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.

Delayed Graft Function in Pediatric Kidney Transplant: Risk Factors and Outcomes.

OBJECTIVES: We aimed to identify risk factors and outcomes of delayed graft function in pediatric kidney transplant. MATERIALS AND METHODS: This retrospective study included all kidney transplant recipients ≤19 years old followed up in our department for a period of 34 years, from January 1989 to December 2022. RESULTS: We included 113 kidney transplant recipients. Delayed graft function occurred in 17 cases (15%). Posttransplant red blood cell transfusion was strongly associated with delayed graft function (adjusted odds ratio = 23.91; 95% CI, 2.889-197.915). Use of allografts with multiple arteries and cold ischemia time >20 hours were risk factors for delayed graft function (adjusted odds ratio = 52.51 and 49.4; 95% CI, 2.576-1070.407 and 1.833-1334.204, respectively). Sex-matched transplants and living donors were protective factors for delayed graft function (adjusted odds ratio = 0.043 and 0.027; 95% CI, 0.005-0.344 and 0.003-0.247, respectively). Total HLA mismatches <3 played a protective role for delayed graft function (adjusted odds ratio = 0.114; 95% CI, 0.020-0.662), whereas transplant within compatible but different blood types increased the risk of delayed graft function (adjusted odds ratio = 20.54; 95% CI, 1.960- 215.263). No significant correlation was shown between delayed graft function and allograft survival (P = .190). Our study suggested delayed graft function as a key factor in allograft rejection-free survival (adjusted odds ratio = 3.832; 95% CI, 1.186-12.377). Delayed graft function was a negative factor for early graft function; patients with delayed graft function had a lower estimated glomerular filtration rate at discharge (P = .024) and at 3 (P = .034), 6 (P = .019), and 12 months (P = .011) posttransplant. CONCLUSIONS: Delayed graft function is a major determinant of early graft function and allograft rejection-free survival. Further research is required to establish proper preventive measures.

An exceptional cause of polyuria-polydipsia syndrome in a 10-year-old boy.

Polyuria-polydipsia syndrome is a frequent symptom in pediatrics, primarily attributed to diabetes mellitus. In the context of diabetes insipidus, this syndrome can stem from central or nephrogenic factors. Sjögren's syndrome, an uncommon autoimmune disease in children, can affect multiple organs. Kidney involvement as described in adults is usually related to glomerular or tubular impairment, often linked to distal tubular acidosis. As a kidney involvement during childhood, Sjögren's syndrome has rarely been reported. Hereby, we present the case of Sjögren's syndrome revealed by polyuria-polydipsia syndrome in a 10-year-old boy.

Predictive factors of urinary tract infections caused by extended-spectrum ß-lactamase-producing Escherichia coli in children: a prospective Tunisian study.

AIM: To identify the predictive factors for the occurrence of community-acquired urinary tract infections caused by Extended-Spectrum ß-Lactamase-Producing Escherichia coli in children. METHODS: This was a single-center prospective observational study of children and young adults with community-acquired urinary tract infections caused by Extended-Spectrum ß-Lactamase-Producing Escherichia coli. The study was conducted in the pediatric nephrology department in Charles Nicolle Hospital, Tunis, Tunisia from January 1st, 2019, to December 31, 2020. Patients ≤20 years with community-acquired urinary tract infection caused by Escherichia coli were included prospectively in our study. RESULTS: We collected 290 urinary tract infections in 218 patients, including 92 urinary tract infections due to Extended-Spectrum ß-Lactamase-Producing Escherichia coli. The mean age of children was 50.10±54.28 months, with a female predominance in 65.2% of cases. Risk factors for the acquisition of multidrug-resistant bacteria were antibiotic therapy in the previous three months, antibiotic prophylaxis, hospitalization in the year preceding the urinary tract infections, and outpatient care in the previous six months (p < 0.05). Resistance to Ceftazidime, Cefotaxime, Cefixime, Gentamicin and Ofloxacin was significantly associated with the presence of an Extended-Spectrum ß-Lactamase strain. Antibiotic resistance was significantly more observed in the age group above 6 years. Co-habitation with health care worker was a risk factor for resistance to Amoxicillin-Clavulanic Acid. CONCLUSION: Understanding the epidemiological profile and risk factors for ESBL-producing UTIs, including Extended-Spectrum ß-Lactamase-producing Escherichia coli in the pediatric population, could improve the therapeutic approach and lead to more rational prescription of antibiotics.

Adrenal neuroblastoma in three year old boy, mistaken for pancreatic tumor: A case report.

