Evaluation of the antiviral activity of new dermaseptin analogs against Zika virus.

Zika virus represents the primary cause of infection during pregnancy and can lead to various neurological disorders such as microcephaly and Guillain-Barré syndrome affecting both children and adults. This infection is also associated with urological and nephrological problems. So far, evidence of mosquito-borne Zika virus infection has been reported in a total of 89 countries and territories. However, surveillance efforts primarily concentrate on outbreaks that this virus can cause, yet the measures implemented are typically limited. Currently, there are no specific treatments or vaccines designed for the prevention or treatment of Zika virus infection or its associated disease. The development of effective therapeutic agents presents an urgent need. Importantly, an alternative for advancing the discovery of new molecules could be dermaseptins, a family of antimicrobial peptides known for their potential antiviral properties. In this study, we carried out the synthesis of dermaseptins and their analogs and subsequently assessed the bioactivity tests against Zika virus (ZIKV PF13) of dermaseptins B2 and S4 and their derivatives. The cytotoxicity of these peptides was investigated on HMC3 cell line and HeLa cells by CellTiter-Glo® Luminescent Cell Viability Assay. Thereafter, we evaluated the antiviral activity caused by the action of our dermaseptins on the viral envelope using the Fluorescence Activated Cell Sorting (FACS). The cytotoxicity of our molecules was concentration-dependent at microgram concentrations Expect for dermaseptin B2 and its derivative which present no toxicity against HeLa and HMC3 cell lines. It was observed that all tested analogs from S4 family exhibited antiviral activity with low concentrations ranging from 3 to 12.5 µg/ml , unlike the native B2 and its derivative which increased the infectivity. Pre-incubating of dermaseptins with ZIKV PF13 before infection revealed that these derivatives inhibit the initial stages of virus infection. In summary, these results suggest that dermaseptins could serve as novel lead structures for the development of potent antiviral agents against Zika virus infections.

Contribution of HLA class I (A, B, C) and HLA class II (DRB1, DQA1, DQB1) alleles and haplotypes in exploring ethnic origin of central Tunisians.

BACKGROUND: Estimation of HLA (Human leukocyte Antigen) alleles' frequencies in populations is essential to explore their ethnic origin. Anthropologic studies of central Tunisian population were rarely reported. Then, in this work, we aimed to explore the origin of central Tunisian population using HLA alleles and haplotypes frequencies. METHODS: HLA class I (A, B, C) and HLA class II (DRB1, DQA1, DQB1) loci genotyping of 272 healthy unrelated organ donors was performed by Polymerase Chain Reaction-Sequence Specific Oligonucleotide (PCR-SSO). We compared central Tunisians with other populations (Arabs, Berbers, Mediterraneans, Europeans, Africans, etc.) using alleles and haplotypes frequencies, genetic distances, Neighbour-Joining dendrogram and correspondence analysis. RESULTS: Among the 19 HLA A alleles, the 26 HLA B alleles, the 13 HLA C alleles, the 15 HLA DRB1 alleles, the 6 HLA DQA1 alleles and the 5 HLA DQB1 alleles identified in the studied population, HLA A*02 (22.8%), HLA B*50 (13.1%), HLA C*06 (21.8%), HLA DRB1*07 (17.8%), HLA DQA1*01 (32.1%) and HLA DQB1*03 (31.6%) were the most frequent alleles. The extended haplotypes HLA A*02-B*50-C*06-DRB1*07-DQA1*02-DQB1*02 (1.97%) was the most frequent HLA six-loci haplotype. CONCLUSION: Central Tunisians were very close to other Tunisian populations, to Iberians and North Africans. They were rather distant from sub-Saharan populations and eastern Mediterraneans especially Arabs although the strong cultural and religious impact of Arabs in this population.

Prevalence and Predictive Factors of Urinary Tract Infection in Kidney Transplant Recipients: A 10-Year Study.

