Adel Kheder

Clinicopathological Characteristics of Obesity-associated Focal Segmental Glomerulosclerosis

Obesity-related glomerulopathy (ORG) is a secondary form of focal segmental glomerulosclerosis (FSGS) occurring in obese patients with a body-mass index higher than 30 kg/m2. It is typically manifested by nephrotic-range proteinuria without full nephrotic syndrome, and progressive renal insufficiency. Characteristic morphologic features include the consistent presence of glomerulomegaly, predominance of perihilar variant of FSGS, and the relatively mild fusion of visceral epithelial cell foot processes. The concept of podocyte depletion as a driver of the glomerular scarring in obesity-associated FSGS is well documented. The underlying mechanisms are likely to be related in part to the oxidative stress and the impairment of the integrity of the slit diaphragm and cell adhesion resulting mainly from angiotensin II and transforming growth factor-β. These proapoptotic cytokines are upregulated in obesity in response to insulin resistance, compensatory hyperinsulinemia and glomerular hyperfiltration-hypertension mediated mechanical stress. This review is designed to discuss the clinicopathologic features of obesity-associated FSGS, with a focus on the podocyte injury, which is involved in the onset and progression of the glomerulosclerotic process. Ultrastructural glomerular lesions are documented.

Risk factors and consequences of delayed graft function.

The impact of delayed graft function (DGF) on the outcome of renal transplantation remains controversial. We analyzed the risk factors for DGF and its impact on graft and patient survival. A total of 354 renal transplants performed between June 1986 and April 2000 were analyzed. Variables analyzed included donor and recipient age, method and duration of renal replacement therapy, HLA mismatch, cold and warm ischemia times, biopsy-confirmed acute rejection, length of stay in the hospital, serum creatinine at the end of first hospitalization as well as graft and patient survival at one, three, five and ten years. The study patients were divided into two groups: patients with DGF (G1) and those without DGF (G2). DGF occurred in 50 patients (14.1%), and it was seen more frequently in patients transplanted from deceased donors (60% vs. 40%, P <0.0001). The cause of DGF was acute tubular necrosis, seen in 98% of the cases. Univariate analysis showed a statistically significant difference between the two groups G1 and G2 in the following parameters: average duration on dialysis (52.3 vs. 36.4 months, P = 0.006), HLA mismatch (44.9% vs. 32.11% P = 0.015), donor age (35.9 vs. 40.2 years, P = 0.026), cold ischemia time (23 vs. 18.2 h, P = 0.0016), warm ischemia time (41.9 vs. 38.6 mn, P = 0.046), length of stay in the hospital during first hospitalization (54.7 vs. 33.2 days, P <0.0001), serum creatinine at the end of first hospitalization (140 vs. 112 μmol/L, P <0.0001) and at three months following transplantation (159 vs. 119 μmol/L, P = 0.0002). Multivariate analysis revealed the following independent risk factors for DGF: deceased donor (RR = 13.2, P <0.0001) and cold ischemia time (RR = 1.17, P = 0.008). The graft survival at one, three, five and ten years was 100%, 93%, 88.3% and 78.3% in G1 versus 100%, 95.9% 92.8% and 82.3% in G2; there was no statistically significant difference. The patient survival at one, three, five and ten years was 100%, 91.3%, 83.6% and 74.4% in G1 versus 100%, 95.9%, 94% and 82.6% in G2 with a statistically significant difference (P = 0.04). Prolonged cold ischemia time and transplantation of kidneys from deceased donors were the main risk factors for DGF in our study. Also, DGF significantly affected patient survival but had no influence on graft survival.

Urinary tract infections following renal transplantation: A single-center experience

Urinary tract infection (UTI) is the most frequent infectious complication among renal transplant recipients and a frequent cause of bacteremia, sepsis and acute graft failure. To evaluate the incidence, risk factors, type of pathogens and long-term effect of UTIs on graft and patient survivals in our center, we performed a retrospective cohort study reviewing the medical records of patients who received a renal transplant at our center from June 1986 to December 2009, excluding patients who lost their grafts in the first month due to arterial or veins thrombosis and acute antibody-mediated rejection. We studied 393 kidney-transplanted recipients; at least one UTI occurred in 221 (53.69%) patients during the follow-up period. The most frequent pathogens isolated in urine culture were Escherichia coli (n = 39, 18.4%) and Klebsiella pneumonia (n = 31, 14.6%). When patients with UTIs were compared with those without UTIs, female gender and use of mycophenolate mofetil or azathioprine seemed to be risk factors for UTIs on univariate analysis. However, female gender was the only independent risk factor on multivariate analysis RR = 1.964 (1.202-3.207), P = 0.007. This study confirmed that UTIs remain a major problem in renal transplant recipients, and female gender was the only independent risk factor.

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.

