Relative risk for cardiovascular morbidity in hemodialysis patients regarding gene polymorphism for IL-10, IL-6, and TNF.

Uremia-related inflammation is prone to be a key factor to explain high cardiovascular morbidity in hemodialysis patients. Genetic susceptibility may be of importance, including IL-10, IL-6, and TNF. The aim was to analyze IL-10, IL-6, and TNF gene polymorphisms in a group of hemodialysis patients and to correlate the findings with cardiovascular morbidity. This study included 169 patients on regular hemodialysis at Zvezdara University Medical Center. Gene polymorphisms for IL-10, IL-6 and TNF were determined using PCR. These findings were correlated with the cardiovascular morbidity data from patient histories. Heterozygots for IL-10 gene showed significantly lower incidence of cardiovascular events (p = 0.05) and twice lower risk for development of myocardial infarction, but experienced twice higher risk for left ventricular hypertrophy. Regarding TNF gene polymorphism, patients with A allele had 1.5-fold higher risk for cerebrovascular accident and cardiovascular events and 2-fold higher risk for hypertension and peripheral vascular disease. Patients with G allele of IL-6 gene experienced 1.5-fold higher risks for cerebrovascular accident. We need studies with larger number of patients for definitive conclusion about the influence of gene polymorphisms on cardiovascular morbidity in hemodialysis patients and its importance in everyday clinical practice.

Effects of conventional versus biocompatible peritoneal dialysis solutions on peritoneal and systemic inflammation, malnutrition and atherosclerosis in CAPD patients.

BACKGROUND: Chronic inflammation, malnutrition and atherosclerosis (MIA syndrome) are important predictors of high mortality in continuous ambulatory peritoneal dialysis (CAPD) patients. We aimed to evaluate the effects of PD solutions (standard vs. biocompatible) on some parameters of MIA syndrome in patients undergoing CAPD. METHODS: 42 stable patients who were on CAPD at least 2.5 years participated in this cross-sectional study. Patients who had severe anemia (Hb < 10 g/l), immunomodulatory therapy, peritonitis or any inflammatory conditions for at least 3 months before the analysis, malignant disease and acute exacerbation of heart failure, were excluded. 21 (50%) patients were treated with standard PD solutions (CAPDP-1), while the remaining 21 (50% of patients) were treated with biocompatible PD solutions (neutral solutions with lower level of glucose degradation products and lower concentration of calcium, CAPDP-2). All patients underwent echocardiography and B-mode ultrasonography of common carotid arteries together with assessments of nutrition status and parameters of systemic and local inflammation. RESULTS: There were no significant differences between the groups concerning age, gender, underlying disease, residual renal function, peritoneal transport characteristics, comorbidity or therapy applied. Patients from group CAPDP-2 had a significantly lower serum level of hs-CRP (3.7 ± 2.6 mg/l vs. 6.3 ± 4.5 mg/l; p = 0.023) and significantly better nutritional status confirmed by mid-arm circumference (p = 0.015), mid-arm muscle circumference (p = 0.002) and subjective global assessment (14.28% of patients in CAPDP-2 vs. 71% of patients in CAPDP-1 were malnourished; p = 0.000). Group CAPD-2 had less frequent left ventricular hypertrophy (p = 0.039), thinner intima-media thickness (p = 0.005), smaller carotid narrowing (p = 0.000) and fewer calcified plaques of common carotide arteries (p = 0.003). No significant difference between the CAPDP groups was observed in serum and effluent levels of inflammatory cytokines (IL-1, IL-6 and TNF-α) and CA-125 effluent level. Logistic regression analysis did not confirm that biocompatibility of PD solutions was an independent predictor of any parameter of MIA syndrome. CONCLUSIONS: According to the present study and logistic regression analysis, the effect of biocompatible CAPD solutions on parameters of malnutrition, inflammation and atherosclerosis have to be confirmed by well-designed and controlled studies in a higher number of patients.