OBJECTIVES: Urinary tract infections are the main infectious complications among kidney transplant recipients and are considered as a potential risk factor for poor graft outcomes. However, the risk factors of urinary tract infections are controversial. The purpose of our study was to estimate the incidence and predisposing factors of urinary tract infections in patients undergoing kidney transplant in our teaching hospital of Sahloul, Tunisia. MATERIALS AND METHODS: We retrospectively analyzed the charts of 141 consecutive adult kidney transplants that were performed at the Department of Nephrology, University Hospital of Sahloul, Tunisia, between January 2007 and April 2016. RESULTS: Of 141 patients, 72 (51.1%) had urinary tract infections after kidney transplant. Mean age was 32.54 ± 12.1 years; 47.6% were male patients, and 52.4% were female patients. The average time between transplant and early urinary tract infections was 11 days (range, 1-30 days). Among our patient group, 87.8% of urinary tract infections occurred within the first 6 months posttransplant. We collected 205 episodes of urinary tract infections: 66.3% were asymptomatic bacteriuria, 10.2% acute cystitis, and 23.4% pyelonephritis. The estimated risk factors for urinary tract infection included only female sex (P < .05); older age (P = .32), longer duration of catheter (P = .34), and high body mass index (P = .46) were not correlated with urinary tract infection. CONCLUSIONS: Despite preventive measures, urinary tract infections remain an important cause of morbidity among kidney transplant recipients. In fact, more than half of kidney transplant recipients had at least 1 urinary tract infection after surgery. Female sex was statistically associated with higher risk of urinary tract infection.

Dermatological Conditions Seen in Kidney Transplant Recipients: Prevalence and Risk Factors.

OBJECTIVES: In kidney transplant, the use of immunosuppressive drugs, indispensable to avoid organ rejection, implies an increased risk of several infectious and neoplastic diseases. Cutaneous infections have a high incidence in kidney transplant recipients and are diagnosed in 55% to 97% of these patients. The objectives of this study were to identify the most frequent skin diseases and their clinical risk factors within a population of kidney transplant recipients. MATERIALS AND METHODS: We reviewed the medical records of 200 kidney transplant recipients at Sahloul Teaching Hospital, Tunisia, between November 2007 and January 2018. We analyzed the clinical data of patients who sought skin consultations with either dermatologists or plastic surgeons within the hospital. We collected patient sociodemographic data, type of donor, and type of immunosuppressive therapy used by recipients. We also obtained history of skin lesions and examination findings. RESULTS: Among 200 patients included in our study cohort, 131 were male and 69 were female. Age ranged from 6 to 75 years with a mean age of 30.51 ± 12 years. Patients had received kidneys from either living or deceased donors, with available data indicating 96.5% living donors and 3.5% deceased donors. The mean time interval from transplant to first skin consultation was 31 month (range, 3 months to 10 years). Prevalence of various skin conditions was 48.5%. We found that 62.9% of cases were skin infections, 59.8% were drug-induced skin conditions, and 2.9% were skin cancers. The estimated risk factors for skin lesions include use of cyclosporin and duration of immunosuppression. CONCLUSIONS: Our study demonstrated the spectrum of skin conditions that can be expected after kidney transplant. Careful dermatological screening and long-term follow-up are needed for these patients to reduce posttransplant skin complications.

The pharmacogenetics of tacrolimus in renal transplant patients: association with tremors, new-onset diabetes and other clinical events.

Our study is the first study to investigate the effect of SNPs in CYP3A5, CYP3A4, ABCB1 and POR genes on the incidence of tremors, nephrotoxicity, and diabetes mellitus. A total of 223 renal transplant patients receiving tacrolimus and mycophenolate mofetil (MMF) were recruited. Both adults and children patients participated in the study. Genotyping was performed using PROFLEX-PCR followed by RFLP. MPA and tacrolimus plasma concentrations were measured by immunoassay. The AUC0-12h of MMF was estimated by a Bayesian method. We found a statistically significant association between the CYP3A5*3 and CYP3A4*1B genotypes and the tacrolimus exposure. We found a lower occurrence of nephrotoxicity (p = 0.03), tremor (p = 0.01), and new-onset diabetes (p = 0.002) associated with CYP3A5*1 allele. The CYP3A4*1B allele was significantly associated with a lower occurrence of new-onset diabetes (p = 0.026). The CYP3A5*1 allele was significantly associated with an increased risk of acute and chronic rejection (p = 0.03 and p < 0.001, respectively). Our results support the usefulness of tacrolimus pharmacokinetics in pre-kidney transplant assessments.

