Subject(s)
Cryoglobulinemia/complications , Eye Diseases/etiology , Facial Paralysis/etiology , Ischemia/etiology , Sjogren's Syndrome/complications , Aged , Cryoglobulinemia/diagnosis , Eye Diseases/diagnosis , Facial Paralysis/diagnosis , Humans , Ischemia/diagnosis , Male , Sjogren's Syndrome/diagnosis , SyndromeABSTRACT
INTRODUCTION: Genetic factors must be considered in etiological diagnosis of urinary lithiasis. The aim of this study was to determine clinical, metabolic characteristics and the progression of hereditary urinary lithiasis in our patients. METHODS: A retrospective study was conducted between 2008 and 2018 and 60 patients were included. Patients were referred to our department from pediatrics departments to be followed-up in adulthood in 9 cases, for etiological investigation in 42 cases and for chronic renal failure in 9 cases. RESULTS: Thirty-five men and twenty-five women were enrolled in this study with a M/F sex ratio equal to 1.4. The mean age at the time of diagnosis of the hereditary character of the urinary lithiasis was 28.6years (3months-63years). The average delay between the onset of the lithiasis disease and the etiological diagnosis was 8years (0-42years). We noted 31 cases of cystinuria, 18 cases of primary hyperoxaluria type 1 with two mutations (I244T in 14 cases, 33-34 Insc in 23 cases) and 11 cases of renal tubulopathy. Fourteen patients were affected with chronic renal failure, of which five were in the end-stage renal disease. Crystalluria was positive in 62% of cases. The morpho-constitutional analysis of stones was performed in 37 cases and it contributed to the diagnosis in 29 cases. After an average follow-up of 16years, we noted normal renal function in 42 cases, chronic renal failure in 7 cases, hemodialysis in 10 cases all with primary hyperoxaluria and transplantation in 1 case. CONCLUSION: The etiological diagnosis of hereditary urinary lithiasis in our study was made with considerable delay. Cystinuria was the most frequent etiology and primary hyperoxaluria was the most serious affection. LEVEL OF EVIDENCE: 4.
Subject(s)
Kidney Calculi/genetics , Adolescent , Adult , Child , Child, Preschool , Disease Progression , Female , Hospitals, Special , Humans , Infant , Kidney Calculi/complications , Kidney Calculi/diagnosis , Kidney Calculi/metabolism , Male , Middle Aged , Nephrology , Retrospective Studies , Young AdultABSTRACT
BACKGROUND: Genetic polymorphisms of interleukin (IL)-17F, associated with functional and/or quantitative change in this glycoprotein, have been described as predisposing to various autoimmune diseases. The proinflammatory IL-17 has some roles in renal transplantation. In this context, the relationship between the most common IL-17F polymorphisms with acute renal allograft rejection susceptibility in Tunisian renal recipients has been investigated. METHODS: We examined 93 renal transplant recipients who were enrolled and classified as follows: GI, 48 transplant recipients who developed at least one episode of acute rejection; and GII, 45 controls, kidney recipients who also were followed for at least 1 year and had stable renal function. Single nucleotide polymorphisms (SNPs) of IL-17F gene, including -1507 C/T (rs18889570), 7384 A/G (rs2397084), 7469 C/T (rs11465553), and 7489 A/G (rs763780), were evaluated using direct sequencing. RESULTS: No statistically significant association of the IL-17F SNPs studied with the onset of acute rejection was observed. However, AA genotype on 7489A/G SNP showed anti-HLA antibodies less than other genotypes and a higher graft survival time (P = .017). CONCLUSION: The AA genotype on 7489A/G SNP of IL-17F and the A allele might be associated with a lower risk of acute rejection with better graft survival.
