Predictive Factors of Renal Graft Failure in Tunisian Children and young adults: A Retrospective Study.

INTRODUCTION: Pediatric end-stage renal disease is a rare but severe condition that causes numerous complications and impairs the quality of life of children. Kidney transplantation is the therapy of choice in pediatric end-stage renal disease. AIM: Our study aimed to identify the predictive factors of renal graft failure after kidney transplantation in Tunisian children and young adults. METHODS: We conducted a retrospective bicentric study of children and young adults (age≤20 years) who had undergone renal transplantation between 1989 and 2019 in Tunisia. We analyzed long-term survival rates and complications after pediatric kidney transplantation and searched for predictive parameters for graft dysfunction. We used a univariate and a multivariate analysis to identify predictive factors of graft survival. RESULTS: A total of 112 patients underwent 115 kidney transplantations. Graft failure occurred in 30% of the cases. The overall 1-, 3-, 5- and 10-year graft survival rates were 92%, 89.1%, 85.9% and 74.5% respectively. The following parameters strongly influenced graft survival: immunosuppressive regimen including an association other than Mycophenolate mofetil- tacrolimus and corticosteroids (p=0.002), year of transplant (p<0.0001 for 1987-2000), deceased donor (p = 0.039), underlying etiology of end-stage renal disease (p=0.045), occurrence of acute or chronic rejection (p<0.001), a urine protein greater than 0.3 g/l per day (p=0.002), post-transplant urologic complications (p=0.002), five-year creatinine level>1.28 mg/dl (p<0.001). The overall 1-, 3-, 5- and 10-year patients survival rates were 97%, 95%, 90.2% and 84.4% respectively. CONCLUSIONS: Our study identified several predictive factors of graft failure in Tunisian children and young adults undergoing renal transplantation.

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.

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.

New familial cases of karyomegalic interstitial nephritis with mutations in the FAN1 gene.

BACKGROUND: Karyomegalic interstitial nephritis (KIN) is a rare disease entity first described by Burry in 1974. The term KIN was introduced by Mihatsch et al. in 1979. KIN is characterized by chronic tubulointerstitial nephritis associated with enlarged tubular epithelial cell nuclei, which leads to a progressive decline of renal function. The prevalence of this disease is less than 1% of all biopsies, and its pathogenesis is unclear. KIN results from mutations in FAN1 (FANCD2/FANCI-Associated Nuclease 1), a gene involved in the DNA damage response pathway, particularly in the kidney. In this study, we report two Tunisian consanguineous families with KIN caused by mutations in the FAN1 gene. METHODS: Direct sequencing of the coding regions and flanking intronic sequences of the FAN1 gene was performed in three affected members. Three prediction programs (Polyphen-2 software, SIFT, and MutationTaster) were used to predict the functional effect of the detected variations. RESULTS: Two causative frameshift variants in the FAN1 gene were identified in each family: The previously described frameshift mutation c.2616delA (p.Asp873ThrfsTer17) and a novel mutation c.2603delT (p.Leu868ArgfsTer22) classified as "pathogenic" according to the American College of Medical Genetics and Genomics (ACMG) guidelines. CONCLUSION: To our best knowledge, this is the first Tunisian study involving familial cases of KIN with mutations in the FAN1 gene. We hypothesize that these findings can expand the mutational spectrum of KIN and provide valuable information on the genetic cause of KIN.

[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.

[Successful treatment with paclitaxel of a visceral relapse of post-transplant Kaposi's sarcoma]. / Succès du traitement par paclitaxel d'une rechute viscérale d'un sarcome de Kaposi après transplantation rénale.

We report the observation of a patient who presented with post-transplant Kaposi's sarcoma after a delay of eight months with a dual cutaneous and palatal localisation. The reduction in immunosuppressive treatment and the introduction of Rapamune® allowed good clinical progress initially with regression of the skin lesions. He subsequently presented later a skin relapse with visceral localisation. Chemotherapy was conducted based on weekly paclitaxel infusions allowing partial remission and maintenance of renal graft function with good clinical tolerance.

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.

Acquired epidermodysplasia verruciformis in renal-transplant recipients.

Acquired epidermodysplasia verruciformis in renal-transplant recipients is associated with a high risk for developing squamous cell carcinoma. An accurate diagnosis and a regular monitoring in this high-risk population must be stressed.

Renal Thrombotique microangiopathy: An unusual renal involvement in Niemann-Pick disease type B.

Renal involvement in Niemann-Pick disease type B is very rare. Kidney check-up and renal biopsy should be performed in any patient presented with hypertension and kidney disease. Histology identifies the lesion, the prognosis, and guide treatment.

