Habib Skhiri

Cytomegalovirus ischemic colitis and transverse myelitis in a renal transplant recipient.

We report a rare case of cytomegalovirus (CMV)-associated ischemic colitis and transverse myelitis (TM) occurring precociously after renal transplantation. A 57-year-old male was transplanted with a cadaveric kidney on 5 June 2009. The patient was CMV seropositive and the donor was seronegative. Transplantation was followed shortly by TM, which resulted in paraplegia. The results of magnetic resonance imaging of the spinal cord showed abnormalities. Twenty days after transplantation, he developed abdominal pain with melena and was diagnosed as having CMV-associated ischemic colitis confirmed by colonoscopy and biopsy. Serological data and identification of the viral genome by polymerase chain reaction were confirmatory for CMV. Treatment consisted of intravenous ganciclovir, followed by polyvalent immunoglobulin. The outcome was favorable. Symptomatic CMV infection is relatively common among the renal transplant population. Early colonoscopy is beneficial for making a quick diagnosis and therefore helps to institute a prompt management of CMV colitis. Myelitis is less common in transplant recipients and diagnosis, therefore, was more difficult.

Short- and long-term outcomes of kidney donors: A report from Tunisia

Kidney transplantation remains the best treatment option of end-stage renal disease. Kidney donations are of particular interest with the currently increasing practice of living-donor transplantation. The purpose of this study was to analyze retrospectively the general health status as well as renal and cardiovascular consequences of living-related kidney donation. A total of 549 living-related kidney donors had donated their kidneys between 1986 and 2007. We attempted to contact all donors to determine short- and long-term outcome following kidney donation. All kidney donors who responded underwent detailed clinical and biochemical evaluation. The data were compared with age-matched health tables of the Tunisian general population. In all, 284 donors (52%) had a complete evaluation. They included 117 men and 167 women with a mean age of 42 ± 12 years. The major peri-operative complications that occurred in these donors included four cases of pneumothorax, six cases of surgical site infection, one case of phlebitis and one case of pulmonary embolism. None of the study cases died. The median length of hospital stay after donor nephrectomy was 6.5 days (range: 3-28 days). The median follow-up period was eight years. The mean creatinine clearance after donation was 90.4 ± 25 mL/min in men and 81.5 ± 27.2 mL/min in women. Proteinuria was >300 mg/24 h in 17 cases (5.9%). Fifty-eight (20.4%) donors became hypertensive and 19.6% of the men and 37.2% of the women became obese. Diabetes mellitus developed in 24 (8.4%), and was more common in patients who had significant weight gain. Our study suggests that kidney donors have minimal adverse effects on overall health status. Regular follow-up identifies at-risk populations and potentially modifiable factors. Creation of a national registry of living donors and their monitoring are an absolute necessity.

Limited Sampling Strategy of Mycophenolic Acid in Adult Kidney Transplant Recipients: Influence of the Post-Transplant Period and the Pharmacokinetic Profile

We aimed to develop an accurate and convenient LSS for predicting MPA‐AUC0–12hours in Tunisian adult kidney transplant recipients whose immunosuppressive regimen consisted of MMF and tacrolimus combination with regards to the post‐transplant period and the pharmacokinetic profile. Each pharmacokinetic profile consisted of eight blood samples collected during the 12‐hour dosing interval. The AUC0–12hours was calculated according to the linear trapezoidal rule. The MPA concentrations at each sampling time were correlated by a linear regression analysis with the measured AUC0–12. We analyzed all the developed models for their ability to estimate the MPA‐AUC0–12hours. The best multilinear regression model for predicting the full MPA‐AUC0–12hours was found to be the combination of C1, C4, and C6. All the best correlated models and the most convenient ones were verified to be also applicable before 5 months after transplantation and thereafter. These models were also verified to be applicable for patients having or not the second peak in their pharmacokinetic profiles. For practical reasons we recommend a LSS using C0, C1, and C4 that provides a reasonable MPA‐AUC0–12hours estimation.

Brown tumors in dialyzed patients with secondary hyperparathyroidism: report of 16 cases.

