Use of CFTR Modulators for Cystic Fibrosis in a Patient with Liver Transplant and ESRD on Hemodialysis.

Cystic fibrosis is an autosomal recessive disorder caused by mutations of the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The most recent therapeutic approach to cystic fibrosis aims to correct structural and functional abnormalities of CFTR protein. CFTR modulators including ivacaftor-tezacaftor-elexacaftor are used in patients with F508del mutation, with clinical improvement. To date, there are no experiences of CFTR modulator therapy in cystic fibrosis patients with organ transplantation and severe renal impairment. We report the case of a patient diagnosed with cystic fibrosis with F508del mutation, who underwent liver transplantation at the age of 19 and started hemodialysis at the age of 24 due to end-stage renal disease secondary to membranous glomerulonephritis. She was treated with Kaftrio (ivacaftor-tezacaftor-elexacaftor) with clinical benefits on appetite, improvement of body mass index, and reduction of pulmonary exacerbations. A reduction of dosage to 75% of the standard dose was required due to alterations of the liver function. Conclusions. Use of CFTR modulators in patient with cystic fibrosis, liver transplant and end-stage renal disease could be considered safe but a clinical and laboratoristic monitoring of hepatic function is needed.

[Acute kidney injury in severely burned patient: prevention and treatment].

Acute Kidney Injury (AKI) is associated with a great increase in morbidity and mortality in severely burned patients and occurs as a complication in more than 25% of these cases. The onset of ARF may be early or late. Early AKI depends mainly on reduced cardiac output resulting from fluid loss, rhabdomyolysis, or hemolysis. Late AKI, instead, is usually a consequence of sepsis and is often associated with multiorgan failure (MOF). The first sign of AKI is the contraction of diuresis despite adequate volemic filling, which is followed by elevation of serum urea and creatinine. Fluid therapy is the main treatment in the burned victim: in the first few hours after injury, it aims to avoid hypovolemic shock and the possible related MOF, while later it becomes the cornerstone of treatment, besides antibiotic therapy in the case of sepsis onset. Particular care must also be taken in the choice of administered drugs in order to avoid possible nephrotoxic damage in addition to burning injury. Hemodialytic renal replacement therapy is used both for water balance management in patients requiring massive fluid infusions and for blood purification purposes to control the metabolic state, acid-base balance, and electrolytes abnormality. Our team has been collaborating for over 25 years in the management of severely burned patients admitted to the Centro Grandi Ustionati at the Bufalini Hospital in Cesena.

Too bad to be true: pseudo-AKI due to traumatic bladder rupture.

Acute Kidney Injury (AKI) is described as a rapid decline in Glomerular Filtration Rate (GFR), reflected by an increase in serum creatinine (SCr) and/or contraction of diuresis. The traditional paradigm considers pre-renal, renal and post-renal causes of AKI. However, there are some settings in which an elevated SCr does not reflect a real decline in GFR. Here we describe the case of a pseudo-AKI, consequence of a massive intraperitoneal urinary leakage due to a traumatic bladder rupture. Besides the pathophysiological considerations, we want to raise awareness about this condition, especially in relation to patients presenting with oliguria, hematuria, apparent AKI, abdominal pain and ascites, particularly after trauma; we do this not only to prevent late diagnosis complications, but also to avoid costly and risky overtreatment.

Association of Extreme Nocturnal Dipping With Cardiovascular Events Strongly Depends on Age.