Subject(s)
Graft Rejection/genetics , Graft Survival/genetics , Interleukin-17/genetics , Kidney Transplantation/adverse effects , Polymorphism, Single Nucleotide , Adult , Alleles , Case-Control Studies , Female , Genotype , Humans , Male , Retrospective Studies , TunisiaABSTRACT
INTRODUCTION: Calcium oxalate stones are the most common urolithiasis. Changes in dietary habits, socio-economic and health status of populations explain its progression. The aim of our study was to determine metabolic factors leading to lithiasis and clarify its causes. PATIENTS AND METHODS: This is a retrospective study of 100 patients with calcium oxalate stones identified by morpho-constitutional study, collected in our department over a period of 5 years (2008-2013). We analyzed clinical, radiological and metabolic data. RESULTS: They were 73 men and 27 women (gender ratio: 2.7), aged meanly of 44.8 years. Dietary survey revealed inadequate calcium intake in 87% of cases. Urinary abnormalities were hypocitraturia (34%), hypomagnesuria (32%) and outflow hypercalciuria (21%). Crystalluria was positive in 44% of cases. Whewellite was the most common crystalline form. Calculi were bilateral (53%), renal (85%) and mainly collected after urological procedures (74%). Infrared analysis showed that 81% of stones have a heterogeneous composition. Pure Whewellite or combined with other compounds was the most frequent (31%). Idiopathic calcium oxalate lithiasis was the most common etiology (69%). Among secondary etiologies, diabetes was most frequently found (10%). CONCLUSION: Our epidemiological study of calcium oxalate stones has allowed us to identify the high frequency of food hyperoxaluria partly explained by a low calcium intake and a diet rich in oxalate phytotherapy. LEVEL OF EVIDENCE: 4.
Subject(s)
Calcium Oxalate , Urolithiasis/epidemiology , Adolescent , Adult , Aged , Calcium Oxalate/analysis , Epidemiologic Studies , Female , Humans , Male , Middle Aged , Retrospective Studies , Risk Factors , Young AdultABSTRACT
Purpose. The aim of this pharmacogenetic study was to evaluate the impact of high-risk alleles in factor H, factor C3 and vascular endothelial growth factor (VEGF) on the response to intravitreal bevacizumab in patients with neovascular age-related macular degeneration (AMD) in a Tunisian population. Methods. Ninety patients with active neovascular AMD treated with intravitreal bevacizumab injections were enrolled in the study. Treatment response was evaluated by comparing BCVA at baseline and at 12 months. Patients were classified into either "poor responders" (PR) or "good responders" (GR). Single nucleotide polymorphism (SNP) genotyping was performed for rs1061170 in FH, rs2230199 in C3 andrs699947, rs2010963 and rs3025039 in VEGF. The association between genotype and visual response at 12 months was assessed. Results. Seventy-seven participants were assigned to the GR group and 13 to the PR group. No correlation was found between FH, C3 and VEGF variant alleles and treatment response. However, haplotype analysis of rs699947 ((- 2578) C/A), rs2010963 ((+ 405) C/G) and rs3025039 ((+ 936) C/T) SNPs revealed that the AGT haplotype was associated with a poor response at 12months (p = 0.048). No association was found between treatment response and the cumulative effect of all high-risk alleles of C3, FH and VEGF. All three types of CNV were found in both groups at a comparable frequency. Conclusions. The VEGF haplotype TGA could be used as a marker for poor visual prognosis in Tunisian patients with neovascular AMD treated with bevacizumab.
Subject(s)
Bevacizumab/administration & dosage , Complement C3/genetics , Vascular Endothelial Growth Factor A/genetics , Wet Macular Degeneration/drug therapy , Wet Macular Degeneration/genetics , Aged , Angiogenesis Inhibitors/administration & dosage , Complement Factor H/genetics , Female , Gene Frequency/genetics , Humans , Intravitreal Injections , Male , Prevalence , Prognosis , Risk Factors , Treatment Outcome , Tunisia/epidemiology , Wet Macular Degeneration/epidemiologyABSTRACT
Renal transplantation that offers a good quality of life still is not performed by the majority of countries of black Africa. We started a pilot project of renal transplantation in Ivory Coast 2 years ago. The present paper reports the preliminary results, difficulties related to the program, and perspectives regarding its expansion. Ten living related kidney transplantations have been performed over a 2-year period. Recipients and their respective donors were male. The mean age of the recipients was 42.8 years (22-57), and the mean age of the donors was 29.4 years (22-43). The mean number of mismatches was 3.2 (0-6). None was immunized. Recipients and donors were all EBV IgG positive and CMV IgG positive. All but 1 case were induced with basiliximab. The mean graft and patient survival time was 16.6 months (6-26). The mean cold ischemic time was 2.27 hours (1-3.32). The mean serum creatinine at discharge was 241.87 µmol/L (115.18-1063.2), at 6 months was 117.20 µmol/l (95.6-139.9), at 12 months was 104.55 µmol/L (62.02-132.9), and at 24 months was 104.55 µmol/L (62.02-132.9). The mean cyclosporine through level (C0) at 6 months was 137.57 ng/mL (70-366), at 12 months was 117.33 ng/mL (62-197), and at 24 months was 78 ng/mL. The mean cyclosporine 2-hour post-administration concentration levels (C2) at 6 months was 764.9 ng/mL (430-1421), at 12 months was 937.17 ng/mL (483-1292), and at 24 months was 690.66 ng/mL (488-853). Main complications were sepsis, adenovirus hemorrhagic cystitis, new-onset diabetes after transplantation, delayed graft function, polycythemia, and cytomegalovirus infection. No clinical rejection was diagnosed over the 2-year period. Patient and graft survival was 100% at a mean post-transplantation time of approximately 16.6 months.