Isolated ventricular noncompaction in patients with chronic renal failure.

Isolated ventricular noncompaction is a rare congenital disorder characterized by the presence of numerous prominent trabeculations and deep intratrabecular recesses which communicate with the ventricular cavity. This disease has a very bad prognosis. Two cases of isolated ventricular noncompaction in patients with chronic renal failure have been described. The first case is a 65-year-old male, on regular hemodialysis for 3.5 years due to mesangioproliferative glomerulonephritis. He was symptomless regarding signs of congestive heart failure, angina pectoris, systemic embolization or arrhythmia. The second case is a patient with chronic renal failure (due to renal calculosis) admitted because of non-ST elevation acute myocardial infarction. In both cases echocardiography revealed an enlarged left ventricle, with extremely thickened walls with two layers: a thin, compacted myocardium on the epicardial side, and a thicker noncompaction endocardial layer. Ratio between noncompaction part of the wall and compaction part was 2.56 in the first and 4.94 in the second case. Blood flow from the left ventricular cavity into recesses was recorded with Color Doppler. Oral anticoagulation therapy was introduced in both of them. Holter ECG in the first patient revealed an intermittent right bandle branch block and in the second patient, premature ventricular contractions. Neurological examination findings were normal in both patients. Echocardiography of first-degree relatives was performed in the first case and it was normal in all 5 relatives. In the second case it was not performed due to technical reasons (relatives live abroad). Regular echocardiographic follow-up of all patients with chronic renal failure is necessary in order to diagnose cardiovascular comorbidities including this rare abnormality and its complications.

Unusual Listeria monocytogenes peritonitis in peritoneal dialysis patient with liver cirrhosis: a case report and review of literature.

Spontaneous Listeria peritonitis is well described in liver failure, but is uncommon in peritoneal dialysis patients. Atypical cases where peritonitis symptoms develop after systemic manifestations are rare and challenging for diagnostic. A 57-year-old peritoneal dialysis patient with history of ethylic cirrhosis was admitted after epileptic seizure. On admission, patient was soporous without signs of peritonitis and meningitis. Patient's peritoneal effluent was clear, with normal leukocytes. Cranial CT scan showed no abnormalities. Laboratory exams revealed positive inflammatory syndrome. Despite antibiotic therapy, next day, symptoms aggravated with coma development. Peritoneal effluent became cloudy and its leukocyte count rose up. Effluent microscopy revealed Gram-positive bacilli. Patient was started with intraperitoneal Vancomycin and Amikacin. Patient's clinical condition deteriorated with lethal outcome. Post-mortem analysis of effluent and blood culture showed growth of L. monocytogenes. Apart from idiopathic etiology, goat-milk curd, that patient had started consuming 10 days before admission, could theoretically be considered as possible infection vehicle. L. monocytogenes peritonitis in peritoneal dialysis patients is rare, but must be considered in immunocompromised or patients with concomitant liver failure, especially after Gram-positive bacilli identification in peritoneal effluent. In case of suspiscion of Listeria peritonitis, Ampicillin should be initiated, because bacteria often poorly respond to currently recommended empiric regimens.

Development of liquid chromatographic method for fosinoprilat determination in human plasma using microemulsion as eluent.

