Impact of Interleukin-17F Gene Polymorphisms in Outcome of Kidney Transplantation in Tunisian Recipients.

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.

Visceral leishmaniasis in adults with nephropathy.

The aim of this study is to evaluate the features of visceral leishmaniasis (VL) in adults with nephropathy, who were not infected with the human immunodeficiency virus. This is a retrospective study of 14 adults hospitalized between 2000 and 2014, with VL and renal involvement. Clinical, biological, and therapeutic data were collected from the patients' medical files. Eleven women and three men, most of whom were from the North of the country, with a mean age of 40.5 years were studied. Lupus was present in five cases, the Sicca syndrome in three cases, diabetes in one case, renal failure on dialysis in two cases, and there were three renal transplant recipients. Major clinical symptoms were fever and weakness in all cases. Enlargement of the spleen was present in eight cases and hepatomegaly in six cases. Biologic inflammatory syndrome and anemia were present in all cases, and pancytopenia was present in seven cases. Renal insufficiency was noted in all cases. Diagnosis of VL was confirmed by bone marrow examination or serology. Treatment consisted of antimoniate in 10 cases and amphotericin B in four cases. Seven deaths were recorded. Clinical symptoms of VL are atypical in patients with nephropathy and therefore, the diagnosis should be suspected in such patients because VL is still endemic in our country.

Cyclosporine therapy in steroid-dependent or steroid-resistant idiopathic focal and segmental glomerulosclerosis.

Focal and segmental glomerulosclerosis (FSGS) is a heterogeneous entity. Previous few studies have evaluated the efficacy of calcineurin inhibitors in primary FSGS and have suggested positive benefit. In this single-center, retrospective study (1975-2014), we report our experience in Tunisian adults with primary FSGS treated with cyclosporine A (CsA). It includes patients histologically proven FSGS and managed in the Charles Nicolle Hospital at Tunis, Tunisia. The dose of CsA was adjusted to maintain a whole blood trough level of 80-150 ng/mL. The observation period was 6.8 ± 3.7 years after CsA treatment. Twenty-three patients with idiopathic FSGS, treated with CsA, were studied. The mean age was 26.69 ± 10.1 years, and the sex ratio was 2.83. Eight patients (35%) had a steroid-dependent nephrotic syndrome (NS), and 15 patients (65%) had for steroid-resistant NS. After a median follow-up of 16.5 months on CsA, we noticed complete remission of the NS in eight cases (35%) after 12.12 ± 8 months, partial remission in five (22%) after 3 ± 0.7 months, dose-dependent remission to CsA (2.87 mg/kg/day) in four (17%), and a no response in six patients (26%). Eleven patients (48%) showed improvement of renal function, while eight (35%) developed end-stage renal disease (ESRD) after 35.7 ± 20.9 months. Predictive factors of progression to ESRD were creatinine clearance <90 mL/min before introduction of CsA (P = 0.0054) and CsA-resistance (P = 0.053). Our study suggests that CsA is effective in the treatment of patients with idiopathic FSGS. Initial renal function and cyclosporineresistance are the predictive factors of ESRD in steroid-resistant or -dependent FSGS.

Toll-like receptor 4 and CD14 gene polymorphisms in Tunisian kidney transplantation.

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.

Bladder perforation in a peritoneal dialysis patient.

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.

Rehospitalization after kidney transplantation during the first year: length, causes and relationship with long-term patient and graft survival.