Subject(s)
Kidney Transplantation/methods , Renal Insufficiency, Chronic/surgery , Adult , Cote d'Ivoire , Cyclosporine/administration & dosage , Cytomegalovirus Infections/drug therapy , Donor Selection , Female , Graft Survival , Humans , Immunosuppressive Agents/administration & dosage , Kidney Transplantation/statistics & numerical data , Living Donors , Male , Middle Aged , Patient Selection , Pilot Projects , Quality of Life , Young AdultABSTRACT
BACKGROUND: Acute and chronic rejections remain an important cause of graft loss after renal transplantation. Currently, activation of innate immune responses through Toll-like receptors (TLRs) is suspected to be implied in the loss of the transplant tolerance. OBJECTIVES: We investigated functional single nucleotide polymorphisms (SNPs) of TLR4 and its coreceptor CD14 in kidney transplantation and looked for any potential role in acute rejection (AR) and chronic allograft nephropathy (CAN) and impact on graft survival. PATIENTS AND METHODS: TLR4 (Asp299Gly) and CD14 (C/T -159) SNPs were detected using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 209 kidney transplant recipients (KTRs) including 132 treated with mycophenolate mofetil (MMF+). AR occurred in 59 patients and 24 were identified as having CAN by biopsy and scored according to the Banff criteria. RESULTS: There were no significant associations between TLR4 and CD14 genotypes and alleles and the occurrence of both AR episodes and CAN. Moreover, TLR4 and CD14 SNPs did not seem to influence kidney graft survival. Analysis according to human leukocyte antigen (HLA) compatibility status, positivity of anti-HLA antibodies, and immunosuppression by MMF confirmed the absence of correlation of the investigated SNPs with the graft outcome. In addition, incidence of post-transplantation infections, including cytomegalovirus (CMV) infections, was not influenced by both TLR4 and CD14 SNPs. CONCLUSION: These results suggest that TLR4 (Asp299Gly) and CD14 (C/T -159) functional SNPs do not play a major role in AR, CAN, and kidney graft survival. Therefore, intragraft monitoring of TLR4/CD14 genes expression by messenger RNA (mRNA) would provide clarity on the exact role of these receptors in graft injuries.
Subject(s)
Graft Rejection/genetics , Kidney Transplantation/adverse effects , Lipopolysaccharide Receptors/genetics , Polymorphism, Single Nucleotide , Toll-Like Receptor 4/genetics , Acute Disease , Adult , Antibodies/blood , Chronic Disease , Communicable Diseases/genetics , Communicable Diseases/immunology , Female , Gene Frequency , Genetic Predisposition to Disease , Graft Rejection/immunology , Graft Survival/genetics , HLA Antigens/immunology , Humans , Immunity, Innate/genetics , Immunosuppressive Agents/therapeutic use , Male , Middle Aged , Phenotype , Risk Factors , Treatment Outcome , Tunisia , Young AdultABSTRACT
To evaluate a possible association between the complement factor H (CFH) Y402H polymorphism and susceptibility to age-related macular degeneration (AMD) in the Tunisian population, as well as the impact of the genotype distribution among different phenotypes and the response to treatment with intravitreal bevacizumab, exon 9 of CFH was analyzed for the Y402H polymorphism by direct sequencing in 135 healthy controls and 127 sporadic unrelated AMD patients classified into the following groups: 12 atrophic AMD (group G1), 115 exudative AMD (G2) and 10 AMD patients who had fibrovascular scarring (G3) that did not allow a precise grading of the phenotype. Seventy patients in G2 were treated with 1.25 mg intravitreal bevacizumab at 6-week intervals until choroidal neovascularization (CNV) was no longer active. The frequency of the CFH 402H allele was significantly higher in AMD patients than in controls (p = 2.62 × 10(-16)). However, subgroup analysis does not reveal any association between the variant allele H and phenotypes of AMD or CNV. Also, there was no significant difference in response to bevacizumab treatment according to Y402H CFH genotype (p = 0.59). A strong association of the 402H allele with susceptibility to AMD in the Tunisian population was confirmed; however, this variant does not appear to be involved in the clinical progression of this disease or in the postintravitreal bevacizumab response.
