Optimization of therapeutic drug monitoring of vancomycin in patients with chronic hemodialysis
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PURPOSE: To validate a simplified vancomycin monitoring algorithm in patients on chronic hemodialysis who required intravenous vancomycin for at least 3 weeks. MATERIALS AND METHODS: In this prospective study, all hemodialysis patients who were admitted between April 1, 2013, and March 31, 2015, in our unit for suspected or confirmed methicillin-resistant Staphylococcus aureus infection that required vancomycin were enrolled. All patients were categorized into two groups. In group 1 (standard vancomycin dosing algorithm), the maintenance doses of vancomycin were adjusted according to the pre-hemodialysis vancomycin concentrations determined before each hemodialysis session. In group 2 (simplified vancomycin dosing algorithm), pre-dialysis vancomycin trough levels were taken before the 2nd and the 6th session of hemodialysis. Maintenance doses were adjusted according to the residual concentrations of vancomycin. RESULTS: A total of 101 blood samples were collected, the average plasma concentration of vancomycin was 13.1 ± 3.8 µg/mL. 64 (63.4%) levels fell out of the therapeutic range. Seven (6.9%) of these exceeded the therapeutic range and 30 (29.7%) were lower. After the loading dose, the average plasma concentration was 11.2 ± 3.4 µg/mL. There were no statistically significant differences between the two groups with respect to the average plasma concentration of vancomycin and the proportion of vancomycin trough levels in the target range. CONCLUSION: The vancomycin dosing algorithm using limited concentration monitoring for hemodialysis patients achieved drug concentrations comparable to those found with more frequent monitoring and resulted in significant cost savings.
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[The role of neutrophils in the formation of peritoneal adhesions]. / Rôle des polynucléaires neutrophiles dans la formation des adhérences post opératoires.

BACKGROUND: The use of antibiotics during peritonitis appears to decrease the formation of postoperative intra peritoneal adhesions and reduce their severity. The effect of this antibiotic is still controversial. AIM: To study the relationship between the decrease postoperative adhesions induced by rifamycin, and the number of neutrophils and the number of intraperitoneal bacteria. METHODS: This is an experimental prospective, randomized singleblind study performed on adult male rats. The product used for the peritoneal lavage was rifamycin s. The animals were randomized into three groups: Group S: intra peritoneal lavage with saline to 9%, R25 Group: intra peritoneal lavage with rifamycin at a dose of 25 mg / kg group and 12.5 R: intra peritoneal lavage with rifamycin at a dose of 12.5 mg / kg. Adhesions score was evaluated according to Zulkhé by the same operator. RESULTS: The adhesion score was significantly lower between groups S and R12.5 (p = 0.000) and group S and group R25 (P = 0.01). However, the difference was not significant between the two groups R 25 and R12.5 compared to S group (p = 0.655). The number of bacteria between the time of caecal resection (before peritoneal lavage) and the time of death or sacrifice was significantly decreased significantly in the groups R25, comparing the group S (p = 0.003). However, there is no significant difference between groups S and R12, 5 (p = 0.106). The number of neutrophils between the time of cecal resection (before peritoneal lavage) and the time of death or sacrifice decreased significantly in the groups R25 and R12, 5 in comparison to the group S. Between the group R25 and the S group, the difference is significant (p = 0.037) as well between the group R12, 5 and S (p = 0.026). However, there is no significant difference between the two groups R 25 and R12, 5 (p = 0.712). CONCLUSION: The action of rifamycin sodium on neutrophils seems to be independent of its antibacterial action. These findings deserve to be explored at the end to clarify the mechanism of neutropenia by intra peritoneal washing with rifamycin and the relationship between neutropenia and post-operative adhesions.

Chronic Kidney Disease, Hypokalemia, and Appendicular Mucocele in a 66-Year-Old Man.

Appendicular mucocele (AM) is a rare and potentially malignant entity linked to obstructive dilatation of the appendix with an intraluminal accumulation of mucoid material. Most AM is asymptomatic or simulates acute appendicitis. We report an exceptional case of AM discovered in the face of hypokalemia and aggravation of chronic kidney disease (CKD) without diarrhea in an old man. Investigations led to the diagnosis of AM in its malignant form complicated by gelatinous ascites. We retained mucinous hypersecretion as the cause of hypokalemia and acute renal failure. Aggressive surgery and intraperitoneal chemotherapy corrected hydroelectrolyte imbalance.

A novel disease-causing mutation in the Renin gene in a Tunisian family with autosomal dominant tubulointerstitial kidney disease.

