Prevalence of chronic kidney disease in Tunisian diabetics: the TUN-CKDD survey.

BACKGROUND: In Tunisia, the prevalence of diabetes mellitus increased from 15.5% on 2016 to 23% by 2023. While Chronic Kidney Disease (CKD) stills the most dreaded complications of diabetes, studies on the prevalence of chronic kidney disease non-dialysis diet are scarce. The aim of this study was to assess the prevalence of chronic kidney disease among the Tunisian diabetic population based on investigators' specialty, demographic criteria (gender, age, duration of diabetes and geographic distribution) and diagnosis criteria (albuminuria and/or eGFR). METHODS: This observational, multicentric, and cross-sectional study enrolled all diabetic subjects from all regions of Tunisia with at least 3 months of follow-up before the inclusion date, from 09 January to 08 February 2023. CKD diagnosis was established based on the KDIGO guidelines. The study was carried out at medical departments and ambulatory clinics of different healthcare providers. Baseline data were collected by investigators using an electronic case report form (eCRF). Continuous variables were described by means, median, standard deviation, and quartiles. Categorical data were tabulated in frequencies and percentages. RESULTS: The overall prevalence of CKD among the 10,145 enrolled patients with diabetes mellitus was 38.7% with a 95%CI [37.8-39.6%]. 50.9% were male, with a mean age of 67.5 (± 11.3) years. The mean diabetes duration was 16.1 years (± 8.9). The highest CKD prevalence was noted among nephrologists (82.2%), while it was similar between the cardiologists and the primary care physicians (30.0%). CKD prevalence was highest among males (43.0% versus 35.1%) and increased proportionally with patients' age and diabetes duration. CKD was more frequent in the Mid-East Area when compared to other regions (49.9% versus 25.3 to 40.1% in other regions). Albuminuria was present within 6.6% of subjects with CKD, and it was found an estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m² within 13.3% of subjects wit h CKD. 18.9% had both criteria. CONCLUSIONS: In Tunisia, CKD among diabetics had a prevalence of 38.7%, approaching European prevalence. The prevalence discrepancy worldwide of CKD can be improved with a larger population size and by implementing standardized practices.

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 (r = 0.94 and 0.91, respectively) but not period 3 (r = 0.76). The C0-predicted and the measured AUC become less and less correlated from period 1 to period 3 (r = 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 (r = 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.

Induction of DNA fragmentation, chromosome aberrations and micronuclei by cisplatin in rat bone-marrow cells: protective effect of recombinant human erythropoietin.

Cisplatin (Cisp) is one of the most effective chemotherapeutic agents. However, at higher doses several side effects may occur. Recombinant human erythropoietin (rhEPO), a glycoprotein regulating haematopoiesis, has recently been shown to exert an important cyto-protective effects in many tissues. The purpose of this study was to explore whether rhEPO protects against Cisp-induced genotoxicity in rat bone-marrow cells. Adult male Wistar rats were divided into six groups of 18 animals each: control group, rhEPO-alone group, Cisp-alone group and three rhEPO+Cisp-groups (pre-, co- and post-treatment condition, respectively). Our results show that Cisp induced a noticeable genotoxic effect in rat bone-marrow cells. In all types of treatment, rhEPO significantly decreased the frequency of micronuclei, the percentage of chromosome aberrations and the level of DNA damage. The protective effect of rhEPO was more efficient when it was administrated 24h before exposure to Cisp.

The Clinical Features and Outcomes of Renal Amyloidosis in Tunisia.

Systemic amyloidosis is a rare disease characterized by clinical polymorphism. Indeed, the kidney is the most common organ involved and represents a real turning point in the disease. We aimed to determine the clinicopathological prognostic factors of renal amyloidosis (RA). We conducted a retrospective study including 40 cases with biopsy-proven RA collected in our department over a period of 10 years. Biochemical, demographic, and clinicopathological findings at diagnosis, as well as the follow-up data, were evaluated for each patient. The prevalence of amyloidosis was 2.7 per 100 nontransplant renal biopsies. The mean age at presentation was 55.5 ± 15.6 years with a male-to-female ratio of 1.85. The diagnosis of RA was confirmed by a renal biopsy in 85% of cases. Amyloid A (AA) amyloidosis was the most common type of amyloidosis (65%), and chronic infections ranked first in the panel of etiologies (41%). Amyloid light chain amyloidosis was mainly associated with multiple myeloma (57%). The median patient survival was 59 months versus 12 months for kidney survival. Age and extrarenal localization were independent predictors of mortality, whereas renal failure at presentation significantly influenced renal survival. The results of our study emphasize the rarity but also the severity of RA. AA amyloidosis was the most common type identified, which was mainly caused by chronic infections. Prevention remains the best solution until we can achieve therapeutic advances in inflammatory diseases.