Subject(s)
Macular Degeneration/genetics , Polymorphism, Single Nucleotide , Aged , Aged, 80 and over , Angiogenesis Inhibitors/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use , Bevacizumab , Case-Control Studies , Complement Factor H/genetics , Female , Fluorescein Angiography , Gene Frequency , Genotype , Humans , Intravitreal Injections , Macular Degeneration/diagnosis , Macular Degeneration/drug therapy , Male , Middle Aged , Polymerase Chain Reaction , Tunisia , Vascular Endothelial Growth Factor A/antagonists & inhibitors , Visual Acuity/physiologyABSTRACT
The dysfunction of the catheter in peritoneal dialysis (PD) is a frequent complication. However, perforation of organs are rare, particularly that of the urinary bladder. This requires an early diagnosis and prompt treatment of patients. We report here the case of a 38-year-old woman having end-stage renal disease due to autosomal-dominant polycystic kidney disease treated by PD since November 2000. Three years later, she was treated for Staphylococcal peritonitis. Four months later, she presented with a severe urge to urinate at the time of the fluid exchanges. The biochemical analysis of the fluid from the bladder showed that it was dialysis fluid. Injection of contrast through the catheter demonstrated the presence of a fistula between the bladder and the peritoneal cavity. She underwent cystoscopic closure of the fistulous tract and the PD catheter was removed. Subsequently, the patient was treated by hemodialysis. One month later, a second catheter was implanted surgically after confirming the closure of the fistula. Ten days later, she presented with pain at the catheter site and along the tunnel, which was found to be swollen along its track. The injection of contrast produced swelling of the subcutaneous tunnel but without extravasation of the dye. PD was withdrawn and the patient was put back on hemodialysis. Bladder fistula is a rare complication in PD and diagnosis should be suspected when patient complains of an urge to pass urine during the exchanges, which can be confirmed by contrast study showing presence of dye in the bladder. PD may be possible after the closure of the fistula, but recurrence may occur.
Subject(s)
Catheters, Indwelling/adverse effects , Kidney Failure, Chronic/therapy , Peritoneal Dialysis/adverse effects , Urinary Bladder Fistula/etiology , Urinary Bladder/injuries , Adult , Cystoscopy , Device Removal , Equipment Design , Female , Humans , Peritoneal Dialysis/instrumentation , Radiography , Renal Dialysis , Treatment Outcome , Urinary Bladder/diagnostic imaging , Urinary Bladder/surgery , Urinary Bladder Fistula/diagnostic imaging , Urinary Bladder Fistula/surgeryABSTRACT
As chemokines and adhesion molecules play major roles in the process by which leukocytes are recruited from the bloodstream into sites of inflammation, genetic variations in the production or activity of molecules may influence susceptibility to acute rejection episodes. This study sought to determine the impact of recipient monocyte chemoattractant protein-1 (MCP-1), chemokine receptor (CCR2, CCR5), and adhesion molecule (ICAM-1, PECAM-1 and L/E selectin) polymorphisms on acute rejection after renal transplantation. We selected 169 healthy blood donors and 173 renal transplant recipients for analysis according to the presence or absence of graft rejection in the first 30 days after transplantation. Using molecular methods DNA was genotyped for 11 polymorphisms of these inflammatory molecules genes. Results were stratified by the incidence of rejection episodes and by human leukocyte antigen (HLA) mismatching. No association was detected between adhesion molecule polymorphisms and the incidence of acute rejection episodes. However, a significant risk of acute renal loss was observed among HLA-identical recipients who possessed the CCR2-64I allele (odds ratio 0.24, 95% confidence interval, 0.05 to 1.06; P=.035). In conclusion, the observed association of CCR2-64I with acute rejection episodes should be added to the spectrum of immunogenetic factors known to be involved in renal allograft rejection.
