T. Ben Abdallah

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.

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.

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.

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.

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.

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.

La fibrose rétropéritonéale

Resume Objectif Nous avons etudie les caracteristiques cliniques, therapeutiques et evolutives de la fibrose retroperitoneale. Methodes Nous avons analyse les observations de fibrose retroperitoneale diagnostiquees entre 1980 et 2002 dans notre hopital, a partir des resumes de 15 patients ayant une fibrose retroperitoneale (FRP). La surveillance therapeutique a ete fondee sur la biologie et la radiologie. Resultats Il s’agissait de 11 hommes et de 4 femmes dont l’âge moyen etait de 44,5 ans avec des extremes de 28 a 64 ans. Tous les malades avaient des douleurs essentiellement lombaires et abdominales. Un syndrome inflammatoire existait dans tous les cas et une insuffisance renale dans 11 cas. Les explorations radiologiques ont montre une hydronephrose uni ou bilaterale dans 14 cas et la plaque de fibrose dans 13 cas. Le traitement a ete constitue de corticoides seuls dans 9 cas, de chirurgie seule dans 3 cas et de chirurgie associee a la corticotherapie dans 3 cas. Dix rechutes a raison de 1 a 5 ont ete observees chez 4 malades apres arret des corticoides. Apres un delai moyen de suivi de 36 mois (18 j a 11 ans) 1 deces a ete observe, 12 patients avaient une fonction renale normale et 2 malades ont garde une insuffisance renale moderee. Conclusion Nous avons confirme la rarete de la fibrose retroperitoneale, la difficulte de son diagnostic, la frequence de la douleur, du syndrome inflammatoire et de l’insuffisance renale. Les corticoides sont efficaces et un suivi regulier est necessaire.

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 patients 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.

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.

Short- and long-term post–renal transplant follow-up at Charles Nicolle Hospital

years, 56.5%; 31 to #45 years, 33.5%; and .45 years, 4%. Primary renal disease was chronic glomerulonephritis in 85 cases (42.5%), chronic pyelonephritis in 43 (21.5%), nephroangiosclerosis in 17 (8.5%), hereditary nephropathy in 11 (5.5%), and unknown in 44 (22%). Initial renal replacement therapy (RRT) was hemodialysis (HD) in 155 cases (77.5%), continuous ambulatory peritoneal dialysis (CAPD) in 24 (12%) and the two techniques combined in 21 (10.5%). For LRD, only first-degree relatives who gave their informed consent were accepted. All patients received ABO compatible and cross-match negative kidneys. At least 3 units of blood transfusions were given to 161 patients (80.5%) and cytotoxic antibodies were screened. All patients received a combination of prednisolone: 2 mg/kg/d on day 0, tapered to 0.2 mg/kg/d on day 90 and azathioprine at 125 mg/d. Antilymphocyte globulin (ALG) or antithymocyte globulin (ATG) was used as prophylactic treatment of graft rejection in 98 cases (48%) during the first 15 days. Cyclosporine was administered in 112 patients (56%) twice daily orally at 5 mg/d beginning on day 3 to 15 days in LRD transplants with one identical haplotype and after corticoresistant acute rejection episodes. The dosages were adjusted to clinical state and cyclosporine blood level (radioimmunoassay). Acute rejection episodes were treated with a combination of pulses of methylprednisolone and ALG/ATG in 75 cases. OKT3 was introduced in six cases when ALG/ATG failed to reverse the rejection. Mycophenolate mofetil was used in 11 cases with cyclosporine nephrotoxicity. The results were expressed as mean 6 standard deviation (SD). Comparisons were made with chi squared test for categorical variables and PLSD Fisher’ test for continuous variables. The survival rates were computed using the actuarial method. P , .05 was considered statistically significant. RESULTS The waiting time on dialysis was 28 6 22 months (1 to 119 months). For LRD, the donors were 96 (52.7%) siblings, 84 (46.2%) parents, and 2 children. HLA matching was 0 mismatches (MM) in 48 cases (26.4%) and 3 MM in 134 (73.6%). Their mean age was 38.6 6 13.4 (16 to 65) years. For CAD, HLA matching was 1 to 6 MM. The cytotoxic antibodies were positive in 27% of cases. Acute tubular necrosis (ATN) occurred in 26 cases (14.3%) of LRD and in 3 (16.7%) CAD. All those patients were hemodialyzed requiring 1 to 10 sessions, but all recovered. The difference between the two groups was not statistically significant (P 5 .07). The mean time of warm ischemia was 44 6 13 minutes for patients who have expressed ATN and 41.9 6 10.9 for those without ATN. The mean time of cold ischemia for CAD was 26.8 6 6 hours. Acute rejection was encountered in 16 (33.3%) cases of LRD with 0 MM, 80 (59.7%) cases of LRD with 3 MM, and 14 (77.8%) cases in the CAD group. The differences between the three groups were statistically significant (P , .0009). Complications Infectious complications were very common (86% of cases). Viral infections occurred in 40% of cases, mostly CMV (21%) and herpes (14%). No HIV infection was seen. Bacterial infections occurred in 60% of cases, mostly urinary tract infections (49%), septicemia (11.5%), and bronchopulmonary infections (5%). Six patients had scabies. Urologic complications occurred in 31 cases: 14 (7%) urinary leaks, 6 (3%) urinary stenosis, 2 ureteral compressions, 4 lymphoceles, 3 urinary lithiasis, and 2 urinary tuberculosis. Vascular complications were seen in eight cases: two arterial thrombosis, two venous thrombosis, three arteriovenous fistulae, and one perirenal hematoma. We noted recurrence of focal segmental glomerulosclerosis in six cases and glomerulonephritis de novo in two cases.