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.

Clinical study on autosomal dominant polycystic kidney disease among North Tunisians.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary renal disease, which usually manifests in adulthood. It is characterized by the development of multiple cysts in the kidneys and many other extrarenal manifestations. We aimed to determine the factors that contribute to the progression of ADPKD to end-stage renal disease (ESRD). In a retrospective multicentric study, we reviewed the records of 569 patients with ADPKD, hospitalized at a nephrology department or followed up at the outpatient department of university and regional hospitals, covering the north and center of the country, during the period 1969-2016. The mean age of the study patients was 48.54 ± 13.68 years and 14% were young adults (<40 years). There were 272 female and 297 male patients (sex ratio: male/female = 1.09). A family history of ADPKD was found in 43.7% of cases. Renal symptoms were dominated by loin pain, renal failure, hypertension, and hematuria, seen in, respectively, 51.9%, 48.2%, 29.1%, and 24.6% of the patients. The median serum creatinine level was 459 µmol/L (range: 47-2454), and hypertension had preceded the onset of ADPKD in 28.8% of cases. Extrarenal manifestations consisted of urologic complications (54.6%), liver cysts (43.5%), cardiac involvement (31.9%), cerebral aneurysms (12.9%), and gastrointestinal involvement (9.4%). ESRD occurred in 43.1% after a mean follow-up of 47 months (range: 0-384). Risk factors for poor renal prognosis were age >40 years (P = 0.009), hematuria (P = 0.034), hemoglobin >14 g/dL (P = 0.0013), high uric acid level (P = 0.001), and leukocyturia (P = 0.02). Death occurred in 59 cases (10.3%), mostly caused by infections (44.1%). In our study, ADPKD was lately diagnosed in most cases. Family screening is important, which will enable early detection and management of the complications associated with ADPKD.

Tubulointerstitial nephritis due to sarcoidosis: Clinical, laboratory, and histological features and outcome in a cohort of 24 patients.

Renal involvement is rare in systemic sarcoidosis. Among renal manifestations, tubulointerstitial nephritis (TIN) is the most commonly reported finding. We conducted the current study to investigate the clinical, laboratory, and histological features and to analyze the outcome of TIN due to sarcoidosis. We present a retrospective, single-center study of patients followed for sarcoidosis and presenting with TIN related to this systemic disease. Twenty-four patients were assessed (22 females/2 males). The mean age at diagnosis of TIN was 46.3 years. Extrarenal manifestations were dominated by thoracic involvement (95.8%), peripheral lymph nodes (54.2%), and skin lesions (33.3%). The mean proteinuria level was 0.68 g/24 h. Renal failure was diagnosed in 83.3% of cases with a median estimated glomerular filtration rate at 14.3 mL/min/1.73 m2. Nine patients presented with hypercalcemia and 12 patients with hypercalciuria. Renal biopsy was performed in 58.3% of cases. Six of the 14 patients presented with noncaseating granulomatous interstitial nephritis and eight with interstitial nephritis without granuloma. Granulomatous infiltration of renal parenchyma was complicated by vasculitis in two cases. Corticosteroid therapy was used in all patients. On follow-up analysis, four patients progressed to end-stage renal disease (ESRD) after a mean duration at 45.5 months. In the remaining patients, kidney function statistically significantly improved after one month of treatment compared to the time when the diagnosis was initially established (P = 0.031). We found that the predictive factors of progression to ESRD were multiorgan involvement (P = 0.032), advanced fibrosis F3 (P = 0.0006), and extensive interstitial granulomas (P = 0.007) and these were independently correlated with ESRD. Corticosteroid therapy seems to be effective in sarcoid TIN, but some degree of persistent renal failure is possible which can be predicted from both histologic findings and initial response to steroid therapy.

Renal amyloidosis in ankylosing spondylitis: A monocentric study and review of literature.

Secondary renal amyloidosis (RA) is the most common type of renal involvement in ankylosing spondylitis (AS). We assessed the epidemiologic and clinico-biological profile of AS patients with RA, to analyze treatment modalities and prognostic aspects, and to determine predictive factors of RA during AS. This was a retrospective study including 13 cases of RA among 212 cases who presented with AS, during the period from 1978 to 2006. The median age of the patients at the time of diagnosing AS was 47 years (range: 19-67). There were 11 males and two females. RA onset was diagnosed after a mean follow-up of 144.6 months (range: 10-505) from the AS diagnosis. We noted erosive peripheral arthritis, lumbar stiffness with bamboo spine, and coxitis in 23.1%, 76.9%, and 30.8% of cases, respectively. Nephrotic syndrome was found in eight patients (61.5%). At the time of diagnosing RA, six patients had renal failure. Amyloid deposits were histologically proven by salivary gland biopsy in six cases (46.1%) and by renal biopsy in seven cases (53.8%). Four patients received a long-course treatment with colchicine but with a good outcome only in two cases. In our series, AS was more severe among patients with RA. Four predictive factors of RA were identified: smoking (P = 0.04), erosive peripheral arthritis (P = 0.002), bamboo spine (P = 0.001), and biologic indicators of inflammation (P = 0.0001). High erythrocyte sedimentation rate was identified as the only independent risk factor of RA during AS (P = 0.0001). Renal function as well as urinalysis should be monitored at regular intervals to detect early renal involvement during AS.

