Predicting long-term outcomes of kidney transplantation in the era of artificial intelligence.

The ability to accurately predict long-term kidney transplant survival can assist nephrologists in making therapeutic decisions. However, predicting kidney transplantation (KT) outcomes is challenging due to the complexity of the factors involved. Artificial intelligence (AI) has become an increasingly important tool in the prediction of medical outcomes. Our goal was to utilize both conventional and AI-based methods to predict long-term kidney transplant survival. Our study included 407 KTs divided into two groups (group A: with a graft lifespan greater than 5 years and group B: with poor graft survival). We first performed a traditional statistical analysis and then developed predictive models using machine learning (ML) techniques. Donors in group A were significantly younger. The use of Mycophenolate Mofetil (MMF) was the only immunosuppressive drug that was significantly associated with improved graft survival. The average estimated glomerular filtration rate (eGFR) in the 3rd month post-KT was significantly higher in group A. The number of hospital readmissions during the 1st year post-KT was a predictor of graft survival. In terms of early post-transplant complications, delayed graft function (DGF), acute kidney injury (AKI), and acute rejection (AR) were significantly associated with poor graft survival. Among the 35 AI models developed, the best model had an AUC of 89.7% (Se: 91.9%; Sp: 87.5%). It was based on ten variables selected by an ML algorithm, with the most important being hypertension and a history of red-blood-cell transfusion. The use of AI provided us with a robust model enabling fast and precise prediction of 5-year graft survival using early and easily collectible variables. Our model can be used as a decision-support tool to early detect graft status.

Toward generalizing the use of artificial intelligence in nephrology and kidney transplantation.

With its robust ability to integrate and learn from large sets of clinical data, artificial intelligence (AI) can now play a role in diagnosis, clinical decision making, and personalized medicine. It is probably the natural progression of traditional statistical techniques. Currently, there are many unmet needs in nephrology and, more particularly, in the kidney transplantation (KT) field. The complexity and increase in the amount of data, and the multitude of nephrology registries worldwide have enabled the explosive use of AI within the field. Nephrologists in many countries are already at the center of experiments and advances in this cutting-edge technology and our aim is to generalize the use of AI among nephrologists worldwide. In this paper, we provide an overview of AI from a medical perspective. We cover the core concepts of AI relevant to the practicing nephrologist in a consistent and simple way to help them get started, and we discuss the technical challenges. Finally, we focus on the KT field: the unmet needs and the potential role that AI can play to fill these gaps, then we summarize the published KT-related studies, including predictive factors used in each study, which will allow researchers to quickly focus on the most relevant issues.

The effects of the CYP3A5*3 variant on tacrolimus pharmacokinetics and outcomes in Tunisian kidney transplant recipients.

INTRODUCTION: Tacrolimus, exhibits interindividual pharmacokinetic variability and a narrow therapeutic index. The influence of the CYP3A5 6986A>G single nucleotide polymorphism (SNP) on this variability remains a topic of debate. AIM: To assess the impact of the aforementioned SNP on tacrolimus area under curve (AUC0-12h), adverse drug reactions (ADRs), and kidney graft outcomes. METHODS: Blood samples were collected from Tunisian kidney transplants over a five-year period during either the early (<3 months) or late (>3 months) post-transplant phases. Through blood concentration (C0) and AUC0-12h of tacrolimus were measured. Patients were prospectively followed to assess graft outcomes. Polymerase chain reaction of restriction fragment length polymorphism was used for CYP3A5 6986A>G genotyping. RESULTS: Fifty Tunisian kidney recipients receiving tacrolimus were enrolled in the study. Acute and chronic graft rejections were observed in eight and three patients, respectively. Twenty-one patients (42%) reported ADRs. C0 and AUC0-12h, showed a significant difference between CYP3A5*1 carriers (mean C0=4 ng.mL-1 and AUC0-12h=94.37 ng.h.mL-1) and CYP3A5*3/3 or poor metabolizers carriers (mean C0=7.45 ng.mL-1; AUC0-12h=151.27 ng.h.mL-1) (p=0.0001; p=0.003, respectively). Supratherapeutic tacrolimus levels were significantly more common in poor metabolizers (p=0.046; Odds-ratio =1.3; confidence interval 95% [1.12-1.66]). The impact of SNP was significant on C0, AUC0-12h, C0/Dose and AUC0-12h/Dose, only in the late phase (p=0.01, 0.002, 0.012, 0.003 respectively). CONCLUSION: CYP3A5*3 variant was significantly associated with tacrolimus pharmacokinetics but had no impact on graft outcomes.