Whether extreme dipping is associated with cardiovascular events (CVE) is unclear. The present study was conducted to test the hypothesis that the prognostic role of extreme dipping varies as a function of age. The analysis was performed in 10 868 participants (53% men) aged 53±15 (mean±SD) years enrolled in 8 prospective studies. Using the ambulatory systolic blood pressure nocturnal decline, we identified 4 groups: dippers (>10%-20%), nondippers (>0%-10%), reverse dippers (≤0%), and extreme dippers (>20%). The association between dipping category and CVE was estimated as a function of age using Cox models adjusted for sex, average 24-hour systolic blood pressure, and traditional risk factors. During a median follow-up of 5.7 years, there were a total of 829 CVE (168 fatal). For extreme dippers, no increase in risk of CVE was observed among the participants <70 years (hazard ratio, 0.99 [95% CI, 0.73-1.34]; P=0.93) compared with dippers. In contrast, among the participants ≥70 years, there was a significant increase in risk (hazard ratio, 1.88 [95% CI, 1.14-3.11]; P=0.013). Among the octogenarians, the hazard ratio (95% CI) for CVE were 2.34 (1.12-4.93) for nondippers (P=0.024), 3.91 (1.75-8.73) for reverse dippers (P=0.001), and 4.12 (1.64-10.37) for extreme dippers (P=0.003) compared with dippers. These data show that extreme dipping is not associated with poorer outcome in people younger than 70 years. A U-shaped relationship between nocturnal blood pressure dipping and adverse outcome is present in subjects older than 70 years. In the octogenarian extreme dippers, the risk of CVEs was 4× higher than in the dippers and similar to that in the reverse dippers.

Amlodipine and celecoxib for treatment of hypertension and osteoarthritis pain.

INTRODUCTION: Osteoarthritis constitutes one of the leading causes of pain and disability worldwide with a significant impact on health-care costs. Patients with osteoarthritis are often affected by a number of cardiovascular comorbidities, including hypertension, which is present in about 40% of cases. Just recently, a single tablet combination of amlodipine besylate, a calcium channel blocker, and celecoxib, a nonsteroidal anti-inflammatory drug, indicated for patients for whom treatment with amlodipine for hypertension and celecoxib for osteoarthritis are appropriate, has been recently approved. Areas covered: We reviewed data from clinical studies that investigated safety and efficacy of the combination of amlodipine and celecoxib in hypertensive patients with osteoarthritis published before 31 August 2018. The literature search was conducted using research Methodology Filters. Expert commentary: The advantages of this single formulation over sequential administration include increased compliance, possibly reduced cost, and less likelihood of dosage-related issues. Moreover, this single tablet formulation combines the anti-inflammatory activity of the celecoxib with the systemic vasodilatation induced by the amlodipine. It is a promising treatment for patients with osteoarthritis and hypertension. Nevertheless, celecoxib may cause a variable degree of blood pressure increase and only a small clinical trial has been conducted before approval to assess interactions related to blood pressure effect between these two molecules.

PK/PD evaluation of fimasartan for the treatment of hypertension Current evidences and future perspectives.

INTRODUCTION: Fimasartan is the ninth and latest Angiotensin Receptor Blockers for the treatment of hypertension. Fimasartan is a derivative of losartan in which the imidazole ring has been replaced. It provides a selective type 1 angiotensin II receptor antagonist effect with noncompetitive, in surmountable binding. Fimasartan is rapidly absorbed following oral administration with an oral bioavailability of 18.6 ± 7.2%. Fimasartan is relatively stable in terms of metabolism and more than 90% of circulating fimasartan moieties in the plasma are in the parent form; fecal elimination and biliary excretion are the predominant elimination pathways of fimasartan. Areas covered: We reviewed data from clinical trials that investigated safety and efficacy of fimasartan in hypertension. Expert opinion: Fimasartan proved good efficacy in blood pressure reduction. In large clinical studies,fimasartan showed an excellent safety profile and when combined with hydrochlorothiazide oram lodipine, it showed a better effect on controlling blood pressure than monotherapy. Fimasartan 60-120 mg once daily has also shown an antihypertensive effect over 24-h. Moreover, preclinical studies demonstrated organ-protecting effects of fimasartan. These results make fimasartan an attractive candidate for the treatment of hypertension. However, it remains to test the benefit of using fimasartan on clinical outcomes.