Plasma Calcium Concentration Modifies the Blood Sodium During Hemodialysis: Lessons from Hard Water Syndrome

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.

Acute Peritonitis Caused by Propionibacterium Acnes in a Peritoneal Dialysis Patient

Propionibacterium acnes is a gram-positive human skin commensal that is involved in the pathogenesis of acne and prefers anaerobic growth conditions. It has been considered as a low virulence pathogen in different clinical conditions. We present the case of acute peritonitis caused by Propionibacterium acnes in a peritoneal dialysis patient.

Renal Allograft Dysfunction Possibly Caused by Amiodarone Nephrotoxicity: a Case-Report

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.

Effect of Melatonin Administration on Prevention of Contrast- Induced Nephropathy following Coronary Angiography

Introduction. Contrast-induced-nephropathy (CIN) is a common complication during angiography that may lead to long-term complications. This study was conducted to investigate the effect of melatonin administration on prevention of CIN in patients who underwent coronary angiography with intra-arterial contrast agents. Method. This is single-blind randomized clinical trial that was performed over 100 patients with indication for coronary angiography. Patients are randomly assigned to two equal groups. All patients in the 12 hours before and 12 hours after the procedure, were received adequate intravenous hydration with normal saline and for the intervention group in addition to hydration, the day before angiography and immediately after angiography 3 mg melatonin was administered. For all patients, serum level of creatinine (Cr), blood urea nitrogen (BUN) and glomerular filtration rate (GFR) before and 48 hours after the procedure were measured. Data were analyzed using SPSS 18 software. Results. Totally 100 participants with the mean age of 64.0±8.2 years were enrolled (63% male). There was no significant difference between intervention and control groups in baseline and demographic characteristics (P> 0.05). Although the mean serum Cr and BUN level increased in both groups, but the mean Cr, BUN and GFR before and after coronary angiography was not statistically significant. Based on the definition of CIN in the current study, 3(6%) patients from intervention group and 2(4%) patients from control group were affected by CIN (P = 0.243). Conclusion. It is likely that, melatonin administration has no significant effect on prevention of CIN following coronary angiography.

Resistant Hypertension and Cardiorenovascular Risk

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.

Secret Underlying Unexplained Abdominal Pain, Neurological Symptoms and Intermittent Hypertension: Acute Intermittent Porphyria

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.

Evaluation of Clinical and Pathological Characteristics of Patients with IgA Nephropathy Based on Oxford Classification System: Should Crescents be Included?

Introduction. None of the classification systems in immunoglobulin A (IgA) nephropathy has been widely agreed or implemented by clinicians or pathologists. In order to meet this need, "Oxford Classification System", which is highly reproducible and predictive for clinical course, was developed in 2009. In the present study, we investigated clinical and pathological characteristics of patients with IgA nephropathy based on current classification and the predictivity of crescent presence on prognosis. Methods. The study comprised 40 patients with diagnosis of primary IgA nephropathy on renal biopsy. The biopsy findings and follow-up parameters of patients were retrospectively re-evaluated. Pathological findings were examined based on the Oxford classification system. The presence of crescent formation in the specimens was noted. Results. The presence of crescent formation was predictive of poor prognosis regarding the glomerular filtration rate (eGFR), the level of proteinuria, and mean arterial pressure (MAP). Conclusion: Considering the importance of crescent formation in prediction of the clinical course and need for immunosuppressive therapy, it is suggested that crescent presence can be included in this classification system.

Five Years of Renal Transplantations in Montenegro: Results and Challenges

First renal transplantation in Montenegro was performed on September 25th, 2012. Since then, 32 transplantations have been performed. Only one was from deceased donor, the remaining were from living donors. 40.4% of all patients with end-stage renal disease currently live with the functioning renal allograft (190 patients on dialysis, 129 transplanted patients). There are 32 patients on the waiting list. Further efforts will be focused on development of the deceased donor program and introduction of the AB0 incompatible renal transplantations.

Monitoring of Renal Allograft Function with Different Equations: What are the Differences?

Introduction. Monitoring of graft function by creatinine concentrations in serum and calculated glomerular filtration rate (GFR) is recommended after kidney transplantation. KDIGO recommendations on the treatment of transplant patients advocate usage of one of the existing mathematical equations based on serum creatinine. We compared clinical application of three equations based on serum creatinine in monitoring the function of transplanted kidney. Methods. A total number of 55 adult patients who received their first renal allograft from living donors at our transplant center in between 2011-2014 were included into the study. Renal allograft GFR was estimated by the Cockroft-Gault, Nankivell and MDRD formula, and correlated with clinical parameters of donors and recipients. Results. The mean age of recipients was 35.7±9.5 (range 16-58), and the mean age of donors was 55.5±9.0 (34- 77) years. Out of this group of 55 transplant patients, 50(90.91%) were on hemodialysis (HD) prior to transplantation. HD treatment was shorter than 24 months in 37(74%) transplant patients. The calculated GFR with MDRD equation showed the highest mean value at 6 and 12 months (68.46±21.5; 68.39±24.6, respectively) and the lowest at 48 months (42.79±12.9). According to the Cockroft&Gault equation GFR was the highest at 12 months (88.91±24.9) and the lowest at 48 months (66.53±18.1 ml/min). The highest mean level (80.53±17.7) of the calculated GFR with the Nankivell equation was obtained at 12 months and the lowest (67.81±16.7 ml/min) at 48 months. The values of Pearson’s correlation coefficient between the calculated GFR and the MDRD at 2 years after transplantation according to donor’s age of r=-0.3224, correlation between GFR and the Cockfroft & Gault at 6 and 12 months and donor’s age (r=-0.2735 and r=-0.2818), and correlation between GFR and the Nankivell at 2 years and donor’s age of r=-0.2681, suggested a conclusion that calculated GFR was lower in recipients who had an older donors. Conclusion. Our analysis showed difference in the calculated GFR with different equations at the same time points. Using one mathematical equation during the total post-transplantation period would be a recommended method in order to eliminate the discrepancy in determining the stage of kidney failure.

Influence of Hemodialysis Treatment on Biochemical Markers of Bone Disease

Introduction. Bone disease is a chronic complication of chronic kidney disease and major clinical problem in hemodialysis (HD) patients. The aim of our study was to assess the influence of treatment longevity on biochemical parameters of mineral and bone metabolism in HD patients, and to identify the most important parameters. Methods. The research was observational and retrospective, involved 70 patients, mean age 58.69±12.54, divided into groups in respect to the duration of dialysis treatment (Group I-5 years, Group II-5-10 years and Group III-over 10 years). Results. Serum phosphorus was increased, but the values tend to increase along with dialysis duration - (Group I: 1.93±0.45; Group II: 1.97±0.50; Group III: 2.01±0.37; p>0,05). Calcium values were also not significantly increased based on the duration of treatment [Group I: 2.3 (2.2-2.41); Group II: 2.46 (2.15-2.6), Group III: 2.35 (2.10-2.52)]. Dialysis and PTH correlated positively in the first group of patients (Rho=0.470, p=0.013). The values of calcium and alkaline phosphatase correlated positively in all patients (Rho=0.351, p=0.003). PTH was significantly higher in the second and third compared to the first group (p=0.009 and p=0.038, respectively), and there was no significant difference between the second and the third group. Interestingly, parathyroidectomized patients had higher PTH values compared to those without parathyroidectomy (557 vs. 359 pg/ml). Conclusion. The most reliable marker for clinical monitoring of bone disease in dialysis patients is PTH. The values of calcium and phosphorus are highly variable and not reliable parameters for bone disease follow-up.