Brown tumors (BTs) are relatively uncommon but they are serious complications of renal osteodystrophy. The objective of this study was to analyze the clinical, biological, and radiological characteristics of 16 patients with BTs provoked by secondary hyperparathyroidism (sHPT) and its response to the decrease in parathyroid hormone levels after parathyroidectomy (PTX). The management of that uncommon condition was also reviewed. We conducted a retrospective study including 16 end‐stage renal disease patients who underwent subtotal PTX between 1997 and 2007 for severe sHPT with BTs. Our study included 10 men and 6 women, whose average age was 34 years. All patients were on dialysis. Ten of them were on dialysis for more than 5 years. The median duration on dialysis was 84 months. Patients included suffered from swellings associated with functional limitations. BTs had multiple locations in 7 patients. Jaw was the most frequent location (62%). Radiography and tomodensitometry demonstrated a mixed radio lucent and radio‐opaque lesions with an expansion of the cortical bone. Bone scan demonstrated an increased uptake of lesions. Chirurgical treatment was indicated in all cases because of severe refractory sHPT with functional limitations and/or disfiguring deformities. In all cases, BTs stopped its progression and even decreased in size. However, it was insufficient in four cases, which required a surgical resection. PTX remains an efficacious approach in resistant cases of sHPT with persistent BTs.

Atypical hemolytic uremic syndrome in the Tunisian population

BackgroundHemolytic uremic syndrome consists of a triad of acquired hemolytic anemia, thrombocytopenia and renal failure.AimOur objectives were to determine epidemiology, clinical and laboratory characteristics of patients with atypical hemolytic uremic syndrome (aHUS) to determine the relationship between the complement protein deficit and aHUS in the Tunisian population.MethodsWe studied retrospectively four cases of atypical HUS in adults admitted in the Nephrology Department of Fattouma Bourguiba Universitary Hospital in Monastir between 2000 and 2008.ResultsThree patients had renal failure that required dialysis. One of them received kidney transplantation with no further recurrence of aHUS. Three patients had normal C3, C4, CFH, and FB levels, and in all patients anti-FH autoantibodies were absent. The kidney biopsy of one patient showed in addition to lupus glomerulonephritis histological findings consistent with TMA. A decrease in C3, C4 and CFH levels in this patient was found both before and after the cure.ConclusionNephrologists should be aware of autoimmune conditions and genetic abnormalities of the complement regulatory genes as possible pathogenic mechanisms in atypical HUS patients.

Tacrolimus therapeutic drug monitoring in Tunisian renal transplant recipients: Effect of post-transplantation period☆

BACKGROUNDnMost previous studies having focused on therapeutic drug monitoring of tacrolimus in renal transplant recipients have assessed the clinical response of patients. The aim of this study is to investigate the influence of post-transplant delay on tacrolimus dose, trough levels (C0) and dose/C0 ratio in a Tunisian renal transplant population.nnnPATIENTS AND METHODSnA retrospective study including 110 renal transplant patients has been performed. Tacrolimus trough concentrations were adjusted according to the target range proposed by the European consensus conference on tacrolimus optimization. Samples for determination of tacrolimus blood level were subdivided according to the post-transplantation period into three groups.nnnRESULTSnThe initial dose required was 0.17 ± 0.05 mg/kg/day during the first 3 months after transplantation. A reduction of 36 and 65% of tacrolimus initial dose during the second (3-12 months) and third period after transplantation (>12 months), respectively, was required to maintain the concentration level within therapeutic range. These results were different from those found in other studies performed in different populations. We hypothesize that these differences in dosing requirement may be due to an interethnic polymorphism in the expression of enzymes involved in tacrolimus metabolism.nnnCONCLUSIONnThese results could provide a simple therapeutic strategy to optimize tacrolimus prescription after renal transplantation in Tunisian population.

Deafness and blindness in a renal transplant recipient with cryptococcal meningitis.

Infections are a major determinant of outcome in kidney transplantation. Opportunistic pathogens are common in kidney recipients and several organs can be affected. Central nervous system infection in transplant recipients is a medical emergency. There is limited information in the literature concerning post-transplantation cryptococcal infection. Deafness and blindness are not classic findings. We report a case of meningocerebral cryptococcosis complicated by deafness and blindness after kidney transplantation. Physicians need to consider the possibility of Cryptococcus neoformans when symptoms persist despite empiric antimicrobial therapy.