Subject(s)
Chemokines/metabolism , Kidney Transplantation/methods , Polymorphism, Genetic , Receptors, CCR2/genetics , Adult , Alleles , Blood Donors , Female , Graft Rejection , HLA Antigens/metabolism , Humans , Inflammation , Kidney Failure, Chronic/genetics , Kidney Failure, Chronic/therapy , Male , TunisiaABSTRACT
INTRODUCTION: Posttransplant diabetes mellitus (PTDM) is a common, serious complication of renal transplantation. The aim of this retrospective study was to estimate the incidence and to identify potential factors predisposing to PTDM. PATIENTS AND METHODS: We evaluated 296 adult nondiabetic patients who underwent kidney transplantation at our center. PTDM was defined according to 2003 international consensus guidelines. Potential factors predisposing to PTDM were analyzed individually and simultaneously using a logistic regression model. RESULTS: Over 2054.5 years of cumulative follow-up, 51 patients (17.2%) developed diabetes corresponding to an annual incidence of 2.5%. PTDM was diagnosed after a median of 2.9 months (range: 0.2-168). The mean age of affect individuals was 33.3±7.4 years. Patients with PTDM were significantly older (P<.0005) and showed an higher body mass index (BMI; P<.004). Univariate analysis revealed that age, BMI, family history of diabetes, vascular nephropathy, and hepatitis C infection were associated with PTDM. Multivariate analysis rescaled the roles of age (relative risk [RR]=1.046/y; P<.04), BMI (RR=1.107/kg/m2, P<.05), vascular nephropathy (RR=7.06, P<.03), and hepatitis C infection (RR=2.72, P<.03) as independent factors predisposing to PTDM. CONCLUSION: Among our relatively young kidney transplant recipients, in whom only 8% received tacrolimus, PTDM was a frequent complication. We suggest that the use of oral glucose tolerance tests to screen patients identifies those predisposed to develop this complication.
Subject(s)
Diabetes Complications/diagnosis , Kidney Transplantation/methods , Adult , Diabetes Complications/epidemiology , Female , Glucose Tolerance Test , Humans , Immunosuppressive Agents/pharmacology , Incidence , Kidney Failure, Chronic/epidemiology , Kidney Failure, Chronic/therapy , Kidney Transplantation/adverse effects , Male , Multivariate Analysis , Postoperative Complications , Regression Analysis , Retrospective Studies , Risk Factors , Tacrolimus/pharmacologyABSTRACT
To investigate the relationship between the soluble HLA-G (sHLA-G) and the appearance of acute renal rejection (AR) episodes we have quantify in this study the level of sHLA-G by enzyme-linked immunosotrbent assay in 42 kidney transplant patients classified in two groups: G1: 17patients with acute rejection (AR+) and G2: 25 patients without AR (AR-). To establish our normal sHLA-G ranges, serum samples from 18 healthy controls were tested. Pre-transplantation sHLA-G levels were significantly increased in patients (mean +/- standard error of the mean, 60.48 +/- 12.18 units/ml) than healthy subjects (19.11 +/- 4.9 units/ml) (p = 0.001). Although the difference was not statistically significant, G1 patients (AR+) revealed lower levels of sHLA-G (mean +/- standard error of the mean, 31.25 +/- 6.71 units/ml) compared to G2 patients (AR-) (53.43 +/- 1721 units/ml). Nevertheless, the course of total sHLA-G levels was nearly identical in patients with and without rejection. Nonparametric analysis revealed that pre-transplantation levels of sHLA-G < 18.00 units/ ml (sensitivity: 87.8% and specificity of 72.2%) were not related to rejection. Also, multivariate analysis regarding anti-HLA antibody status, recipient age and gender showed that sHLA-G could not be an independent risk factor for renal graft rejection. However, a higher sera levels of sHLA-G seemed to contribute to better kidney allograft survival rate after 10 years of follow-up (significance tendency: p = 0.091) as shown by the survival analysis. Because of the small number of subjects studied, these results must be treated with caution. A much larger cohort of kidney transplant patients according to acute rejection would seem necessary to confirm these findings.