Neuroblastoma is the most common extracranial solid tumor in children, often manifests in the retroperitoneal region. We present a case of a 3-year-old boy with no previous medical history, presented for abdominal distension. Physical examination revealed a distinct, mobile, solid mass situated in the left lumbar region. Abdominal magnetic resonance imaging displayed a well delimited, well-encapsulated mass attached to the tail of the pancreas. Urinary catecholamine metabolite levels were negative. Surgical exploration revealed that the tumor was primitively related to the left adrenal gland, and a complete resection was performed. The postoperative recovery was uncomplicated. NMYC oncogene was non-amplified.

Unusual cause of cerebral calcifications in an 8-year-old girl.

Key Clinical Message: Genetic counseling and genetic screening for hyperoxaluria should be recommended for children with urinary lithiasis for early management to avoid progression to oxalosis especially if there is a family history of lithiasis.Primary hyperoxaluria type 1 (PH1) is caused by a deficiency of the liver peroxisomal enzyme alanine-glyoxylate aminotransferase (AGT) resulting in overproduction of calcium oxalates. In its later stage, a systemic deposit of calcium oxalates is observed. We present the case of an 8-year-old girl with exceptional neurological involvement secondary to this disease.

Type II pleuropulmonary blastoma mistaken for rhabdomyosarcoma: A case report.

INTRODUCTION: Pleuropulmonary blastoma (PPB) is rare, representing 0.3 % of all pediatric cancers. PPB is classified into three subtypes and may progress from type I to types II and III, with a worse prognosis. Given its rarity, the diagnosis is frequently challenging. CASE PRESENTATION: We report an occurrence of PPB in a 3-year-old girl, who presented recurrent pneumopathy. Imaging investigations revealed a large solid lesion in the left hemithorax. Biopsy followed by histological analysis suggested rhabdomyosarcoma. The patient received neoadjuvant chemotherapy before proceeding to complete tumor excision. Surgical exploration revealed that the tumor was primitively related to parietal pleura and lower lobe of left lung. Histopathology of the tumor retained a definitive diagnosis of PPB type II. Postoperative course was uneventful, and a cerebral MRI ruled out brain metastasis. Adjuvant chemotherapy was administered. DISCUSSION: Clinical expression of PPB is nonspecific and variable. It ranges from a dry cough to respiratory distress. Standard radiography is the first examination to perform and CT is the gold standard for characterization thoracic masses. Surgery and chemotherapy are the pillars of treatment. Indications depend on the tumor type, its extent and its resectability. CONCLUSION: PPB is an aggressive tumor that occurs only in children. Due to the rarity of PPB, evidence on optimal treatment is still insufficient. Careful follow-up is necessary searching for local recurrence or metastasis.

ePHex: a phase 3, double-blind, placebo-controlled, randomized study to evaluate long-term efficacy and safety of Oxalobacter formigenes in patients with primary hyperoxaluria.

BACKGROUND: Primary hyperoxalurias (PHs) are rare genetic diseases that increase the endogenous level of oxalate, a waste metabolite excreted predominantly by the kidneys and also the gut. Treatments aim to improve oxalate excretion, or reduce oxalate generation, to prevent kidney function deterioration. Oxalobacter formigenes is an oxalate metabolizing bacterium. This Phase III, double-blind, placebo-controlled randomized trial investigated the effectiveness of orally administered Oxabact™, a lyophilized O. formigenes formulation, at reducing plasma oxalate levels in patients suffering from PH. METHODS: Subjects (≥ 2 years of age) with a diagnosis of PH and maintained but suboptimal kidney function (mean estimated glomerular filtration rate at baseline < 90 mL/min/1.73 m2) were eligible to participate. Subjects were randomized to receive Oxabact or placebo twice daily for 52 weeks. Change from baseline in plasma oxalate concentration at Week 52 was the primary study endpoint. RESULTS: Forty-three subjects were screened, 25 were recruited and one was discontinued. At Week 52, O. formigenes was established in the gut of subjects receiving Oxabact. Despite decreasing plasma oxalate level in subjects treated with Oxabact, and stable/increased levels with placebo, there was no significant difference between groups in the primary outcome (Least Squares mean estimate of treatment difference was - 3.80 µmol/L; 95% CI: - 7.83, 0.23; p-value = 0.064). Kidney function remained stable in both treatments. CONCLUSIONS: Oxabact treatment may have stabilized/reduced plasma oxalate versus a rise with placebo, but the difference over 12 months was not statistically significant (p = 0.06). A subtle effect observed with Oxabact suggests that O. formigenes may aid in preventing kidney stones. A higher resolution version of the Graphical abstract is available as Supplementary information.