A Population Pharmacokinetic Model to Predict the Individual Starting Dose of Tacrolimus for Tunisian Adults after Renal Transplantation.

BACKGROUND: Tacrolimus is the most frequently used immunosuppressive drug for preventing renal rejection. However, its use is hampered by its narrow therapeutic index and large intra and interpatient variability in pharmacokinetics. The objective of this study was to externally validate a tacrolimus population pharmacokinetic model developed for the Dutch population and adjust the model for the Tunisian population for use in predicting the starting dose requirement after kidney transplantation. METHODS: Data on tacrolimus exposure were obtained from kidney transplant recipients (KTRs) during the first 3 months post-transplantation. External validation of the Dutch model and its adjustment for the Tunisian population was performed using nonlinear mixed-effects modeling. RESULTS: In total, 1901 whole-blood predose tacrolimus concentrations from 196 adult KTRs were analyzed. According to a visual predictive check, the Dutch model underestimated the starting dose for the Tunisian adult population. The effects of age, together with the CYP3A5*3 and CYP3A4*22 genotypes on tacrolimus clearance were significantly different in the Tunisian population than in the Dutch population. Based on a bodyweight-based dosing, only 21.9% of tacrolimus concentrations were within the target range, whereas this was estimated to be 54.0% with the newly developed model-based dosing. After adjustment, the model was successfully validated internally in a Tunisian population. CONCLUSIONS: A starting-dose population pharmacokinetic model of tacrolimus for Tunisian KTRs was developed based on a previously published Dutch model. Using this starting dose could potentially increase the percentage of patients achieving target tacrolimus concentrations after the initial starting dose.

Analysis of Pathogens of Urinary Tract Infections Associated with Indwelling Double-J Stents and Their Susceptibility to Globularia alypum.

Ureteral double-J stents are frequently used to prevent urinary obstruction. They can develop bacterial colonization and encrustation, which leads to persistent infections that seldom respond to antibiotic treatment. Thus, the goal of this study was to evaluate the local spectrum of bacterial pathogens and their susceptibility to natural compounds. A total of 59 double-J ureteral stents from 59 consecutive patients were examined. The samples were inoculated on agar culture mediums. Extracts of Globularia alypum L. were evaluated for their antibacterial activity with the diffusion and broth dilution methods; for antibiofilm activity, the crystal violet assay was used. The identification and the quantification of the different constituents of extracts were determined by reverse-phase high-performance liquid chromatography (RP-HPLC). Bacterial growth was found in three patients (5.1%). Enterococcus faecalis (1.7%), Acinetobacter baumanii (1.7%), and Pseudomonas putida (1.7%) strains were more commonly detected. They were resistant to several common antibiotics. All extracts presented several components, mainly nepetin-7-glucoside and trans-ferulic-acid, and they had antibacterial activity (MIC = 6.25 mg/mL and MBC = 6.25 mg/mL), and antibiofilm (59.70% at 25 mg/mL) properties, especially against Acinetobacter baumanii. The results achieved confirm the important role of this plant as a source of therapeutic activities.

Nephrotic syndrome with Minimal Change Disease and Atopy in NorthAfrican adults.

INTRODUCTION: In adults, minimal change disease (MCD) accounts for 15 to 25% of nephrotic syndrome (NS). Numerous reports have suggested a link between NS and atopy. However, data on treatment and prognosis of NS associated with allergy are limited. AIM: To examine the presenting characteristics, treatments and outcomes of adults with allergic MCD in a North African center. METHODS: This was an observational study using retrospectively collected data. Patients were recruited from the Nephrology department of Sahloul Hospital (Sousse, Tunisia) from January 2006 to December 2020. Adults with a biopsy proved MCD, which was associated with atopy, were included. RESULTS: Fifteen patients (eight males, age mean±SD: 34±13 years) were included. High eosinophil and immunoglobulin E (IgE) levels were noted in three and twelve patients respectively. The IgE mean level at the initial presentation was 1431 IU/ml. Allergic skin tests were positive in nine patients. All patients were treated with corticosteroids, five had anti-histamine therapy and five had hyposensitization therapy, which was successful in two patients. Thirteen patients had relapsed during follow-up. Mean eosinophil level was significantly higher in patients with frequent relapses compared to those with infrequent relapses (5415/mm³ vs. 239.12/mm³, respectively, p=0.022). Two patients had progressed to chronic renal failure. CONCLUSION: It is important to search for atopic disorders in patients with MCD to better control this disease and use specific treatments. However, the efficacy of anti-allergic therapies has to be proven.

