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.

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.

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.

Incidence and risk factors for post-renal transplant diabetes mellitus.

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.

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.

[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.

[Peritoneal dialysis in the elderly]. / La dialyse peritoneale chez le sujet age.

BACKGROUND: Peritoneal dialysis is used more and more as treatment of substitution of the end stage renal disease at the old subjects of more than 65 years and its effectiveness and its good tolerance were shown. AIMS: To study the epidemiological and clinical profile of these patients, the indication and the advantages of PD, the various complications, the elements of prognostic and the survival of the patients and the technique. METHODS: We made a retrospective study including a series of 13 old patients of more than 65 years and treaties by PD during the period extending from the 1983/2/11 to the 2005/12/31. They are 10 men and 3 women on average of 70 +/- 3.1 year and representing 3.62% of the totality of the patients. The diabetic and vascular nephropathies represent the first cause of ESRD. RESULTS: The PD was used of first intention at 53.84% of the patients whose majority suffers from a malnutrition due to advanced age, anorexia, psychological disorders, bad dental state and uraemia. The cardiovascular complications are frequent in this age bracket explaining heavy morbidity. The pulmonary and urinary infectious complications are also frequent. The more frequent peritonitis compared to the literature, are comparable between the 2 age brackets < and = with 65 years and the mode of PD (APD or CAPD). The time separating the beginning from PD and which has occurred of the peritonitis is shorter in APD. The lesions of renal osteodystrophy are found among 6 patients: 3 cases of hyperparathyroidism and 3 cases of adynamic osteopathy. The return in HD is rare due to dysfunction of the catheter. The survival of the patients is 92.8% at 1 year and 60.8% at 5 years; that of the technique is worse with 88.3% at 1 year and 33.7% at 5 years Eight patients died (61.5%) because of cardiovascular diseases and of the infections. We found a correlation statistically significant between the survival of the patients and the mode of PD, on the other hand any correlation was not found with the age or the sex. The survival of the technique is not correlated to a significant degree with the age, the sex and the mode of PD. CONCLUSION: Peritoneal dialysis is used of first intention at more half of the old subjects and remains a last recourse for haemodialysis which have an initially vascular problem. The family support and the good nurse allow these patients to adhere well to the technique. The cardiovascular diseases and the infections are responsible for heavy morbi-mortality. The survival of the technique is worse than that of the patients.

Impact of dialysis modality on posttransplantation results in kidney transplantation.

Studies looking at the type of pretransplantation renal replacement therapy on graft and patient survivals after kidney transplantation have produced conflicting results. Therefore, we studied the effect of pretransplantation dialysis modality (peritoneal dialysis [PD] or hemodialysis [HD]) on transplant outcomes. We performed a retrospective study of 78 patients (39 PD and 39 HD) who had their first renal transplantation between January 1986 and December 2004. Comparisons between groups were made using chi-square tests for qualitative parameters and nonpaired Student t tests for continuous variables. Comparisons between actuarial curves of patient and technique survivals used log-rank tests. The percentages of recipient males, cadaveric donors, transplant-induced diabetes, mean period of dialysis, mean transplantation follow-up, mean duration of first hospital stay, first infection, acute tubular necrosis, and acute rejection episodes were not significantly different among PD versus HD patients, whereas recipient and donor mean ages were significantly higher in HD and PD patients, respectively. There were no differences in graft and recipient survivals among PD versus HD patients. After kidney transplantation, there was no difference between PD and HD patients concerning percentages of infection, acute tubular necrosis, acute rejection episodes or graft and recipient survivals.

Impact of initial blood pressure on the mortality of diabetics undergoing renal replacement therapy.

The aim of this study was to determine the blood pressure (BP) profiles and their impact on mortality among a cohort of uremic diabetics treated by hemodialysis. The studied population includes all type II diabetics starting hemodialysis for end-stage renal disease between 1990 and 1996. There were 221 patients (144 men, 77 women) aged from 37 to 78 years, were all followed until death or December 2003 without any censored data. Survival analysis to identify predictors of death was performed using the actuarial method, Cox proportional model, including systolic, diastolic, mean, and pulse blood pressures (SBP, DBP, MBP, PP). One hundred seventy-eight patients (80.5%) were hypertensive at the start of dialysis. Hypertension preceded the diagnosis of diabetes in eight cases (4.5%); 154 patients (86.5%) received antihypertensive drugs and only 23 (14.9%) had well-controlled hypertension. Our population was subdivided into four groups according to their BP levels at the time of beginning of dialysis; G1 (19.5%): normal BP (SBP [90 to 140] and DBP [60 to 90]); G2 (30.3%): Hypertension stage 1 (SBP [140 to 160] and/or DBP [90 to 100]); G3 (32.1%): hypertension stage 2 (SBP [160 to 180] and/or DBP [100 to 110]); G4 (18.1%) hypertension stage 3 (SBP [180 to 220] and/or DBP [110 to 120]). Mean age and comorbidities were similar among the four groups. During a cumulative follow-up period of 872 patient-years, 191 patients died, representing a rate of 21.9 per 100 patient-years; 20.42% of these deaths occurred during the first 3 months of dialysis. Normotensive patients showed lower survival rates without any significant difference in comparison with those of other hypertensive groups. None of the initial BP parameters (SBP, DBP, PP, MBP, hypertension stages) seemed to influence early or global mortalities, which were rather related to the urgent onset of renal replacement therapy, to age, to serum albumin, and to the score of associated morbidities. We conclude that mortality of our hemodialyzed diabetics was not influenced by the blood pressure parameters recorded at the onset of dialysis.