstitial fibrosis (IF). Currently, assessed by semiquantitative analysis in the Banff classification, IF quantification is limited by pathologist's subjective interpretation. METHODS: We have designed algorithms dedicated to quantify IF by computerized color image analysis. This innovative and objective software automatically extracts the green areas characteristic of IF in Masson's trichrome based on color image segmentation followed by removal of nonspecific IF staining (capsula, sclerosis glomeruli and normal glomeruli, normal basement membrane) and computes an index. It also counts automatically the number of glomeruli. Sixty-seven Masson stained renal transplant biopsies at various IF stages were imaged using a digital color camera mounted on a microscope. We tested the robustness of the method against varying acquisition parameters. RESULTS: We demonstrated that the parameters do not have an impact on this quantification and that the algorithm is able to handle biopsy color variations. The intra- and interobserver reproducibility was good (P<0.003). The kappa coefficient that was performed on another set of 90 biopsies to evaluate the concordance of our method with an expert Banff quantification was 0.68, indicating a substantial agreement. Finally, the computerized IF correlated with renal function. CONCLUSION: This study demonstrates that computerized color image analysis is a reliable and reproducible method to evaluate renal IF in routine practice and in multi-centric studies.
Subject(s)
Image Processing, Computer-Assisted/methods , Kidney Transplantation/pathology , Kidney/pathology , Algorithms , Biopsy , Color , Fibrosis , Humans , Kidney/physiology , Observer Variation , Reproducibility of Results , Software , Transplantation, HomologousABSTRACT
Renal insufficiency is a common complication early after hematopoietic cell transplantation (HCT). We retrospectively examined the incidence, risk factors and associated mortality of acute renal failure (ARF) in a cohort of 101 consecutive allogeneic HCT patients. These patients were reviewed to determine their baseline characteristics, the presence of co-morbid conditions and mortality rates at one year. ARF was defined by the doubling of the baseline serum creatinine (Scr) levels. The mean age of the 101 study patients was 34 ± 11.8 years. Of them, 58 (57.4%) had ARF, yielding an incidence of 2.6% per week during the first year following HCT. The peak frequency of ARF occurred during the second week (29.3%). The need for hemodialysis, a proof of the severity of ARF, was seen in 12 cases (20.7%). On univariate analysis, the Scr at one month greater than 90 µmol/L (P = 0.008), use of aminoglycosides (P < 10 -3 ), the presence of veno-occlusive disease (VOD) (P < 10 -3 ) and the need for admission to the intensive care unit (ICU) (P = 0.003) were associated with a significantly increased risk of ARF. On multivariate analysis, the independent variables associated with an increased risk for ARF were the presence of VOD [P = 0.07, relative risk (RR) = 2.06] and use of aminoglycosides (P < 10 -3 , RR = 11.2). The overall mortality rate among the study patients was 35.6% at the end of the first year. On multivariate analysis, only the use of aminoglycosides (P = 0.02, RR = 0.31), admission to the ICU (P < 10 -3, RR = 7.29) and the development of ARF (P = 0.001, RR = 8.97) were independent predictors of mortality. Our study shows that ARF is highly prevalent during the early period following HCT and increases mortality, particularly if dialysis dependent. It frequently occurs following VOD and aminoglycoside use. As the prognosis is rather grim, it is very important that the associated factors be identified early, for an effective prevention of this disease.
Subject(s)
Acute Kidney Injury/etiology , Bone Marrow Transplantation/adverse effects , Acute Kidney Injury/blood , Acute Kidney Injury/mortality , Adult , Aminoglycosides/therapeutic use , Creatinine/blood , Critical Care , Humans , Incidence , Male , Middle Aged , Multivariate Analysis , Retrospective Studies , Risk Factors , Survival Rate , Vascular Diseases/complications , Young AdultABSTRACT
Renal transplantation in patients with autosomal dominant polycystic kidney disease (ADPKD) is a medical and surgical challenge. Detailed longitudinal epidemiological studies on large populations are lacking and it is mandatory to care better for these patients. The success of such a project requires the development of a validated epidemiological database. Herein, we present the results of the largest longitudinal study to date on renal transplant in patients with ADPKD. The 15-year outcomes following renal transplantation of 534 ADPKD patients were compared with 4779 non-ADPKD patients. This comprehensive, longitudinal, multicenter French study was performed using the validated database, DIVAT (Données Informatisées et VAlidées en Transplantaion). We demonstrate that renal transplantation in ADPKD is associated with better graft survival, more thromboembolic complications, more metabolic complications, and increased incidence of hypertension, whereas the prevalence of infections is not increased. This study provides important new insights that could lead to a better care for renal transplant patients with ADPKD.