Sarcoid-Like Reaction in the Kidney Following Rituximab for Mantle Lymphoma in a 60-Year-Old Man.

The sarcoid-like reaction is a rare autoinflammatory disease that can affect lymph nodes or organs but does not meet the diagnostic criteria for systemic sarcoidosis. Several drug classes have been associated with the development of a systemic sarcoid-like reaction, which defines drug-induced sarcoidosis-like reactions and can affect a single organ. Anti-CD20 antibodies (rituximab) have rarely been reported as responsible for this reaction and this adverse effect has mainly been described during the treatment of Hodgkin's lymphoma. We report a unique case of a sarcoid-like reaction complicating rituximab following the treatment of a mantle cell lymphoma and interesting only the kidney. The 60-year-old patient presented with severe acute renal failure 6 months after the end of his r-CHOP protocol and the urgent renal biopsy revealed acute interstitial nephritis rich in granulomas without caseous necrosis. After ruling out other causes of granulomatous nephritis, a sarcoid-like reaction was retained since infiltration was limited to the kidney. The temporal relationship between rituximab administration and the sarcoid-like reaction onset in our patient supported the diagnosis of a rituximab-induced sarcoidosis-like reaction. Oral corticosteroid treatment led to rapid and lasting improvement in renal function. Clinicians should be warned of this adverse effect and regular and prolonged monitoring of renal function should be recommended during the follow-up of patients after the end of treatment with rituximab.

Thrombotic microangiopathy due to acquired complement factor I deficiency in a male receiving interferon-beta treatment for multiple sclerosis.

AIMS: Interferon-beta (IFNß), the most widely prescribed medication for multiple sclerosis, is generally considered safe. Nevertheless, rare serious and/or life-threatening side effects have been reported such as thrombotic microangiopathy. A few mechanisms have been proposed to explain how interferon causes thrombotic microangiopathy, but immunological studies have been unable to pin this phenomenon down to a single pathophysiologic pathway. The aim of this article was to report a new mechanism explaining Interferon beta related thrombotic microangiopathy. METHODS: We report thrombotic microangiopathy in a 28-year-old male receiving interferon-beta treatment for multiple sclerosis. RESULTS: After three years of starting interferon beta therapy, the patient presented with malignant hypertension causing seizures, rapidly progressive renal failure requiring haemodialysis and haemolytic anaemia. Corticosteroid and plasma exchange sessions permitted haemolysis control. Nonetheless, the patient remained hemodialysis-dependent. Exploration of the complement system found a complement factor I deficiency whose activity normalized at the control carried out after 2 years. CONCLUSION: IFNß treatment may cause complement factor I deficit, which can lead to thrombotic microangiopathy and severe renal failure.

Severe Acute Interstitial Nephritis, Dermatitis, and Hemolytic Anemia due to Polyparasitic Infection in an Immunocompetent Male Patient.

Acute interstitial nephritis (AIN) is a relevant cause of acute renal failure. Drugs are the predominant cause, followed by infections and idiopathic lesions. AIN, as a form of hypersensitivity reaction, is an uncommon manifestation in the setting of human parasitic infections. We report a case of a polyparasitic infection (Giardia lamblia, Entamoeba coli, and Endolimax nana) resulting in a severe biopsy-proven AIN in a 61-year-old male patient. Despite the antiparasitic treatment followed by corticosteroid therapy, and during the 6-month follow-up period, the patient remained dialysis-dependent, and he developed autoimmune hemolytic anemia. Extensive search for another infection or neoplasia was negative. Immunological tests were also negative. The resulting hypersensitivity reaction to the triple parasite infection would have led to fatal evolution for the kidneys affected by this unusual type of AIN.