Subject(s)
Graft Rejection/blood , HLA-G Antigens/blood , Kidney Transplantation , Adult , Female , Humans , Male , TunisiaABSTRACT
Crohn's disease (CD) and ulcerative colitis (UC) have complex genetic background that is characterised by more than one susceptibility locus. To detect a possible association between the functional polymorphisms of the chemokine receptors CCR5, CCR2 and MCP-1 genes and susceptibility to CD and UC in Tunisian population, polymorphisms of CCR5-delta32, CCR5-59029-A/G, CCR2-V641 and MCP-1-2518-G/A were analysed in 194 Inflammatory bowel disease (IBD) patients and 169 healthy blood donors using PCR-RFLP and PCR-SSP methods. The patients were classified in 126 patients with CD and 68 patients with UC. The genotypic and allelic frequencies of all polymorphisms studied, did not reveal significant differences between patients and conrols and among CD and UC patients. However, analysis of CD patients revealed that those without homozygosous G/G genotype are more frequently in remission compared to those with this genotype (OR: 0.4, 95% CI: [0.174-0.928]; p = 0.03). Also, the frequency of the CCR2-641 muted allele was statistically higher in CD patients in remission disease than those in active form (OR: 0.267 95% CI: [0.09-0.78]; p = 0.01). Adjustment for known covariates factors (age, gender and immunosuppressive regimen) confirmed these univariate findings and revealed that the CCR5-59029-A/G and CCR2-V64I genotype were associated to remission form of CD (OR: 263; 95% CI: [1.01-6.80]; p = 0.047 and OR: 4.64; 95% CI: [1.01-21.31]; p = 0.049 respectively). In conclusion, the present study supports the involvement of chemokine receptor (CCR2 and CCR5) polymorphisms in activity degree of the IBD disease in Tunisian patients.
Subject(s)
Chemokines/genetics , Inflammatory Bowel Diseases/genetics , Polymorphism, Genetic , Receptors, Chemokine/genetics , Adult , Female , Humans , Male , TunisiaABSTRACT
Despite initiatives to increase cadaveric donation, there is still a shortfall in donor organs. Kidneys from living donors now makes a significant contribution to increasing the number of organs available for transplantation in Tunisia. We performed a retrospective study of 405 kidney transplantations, including 321 (79.3%) from living donors performed from June 1986 to December 2007. We obtained information on only 162 (50.4%), namely, 64 men (39.5%) and 98 women (60.5%), whose mean age at the time of donation was 42.3 ± 12.2 years. Twelve (8.22%) perioperative complications occurred: wound infections (n = 4), pneumothorax (n = 4), phlebitis (n = 1), hematomas (n = 2), and urinary infection (n = 1). The mean follow-up period was 117.4 ± 74.4 months. Hypertension occurred in 42 donors (25.9%) with mean values of 134 ± 20 for systolic and 79 ± 10 for diastolic blood pressure. Twelve donors (7.4%) developed proteinuria (mean proteinuria, 0.08 ± 1.25 g/d). Renal insufficiency was found in 28 donors (19.44%), 2 of whom developed chronic renal failure requiring dialysis at intervals of 36 and 84 months. In both cases, we diagnosed a familial form of focal segmental glomerulosclerosis. Two donors (1.2%) died within 10 years after kidney donation due to senility. The relatively favorable outcomes suggest that living-donor kidney transplantation is an acceptable approach, in view of the superior results it yields in recipients. However, efforts to increase the number of cadaveric donors in Tunisia should be made. It is also important to develop a registry of long-term kidney function after kidney donation.
Subject(s)
Living Donors , Outcome Assessment, Health Care , Adult , Female , Humans , Male , Middle Aged , Postoperative Complications , Retrospective Studies , TunisiaABSTRACT
Allograft rejection is an immune response relying on the proliferation and the differentiation of T cells. CTLA-4 is a co-stimulatory molecule, expressed on activated T lymphocytes, which has been shown to play a crucial role in the down-regulation of T-cell activation. Herein, we have examined the impart of a genetic marker in the CTLA-4 gene on renal transplant outcomes. A cohort of 144 renal recipients and 100 healthy subjects were genotyped by the fragments analysis method using an automated sequencer. Patients were classified into two groups: Group I included 31 HLA-identical haplotype allograft recipients and Group II, 113 showing one or more HLA haplotype mismatches. Forty patients (27.78%) developed at least one acute rejection episode (ARE): 9 in Group I and 31 in Group II. Before transplantation, 20 patients were lymphocytotoxic antibodies (LCT) positive: 4 Group I, 2 of whom developed an ARE, and sixty in Group II, including 8 with an ARE. The occurrence of an ARE was associated with the presence of LCT before transplantation among the entire cohort of patients (P = .032) and among Group II (P = .037). The allelic frequencies of (AT)n polymorphism did not reveal significant differences between patients and controls. The most prevalent alleles were the 88 bp (51% in controls and 44.44% in patients) and the 106 bp (8% and 10.76%, respectively). We noticed an increase of the 120 bp allele frequency among patients who had undergone an ARE compared with those who did not display this complication (8.75% vs 3.85%). Likewise, among LCT-negative Group I, recipients the incidence of the 120 bp allele was higher in ARE than non-ARE patients. Although the differences were not statistically significant, we propose that the 120 bp allele of the CTLA-4 gene (AT)n microsatellite a predisposes to acute rejection episodes in renal transplantation.