Fosinopril sodium presents a prodrug for the active angiotensin converting enzyme (ACE) inhibitor, fosinoprilat. The dual elimination of fosinoprilat by the liver and the kidney distinguishes fosinopril from other angiotensin converting enzyme inhibitors. Such ways of elimination are important for antihypertensive therapy of patients on haemodialysis. The paper presents development and evaluation of a new and sensitive liquid chromatographic (LC) method for the analysis of fosinoprilat in plasma obtained from patients on haemodialysis. A microemulsion system mixture as mobile phase has been used for the separation and analysis of fosinoprilat in plasma samples. The plasma samples were injected directly onto the HPLC system (Waters Breeze) after appropriate sample dilution with mobile phase. Separations were performed on the Bakerbond ENV 4.6 mm x 150 mm, 5 microm particle size column with UV detection at 220 nm. The flow rate was 1.00 mL min(-1). The mobile phase consisted of 1.0% (w/v) of diisopropyl ether, 2.0% (w/v) of sodium dodecyl sulphate (SDS), 6.0% (w/v) of n-propanol and 91% (w/v) of aqueous 25 mM di-sodium hydrogen phosphate, pH adjusted to 2.8 with 85% orthophosphoric acid. The developed method was then subjected to method validation according to the criteria stated in the FDA bioanalytical method validation guidance. The results for specificity, linearity, low limit of quantification (LLOQ), precision, accuracy and stability were within the accepted criteria. The unique approach applied in this paper makes possible the determination of fosinoprilat even in the presence of metabolites of other drugs, so the method can be used for obtaining the reliable results in a fast and simple way.

Fatal uremic leontiasis ossea in long-lasting uncontrolled hyperparathyroidism: a case report.

BACKGROUND: Leontiasis ossea is a rare medical condition, with characteristic overgrowth of the facial and cranial bones. Reports about this uremic complication are less frequently reported, probably due to better dialysis and better medical control of secondary hyperparathyroidism. DESCRIPTION OF CASE: We report the case of a 36-year-old female patient who had been treated with chronic hemodialysis and who developed secondary hyperparathyroidism. CONCLUSION: In noncompliant patients with uncontrolled secondary hyperparathyroidism uremic leontiasis may develop in which case the treatment is rarely successful or may even be contraindicated due to other comorbid conditions. Hippokratia 2015; 19 (3): 266-267.

Anemia in Balkan endemic nephropathy.

The severity of anemia in patients at different stages of the evolution of two tubulointerstitial nephropathies, Balkan endemic nephropathy and chronic pyelonephritis, was compared to clarify the previous observations that anemia appears earlier and is more severe in Balkan endemic nephropathy than in other renal diseases. The role of erythropoietin insufficiency as the cause of anemia in endemic nephropathy was studied as well. The severity of anemia increased with the impairment of renal function in endemic nephropathy and was similar to anemia in chronic pyelonephritis. However, in patients with endemic nephropathy at the initial stage of renal insufficiency significantly lower red cell concentrations were found compared with control subjects from the endemic region. In contrast, patients with pyelonephritis did not have decreased red cell concentrations at the early phase of their renal failure, suggesting that earlier appearance of anemia is characteristic for endemic nephropathy. To confirm this finding a study involving larger number of patients would be necessary. The serum erythropoietin levels, inappropriately low for the degree of anemia in patients with renal failure, were unrelated to the type of tubulointerstitial nephropathy.

Chronic peritoneal dialysis in the elderly: a review.

During the past few decades, the pattern of end-stage renal disease has changed significantly with the emerging predominance of elderly patients. Because this heterogeneous population is characterized by a physiological decline in function of all organs, the nephrologist must contemplate the special needs of individual patients when they develop end-stage renal disease. Before the initiation of dialysis, these patients must be given detailed information to help them select the particular mode that will maximize their quality of life. According to available data, peritoneal dialysis offers some advantages for elderly patients, such as hemodynamic stability, steady-state metabolic control, good control of hypertension, independence from hospital, and avoidance of repeated vascular access. Early referral promotes the establishment of peritoneal access and minimizes the consequences of uremia, subsequent morbidity, and frequent hospitalization. Elderly patients are compliant and highly motivated to cooperate with their treatment. They have no higher modality-related complications than younger patients and their quality of life is satisfactory. Although most have comorbid conditions that interfere with self-performance of dialysis, such as impaired vision and reduced physical and mental activity, they can perform peritoneal dialysis successfully if they have a high level of family support. Patients who do not have family support may have successful peritoneal dialysis if they have access to a network of medical and social support, that is, private home nurses, rehabilitation and chronic care dialysis units, or nursing homes.

Experience with a large dose (500 mg) of intravenous iron dextran and iron saccharate in peritoneal dialysis patients.