INTRODUCTION: There is a wide interest in epidemiologic studies assessing different causes of post-kidney transplantation rehospitalization. However, there is a paucity of knowledge on the long-term survival and graft function of rehospitalized kidney transplant recipients during the first year. Knowledge of posttransplant rehospitalization causes may help guide the preventive program at the first year. In our study, we assess causes for hospitalization and investigate the long-term patient and graft survival after non-fatal rehospitalization in kidney recipients during the first year. MATERIALS AND METHODS: We retrospectively studied the medical histories of 419 kidney transplant recipients whose operations were performed between 1986 and 2009 at Charles Nicolle Hospital, in Tunis, Tunisia. Among these patients, a total of 296 posttransplant rehospitalizations of kidney transplant recipients during the first year occurring in 191 (45.5%) patients were assessed. Clinical characteristics of the patients, including gender, age, reason for kidney failure, weight, height, blood group, length of pretransplant dialysis, immunosuppressive regimen, postoperative complications, the length of hospital stay, transplantation-admission interval, causes of rehospitalizations, graft loss, and mortality rate were reviewed. For donors, these demographics included age, gender, blood group, type of donor (deceased or living), and relationship to the recipient. Because rehospitalizations are possible for more than one cause, the sum of frequencies of rehospitalization causes is more than 100%. RESULTS: There was 1 rehospitalization in 121 patients, 2 rehospitalizations in 47 patients, 3 rehospitalizations in 15 patients, 4 rehospitalizations in 5 patients, 5 rehospitalizations in 2 patients and 6 rehospitalizations in 1 patient. Rehospitalization was more frequent for diabetic patients without significant association. The causes of rehospitalization were infection in 221 cases (55.5%), renal dysfunction in 106 cases (26%), cardiovascular event in 10 cases (2.4%), and diabetic ketoacidosis in 11 cases (2.7%). The length of hospital stay was 22.5 ± 29.6 days, 20.15 ± 22.16 days, 25 ± 30 days and 23.4 ± 27.5 days, respectively, in the first, second, third, and fifth rehospitalizations. Median hospital stay for all rehospitalizations was between 14 and 16 days. The risk factors of rehospitalization were: use of mycophenolate mofetile (P = .0072), use of cyclosporine (P = .0073), and cytomegalovirus infection (P < .001). There was no significant correlation between rehospitalization and either lost of graft and death. CONCLUSIONS: During the first year after kidney transplantation, rehospitalization was especially required because of infections and renal dysfunction. The risk factors of rehospitalization were cadaveric graft, use of mycophenolate mofetil, use of cyclosporine, and cytomegalovirus infection. To prevent and minimize rehospitalizations during the first year, a specific preventive program based on infection prevention and graft function monitoring should be established.

Genetic polymorphisms of inflammatory molecules in Tunisian kidney transplantation.

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.

Malformative uropathies and kidney transplantation.

INTRODUCTION: Malformative uropathies are a frequent cause of end-stage renal disease (ESRD) requiring renal replacement therapy (RRT). Medical management of urinary tract infections and advances in surgical reconstruction procedures resulted in good outcomes of kidney transplantation among these patients. The aim of this article was to describe the epidemiological profiles and outcomes of patients who underwent transplantation for ESRD related to malformative uropathies. PATIENTS AND METHODS: Among 493 kidney recipients at our center from 1986 to 2009, 47 had malformative uropathies as the cause of ESRD. We retrospectively studied the incidence of acute rejection episodes, acute tubular necrosis, as well as patient and graft survivals, comparing these results to those observed in patients without malformative uropathies using chi-square tests for qualitative parameters and nonpaired Student t tests for continuous variables. Log-rank tests were used for comparisons of survival curves. RESULTS: The 47 patients, representing 9.53% of our kidney transplant recipients, included 27 men and 20 women (sex ratio=1.35) with an overall mean age of 27.6±9.1 years (range, 10-49). The common etiology was vesico-ureteral reflux (78.7%). Hemodialysis was the main RRT modality (68%) with a median duration of 41 months. Also, 82.9% of patients received transplants from living donors. Acute tubular necrosis occurred in 4 of these (8.5%) versus 22.06% of the other patients (P=.03). Acute rejection episodes were observed in 13 of these patients (27.6%) versus 23.1% of the other patients (P=not significant [NS]). After a cumulative follow-up period of 3744 months (median, 41.8 months), 5 patients had died (1.6 death/y/100 patients) and 5 had lost their allografts and returned to dialysis (1.6 case/y/100 patients). Graft survival rates at 1, 5, and 10 years were 97.8%, 93.2%, and 79.9%, which were comparable with 95.9%, 87.6%, and 78.9% among the other patients, respectively (P=NS). Patient survival rates at 1, 5, and 10 years were 100%, 88.5%, and 82.6% versus 96%, 87.6%, and 79.6%, respectively (P=NS). CONCLUSION: Kidney transplantation in patients with malformative uropathies is increasingly frequent. The incidence of acute rejection episodes as well as patient and graft survivals were comparable with those of subjects without malformative uropathies.

Allograft renal rejection and chemokine polymorphism.