Mycophenolate mofetil-related pancolitis in a kidney transplant recipient.

Gastrointestinal adverse effects are common with mycophenolate mofetil administration, especially diarrhea. We report a case of mycophenolate mofetil-related colitis in a kidney transplant recipient. Colonoscopy revealed an ulcerative diffuse colitis. The colonoscopic biopsy specimen showed mild crypt distortion, accompanied by cryptitis and focal graft-versus-host disease like changes. The patients symptoms improved after we discontinued the mycophenolate mofetil. A repeat colonoscopy 2 months after we discontinued the mycophenolate mofetil showed reparative changes. Mycophenolate mofetil is an important drug in organ transplant immune-suppression regimens; however, with its widespread use, additional adverse effects continue to be recognized.

Cytomegalovirus Ocular Involvement in a Kidney Transplant Recipient.

Cytomegalovirus remains the most common infection after kidney transplant. We report cytomegalovirus retinitis and anterior uveitis, which developed consecutively within 1 year in a kidney transplant recipient. A 25-year-old man presented 5 months after transplant with decreased visual acuity in his left eye. Fundus examination revealed bilateral areas of necrotizing retinitis with intraretinal hemorrhages. The confirmation of cytomegalovirus disease was based on clinical findings and positive polymerase chain reaction for cytomegalovirus in plasma and in aqueous humor. The patient was treated with intravenous ganciclovir for 21 days and then with valacyclovir for 3 months. The patients symptoms improved, and fundus examination revealed resolution of retinitis with appearance of retinal scarring. One year later, the patient presented with cytomegalovirus anterior uveitis associated with increased intraocular pressure, which was treated with antiviral agents, antiglaucomatous eye drops, and trabeculectomy. Cytomegalovirus ocular involvement for our immunocompromised patient presented in 2 consecutive forms: bilateral retinitis and anterior uveitis. Early diagnosis and treatment of active cytomegalovirus retinitis and uveitis remain crucial to prevent their progression to irreversible visual impairment.

Development of Limited Sampling Strategies for the Estimation of Tacrolimus Area Under the Curve in Adult Kidney Transplant Recipients According to the Posttransplantation Time.

Background: Limited sampling strategies (LSS), using few sampling times after dosing, have been used to reliably predict tacrolimus area under the 12-hour concentration–time curve (AUC). Because the pharmacokinetics of tacrolimus is subject to significant changes over the exposure time to this drug, it can be hypothesized that the reliability of the LSS would also change. This study aimed to develop a reliable and practical LSS allowing the estimation of tacrolimus AUC in Tunisian kidney transplant recipients taking into account the posttransplantation time. Methods: Thirty Tunisian patients were enrolled into 3 groups (10 in each group) according to the posttransplantation period: period 1: between 1 day and 3 months, period 2: between 3 and 12 months and period 3 over 12 months, as defined by the European consensus conference on the therapeutic drug monitoring of tacrolimus. Samples were collected just before and 0.5, 1, 2, 4, 6, 8, and 12 hours after tacrolimus administration. The full pharmacokinetic profiles obtained from these timed concentration data were used to choose the best sampling times. Error indices (mean absolute prediction error and the root mean squared prediction error) were used to evaluate the predictive performance. Results: Among the 1-point estimations, the C4-predicted AUC showed the highest correlation with the measured one during period 1 and period 2 (r2 = 0.94 and 0.91, respectively) but not period 3 (r2 = 0.76). The C0-predicted and the measured AUC become less and less correlated from period 1 to period 3 (r2 = 0.81, 0.75, and 0.66), respectively. Only the model including the C0/C2 provided a high correlation between predicted and measured tacrolimus AUC regardless of the posttransplant period (r2 = 0.95, 0.96, 0.98 and root mean squared prediction error = 4.1, 5.8, 4.2 during periods 1, 2, and 3, respectively). Conclusions: Our data clearly indicate that the predictive performance of LSS is prone to change according to the posttransplantation time. A 2–time point LSS was found to be sufficient to predict tacrolimus AUC. The LSS using C0 and C2 is reliable, accurate, and practical to estimate the AUC of tacrolimus regardless of the posttransplantation time.