The pharmacogenetics of mycophenolate mofetil in Tunisian renal transplant patients.

Aim: The effects of variants in IMPDH, UGT1A9, UGT1A8, UGT2B7 and SLCO1B1 genes on the efficacy and safety of mycophenolate mofetil (MMF) in the Tunisian population were investigated. Materials & methods: A total of 245 kidney transplant patients being treated with MMF were recruited and cotreated with cyclosporine or tacrolimus. Genotyping was performed using the polymerase chain reaction-restriction fragment length polymorphism method. MMF, cyclosporine and tacrolimus trough levels were measured by immunoassay. The AUC (AUC0-12hMPA) was estimated by a Bayesian method. Results: In the tacrolimus-treated group, anemia and diarrhea were associated with the UGT1A9-98C and UGT1A9-275T alleles, respectively (p < 0.05). In the cyclosporine-treated group, leukopenia was associated with the SLCO1B1-521T allele (p < 0.05). Both groups had an increased risk of rejection (p < 0.05) associated with the variant alleles of IMPDH2-3757T>C, UGT1A9-2152C>T and UGT1A9-275C>A and the common allele of SLCO1B1-388A>G. However, no significant association was found between the studied genotypes and AUC0-12hMPA or cotreatment levels. Conclusion: The results constitute preliminary evidence for the inclusion of the pharmacogenetics of MMF in kidney pretransplantation evaluations.

New-Onset Diabetes as a Complication After Kidney Transplant: Incidence and Outcomes.

OBJECTIVES: Diabetes after kidney transplant is a common complication. It may increase the risk of cardiovascular disease and mortality after kidney transplant. The aim of this study was to examine the effects of diabetes that developed after transplant on outcomes in kidney transplant recipients. MATERIALS AND METHODS: This study included renal allograft recipients without diabetes who received transplants from 2008 to 2019 in our Department of Nephrology at Sahloul Hospital (Tunisia). Demographic and clinical data at transplant time and clinical events during the study period were collected. Patient and graft survival rates were analyzed. Patients with and without diabetes after transplant were compared. RESULTS: In the 257 patients (median age of 36 years) included in our study, the overall incidence of diabetes after transplant was 21.8%. Laboratory data (serum cholesterol, serum creatinine at discharge, and 24-hour proteinuria) were similar in those with and without diabetes after transplant. We observed no significant differences in cardiovascular diseases and infectious complication rates between patients with and without diabetes after transplant. There was also no significant difference in graft loss at 5 years between those with and without diabetes after transplant (P = .582). The 5-year patient survival rate in kidney transplant recipients with diabetes after transplant was 87.5%. There was no significant difference in death rate between those with and without diabetes after transplant (P = .566). CONCLUSIONS: Diabetes after transplant affected graft and patient survival and increased the incidence of posttransplant cardiovascular disease. The incidence and impact of diabetes after transplant can be minimized through pre- and posttransplant screening to identify patients at higher risk.

Acute Kidney Injury due to Povidone-Iodine.

Povidone-iodine is a broad-spectrum antiseptic applied topically to treat wounds and prevent their infection. Despite the apparent innocuousness of this agent, several cases of acute kidney injury (AKI) due to iodine toxicity have been reported. We report a case of severe AKI that occurred in a 32-year-old female three days after a hysteroscopy for the diagnosis of primary sterility using povidone-iodine as the local antiseptic agent. We made a clinical diagnosis of tubular necrosis related to iodine toxicity in view of the clinical presentation and high blood iodine concentration. The patient was treated with hemodialysis until urine output and renal function improved. Physicians must be aware of the possible nephrotoxicity secondary to povidone-iodine use. Patients receiving povidone-iodine, especially those who already suffer from kidney failure, should be closely monitored. The discontinuation of this agent, with the use of hemodialysis, is usually effective.

Prevalence and risk factors of hypertension following nephrectomy in living kidney donors.