Chemokines play a major role in the process by which leukocytes are recruited from the bloodstream into the sites of inflammation. Genes for the chemokine receptors CCR5, CCR2 and MCP-1 are characterized by functional polymorphisms implicated in transplant rejection. To investigate this association, we analyzed polymorphisms of CCR5-∆32, CCR5-59029-A/G, CCR2-V64I and MCP-1 G/A (-2518) in 173 renal transplant recipients and 169 healthy blood donors. The patients were classified in two groups: Group-1 (G-1) included 33 HLA-identical recipients and Group-2 (G-2) included 140 (one or more) mismatched graft recipients. Forty-two patients had developed acute rejection episodes (ARs): seven in G-1 and 35 in G-2. Thirteen G-2 patients developed chronic allograft dysfunction (CAD). The genotypic and allelic frequencies of all polymorphisms studied did not reveal significant differences between patients and controls and among G-1 and G-2 recipients. However, a significant risk of acute renal transplant rejection was found in G-1 patients who possessed the CCR2-64I allele (odds ratio 0.24, 95% confidence inter-val [CI], 0.05-1.06; P = 0.035). There was no significant association of this polymorphism and CAD. In conclusion, the observed association of CCR2-64I with AR should be added to the spectrum of immunogenetic factors known to be involved in allograft renal loss.

Soluble human leukocyte antigen-G (SHLA-G) in Tunisian kidney transplantation.

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.

Short- and long-term outcomes of living donors in Tunisia: a retrospective study.

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.

Nephrolithiasis-induced end stage renal disease.

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.

Dissecting aortic aneurysm in maintenance hemodialysis patients.

The dissecting aortic aneurysm (DAA) is a rare pathology that may result in fatal outcome. We report follow up of three cases of DAA patients undergoing maintenance hemo-dialysis who were managed conservatively.

Kidney transplantation during autoimmune diseases.

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.

Hyalohyphomycosis caused by Paecilomyces lilacinus after kidney transplantation.

Hyalohyphomycosis caused by Paecilomyces has rarely been described among solid organ recipients. Its management is elusive without an established consensus concerning antifungal therapy. Herein we have reported a case of extensive cellulitis caused by Paecilomyces lilacinus observed in a 48-year-old kidney transplanted woman with hepatitis C. Kidney transplantation from a cadaveric donor was performed in October 2006 with an uneventful early course except for posttransplant diabetes mellitus and a reversible acute rejection episode. Cutaneous nodular and verrucous lesions of the left leg appeared in August 2007. In a few weeks, these lesions become ulcerated, hemorrhagic, and painful. The diagnosis was made on the basis of microbiologic culture and histological examination. There was no improvement in the skin lesions after 6 weeks treatment with itraconazole, but voriconazole yielded a good response within the first 2 weeks. There was a good tolerance to antifungal therapy; graft function and liver tests remained normal. We concluded that an increasing emerging of fungal infections is observed with the introduction of more powerful immunosuppressive drugs. Diagnosis and management of such infections is elusive. Preventive measures should be considered including the adaptation of immunosuppressive therapy among at-risk patients especially those with hepatitis C virus infection and diabetics.

The first year renal function as a predictor of long-term graft survival after kidney transplantation.

This study examined the impact of graft function at the end of the first year after kidney transplantation on long-term graft survival. We analyzed the roles of serum creatinine (Scr) and other variables as predictors of graft survival among 235 adult kidney transplant patients. The subjects were divided into 3 groups according to their Scr at the end of the first year: group 1, Scr < 100 micromol/L; group 2, 100 micromol/L < or = Scr < or = 150 micromol/L; and group 3, Scr >150 micromol/L. The annual rate of graft loss of 0.7% (95% confidence interval [CI], 0.63-0.77) in group 1, was lower than those in group 2 (2.1%; 95% CI, 2.02-2.18; P < .0001) and group 3 (6%; 5.74-6.26; P < .0001). Regression analysis showed the role of recipient age at the time of operation, and Scr level at the end of the first year to be independent predictors of graft loss. Graft survival was not influenced by any other studied parameter, including donor age, year of procedure, warm ischemia time, history of acute tubular necrosis, and occurrence of an acute rejection episode. We conclude that the 1-year Scr value predicts long-term renal graft survival, representing a simple, practical tool to identify recipients with an high risk for late graft failure.

Kidney transplantation: Charles Nicolle Hospital experience.