Management of patients with cardiovascular diseases during Ramadan.

During the month of Ramadan, over one billion Muslims observe a water and food fast from sunrise to sunset. The practice of this religious duty causes marked changes in eating and sleeping habits. With the increasing incidence of cardiovascular (CV) risk factors, the number of patients with CV pathologies who wish to fast is increasing worldwide, and in Tunisia, which is ranked as a high CV risk country. If fasting has been shown to be beneficial for the improvement of some metabolic parameters, its practice in patients with CV pathology remains debated. The Tunisian Society of Cardiology and Cardiovascular Surgery (STCCCV) in consultation with the National Instance of Evaluation and Accreditation in Health (INEAS) has established this document in the form of a consensus after having analysed the literature with the aim of addressing these questions: -What is the impact of fasting in patients with CV pathologies? -How to stratify the risk of fasting according to CV pathology and comorbidities? -How to plan fasting in patients with CV diseases? -What are the hygienic and dietary measures to be recommended during fasting in patients with CV pathologies? -How to manage medication during the month of Ramadan in patients with CV diseases?

Peritoneal dialysis in Tunisia: complications, technique and patient's survival (twenty-seven years of experience in a single center).

INTRODUCTION: peritoneal dialysis (PD) is a renal replacement therapy method that offers various advantages to end-stage renal disease patients. The aim of our study was to analyze patient characteristics, peritonitis and clinical outcome over a 27-year period of PD in our center. METHODS: retrospective study of incident patients on PD from January 1990 to December 2017. A total of 304 patients were enrolled in the study group. All patients over 15 years of age entering the dialysis program were included in the study. Patients dropping out from PD within three months were all excluded. Biochemical and demographic variables, peritonitis episodes and patient and technique survival were analyzed. RESULTS: the PD prevalence in our center was 4.5% during the study period; the mean age was 46.47 ± 18.6 years; diabetic nephropathy was the main cause of chronic kidney disease: 35.5% (n=108). Cardiovascular disease was the main cause of death: 39.6% (n=34). The peritonitis rate was 0.68 episode per patient-year. Ultrafiltration failure was the most important cause of PD withdrawal: 43% (n=60). Occurrence of peritonitis was the only independent predictor of technique failure: adjusted relative risk [aRR] 5.07, 95% CI 2.69-9.58; p<0.001. The overall non-adjusted patient survival was around 100%, 95% and less than 20% at 1, 4 and 25 years respectively basing on the Kaplan-Meier analysis. The group undergoing renal transplantation had the best survival rate. CONCLUSION: peritonitis remains the most common complication as well as the most provider of technique failure and patient´s transfer to hemodialysis. The technique survival was better in case of absence of peritonitis. However, our series showed the superiority of hemodialysis over PD in terms of overall patient survival.

Hemophagocytic Syndrome in a Pregnant Renal Transplant Recipient Associated With Cytomegalovirus Infection.