Primary hyperoxaluria type 1: Clinical, genetic, and evolutionary characteristics in Tunisian children.

INTRODUCTION: There are three types of primary hyperoxaluria, with type 1 considered the most severe. AIM: To analyze the clinical, genetic, and evolutionary characteristics of type 1 primary hyperoxaluria with pediatric onset. METHODS: This was a retrospective, descriptive study that included Tunisian children under the age of 18 at the time of diagnosis over a period of 25 years (January 1, 1996, to December 31, 2022). RESULTS: Thirty-five patients were included, with a mean age of 4.1 years. The most common presenting circumstances of the disease were nephrolithiasis and end-stage renal failure. The average serum creatinine level was 225.42 µmol/l. Five mutations were identified, with the p.Ile244Thr mutation being the most prevalent. Nephrocalcinosis, surgical intervention, and a creatinine level ≥57 µmol/l were predictive of progression to end-stage renal failure. The infantile form was predictive of mortality. CONCLUSIONS: Screening for the disease would improve the prognosis of this condition.

Primary focal segmental glomerulosclerosis in children: epidemiology, clinical presentation and prognosis.

INTRODUCTION: Focal segmental glomerulosclerosis is a histopathological entity. AIM: To analyze the epidemiological, clinical and histological profile of primary focal segmental glomerulosclerosis in children, as well as their prognostic factors. METHODS: This was a retrospective cross-sectional study over a period of 20 years (2001-2020), conducted in the Department of Pediatrics at Charles Nicolle Hospital in Tunis, which included children followed for primary focal segmental glomerulosclerosis. RESULTS: There were 35 children, 19 boys and 16 girls. The median age was 4.5 years. Nephrotic syndrome was seen in 88% of patients. Macroscopic hematuria was found in 4 cases, hypertension in 8 cases and renal failure in 7 cases at presentation. The most common variant was the not otherwise specified variant (77.1%). Steroid-sensitive nephrotic syndrome was observed in 71% of cases, and steroid-resistance in 29% of cases. Treatment with cyclosporine was indicated in 23 patients with complete remission rate of 56.5%. 42,8% children had progressed to chronic kidney disease, including an end-stage renal disease in 11.5% of cases. Only the presence of a family history of kidney disease was found as a predictive factor of progression to chronic kidney disease and end-stage renal disease. Renal survival rates were estimated at 100% at 3 years, 85% at 5 years and 73% at 10 years. CONCLUSION: Identification of patients at high risk for chronic kidney disease progression, such as those with a family history of kidney disease or those who have failed to respond to corticosteroids, would allow therapeutic adjustments.

Spontaneous hemothorax in a 10-year-old boy with COVID-19.

Spontaneous hemothorax occurs in the absence of trauma or iatrogenic causes. Etiologies of spontaneous hemothorax in children include connective tissue disease, neoplasia and coagulopathy, which is associated with thromboembolic events. We present the case of a 10-year-old chronic hemodialysis patient with spontaneous hemothorax with a concurrent COVID-19 infection.

Monogenic urinary lithiasis in Tunisian children: 25 years' experience of a referral center.

OBJECTIVE: To describe the clinical, biochemical and evolutive profile of monogenic urinary lithiasis in Tunisian children followed up in a reference service, during a 25 years period. METHODS: This was a single-center retrospective observational study of children with urolithiasis, conducted in the pediatric nephrology department in Charles Nicolle Hospital, Tunis, Tunisia over 25 years (January 1st, 1996 to December 31, 2020). Children≤18 of age with urolithiasis with or without nephrocalcinosis related to a monogenic disease were included in our study. RESULTS: A total of 66 children were included in our study. Patients were 5.92±3.48 years of age at the time of urolithiasis diagnosis, and 5.33±3.66 years of age at the time of the underlying pathology diagnosis. The inherited urolithiasis disorders found in our series were: primary hyperoxaluria in 44 cases, cystinuria in 9 cases, Lesch Nyhan syndrome in 5 cases. Renal tubular acidosis was found in 3 cases, and hereditary xanthinuria in 2 cases. Bartter syndrome, adenine phosphoribosyltransferase deficiency and Hereditary hypophosphatemic rickets with hypercalciuria were found in 1 case each. After an average follow-up of 6.45±3.79 years, six patients were in end-stage renal disease. Three patients had died, all of them being followed for primary hyperoxaluria type 1. CONCLUSIONS: Monogenic urinary lithiasis, although rare, are most likely under-diagnosed in countries with high consanguinity such as Tunisia. The screening of these diseases seems to be of primary importance because of their significant morbidity.