Subject(s)
3' Untranslated Regions , Antigens, CD/genetics , Graft Rejection/genetics , Kidney Transplantation , Repetitive Sequences, Nucleic Acid , Adult , Alleles , CTLA-4 Antigen , Case-Control Studies , Female , Genetic Predisposition to Disease , Haplotypes , Humans , Male , Polymorphism, Genetic , Transplantation, Homologous , TunisiaABSTRACT
AIM: To identify the risk factors of post renal transplant lymphocele. PATIENTS AND METHOD: Over a period of 20 years (1986-2006) we carried out 377 renal transplants on 372 patients. Thirty cases of lymphocele were recorded (8%). The medical history of patients was retrospectively examined in order to identify the risk factors of this complication among the data relating to recipents, donors, the operation itself and post operative incidents. The different parameters liable to correlate with the incidence of lymphocele were subjected to a univaried then multivaried statistical study. RESULTS: Unifactorial analysis identified four predictive factors related to the incidence of lymphocele. They were the age of the recipient greater or equal to 35 years old, the cadaverous origin of the transplanted organ, the duration of ischemy greater or equal to 24hours for the kidneys of deceased donors, and immunosuppressor treatment associated with Mycophenolate mofetil-Cyclosporine. The only independent risk factor significant in multifactorial analysis was the cadaverous origin of the transplanted organ. CONCLUSION: Our study showed that the cadaverous origin of the transplanted organ would appear to play an important role in the genesis of post renal transplant lymphocele. A better preparation of the organs of cadaverous origin before their implantation with meticulous ligature of the hilum of lymph nodes could reduce the incidence of this complication. This observation, as well as the benefit of such a procedure, remains to be confirmed by studies on a larger scale.
Subject(s)
Kidney Transplantation/adverse effects , Lymphocele/etiology , Adolescent , Adult , Child , Female , Humans , Lymphocele/epidemiology , Male , Middle Aged , Retrospective Studies , Risk Factors , Young AdultABSTRACT
This study aimed to investigate HLA-DRB1 alleles in rheumatoid arthritis (RA) patients from Tunisia and to examine the effect of these alleles on disease severity. HLA-DRBI alleles and sub-typing of DRBI*04 and *01 were determined in 90 patients and 100 healthy controls, by PCR-SSP. HLA-DRB1*04 was significantly higher in patients (51.1%) than in controls (27%) [OR=2.83, p=0.00066]. DRBJ*0405 was found to be the unique DR4 allele associated with RA (28.88% vs 6%) [OR=6.36, p=0.000059]. A significant decrease in the frequency of HLA-DRB1*0701 was observed in RA patients (16.66%) compared to controls (36%) [p=0.0026]. However, the frequency of patients carrying the shared epitope (SE) QRRAA, was slightly increased compared with controls (37.8% vs 23%) [OR=2.03, p=0.039]. We found that the presence of rheumatoid factor, HLA-DR4 and HLA-DRBI*0405 were not significantly associated with bone erosions or the presence of extra-joint involvement. In our population, the SE (QRRAA) expressed in DRBI*04 alleles is related to the susceptibility to RA but it is not involved in RA severity in Tunisia, while DRBI*0701 might protect against this disease.