OBJECTIVE: To compare efficacy in anemia correction and side effects of large doses of intravenous (IV) iron dextran and iron saccharate preparations in peritoneal dialysis (PD) patients. SETTING: Tertiary-care teaching hospital of University of Toronto. DESIGN: Retrospective analysis of 379 PD patients who attended PD clinics in past 5 years. Of these 379 patients, 62 were selected to receive IV iron based on ferrokinetic markers of iron deficiency, noncompliance to or ineffectiveness of oral iron, or increased erythropoietin (EPO) requirement. INTERVENTION: Sixty-one patients received two IV iron injections of 500 mg each, 1 week apart, 33 patients received iron dextran, 23 received iron saccharate, and 5 received both iron dextran and iron saccharate. One patient developed anaphylaxis to a test dose of iron dextran and was excluded from further therapy. Blood samples were collected before and 3 and 6 months after iron infusions. RESULTS: At 3 months, the group's average hemoglobin rose from 98.3+/-18.3 g/L to 110.6+/-16.4 g/L (p < 0.0001). Ferritin rose from 104.9+/-115.4 microg/L to 391.5+/-294.1 microg/L (p < 0.0001), and transferrin saturation from 0.17+/-0.07 to 0.26+/-0.19 (p < 0.0001). Erythropoietin requirements fell from 7278.7 IU/week to 5900 IU/week (p < 0.01). Five of the 34 patients who received iron dextran developed minor side effects and 1 patient had anaphylaxis to the test dose. Of the 23 patients who received iron saccharate, 1 had an anaphylactic reaction and 2 had transient chest pain, which subsided without therapy. Overall, there were more side effects with iron dextran (7.4% of injections) compared to the iron saccharate group (4.3% of injections), but this difference was statistically insignificant. Although statistically insignificant, there was an increase in the number of peritonitis episodes during the 6 months after IV iron infusion, especially with iron dextran, compared to the peritonitis episodes during the 6 months before iron infusions. CONCLUSION: Our study indicates that IV iron in PD patients is effective in restoring iron stores and in decreasing EPO requirements. One anaphylactic reaction occurred in each group. Our data suggest that as much caution be exercised with iron saccharate as with iron dextran. The slight trend toward increased peritonitis rates after iron infusions needs to be investigated in a larger group of patients.

Cytogenetic analyses reveal "atypical cells" in the peritoneal dialysis effluent.

Cytogenetic analyses were performed on dividing cells from the peritoneal effluent of 26 patients undergoing chronic peritoneal dialysis (CPD). Numerical and structural abnormalities of karyotype served as the diagnostic criteria for "atypical cells." The following cytogenetic abnormalities were observed in 7 patients: hyperdiploidy (in 6 patients), hypodiploidy (in 2 patients), and marker chromosomes (in 2 patients). In 3 patients more than one chromosome abnormality was present. Dividing cells with normal mitoses were observed in 11 patients, while in the remaining 8 patients no dividing cells could be found. There were no differences in age, sex, duration of dialysis, and peritonitis incidence between patients with pathological mitoses and those without it. The question whether this unexpected finding is a consequence of immunosuppressed uremic status, dialysis procedure, or some other factor remains to be elucidated.

Anemia is independently associated with NT-proBNP levels in asymptomatic predialysis patients with chronic kidney disease.