Thromboembolic complications in children with primary nephrotic syndrome: A Tunisian series.

INTRODUCTION: Nephrotic syndrome is a common pathology in children. Despite its good prognosis, it can become complicated and threaten the patient's vital and functional prognosis. Thromboembolic complications are rare but serious. AIM: To study the main thromboembolic events and their outcome during primary nephrotic syndrome in children. METHODS: It was a retrospective study of the records of children followed for primary nephrotic syndrome who presented one or more thromboembolic events. RESULTS: Twenty thromboembolic events in 19 children were identified (15 boys and 4 girls). The average age was 5.13±3.4 years at the time of NS diagnosis. The location of the thrombosis was venous in 14 cases. Cerebral venous thrombosis was noted in seven cases, pulmonary thromboembolism in five cases. We noted deep venous thrombosis of lower limbs in three cases, occlusive mesenteric ischemia in two cases, vein portal thrombosis in one case, renal vein thrombosis in one case, and thrombosis of a peripheral artery in one case. CONCLUSION: Venous and arterial thrombotic complications can occur in children with nephrotic syndrome. Clinical features may be subtle; therefore, neuroimaging and angiographic techniques are essential for diagnosis.

Lupus Nephritis in Tunisian Children: Predictive Factors of Poor Outcomes.

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disorder of unknown etiology. Lupus nephritis (LN) is one of the most severe clinical manifestations observed in patients with SLE; it is more frequent and more severe in children than in adults. The aim of our study was to assess the predictive factors of poor outcomes in Tunisian children with LN. This was a multicenter retrospective observational study on 40 pediatric patients with biopsy-proven LN from five nephrology departments in Tunisia. The patients were 12.33 ± 3.3 years of age at the time of their kidney biopsy. Eleven patients developed end-stage renal disease (ESRD) (27.5%), and seven patients died. Overall, 18 (45%) patients reached our composite endpoint (ESRD or death). An age at diagnosis of more than 14 years, elevated serum creatinine at the time of the kidney biopsy, the existence of wire loops, thromboembolic complications as well as infectious complications are the most important clinical features associated with an increased risk of ESRD. Predictive factors of death were a baseline creatinine level of more than 2.26 mg/dL, a high proteinuria at baseline, fibrous crescents determined by renal biopsy, thromboembolic complications, infectious compli-cations, and ESRD. In summary, our results suggest that early and appropriate management is the best guarantee of a good renal outcome in children with LN.

Giant pulmonary hydatid cyst in children.

Hydatid disease is still endemic in Tunisia. It is mostly seen in young people less than 40 years and children are affected in one third of cases. The lungs are the predominant location in children. Our study aims to define the particularities of children PHC's (pulmonary hydatic cyst) management, the characteristics of giant cyst and to study predictive factors of complications. We included retrospectively 105 children with PHC followed between 1999 and 2019. Patients were aged less than 16 years with surgically confirmed diagnosis of PHC. Two groups of cysts were defined: giant cysts which were 10 cm across or more, and no giant cysts.The sex-ratio was 1.38 with a mean age of 10.5±3 years. The symptomatology was dominated by cough (59%), thoracic pain (51%) and hemoptysis (46%). Giant cysts were observed in 24 (22.9%) patients. Dyspnea (29% vs 5% p<0.001) and thoracic pain (88% vs 41% p<0.001) were significantly more frequently reported in giant cysts. Eighty-six patients had a single cyst (83%) and 19 had multiple cysts (17%). Giant cysts accounted for 22,9% (24 cases). Thoracic ultrasonography was diagnostic in 77.4%. The thoracic CT scan was performed in 27 children with inaccessible cysts in thoracic ultrasonography or in diagnostic doubt.Patients were all treated surgically. Surgical procedures consisted of cystectomy (59%), pericystectomy (18%) and pulmonary resection when parenchyma was destroyed (23%). Parenchymal resection was more often performed in complicated cysts (27% vs 20% p>0.05) and in giant cysts (41% vs 18% p<0.05). A two-stage thoracotomy was performed in the 4 patients with bilateral cysts. Thirteen patients presented immediate post-operative complications which occurred more frequently in complicated and giant cysts. Hospital stay was longer in complicated cysts (16±9 days vs 7±3 days; p<0.001) and in giant cysts (14±9 days vs 11±8 days; p>0.05). In endemic regions, the diagnosis of PHC in children should be based on the combination of thoracic radiography and ultrasonography which are effective, not costly, safe and accessible. Complicated and giant PHC cause lung damage leading to extensive parenchymal resection. They are more associated with post-operative complications prolonging hospital stay and increasing expenses.