Overall of kidney transplant recipients with a pretransplantation cancer history.

No significant morbidity from recurrence cancer and no development of secondary type of cancers in pre-existing malignancies. We must be careful about risk of rejection.

Encapsulating Peritoneal Sclerosis after kidney Transplantation: Success of Medical Treatment.

Encapsulating peritoneal sclerosis (EPS) is an infrequent but serious complication of long-term peritoneal dialysis (PD). EPS may become clinically apparent when patients are on PD (classical EPS) or after undergoing kidney transplantation (post-transplantation EPS). This presentation of EPS seems to occur shortly after kidney transplantation in former PD patients. In this report, we present our experience in our first case of patient diagnosed with EPS after kidney transplantation.

[Emphysematous pyelonephritis and cystitis: An exceptional complication in a kidney transplant recipient]. / Pyélonéphrite et cystite emphysémateuses : une complication exceptionnelle chez un transplanté du rein.

Emphysematous pyelonephritis is a rare and severe infectious complication characterized by the presence of gas in the renal parenchyma, excretory cavities and surrounded tissues. It is due to the development of non-anaerobic gasifier bacteria. We report a new rare case of emphysematous pyelonephritis in a kidney transplant recipient, particular by its occurrence in a non-functional graft and its exceptional association with emphysematous cystitis.

End-stage renal disease at dialysis initiation: Epidemiology and mortality risks during the first year of hemodialysis.

Chronic kidney disease (CKD) treated by hemodialysis (HD) is a worldwide major public health problem. Its incidence is getting higher and higher, leading to an alarming social and economic impact. The survival of these patients is significantly low, especially during the first year of treatment. The purpose of our study was to identify the epidemiological and clinico-biological characteristics of patients at the HD initiation and to reveal the predictive factors of mortality at three months and one year of HD. This is a prospective, analytical, and descriptive study dealing with 229 patients with an end-stage renal disease (ESRD), followed up in the Nephrology Department of Charles Nicolle Hospital and La Rabta Hospital in Tunisia, that was started HD between January and June 2017. A multivariate logistic regression analysis allowed us to identify the independent predictors of mortality at three months and one year. The average age was 60.2 ± 15.3 years, with a gender ratio of 1.41. Seventy-eight percent of patients had more than two comorbidities, 59% had diabetes, and 88% had hypertension. Diabetic nephropathy was the leading etiology of kidney disease (48.9%), while 11% of nephropathies were of unknown etiology. Only 58% were early referred to a nephrologist. The average glomerular filtration rate at HD initiation was 6.06 ± 2.33 mL/min/1.73 m2. Hypocalcemia and hyperphosphatemia were noted, respectively, in 60.8% and 84.9% of cases. Anemia was objectified in 98.6% of cases. HD was started in an emergency in 56.8% of cases. One of the most urgent indications was acute pulmonary edema (APE) for 43.8% of patients. Only 10.5% of patients had functional arteriovenous fistula at the dialysis initiation. Patients were hemodialyzed one, two, or three sessions per week, respectively, in 23.2%, 26.6%, and 50.2% of cases. The crude mortality rate was 25% and 13% in, respectively, one year and three months of HD. On multivariate analysis, we identified heart failure and insufficient dialysis dose per week as predictive factors of mortality at the 1st year of HD. C-reactive protein more than 21 mg/L, insufficient dialysis per week, modified Charlson Comorbidity Index less than 6, and APE at the dialysis initiation were identified as predictive factors of three-month mortality. Despite the short period of study, this work revealed the alarming conditions of patients at HD initiation. This critical situation is due to the delay in CKD diagnosis, the late nephrologist referral, and the lack of preparation before HD initiation.

Prevalence and risk factors of hypogonadism in men with chronic renal failure.