Hemophagocytic syndrome is a disorder of the mononuclear phagocytic system resulting in uncontrolled hemophagocytosis and cytokine overproduction. We report the first case of hemophagocytic syndrome, which occurred in a pregnantfemale patient 14 years after kidney transplant who displayed an atypical presentation and who had septic shock following cytomegalovirus infection. The patient, a-39-year-old woman at 27 weeks gestation with end-stage renal disease of unknown etiology, was admitted 14 years after living-donor kidney transplant (donor was her father) with high-grade fever, cough, and pancytopenia. Her immunosuppressant regimen included tacrolimus, azathioprine, and prednisone. Initially, she was hospitalized in the intensive care unit for septic shock without an identifiable focus of infection. She received intravenous broad-spectrum antibiotics before being transferred to our department following optimization of her hemodynamic status. Hemophagocytic syndrome was suspected, and bone marrow aspirate was performed, revealing macrophages with hemophagocytic activity. We confirmed the diagnosis of hemophagocytic syndrome given the presence of more than 5 criteria. We extensively investigated the underlying cause of hemophagocytic syndrome, and we diagnosed cytomegalovirus-induced hemophagocytic syndrome in a pregnant patient receiving immunosuppressive therapy after kidney transplantation. She was treated with corticosteroids and intravenous immunoglobulin. At 31 weeks gestation, she underwent a cesarean section; the baby developed newborn respiratory distress syndrome and died despite adequate resuscitation. We administered ganciclovir for 15 days following an increased cytomegalovirus viral load after delivery, leading to complete recovery.To date, optimal therapeutic and diagnostic guidelines for pregnancy-related hemophagocytic syndrome in female kidney transplant recipients are not well defined, and both patient and allograft survival rates remain low.

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 patient's 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.

One year course of oral sulodexide in the management of diabetic nephropathy.

BACKGROUND: Diabetic nephropathy is a multifactorial diabetic complication whose long-term consequences involve chronic renal insufficiency and increased rate of cardiovascular death. Besides oxidative stress, and hemodynamic changes, glycosaminoglycans (GAGs) are an additional component implicated in the onset of glomerular abnormalities. GAG replacement therapy was envisaged in the nineties for the treatment of diabetic nephropathy and sulodexide is the most extensively investigated GAG to reduce albuminuria in diabetic patients. METHODS: In this study we have evaluated the effect of a long-term course of oral sulodexide at a moderate dosage in the treatment of patients affected by diabetic nephropathy. Thirty patients with type 1 and 2 diabetes mellitus (DM) have been treated with 50 mg/ daily oral sulodexide for 12 months while thirty matched diabetic patients constituted the control group. All the patients attended monthly visits and controls of biochemical and metabolic parameters. RESULTS: At 12 months albuminuria was greatly reduced in patients treated with sulodexide and increased in the control group (260% and +29% vs baseline, respectively; p = 0.0001). The drug appeared active in both type 1 and type 2 diabetes and in both micro- and macroalbuminuric patients. No change in metabolic control and no systemic side effects were reported. CONCLUSIONS: In our diabetic patients sulodexide therapy has been proven to greatly reduce albuminuria, and to have the potential to delay progression from incipient to overt nephropathy.

[Twin pregnancy after renal transplantation: first case reported in Tunisia]. / La grossesse gemellaire et la transplantation renale a propos d'une premiere observation Tunisienne.

Women with end-stage renal disease or on regular dialysis have low fertility. Renal transplantation restores not only normal renal and endocrine functions but also the reproductive function as well and this conception becomes possible. Pregnancy in transplanted women is at higher risk and necessitates a multidisciplinary follow up. We report the course and out come of two successful pregnancies, the second was the first case of twin pregnancy in Tunisia in a transplanted woman. Our patient is 35 years old had a chronic renal insufficiency, secondary to interstitial nephropathy. After six years of hemodialysis, she had received a renal graft from a living donor (his brother). A double drug immunosuppression was given (Prednisolone - Azathioprine). Two years later, she became pregnant and delivered a normal baby at term, and one year later she had a twin pregnancy that ended successfully and delivered by caesarian section a two babies with different sex. Pregnancy after renal transplantion must be considered as a risk factor for any subsquent pregnancy, and the risk nicreases in case of twin pregnancy.

Ochratoxin A and human chronic nephropathy in Tunisia: is the situation endemic?