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.

Outcome of Kidney Transplant in Patients with Polycystic Kidney Disease: A Single-Center Study in Tunisia.

OBJECTIVES: Autosomal dominant polycystic kidney disease is a common cause of end-stage renal disease and a common indication for renal transplant. This study was undertaken to evaluate the demographics, outcomes, and complications of renal transplant in patients with autosomal dominant polycystic kidney disease compared with other nephropathies. MATERIALS AND METHODS: In a retrospective case-control design, we reviewed the records of 7 patients with autosomal dominant polycystic kidney disease from a total of 701 renal transplant patients over a 30-year period (1986-2016). For each patient, a matched control was selected based on sex, age, year of transplant, and type of kidney donor. We excluded patients who underwent kidney transplant abroad and those with a follow-up period of less than 2 years. RESULTS: The number of patients with autosomal dominant polycystic kidney disease requiring transplant at our center was estimated at 0.23 per year, and the condition represented 1.57% of initial nephropathy causes. The mean patient age at transplant was 50.8 ± 8.05 years. There were 5 male and 2 female patients in the case group, with a male-to-female ratio of 2.5. The source of the graft was predominantly a living related donor (5/7). Four patients had extrarenal manifestations, the most common of which were liver cysts (3 patients). Rejection occurred in a single study patient (14.2%) and in 4 control patients (57.1%; P = .51). Two patients did not develop any complications. Complications noted after transplant included infection (3/7 cases vs 2/7 controls; P= .67) and cerebrovascular accidents (2/7 cases vs 0/7 controls). CONCLUSIONS: Further studies with longer follow-up and greater numbers of patients are needed to compare more precisely the complications and results of transplant between patients with autosomal dominant polycystic kidney disease and other kidney transplant recipients.

Efficacy and safety of calcium acetate-magnesium carbonate in the treatment of hyperphosphatemia in dialysis patients.

A phosphate binder combining calcium and magnesium offers an interesting therapeutic option to control hyperphosphatemia in dialysis patients. We investigated the effectiveness and tolerance of calcium acetate-magnesium carbonate (Ca-Mg). This is a 16-week prospective study including 16 dialysis patients. After an initial two-week washout period, serum phosphorus (sPho) ≥1.8 mmol/L, serum calcium (sCa) ≤2.6 mmol/L, and serum magnesium ≤1.5 mmol/L were the main inclusion criteria. The initial dose of Ca-Mg depended on sPho level and was titrated for every two weeks to have a sPho ≤ 1.8 mmol/L. A second two-week washout period followed the 12 weeks of treatment. Ca-Mg significantly reduced the mean sPho levels from 2.14 to 1.75 mmol/L by the end of the 12-week treatment period (P <0.006). Two weeks after the completion of the Ca-Mg study, the mean sPho levels increased to 2.2 mmol/L. The mean sCa levels did not significantly change during the Ca-Mg trial. The mean serum intact parathyroid hormone declined significantly from 446 pg/mL at the beginning of the study to 367 pg/mL at the end of the 12-week treatment period (P = 0.0002). Digestive tolerance was good in all patients which allowed good compliance. There were no episodes of hypercalcemia. However, six patients had a moderate hypermagnesemia (21 episodes) requiring adjustment of treatment dose. The Ca-Mg proved to be effective in the control of hyperphosphatemia in dialysis patients with good clinical and biological tolerance. Thus, in patients with hypercalcemia or poor tolerance to calcium carbonate, Ca-Mg might be a good alternative.

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.

Light chain nephropathy.

Light chain deposition disease (LCDD) is characterized by the tissue deposition of monotypic immunoglobulin light chains of either kappa or lambda isotype. It is the archetypal systemic disease that is most frequently diagnosed on a kidney biopsy, although the deposits may involve several other organs. This brief review focuses on the clinicopathological features of LCDD-associated nephropathy with an emphasis on the diagnostic and therapeutic difficulties related to this elusive condition.