AIM: To determine the prevalence and the risk factors of hypogonadism in men with chronic renal failure (CRF). METHODS: We conducted a cross sectional analysis in 48 men with CRF. Total testosterone, prolactin, and gonadotropins were measured in all patients. Hypogonadism was defined by a low level (<10 nmol/l) or a low normal level (10-14 nmol/l) of total testosterone. RESULTS: The mean age was 53.31±10.22 years. Renal impairment was mild, moderate, severe and at end stage in 9,14,4 and 21 patients, respectively. Nineteen patients had been undergoing extra-renal purification. The average of total testosterone was 13.44±6.17 nmol/L. It was lower in patients with diabetic nephropathy (p=0.004). Hypogonadism was diagnosed in 22 patients (46 %). In this group, gonadotropins were normal in 21 cases and elevated in only one case. Hyperprolactinemia was retained in six patients. Type 2 diabetes (OR: 3.96; p=0.02) and diabetic nephropathy (OR=4.26; p=0.01) were the only risk factors of hypogonadism in our patients. CONCLUSION: Our results had demonstrated a high prevalence of hypogonadism in males with chronic renal failure. This hormone disorder was associated with type 2 diabetes and diabetic nephropathy.

Mycophenolate Mofetil-induced Oral Ulcerations in a Kidney Transplant Recipient.

INTRODUCTION: Mycophenolate Mofetil (MMF) is an immunosuppressive drug usually used in kidney transplants to prevent rejection. It has various adverse effects such as leucopenia, anemia, diarrhea but Mouth ulcers are rarely reported. METHOD: We present a case report of MMF-induced mouth ulcers in an African patient. CASE REPORT: A 41-year-old African-male patient has painful oral ulcers which developed 5 months after kidney transplantation. The immunosuppressive maintenance regimen comprised Steroids, Tacrolimus and MMF. RESULT: These ulcers were firstly related to a fungic or viral infection so the patient was prescribed Fluconazole and Aciclovir without any improvement. Then, Tacrolimus blood level was checked and it was in a therapeutic range. Finally, we decide to stop MMF and the ulcers healed quickly. DISCUSSION: Oral ulcers are frequently seen complications in immunosuppressant patient but are rarely described with MMF. These ulcers can become large and very painful and degrade patient's life quality. So when infections causes are excluded, we have to keep in mind that these ulcers can be a drug adverse effect.

Monoclonal gammopathy of renal significance with light-chain deposition disease in kidney transplantation.

Light-chain deposition disease (LCDD) reoccurs almost invariably after renal transplantation, leading to early graft loss. We report a case of LCDD with monoclonal gammopathy of renal significance diagnosed in the post-transplant period in a 28-year-old male and we discuss the diagnostic and therapeutic challenges in the clinical course.

Thirty Years of Experience at the First Tunisian Kidney Transplant Center.

OBJECTIVES: The aim of this study was to report the results of 30 years of experience at the first kidney transplant center in Tunisia. MATERIALS AND METHODS: All kidney transplants performed at the center between June 1986 and June 2016 were included. The study period was divided into 3 decades. Recipient and donor data and follow-up information were obtained from a local database and patient medical records. Comparative analyses were performed using the t test for continuous variables and the Χ² test for qualitative variables. Patient and graft survival rates were calculated according to the actuarial method, and comparison of survival curves was performed according to the logrank test. RESULTS: The mean age of recipients was 32.7 ± 11.5 years (range, 6-65 y) with a gender ratio of 2.2. Duration of prekidney transplant dialysis varied from 2 months to 20 years (median, 27.5 mo); 1.7% of patients underwent transplant preemptively. Kidneys were recovered from deceased donors in 21.2% of cases and from living donors in 78.8%. The proportion of deceased donors dropped from 27.4% during the period 2006-2010 to 12.9% during the period 2011-2015 (P < .04). Patient survival rates at 1, 5, 10, 15, and 20 years were 96%, 89.3%, 79.5%, 71.1%, and 65.4%. Graft survival rates were 95%, 86.5%, 76.2%, 66.3%, and 57.2%. The annual graft loss was 2.9%, with a mortality rate of 2.4% and without significant differences between patients receiving deceased-donor and living-donor organs. CONCLUSIONS: Kidney transplant activity remains suboptimal in our country. The reduction in deceased-donor organs could be related to the political transformations facing our country with their resulting social and economic consequences. Efforts should be made to increase governmental resources and to improve both public awareness of organ donation and the motivation of transplant teams.