Subject(s)
Arthritis, Rheumatoid/genetics , HLA-DR Antigens/genetics , Adult , Alleles , Amino Acid Sequence , Female , HLA-DRB1 Chains , Humans , Male , TunisiaABSTRACT
INTRODUCTION: Nephrolithiasis still remains a too frequent and underappreciated cause of end stage renal disease (ESRD). METHODS AND PATIENTS: Of the entire cohort of 7128 consecutive patients who started maintenance dialysis in our nephrology department between January 1992 and December 2006, a total of 45 patients (26 women, 19 men) had renal stone disease as the cause of ESRD. The type of nephrolithiasis was determined in 45 cases and etiology in 42. The treatment and evolution of stone disease and patient's survival were studied. RESULTS: The overall proportion of nephrolithiasis related ESRD was 0.63%. The mean age was 48.4 years. Infection stones (struvite) accounted for 40%, calcium stones, 26.67% (primary hyperparathyroidism:15.56%; familial hypercalciuria: 4.44%, unknown etiology: 6.66%), primary hyperoxaluria type 1, 17.78% and uric acid lithiasis in 15.56% of cases. The mean delay of the evolution of the stone renal disease to chronic renal failure was 85.8 months. The feminine gender, obesity and elevated alkaline phosphatases >128 IU/L were significantly correlated with fast evolution of ESRD. The median evolution to ESRD was 12 months. The normal body mass index (BMI), medical treatment of stone and primary hyperoxaluria type 1 were correlated with fast evolution to ESRD. All patients were treated by hemodialysis during a mean evolution of 60 months. Sixteen patients died. The patient's survival rate at 1, 3 and 5 years was 97.6, 92.8 and 69% respectively. Hypocalcemia, cardiopathy and normal calcium-phosphate product were significantly correlated with lower survival rate. CONCLUSION: Severe forms of nephrolithiasis remain an underestimated cause of ESRD. These findings highlight the crucial importance of accurate stone analysis and metabolic evaluation to provide early diagnosis and efficient treatment for conditions leading to ESRD.
ABSTRACT
CTLA-4 and CD28 are T lymphocyte receptors involved in the regulation of T-cell activation. Allograft rejection is an alloimune response which is strongly dependent on T-cell proliferation. Thus, we examined the relationship between CTLA-4 and CD28 gene polymorphisms and renal transplant outcomes. We genotyped 141 renal recipients and 229 healthy controls using PCR-SSP methods for the (-318) C/T polymorphism in the promoter region of the CTLA-4 gene and IVS3 (+17) T/C on intron 3 of the CD28 gene, and by PCR-RFLP method for exon 1 (+49) A/G and CT60 G/A within the 3'-untranslated region (UTR) of the CTLA-4 gene. Patients were classified into two groups: Group I included 23 HLA-identical haplotype allograft recipients and group II, 118 recipients with one or more mismatches in HLA haplotypes. Thirty-six patients developed at least one acute rejection episode (ARE). No significant differences were observed between the genotypes or the allele distribution between ARE and non-ARE patients. However, in group I, (+49) A and CT60 (G) allele frequencies were lower in patients with ARE than those without ARE (0.100 and 0.400 vs 0.361 and 0.722 respectively). However, the difference was not significant. Our study suggested that these alleles may confer protection against renal allograft loss.
Subject(s)
Antigens, CD/genetics , CD28 Antigens/genetics , Graft Rejection/genetics , Kidney Transplantation/physiology , Polymorphism, Genetic , Polymorphism, Single Nucleotide , 3' Untranslated Regions/genetics , Acute Disease , Adult , Amino Acid Substitution , CTLA-4 Antigen , Exons , Female , Genotype , Graft Rejection/epidemiology , Graft Rejection/immunology , HLA Antigens/genetics , Humans , Kidney Transplantation/immunology , Male , Polymerase Chain Reaction , Polymorphism, Single-Stranded Conformational/geneticsABSTRACT
Herein, we report the results of kidney transplantation in 9 of 376 patients who underwent kidney transplantation at our center between 1986 and 2007 because of chronic renal failure associated with autoimmune disease. Four of the 9 patients had systemic lupus erythematosus, 3 had Wegener granulomatosis, and 2 had Goodpasture syndrome. Six patients received organs from living donors, and 3 received cadaver organs. Infections were frequent and included cytomegalovirus and urinary tract infection in most cases. There was no difference in occurrence of metabolic and cardiovascular complications in our study patients compared with other transplant recipients. Incidence of allograft loss (n = 1) was similar to that in our entire transplantation population, with an overall rate of 2.9%. We conclude that kidney transplantation is a reasonable therapeutic option in patients with autoimmune disease with end-stage renal disease because of good graft and patient survival compared with kidney recipients without autoimmune diseases.