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.

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?

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.

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.

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.

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.

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.

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.

[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.

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.

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.

Indocyanine green angiography findings in patients with nonfamilial amyloidosis.

PURPOSE: The purpose of this study is to assess indocyanine green angiographic findings in patients with nonfamilial amyloidosis. METHODS: The method used was a prospective study including seven patients (14 eyes) with nonfamilial amyloidosis. All patients underwent detailed ophthalmic clinical examination, fundus photography, and indocyanine green angiography (ICGA). Fluorescein angiography (FA) was performed in four patients. RESULTS: Of the seven patients, four (57.1 %) were male. Mean age was 49.5 years. Six patients had renal amyloidosis and one patient had systemic amyloidosis. Mean best-corrected visual acuity was 20/25. Fundus and FA findings included cotton-wool spots (28.5 %), retinal hemorrhages (14.3 %), retinal pigment epithelial changes (21.4 %), serous retinal detachment (7.1 %), optic disk edema or staining (7.1 %), area of peripheral retinal capillary non-perfusion (7.1 %), disseminated peripheral punctiform hyperfluorescence (21.4 %), and subretinal pooling (7.1 %). Fundus examination results were unremarkable in eight eyes (57.1 %). ICGA showed abnormal findings in all eyes. These included diffuse or focal/multifocal choroidal vascular staining appearing at the late phase and prevailing in peripheral fundus (100 %), hyperfluorescent fleecy lesions appearing at the late phase and also prevailing in peripheral fundus (28.5 %), hypofluoresent areas of variable sizes (85.7 %), and pinpoints (71.4 %). CONCLUSIONS: Our results show that a subclinical, fairly typical choroidal involvement, detectable only by ICGA, is common in patients with nonfamilial amyloidosis. ICGA may be useful in better understanding the pathogenesis of amyloidosis choroidopathy and in establishing a diagnosis of amyloidosis in atypical or incomplete clinical presentations.

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.

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.