Introduction. Extracellular sodium (Na+) concentration is maintained within a tight physiological range due to hormonal control, that mainly modulates thirst, Na+ and water renal excretion. Extra-renal regulation of Na+ and water homeostasis is only partially understood. Recently it has been debated whether the osmotically inactive Na+ storage is fixed or variable. Methods. In the present study, fourteen End-Stage Renal Disease (ESRD) patients treated by chronic hemodialysis underwent by accident to a sharp increase in plasmatic calcium (Ca+2) levels due to the failure of the water control system, leading to the so-called hard water syndrome. The levels of plasmatic Ca+2 after 1 hr of hemodialysis were correlated with urea, Na+, potassium (K+) and creatinine levels. Eleven ESRD patients treated with hemodialysis under similar conditions were used as controls. Results. The hard water syndrome resulted in hypercalcemia, while mean plasma levels of Na+, K+ and urea were not different compared to controls. Plasma creatinine levels were slightly but significantly higher that control. A correlation analysis on the measured variables has showed a positive correlation between plasma Ca+2 and Na+ levels (Pearson=0.428, p=0.032), and the absence of any correlation with K+, creatinine and urea concentration. Conclusions. Our study suggests that acute changes in plasmatic Ca+2 levels may affect Na+ concentration in the absence of renal function; it is possible that hypercalcemia may trigger Na+ release from the osmotically inactive storage. These data further support previous observations on the interplay of sodium and calcium at extrarenal sites.
Harun Akar, Emin Taskiran, Dilek Taskiran and Oytun Erbas
Diabetes is a rapidly growing problem of the community health. The resulting morbidity and mortality are responsible for the complications of diabetes. Nephropathy caused by diabetes often causes serious morbidity and mortality. In this review, we discuss the current approaches to prevent diabetic nephropathy based on the available literature evidence.
Nikolina Basic-Jukic, Lea Katalinic, Marijana Coric, Monika Kocman, Branimir Krtalic and Petar Kes
Amiodarone is a potent inhibitor of CYP3A4 and can increase serum concentrations of drugs that are substrates of this enzyme system. Immunosuppressive drugs are also metabolized through the cytochrome metabolic pathway what may lead to important drug-drug interactions. A 60-year-old female received her second allograft from the deceased donor and was treated with tacrolimus, mycophenolate mofetil and steroids. Amiodarone was introduced for treatment of paroxysmal atrial fibrillation four days after the transplantation. One month after the discharge she was readmitted to hospital for evaluation of the creeping creatinine. Biopsy showed borderline acute rejection. She received 3 boluses of 6- methilprednisolone but creatinine continued to rise. Repeated biopsy was without signs of rejection with mild interstitial fibrosis/tubular atrophy, mild global glomerulosclerosis and moderate arterial sclerosis. However, tubular vacuolization was prominent. After careful revision of her therapy we decided to replace amiodarone with sotalol. One week later her creatinine fell from 350 to 220 μmol/l and remained stable. This case illustrates possible amiodarone nephrotoxicity in a renal transplant recipient. We suggest that patients who need amiodarone in combination with tacrolimus be closely monitored by both cardiologists and nephrologists, with frequent determinations of tacrolimus trough levels and serum creatinine measurements.
Ingrid Prkacin, Petra Vrdoljak, Gordana Cavric, Damir Vazanic, Petra Pervan and Visnja-Nesek Adam
Studies have documented independent contribution of sympathetic activation to the cardiovascular disease continuum. Hypertension is one of the leading modifiable factors. Most if not all the benefit of antihypertensive treatment depends on blood pressure lowering, regardless how it is obtained. Resistant hypertension is defined as blood pressure that remains uncontrolled in spite of the concurrent use of three antihypertensive drugs of different classes. Ideally, one of the three drugs should be a diuretic, and all drugs should be prescribed at optimal dose amounts. Poor adherence to antihypertensive therapy, undiscovered secondary causes (e.g. obstructive sleep apnea, primary aldosteronism, renal artery stenosis), and lifestyle factors (e.g. obesity, excessive sodium intake, heavy alcohol intake, various drug interactions) are the most common causes of resistant hypertension. Cardio(reno)vascular morbidity and mortality are significantly higher in resistant hypertensive than in general hypertensive population, as such patients are typically presented with a long-standing history of poorly controlled hypertension. Early diagnosis and treatment is needed to avoid further end-organ damage to prevent cardiorenovascular remodeling. Treatment strategy includes lifestyle changes, adding a mineralocorticoid receptor antagonist, treatment adherence in cardiovascular prevention and, in case of failure to control blood pressure, renal sympathetic denervation or baroreceptor activation therapy. The comparative outcomes in resistant hypertension deserve better understanding. In this review, the most current approaches to resistant hypertension and cardiovascular risk based on the available literature evidence will be discussed.