The aim of our retrospective study was to analyze the short- and long-term follow-up of 298 renal transplantations performed between June 1986 and May 2005. All were first transplantations except 4 cases, with 54 from cadaveric and 244 from living donors. The recipients included 196 males and 102 females of overall mean age of 31.21 +/- 8.9 years (range, 16-61 years). A combination of prednisolone and azathioprine was presented for 212 patients or mycophenolate mofetil for 86 patients. Polyclonal or monoclonal antibodies were used as induction therapy in 183 cases. Cyclosporine was administered to 188 cases and tacrolimus only to 16. HLA matching was 0 mismatches (MM) in 65 cases; 1 or 2 MM in 113; 3 MM in 99; and > or =4 MM in 21. Acute tubular necrosis occurred in 45 cases. One hundred eighteen patients experienced at least 1 acute rejection episode: 102 cases (41.8%) among living and 16 (29.6%) among cadaveric kidneys donor (P = .0007). The actuarial patient and graft survival rates at 1, 5, 10, 15, and 20 years were 95.9%, 87.4%, 77.5%, 65.6%, and 60.8%, and 94.9%, 84.5%, 75.4%, 65.4%, and 53%, respectively. Sixty-three patients died and 72 patients returned to dialysis. Our results were comparable to experienced centers. However, the member of kidney transplantations does not match the increased number of patients on renal replacement therapy. It is advisable to promote obtaining organs from brain-dead donors.

The PTPN22 C1858T (R620W) functional polymorphism in kidney transplantation.

To investigate the association between kidney transplant rejection and PTPN22 (protein tyrosine phosphatase non-receptor 22) polymorphism, genomic DNA of 175 renal transplant recipients and 100 healthy blood donors were genotyped by restriction fragment length polymorphism-polymerase chain reaction. The patients were classified in two groups: G1 included 33 HLA-identical recipients and G2 included 142 with one or more HLA mismatches. Forty-nine patients developed an acute rejection episode (ARE): 8 in G1 and 41 in G2. The allelic frequencies of PTPN22 R620W revealed a significant difference between patients and controls. In fact, the W-allele was significantly more frequent in graft recipients than in blood donors (0.05 vs 0.01, P < .05). Furthermore, the frequency of this allele was increased in G1 patients with an ARE (0.188) compared with those without an ARE (0.040), but the difference was not statistically significant. Thus, we concluded that the PTPN22 W-variant allele could be involved in the susceptibility to acute allograft rejection in Tunisian kidney transplant patients.

Mannose binding lectin (+54) exon 1 gene polymorphism in Tunisian kidney transplant patients.

Mannose-binding lectin (MBL), a collagen-like serum protein, is a key component of innate immunity. MBL binding to carbohydrates present on pathogens mediates lectin-dependent activation of the complement pathway. There is growing interest in the importance of innate immunity in host defense, particularly when adaptive immunity is compromised. Three single nucleotide polymorphisms (SNPs) of the MBL gene have been described in the first exon to be associated with low MBL serum concentrations as well as impaired MBL structure and function. Clinical studies have shown that these MBL SNPs are associated with increased susceptibility to infections, especially in immunocompromised patients. To investigate the association between acute kidney transplant rejection and polymorphism at codon 54 of the MBL gene, the DNA genomic of 133 renal transplant recipients and 117 healthy blood donors was analyzed by restriction fragment length polymorphism-polymerase chain reaction. The patients were classified into two groups: group 1 included 32 HLA-identical recipients and group 2, 101 one haplo-identical recipients. Forty-eight (36.1%) subjects had developed one or more acute rejection episodes (AREs) within the first 6 months after transplantation: 9 in group 1 (28.12%) and 39 in group 2 (38.61%). The genotype and allele frequencies of (+54) MBL gene polymorphism among patients and controls did not reveal a significant difference. However, the frequency of MBL-B mutant allele was increased among patients with AREs compared with those without AREs: group 1 (0.167 vs 0.065) versus group 2 (0.205 vs 0.105). Although the difference was not significant, perhaps because of the small number of patients, the MBL at codon (+54) polymorphism could be involved in the susceptibility of Tunisian kidney transplant recipients to acute allograft rejection episodes.

[Association of disseminated nocardiosis and Kaposi's sarcoma after kidney transplantation]. / Nocardiose disséminée associée à un sarcome de Kaposi après transplantation rénale.

We report a 40-year-old kidney recipient who developed disseminated nocardiosis associated with cutaneous Kaposi's sarcoma. The withdrawal of immunosuppressive therapy and prolonged antibiotic therapy, including imipenem and trimethoprim-sulfamethoxazole, resulted in a favourable outcome of both disorders. Three years later, graft function remains stable with a complete regression of skin and pulmonary abnormalities. This case report illustrates the predisposing role of immunosuppressive treatment in the occurrence of infectious and neoplastic complications observed after solid-organ transplantation.