Living donor kidney transplantation is the treatment of choice for the patients with end-stage renal disease, especially where deceased donor programs are limited. There are limited data on the outcomes of living kidney donors (LKD) from developing countries, especially from North Africa. The aim of this study is to evaluate the prevalence of hypertension (HTN) in LKD and to analyze its risk factors. This is a longitudinal monocentric study, and the donors who underwent nephrectomy for donation between 2006 and 2015 were included. Ninety-two donors were assessed. The mean age at the time of nephrectomy was 42.8 ± 10 years (21-68 years). The sex ratio was 0.6. At the time of donation, the median systolic blood pressure was 120 mm Hg and the median diastolic blood pressure was 70 mm Hg. HTN was noted in 4% of donors. The median follow-up duration was 26 months. Two years after donation, the prevalence of HTN was 28% in the study group (8% male and 20% female). The mean time to development of HTN was 16 months. Associations between HTN after donation and the cardiovascular family history, age >40 years, HTN, obesity, android obesity, glomerular filtration rate GFR <90 mL/min/1.73 m2, perioperative HTN, and dyslipidemia were noted. The multivariate analysis showed that obesity at the time of donation was a risk factor for HTN (odds ratio = 4.8; P = 0.04). Obese donor [body mass index (BMI) ≥30)] has higher risk of HTN after nephrectomy than nonobese donor.

Long-term clinical outcomes of peritoneal dialysis patients: 10-year experience of a single unit from Tunisia.

Published data on the outcome of maintenance peritoneal dialysis (PD) since the initiation of PD in Tunisia is poor. The purpose of this study is to report long-term clinical outcomes of PD patients through a 10-year experience at a single unit. This is a retrospective review of the medical records of 182 PD patients who were followed up from January 2006 to June 2016. All patients were followed till death, renal transplant, switch over to hemodialysis (HD) or the end of the study in June 2016. The mean age of the incident patients was 43.93 ± 16.95 years. Nineteen (10.4%) were aged >65 years and 59.3% were male. The average duration of follow-up was 27.75 ± 26.18 months. The mean duration of PD treatment was 27.75 ± 26.18 months. There were 186 episodes of peritonitis that occurred over the total study period (54 episodes during the 1st year). The overall incidence of peritonitis during the 10-year study period was 1 per 27.25 patient months. Mechanical complications were noted in 31.2% of cases. Thirty- two (17.6%) patients had catheter displacement. Only 26 cases of hemoperitoneum (14.3%) were recorded. Death occurred in 23.1% of cases. Twenty-two patients (27.5%) were transplanted; 56 patients (70%) were transferred to HD, one patient had renal recovery and one case had voluntarily interrupted PD. In Kaplan-Meier curves of residual renal function (RRF) loss, there was a significant difference between peritonitis group and peritonitis-free group (P = 0.01). Technique and patient survival were associated with diabetes with a significant difference. The main cause of technique failure was peritonitis (61.4%). Moreover, the main repertoried causes of death were cardiovascular and septic causes. The mortality of diabetic and elderly PD patients was higher than mortality in nondiabetic and nonelderly groups, respectively, in our study. Peritonitis was associated with loss of RRF and technique failure.

Alternaria alternata peritonitis in a patient undergoing continuous ambulatory peritoneal dialysis.

Fungal peritonitis is a serious complication of peritoneal dialysis (PD) leading to loss of ultrafiltration and discontinuation of PD treatment. The most frequently isolated fungi are Candida albicans and, filamentous fungi such Alternaria alternata species are found only rarely. We report the case of a 75-year-old woman who developed peritonitis due to this black fungus.

Effect of intraperitoneal injection of sulodexide on peritoneal function and albumin leakage in continuous ambulatory peritoneal dialysis patients.