Andac Komac, Elif Gram, Feray Gulec and Harun Akar
A 21-year-old female patient with abdominal pain, vomiting and constipation was admitted to the hospital with the possible diagnosis of diabetic ketoacidosis. Due to increased abdominal pain and constipation the patient underwent a surgery with the diagnosis of ileus. However, no pathological findings were found in the abdominal organs apart from serous fluid in the abdominal cavity. The patient became hypertensive, tachycardic and had an episode of seizures postoperatively. Neurological manifestations with unexplained abdominal pain indicated a diagnosis of acute intermittent porphyria (AIP). Acute intermittent porphyria diagnosis is based on elevated urinary δ-aminolevulinic acid (ALA) and porphobilinogen (PBG) levels as well as hydroxymethylbilane synthase (HMBS) IVS13-2 A>G heterozygous mutation. Familial Mediterranean Fever (FMF) gene mutations were not confirmed. Porphyria should be considered in the differential diagnosis of patients with recurrent abdominal pain, neurological symptoms and lack of FMF gene polymorphism.
To evaluate the clinical outcomes in patients with cancer of an unknown primary site (CUP), who were treated by gastrointestinal oncologists.
We retrospectively studied 29 patients with CUP who were presented at the Department of Gastroenterology, Kitasato University Hospital from October 2005 to October 2013, and were treated by the gastrointestinal oncologists. The patients were divided into two groups, namely chemotherapy group and symptomatic therapy group, and the clinical characteristics and survival times were compared. The clinical course was studied according to the histologic type (adenocarcinoma or non-adenocarcinoma), prognostic subset (favorable or unfavorable), and the presence or absence of chemotherapy.
The chemotherapy group comprised 19 patients, and the symptomatic therapy group comprised 10 patients. The median survival time was 11 months in the chemotherapy group and 3 months in the symptomatic therapy group. Twenty-two patients had adenocarcinoma, and 7 had non-adenocarcinoma. Of the 22 patients with adenocarcinoma, 2 belonged to the favorable prognostic subset and received chemotherapy. One of these patients died of cancer at 47 months, and the other was alive and disease free at 58 months. Among the 20 patients with adenocarcinoma in the unfavorable prognostic subset, 16 received chemotherapy and had a median survival of 16 months. Seven (44%) of these patients survived for at least 21 months, and 3 patients who could receive 3 or more regimens survived for at least 46 months.
It might be appropriate for gastrointestinal oncologists to treat CUP on the basis of clinical experience, depending on the situation.
Ayman Geddawy, Yasmine F. Ibrahim, Nabil M. Elbahie and Mohammad A. Ibrahim
Chronic hepatitis C virus (HCV) infection is a leading cause of chronic liver disease. The introduction of direct acting antiviral agents (DAAs) for its treatment represents a major advance in terms of sustained virologic response (SVR) rates and adverse effect profiles. Mechanistically, DAAs inhibit specific HCV non-structural proteins (NS) that are vital for its replication. Boceprevir, telaprevir, simeprevir, asunaprevir, grazoprevir and paritaprevir are NS3/4A inhibitors. Ombitasvir, ledipasvir, daclatasvir, elbasvir and velpatasvir are NS5A inhibitors. Sofosbuvir and dasabuvir are NS5B inhibitors. Currently, a combination of two or more DAAs is the corner stone for the treatment of HCV infection. However, the success of DAA therapy is facing several challenges, including the potential of drug-drug interactions and resistant variance. Moreover, the shortage of relevant clinical pharmacological data and drug interaction regarding DAA is a clinical concern. The present review discusses the clinical pharmacology of DAAs with special emphasis on drug-drug interaction.
Rafael Torres-Valadez, Sonia Roman, Alexis Jose-Abrego, Maricruz Sepulveda-Villegas, Claudia Ojeda-Granados, Ingrid Rivera-Iñiguez and Arturo Panduro
Background and Objective
Liver cirrhosis is usually detected at the later stages of disease. This study is aimed to detect liver damage in patients with chronic liver disease using transitional elastography (TE) and to assess the biochemical parameters associated with liver damage.
In 578 patients, chronic liver disease based on etiology was diagnosed by clinical and laboratory tests. Liver damage was evaluated with TE (FibroScan®), while its association with biochemical parameters was performed using the logistic regression tests.
Overall, the main etiologies of liver damage were hepatitis C virus (HCV) (37%), alcoholic liver disease (ALD) (33%) and non-alcoholic steatohepatitis (NASH) (26%). Patients were 40 to 50 years of age. ALD and hepatitis B prevailed in men, whereas HCV and NASH in women. The stages of fibrosis were F0 (n = 121, 21%), F1 (n = 122, 21%), F2 (n = 58, 10%), F3 (n = 46, 8%) and F4 (n = 87, 15%). In patients with liver cirrhosis, ALD (n = 96/217, 45%), HCV (n = 94/217, 43%) and NASH (n = 21/217, 10%) were the leading etiologies. Platelets count (OR=3.31, 95%CI 1.61-6.78), glucose (OR=3.07, 95%CI 1.50-6.26), gamma-glutamyl-transferase (OR=3.60, 95%CI 1.79-7.25), albumin (OR=3.89, 95%CI 1.61-9.36), and total bilirubin (OR=3.93, 95%CI 1.41-10.91) were associated to advanced stages of fibrosis (F3-F4) regardless of etiology. The concordance and positive predictive values of these parameters were higher as compared to other scores.
Asymptomatic liver disease due to HCV, ALD and NASH prevailed in young adults. Advanced liver damage assessed by TE was associated with five biochemical parameters. In conjunction, both methodologies may be useful for the early detection of fibrosis and cirrhosis in Latin America.