Autosomal dominant tubulointerstitial kidney disease (ADTKD) is a rare group of disease that affect the tubules of the kidney. There are 4 known subtypes of ADTKD classified based on causative genes and clinical features. In our study, we aimed to identify the causative subtypes of ADTKD in a Tunisian ADTKD family (3 affected members), in whom standard nephrological diagnosis did not provide clear subtype of ADTKD, until genetic testing was performed. Sanger sequencing was performed for UMOD, HNF1ß and REN genes. Mutational analysis allowed us to detect a heterozygous mutation in the REN gene: c.1172C > G, (p.T391R) in exon 10. In silico analyses predicted that the novel likely pathogenic mutation affect protein stability and 3D structure. Our study highlights the importance of establishing a genetic diagnosis to identify the subtype of ADTKD for better patient care. To the best of our knowledge, we report here a first Tunisian ADTKD-REN family.

[Epidemiological profile of terminal chronic renal failure in the region of Sfax]. / Profil épidémiologique de l'insuffisance rénale chronique terminale dans la région de Sfax.

INTRODUCTION: Terminal chronic renal failure is a truly global public health problem. In 2011, the cost of management of patients on dialysis has surpassed 90 million dinars (37.000 euro) in Tunisia, nearly 5% of the overall health spending. A better knowledge of the epidemiological profile of terminal chronic renal failure contributes to the implementation and evaluation of health strategies aimed to improve prevention and disease management. This study aimed to describe the epidemiological profile of incident cases in the Sfax Governorate over the period of 10 years. METHODS: We conducted a descriptive retrospective study over the period from January 2003 to December 2012. The incident cases of terminal chronic renal failure in the Sfax Governorate were included in the study. RESULTS: The diagnosis of terminal chronic renal failure was made in 1708 cases: 957 men and 751 women (sex-ratio = 1.27). The average age was 58.4 years [10-100 years]. The study of the evolution of the average age during the study period showed a tendency to increase with positive correlation coefficient (0.749) and p = 0.006. The main causal nephropathy was diabetic nephropathy (21.5%), with a significant increase in its frequency from one year to the other (positive correlation coefficient (0.770) with p = 0.009). Hemodialysis was the dialysis technique of choice, performed in 96% of patients. CONCLUSION: A national registry is indispensable in order to better understand the epidemiological profile of terminal chronic renal failure in Tunisia and to improve its management.

Minimal change disease in horseshoe kidney.

The horseshoe kidney is a frequent urological birth defect. The most frequent complications are urinary tract infections, stones and hydronephrosis. The occurrence of glomerular disease in horseshoe kidney is rare. Therefore, we report the first case of minimal change disease occurring in a patient with horseshoe kidney in literature. A 22-year-old Caucasian man without personal or family medical history admitted to the pneumology department for a pulmonary artery embolism. In presence of a generalized oedema, a biological assessment was performed yielding intense nephrotic syndrome with urine protein excretion 22g/day. The abdominal ultrasound revealed a horseshoe kidney. Hence a scanno-guided kidney biopsy was taken yielding minimal change disease. High dose steroids were started, then gradually tapered with good response. Horseshoe kidney is the most common renal fusion anomaly, with a prevalence of 0.25% among the general population. The occurrence of glomerular nephropathy in horseshoe kidney has been reported in few cases. We report the first case of minimal change disease occurring in a patient with horseshoe kidney in literature. The mechanism of the association between the horseshoe kidney and these renal pathologies could not be explained in the previous reports. There is no literature data indicating a high rate of glomerulonephritis in horseshoe kidneys. The co-incidence of two renal diseases in this patient can be only a coincidence. The question that arises is whether this glomerulopathy is associated or not with this anatomical abnormality. Further studies are needed to answer this question.

A double mutation in AGXT gene in families with primary hyperoxaluria type 1.

Primary hyperoxaluria type 1 (PH1) is a severe autosomal recessive inherited disorder of glyoxylate metabolism caused by mutations in the AGXT gene on chromosome 2q37.3 that encodes the hepatic peroxisomal enzyme alanine:glyoxylate aminotransferase. These mutations are found throughout the entire gene and cause a wide spectrum of clinical severity. Rare in Europe, PH1 is responsible for 13% of the end stage renal failure in the Tunisian child. In the present work, we identified the double mutation c.32C>T (Pro11Leu) and c.731T>C (p.Ile244Thr) in AGXT gene in five unrelated Tunisian families with PH1 disease. Our results provide evidence regarding the potential involvement of c.32C>T, originally described as common polymorphism, on the resulting phenotype. We also reported an extreme intrafamilial heterogeneity in clinical presentation of PH1. Despite the same genetic background, the outcome of the affected members differs widely. The significant phenotypic heterogeneity observed within a same family, with a same genotype, suggests the existence of relevant modifier factors.