Peritoneal protein loss is one of the inevitable consequences during continuous ambulatory peritoneal dialysis (CAPD). Our objective was to study the effect of sulodexide on the protein loss and efficiency of dialysis. This study included six patients receiving CAPD treated with sulodexide at the dose of 600 IU/day given by intraperitoneal injection for 10 days. Clinical and biologic parameters were assessed before starting the treatment (D0 and after 10 days of treatment (D10. We also evaluated the benefit of therapy persisting 20 days after the end of treatment (D30. The sulodexide administration produced a significant improvement of the peritoneal function as determined by a significant increase in the following ratios measured at the 4 th h of dwell time on D0 and D30: dialysate-to plasma (D/P) creatinine from 0.63 ± 1.45 to 0.85 ± 0.073 (P = 0.028) and D/P urea from 0.63 ± 0.15 to 79 ± 0.2 (P = 0.048). A significant decrease of albumin leakage was observed, which was 0.90 ± 0.40 g/L at baseline, 0.67 ± 0.36 g/L on the 10 th day, and 0.43 ± 0.22g/L 20 days after the end of treatment. Within 10-day treatment period, use of sulodexide resulted in a reduction in the peritoneal loss of albumin, in addition to improvement of the quality of dialysis and the residual renal function among these patients.

Identification of a novel AGXT gene mutation in primary hyperoxaluria after kidney transplantation failure.

Primary hyperoxaluria is a genetic disorder in glyoxylate metabolism that leads to systemic overproduction of oxalate. Functional deficiency of alanine-glyoxylate aminotransferase in this disease leads to recurrent nephrolithiasis, nephrocalcinosis, systemic oxalosis, and kidney failure. The aim of this study was to determine the molecular etiology of kidney transplant loss in a young Tunisian individual. We present a young man with end-stage renal disease who received a kidney allograft and experienced early graft failure. There were no improvement in kidney function; he required hemodialysis and graft biopsy revealed calcium oxalate crystals, which raised suspicion of primary hyperoxaluria. Genetic study in the AGXT gene by PCR direct sequencing identified three missense changes in heterozygote state: the p. Gly190Arg mutation next to two other novels not previously described. The classification of the deleterious effect of the missense changes was developed using the summered results of four different mutation assessment algorithms, SIFT, PolyPhen, Mutation Taster, and Align-GVGD. This system classified the changes as polymorphism in one and as mutation in other. The patient was compound heterozygous mutations. Structural analysis showed that the novel mutation, p.Pro28Ser mutation, affects near the dimerization interface of AGT and positioned on binding site instead of the inhibitor, amino-oxyacetic acid (AOA). With the novel AGXT mutation, the mutational spectrum of this gene continues to broaden in our population. The diagnosis of PH1 was not recognized until after renal transplant with fatal consequences, which led us to confirm the importance of screening before planning for kidney transplantation in population with a relatively high frequency of AGXT mutation carriers.

BK and JC virus infections in healthy patients compared to kidney transplant recipients in Tunisia.

The human polyomaviruses BKPyV and JCPyV are members of Polyomaviridae family and after primary infections they persist as latent infection especially in the kidneys. BKVPy reactivation is mainly related to a renal nephropathy and JCV reactivation can induce the progressive multifocal leukoencephalopathy. The aim of this study was to investigate and to compare the presence of BKPyV and JCPyV in urine and plasma samples from immunocompromised and immunocompetent groups. The viral detection and quantification was done by a real time PCR from 100 healthy individuals and from 72 kidney transplanted patients (KTx) enrolled in a prospective study. Polyomavirus DNA urinary shedding was identified in 19% of healthy person, BKPyV in 6%; JCPyV more frequent in 13%. No individuals in this group developed polyomavirus viremia. BKPyV and JCPyV viruria was seen in 36% and 28% of KTx respectively, and 11% had a concomitant BKPyV and JCPyV viruria. Only BKPy viremia was detected in 5.5% of the KTx. In healthy persons, JCPyV shedding was associated with older individuals. However, in KTx, BKPyV was associated with younger age and male gender. No significant association was found between the patient's origin and BKPyV or JCPyV infection. In conclusion and consisting with previous reports, BKPyV and JCPyV prevalence and urinary loads were significantly higher in immunosuppressed compared to non-immunosuppressed individuals. In Addition and by contrast to KTx, JCPyV was more frequent than BKPyV in healthy individuals. Furthermore, the shedding of both polyomaviruses was differently associated with the age and the sex according to each population.