Post kidney transplantation Kaposi's sarcoma: the experience of a Mediterranean North African center.

BACKGROUND: The aim of this study was to determine the overall and specific incidences of Kaposi's sarcoma (KS) in a cohort of 568 kidney transplant recipients (KTR) in a single North African Mediterranean center. PATIENTS AND METHODS: The records of 568 patients, who underwent kidney transplantation (KT) between June 1986 and December 2013, were retrospectively reviewed. Incidence was calculated by dividing the number of the different events by the total duration of follow-up. Survival rates and cumulated frequencies of KS were calculated according to the actuarial method. RESULTS: Twelve patients developed KS corresponding to an overall prevalence of 2.1% and an annual incidence of 0.27% patient-years. Median time to diagnosis of KS was 23.3 months. Eleven patients presented with skin lesions; three had oral localizations and one had conjunctival involvement. Asymptomatic gastric localization was observed in one patient. Therapeutic management, consisting in reduction of immunosuppression in all cases and their conversion to sirolimus in four patients, resulted in complete regression of KS in seven patients. Graft loss was observed in three cases and four patients died of unrelated- KS causes. CONCLUSION: KS is the most post KT malignancy observed in our country and is characterized by a predominance of limited superficial forms.

[The epithelial-mesenchymal transition and fibrosis of the renal transplant]. / La transition épithélio-mésenchymateuse et la fibrose du transplant rénal.

Epithelial-mesenchymal transition (EMT) is a process by which differentiated epithelial cells undergo a phenotypic conversion and acquire a mesenchymal phenotype, including elongated morphology, enhanced migratory and invasion capacity, and greatly increased production of extracellular matrix (ECM) components. This phenomenon plays a pivotal role in embryonic development, wound healing and tissue regeneration. It has also been involved in organ fibrosis. Some studies suggest that following injury, renal tubular epithelial cells undergo reprograming in mesenchymal cells, and thus constitute an important source of de novo myofibroblasts invading the renal interstitium and contributing to fibrosis. However, an increasing number of studies raise doubts about the existence of this process in vivo. The role of EMT in the development of renal fibrosis remains a matter of intense debate and may depend on the model studied. In this review, we describe the role of EMT in the development of fibrosis of renal graft, and then we propose approaches for detecting and treating renal fibrogenesis by targeting TEM.

[Acute tubular necrosis in kidney transplantation]. / La nécrose tubulaire aiguë en transplantation rénale.

BACKGROUND: The acute tubular necrosis (ATN) is common after kidney transplantation. Acute tubular necrosis (ATN) is multifactorial and represents one of the main causes of the delayed graft function. Its impact on graft and patients survival is documented. AIMS: To study the prevalence of the ATN in kidney transplanted patients, the acute rejection rate and their impact on the graft and the patient survival. METHODS: We retrospectively studied the frequency of ATN, its causes and its impact on patient and graft survival in 255 kidney transplanted patients between 1986-2006. RESULTS: Thirty-nine patients had ATN (15.29%). They are 25 men and 14 women with mean age of 30.1 ± 12.6 years (8-61) followed for an average of 98 ± 61.76 months. The majority was treated by hemodialysis (79.48%) and half of them were transplanted from kidney of deceased donor. All patients received anti lymphocyte serum and the majority anticalcineurins (69.23%). The outcome was favorable in 26 patients (66.66%) with recovery of diuresis and normalization of renal function after 6 weeks on average. An acute rejection was diagnosed in 21 patients (53.48%). The mean creatinine at 1, 5 and 10 years was 135.3, 159.9 and 121.4 µmol / l. Eight patients had creatinine ² 130 µmol / l at 10 years. Ten patients died from infectious and cardiovascular causes. By comparing the 2 groups ATN + and ATN - we found a statistically significant correlation between ATN and cold ischemia (10 ± 10.9 vs 1.2 ± 4.7 hours, p <0.0001) and the interval between the start of dialysis and transplantation (42.18 ± 38.44 vs. 31.1 ± 25.2 months, p= 0.02). No statistical correlation was found between the ATN and gender, age of recipient and donor, warm ischemia, acute rejection, chronic rejection and graft and patient survival at 1, 5 and 10 years. CONCLUSION: The ATN is more common among transplanted patients from deceased donors. It had good evolution in the majority of cases and it's correlated to cold ischemia and duration of dialysis. Finally, it has no impact on patients and graft survival.