Insuffisance rénale aiguë secondaire à la povidone iodée

Resume Introduction La povidone iodee est un antiseptique largement utilise surtout en usage cutane. Malgre son innocuite, des cas d’insuffisance renale aigue rentrant dans le cadre d’une toxicite a l’iode ont ete rapportes. Observation Une femme âgee de 37 ans, sans antecedents particuliers etait suivie pour une sterilite primaire de 4 ans. Elle a eu, dans le cadre de l’exploration de cette sterilite, une hysteroscopie avec opacification par de la povidone iodee. En post operatoire immediat, une insuffisance renale aigue oligurique s’est developpee. Apres traitement par diuretiques et 5 seances d’epuration extra renale, l’evolution etait favorable avec declenchement de la diurese a J18 suivi d’une normalisation de la fonction renale. Discussion La toxicite a l’iode est plus importante quand la povidone iodee est administree in situ au contact des muqueuses. L’insuffisance renale aigue est a type de necrose tubulaire aigue comme chez cette patiente. En l’absence d’autre cause, cette insuffisance renale aigue a ete rattachee a la povidone iodee. Conclusion L’insuffisance renale aigue secondaire a la toxicite a l’iode reste possible surtout si la povidone iodee est administree au contact des muqueuses. L’evolution est en general favorable apres l’arret du contact avec cet agent et le traitement symptomatique.

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.

CHRONIC SUBDURAL HAEMATOMA AND AUTOSOMAL POLYCYSTIC KIDNEY DISEASE: REPORT OF TWO NEW CASES

SUMMARY:  Chronic subdural haematoma (SDH) was recently described in some patients who were suffering from autosomic dominant polycystic kidney disease (ADPKD). It results in various neurological symptoms mimicking those related to intracranial aneurysms, which are relatively frequent in such patients. The authors report two cases of chronic SDH observed in two patients known to have advanced renal failure attributed to ADPKD. Medical imaging failed to reveal features of associated intracranial abnormalities such as aneurysms or arachnoid cysts. Surgical drainage resulted in a good recovery without relapse during a long period of follow up that exceeded 10 years in the first case.

Acute renal failure by ingestion of Euphorbia paralias

Euphorbia paralias is known in traditional medicine as an anti-inflammatory agent, a purgative and for its local anesthetic property. To the best our knowledge, renal toxicity of this substance has not been previously reported. In this paper, we report the case of a 29-year-old male who developed renal damage following ingestion of Euphorbia paralias. He had been on follow-up for nephrotic syndrome since 1986, although irregularly, with several relapses but each responding well to steroid therapy. A kidney biopsy had not been performed earlier due to refusal by the patient. He was off steroids since April 2008 because the patient developed osteoporosis. He was admitted with general malaise and oliguria to our department in May 2009, following repeated vomiting and watery diarrhea for three days. On examination, he was edematous but had normal vital signs except for a pulse rate of 120/min. Hemoglobin was only 5.5 g/dL but with normal white cell and platelet counts. Blood biochemistry showed evidence of advanced renal failure with a serum creatinine level of 1835 μmol/L and urea at 44.6 mmol/L, sodium of 132 μmol/L and potassium at 4.3 mmol/L. He had features of nephrotic syndrome with severe hypoproteinamia and 24-h urinary protein of 10.45 g. Ultrasonography revealed enlarged kidneys with a reduced echogenecity of the medulla and the papillae. Subsequently, after hemodialysis with blood transfusion, a kidney biopsy was performed that showed focal segmental glomerulosclerosis associated with an acute tubular injury. On intensive interrogation, the patient gave a history of ingesting boiled Euphorbia paralias as a native treatment for edema, ten days prior to the onset of the current illness. A diagnosis of acute renal failure (ARF) resulting from the possible nephrotoxic effect of Euphorbia paralias poisoning was made. He was treated with intermittent hemodialysis and corticosteroids. Serum creatinine values improved after 48 days. At six months following the intoxication, serum creatinine of the patient was 240 μmol/L. In cases of unexplained ARF, a toxic mechanism should always be considered and acute renal failure caused by Euphorbia paralias should be included as a cause if renal toxicity is suspected in those places where it is being used as a native medicine.

Mycobacterium tuberculosis Infection following Kidney Transplantation

Introduction and Aims. Post-transplant tuberculosis (TB) is a problem in successful long-term outcome of renal transplantation recipients. Our objective was to describe the pattern and risk factors of TB infection and the prognosis in our transplant recipients. Patients and Methods. This study was a retrospective review of the records of 491 renal transplant recipients in our hospital during the period from January 1986 to December 2009. The demographic data, transplant characteristics, clinical manifestations, diagnostic criteria, treatment protocol, and long-term outcome of this cohort of patients were analyzed. Results. 16 patients (3,2%) developed post-transplant TB with a mean age of 32,5 ± 12,7 (range: 13–60) years and a mean post-transplant period of 36,6months (range: 12,3 months–15,9 years). The forms of the diseases were pulmonary in 10/16 (62,6%), disseminated in 3/16 (18,7%), and extrapulmonary in 3/16 (18,7%). Graft dysfunction was observed in 7 cases (43,7%) with tissue-proof acute rejection in 3 cases and loss of the graft in 4 cases. Hepatotoxicity developed in 3 patients (18,7%) during treatment. Recurrences were observed in 4 cases after early stop of treatment. Two patients (12.5%) died. Conclusion. Extra pulmonary and disseminated tuberculosis were observed in third of our patients. More than 9months of treatment may be necessary to prevent recurrence.