Subject(s)
Kidney Transplantation/adverse effects , Polycystic Kidney, Autosomal Dominant/surgery , Adult , Databases, Factual , Diabetes Mellitus/etiology , Female , France/epidemiology , Graft Survival , Humans , Incidence , Kidney Transplantation/mortality , Longitudinal Studies , Male , Middle Aged , Polycystic Kidney, Autosomal Dominant/complications , Polycystic Kidney, Autosomal Dominant/epidemiology , Pulmonary Embolism/etiology , Treatment Outcome , Venous Thrombosis/etiologyABSTRACT
BACKGROUND: Apart from their important role in mediating calcium homeostasis, vitamin D derivatives regulate numerous vitamin D receptor-mediated renoprotective cellular functions including cell differentiation, negative regulation of inflammation, and fibrosis. Renal models of chronic kidney injury and clinical observational studies have suggested that vitamin D analogues may protect against the epithelial-to-mesenchymal transition (EMT), interstitial inflammation, and fibrosis. METHODS: The aim of this retrospective study is to test whether oral supplementation with cholecalciferol (vitamin D3) between 3 and 12 months posttransplantation confers a structural and functional nephroprotection in a population of 64 renal transplant patients, using historical controls. We analyzed glomerular filtration rates using iohexol clearance, urinary procollagen III aminoterminal propeptide excretion, and epithelial phenotypic changes as markers of the EMT and Banff scores at 3 and 12 months after transplantation in 64 renal transplant recipients with or without cholecalciferol supplementation between months 3 and 12. RESULTS: Cholecalciferol supplementation in stable renal transplant recipients did not prevent EMT, interstitial fibrosis, tubular atrophy, or renal function deterioration. CONCLUSION: Our results challenge the experimental data, suggesting that vitamin D-analog supplementation confers nephroprotection. These findings should be confirmed by randomized prospective studies.
Subject(s)
Cholecalciferol/administration & dosage , Kidney Transplantation/pathology , Kidney Transplantation/physiology , Adult , Epithelial-Mesenchymal Transition/drug effects , Glomerular Filtration Rate/drug effects , Humans , Kidney/drug effects , Kidney/pathology , Kidney/physiopathology , Peptide Fragments/urine , Procollagen/urine , Retrospective Studies , Time FactorsABSTRACT
We aimed to assess the impact of graft placement in dual renal transplantation on the risk for single graft loss and to report recipient outcomes. Between 2004 and 2007, 55 dual renal transplants were performed at our institution. Allografts were placed bilaterally (one in each iliac fossa) in 42 patients and unilaterally (both in the same iliac fossa) in 14 patients. Nine recipients (16.4%) underwent explantation of a single graft as a consequence of vascular thrombosis designated as the SINGLE group, whereas 46 had two functional allografts (DUAL group). There was a higher rate of graft loss in case of unilateral placement (n = 5/14) compared with bilateral placement (n = 4/41) (35.7% vs. 9.8%, P = 0.035). One-year glomerular filtration rate was significantly lower in the SINGLE group (29.4 ml/min/1.73 m(2) vs. 49.4 ml/min/1.73 m(2) in the DUAL group, P < 0.05). Significantly, none of the nine recipients of the SINGLE group returned to dialysis with a mean follow-up of 34.1 months. Graft survival at 1 year was 100% and 97.9% in SINGLE and DUAL groups, respectively. Unilateral placement of both allografts is associated with an increased risk of single graft loss and therefore lower renal function at 1 year. However, this strategy is safe in selected indications.