Ochratoxin A (OTA) is a nephrotoxic mycotoxin that is being increasingly considered as the main causal agent of Balkan endemic nephropathy (BEN), a fatal kidney disease associated with the end stage of urothelial tumours. However, despite the considerable amount of data, it is still controversial whether OTA plays a causative or only a subordinate role in the induction of this human nephropathy. Tunisia for years had to confront a very similar human nephropathy, which is tentatively called chronic interstitial nephropathy of unknown cause. This study tends firstly to consolidate the suspected link between this Tunisian chronic interstitial nephropathy (CIN) of unknown cause and the presence of OTA in the blood and food of such patients, and second to enlighten the endemic character of this particular nephropathy. Therefore, in four consecutive inquiries, performed within the period 1991-2000, blood and food OTA contaminations were assayed and compared for 954 nephropathy patients and 205 healthy subjects from the Tunisian general population. This survey was also designed to show that, although the whole population is likely to be exposed to OTA, specific people living in conditions showing similarities with the Balkans do have a kidney disease apparently linked to ochratoxin in food. The results showed that the highest incidences were found in patients with CIN of unknown cause. Indeed, the percentages of OTA-positive samples ranged from 93% to 100%, whereas it was only from 62% to 82% in healthy subjects. Mean OTA concentrations were also higher in patients with CIN of unknown cause than in controls (44.4 +/- 19 microg/L to 55.6 +/- 19 microg/L as opposed to 1.22 +/- 1.2 microg/L to 3.35 +/- 2.32 microg/L, respectively). This study emphasizes further the implication of OTA on this particular human nephropathy and underlines the probable causative role of OTA in the onset of this disease. It is important to note that the highest levels of food OTA contamination were found in the group presenting with CIN of unknown cause, indicating that, similar to the case in the Balkans, people are exposed to OTA essentially by their food.

Angiogenic activity in the sera of patients with post-kidney transplant erythrocytosis.

Post-kidney transplant erythrocytosis (PTE) is one of the hematological complications in the renal transplant patients. While its pathogenesis still remains to be elucidated completely, a number of therapies are available for the management of PTE. The aim of this prospective study was to investigate whether angiogenesis may be involved in the pathogenesis of post-transplant erythrocytosis by comparing its level with those of different classes of erythrocytosis [polycythemia vera (PV), idiopathic erythrocytosis and secondary erythrocytosis]. The angiogenic activity was evaluated by the assessment of the serum vascular endothelial growth factor (VEGF) levels, as one of circulating angiogenic factor, using a standardized enzyme-linked immunosorbent assay commercial kit in 13 PTE (2 F/11 M), in 75 untreated erythrocytosis non-transplant patients and in 21 healthy subjects controls. The results indicated that VEGF was overproduced in advanced and untreated PV patients and to a lesser degree in idiopathic erythrocytosis thus confirming an increased angiogenic activity. However, there is no evidence of increased angiogenesis in PTE and in secondary erythrocytosis. The absence of angiogenesis in PTE and its presence in PV is another argument that the pathogenesis of these two entities is different.

Cutaneous alternariosis in a renal transplant recipient.

Alternariosis is a fungal infection that is usually described in immunocompromised patients. We report a case of cutaneous alternariosis in a renal transplant recipient caused by Alternaria tenuissima. The diagnosis was supported by histopathologic (ie, yeastlike cells, filamentous structures) and mycologic findings from a cutaneous biopsy. Cutaneous lesions regressed 1 month following a decrease in the dosage of immunosuppressive therapy. The patient also was treated with intravenous amphotericin B followed by oral fluconazole without improvement. Cryotherapy remarkably accelerated healing of the lesions.

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-AUC(0-12 hours) 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 AUC(0-12 hours) 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 AUC(0-12). We analyzed all the developed models for their ability to estimate the MPA-AUC(0-12 hours). The best multilinear regression model for predicting the full MPA-AUC(0-12 hours) 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-AUC(0-12 hours) estimation.

[Post-infectious glomerulonephritis: unusual etiology of postpartum acute renal failure]. / La glomérulonéphrite aiguë postinfectieuse : une cause inhabituelle d'insuffisance rénale aiguë du post-partum.

Severe pre-eclampsia and acute tubular necrosis due to hemorrhagic shock are the major causes of postpartum acute renal failure. Cortical necrosis and haemolytic uraemic syndrome are less frequently. Post-infectious glomerulonephritis as a cause of postpartum acute glomerular disease and renal failure has been rarely reported. We report a patient with postpartum acute glomerulonephritis who presented nephritic syndrome, the diagnosis of which was confirmed by renal biopsy.

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.

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.

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 patient's 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.