[Association of post-transplant lymphoproliferative disease and visceral leishmaniasis after kidney transplantation]. / Association d'un syndrome lymphoprolifératif et d'une leishmaniose viscérale après transplantation rénale.

Malignancies and opportunistic infections are frequently observed after solid-organ transplantation. Their occurrence strongly affects recipient survival. We report the case of a 29-year-old Tunisian kidney-recipient who was diagnosed simultaneously with post-transplant lymphoproliferative disease (PTLD) and visceral leishmaniasis (VL). Withdrawal of immunosuppressive therapy together with antiparasitic treatment using liposomal amphotericin B, and anti-CD20 antibodies medication resulted in cure of leishmaniasis and remission from PTLD. This case is of clinical interest because of the uncommon association of VL with PTLD after solid organ transplantation. It is also original by the favourable outcome of VL and PTLD, both known as life-threatening diseases. Also, it illustrates the predisposing role of immunosuppressive therapy in occurrence of opportunistic infections and malignancies after solid organ transplantation.

[Pheochromocytoma in end-stage renal disease patient treated by peritoneal dialysis]. / Phéochromocytome surrénalien chez un insuffisant rénal chronique en dialyse péritonéale.

Pheochromocytoma is a rare tumor responsible for paroxysmal hypertension which is difficult to control. Diagnosis is important because it represents a curable form of hypertension. Few cases of pheochromocytoma patients with end-stage renal failure were reported in the literature. These cases are specially responsible for diagnosis and therapeutic problems. We report here a case of an end-stage renal failure patient who has pheochromocytoma, he was treated by automated peritoneal dialysis. The patient is a 47-year-old man who has an IgA glomerulonephritis. On peritoneal dialysis, his blood pressure level remains high despite four antihypertensive drugs association and adequate dialysis. Furthermore, the patient suffered from headaches, sweats and palpitations. This leads to suspect pheochromocytoma. Thus, urinary excretion rates of metanephrines and normetanephrines were high. Radiographic diagnosis tests were negative but MIBG scintigraphy was able to localise the tumor in the left suprarenal gland. He had coelioscopic left adrenalectomy without complications, microscopic studies showed an hyperplasia of the adrenal medulla. Soon after surgery his blood pressure was well controlled by one antihypertensive drug. We conclude that refractory hypertension, as a possible diagnosis, is uncommon in peritoneal dialysis patients. Pheochromocytoma must be eliminated by careful evaluation.

[Myeloma, Kaposi's sarcoma and HHV8 infection in hemodialyzed patient]. / Myelome multiple, maladie de Kaposi et infection par le HHV8 chez un hemodialyse chronique.

BACKGROUND: The association between Kaposi's sarcoma, Human Herpes Virus 8 infection and multiple myeloma is still controversial especially in hemodialysed patient. AIM: report a new case of this association. OBSERVATION: We report the case of a 83 year old man in whom the diagnosis of multiple myeloma of IgA/kappa had been made in December 2003 with end stage renal failure requiring hemodialysis. Initially, it had been treated with Melphalan, Cyclophosphamide, Prednisolone and Vincristine and secondary by Melphalan and Prednisone. Three months later, he had developed extensive porpour lesions in his lower limbs. Skin biopsy had been informed of Kaposi's sarcoma. Human Herpes Virus 8 test was positive. CONCLUSION: Our observation is another case supporting the hypothesis that Kaposi's sarcoma and multiple myeloma share a common aetiology such as Human Herpes Virus 8. The immunodepressed state related to aging, multiple myeloma, chemotherapy and hemodialysis was the probable factor responsible of rapidly progressive Kaposi's sarcoma in our patient. The association myeloma and Human Herpes Virus 8 infection is still controversial.