BACKGROUND: Although anemia and renal dysfunction are related to increased natriuretic peptides levels in heart failure patients, less is known about this relationship in asymptomatic predialysis patients with chronic kidney disease (CKD). The aim of this study was to investigate relationship between hemoglobin (Hb) concentration, N-terminal proBNP (NT-proBNP) levels and echocardiographic findings in these patients. METHODS: The study included 61 patients with CKD stage IV-V (34 male, mean age 62.6 ± 13.6 years) and 22 age- and sex -matched healthy persons as control group. All participants underwent clinical, laboratory and echocardiographic examination, including Tissue Doppler Imaging and colour M-mode Doppler. RESULTS: Patients with CKD had lower Hb levels (p<0.001), and higher levels of NT-proBNP (p<0.001) than healthy controls. Patients were divided into two groups according to their mean Hb levels: group A, Hb<10.3 g/dL and group B, Hb≥10.3 g/dL. Patients from group A was significantly older (p<0.001), left ventricular mass index was significantly higher (LVMI, p<0.001), LV diastolic function was worse (septal and lateral E'/A' ratio: p<0.05 and p<0.01, respectively), and the level NT-proBNP was higher (p<0.001) compared to patients from group B. The natural logarithm of NT-proBNP (lnNT-proBNP) showed highly significant correlation with Hb (p<0.001) and significant correlation with estimated glomerular filtration rate (p=0.035) in CKD patients. Multiple regression analysis revealed Hb levels (p<0.01), cholesterol (p<0.001), LV ejection fraction (p<0.001) and septal E/E' ratio (p<0.01) as the independent variables predicting as much as 54% variability of lnNTpro-BNP. CONCLUSIONS: The increased NT-proBNP levels in asymptomatic patients with advanced CKD were independently associated with echocardiographic parameters of LV function, but anemia may represent one of the important confounder of the relationship between NT-proBNP and cardiovascular abnormalities.

[Is there a correlation between C-reactive protein and calcification inhibitors with cardiovascular parameters and risk factors in hemodialysis patients?]. / Korrelieren C-reaktives Protein und Verkalkungsinhibitoren bei Hämodialyse-Patienten mit kardiovaskulären Parametern und Risikofaktoren?

BACKGROUND AND OBJECTIVE: Patients on hemodialysis exhibit a drastically increased cardiovascular mortality. Inflammation, hyperphosphatemia and lack of calcification inhibitors are uremia-associated risk factors for vascular calcification. Functional and morphological vascular parameters are used to assess cardiovascular risk. The aim of our study was to analyse the relation between pulse wave velocity (PWV) and intima-media-thickness (IMT) with calcification inhibitors. METHODS: A cohort of 97 hemodialysis patients was consecutively selected and investigated (age 56 +/- 9 years). Carotid-femoral PWV, carotid IMT, left ventricular ejection fraction and septum thickness were determined. These parameters were correlated with serum levels of CRP and calcification inhibitors (fetuin-A and osteoprotegerin [OPG]). RESULTS: Both PWV and IMT showed a positive correlation with age and systolic blood pressure and a negative correlation with Kt/V (dialysis efficiency). Additionally, fetuin-A was negatively associated with CRP and positively with cholesterol and triglycerides. Serum levels of the calcification inhibitors fetuin-A and OPG were not correlated to PWV or IMT. CONCLUSION: The lack of correlation of calcification inhibitors with PWV and IMT means that functional and morphological measurements of vascular properties can not necessarily be replaced by analysing "biomarkers".

Evaluation of oxidative stress after repeated intravenous iron supplementation.

Parenteral iron has been recommended for the treatment of iron deficiency in the majority of maintenance hemodialyzed (HD) patients. However, iron supplementation and consequent over saturation of transferrin and high iron levels, may aggravate oxidative stress already present in these patients. This study aimed to further clarify the role of repeated intravenous iron therapy as a supplementary cause of oxidative stress in HD patients. Markers of free radical activities (carbonyl reactive derivatives, CRD, thiol groups, SH, malondialdehyde, MDA) and antioxidant enzyme activities (superoxide dismutase, SOD and glutathione peroxidase, GPX) were determined in plasma and red blood cells (RBC) of 19 hemodialysis patients given a total iron dose of 625 mg (ferrogluconat, Ferrlecit, 62.5 mg). Blood samples were taken before the first and after the last dose of iron. Twenty apparently normal subjects served as healthy controls. Before iron treatment, HD patients exhibited increased concentrations of MDA and CRD in plasma and red blood cells, accompanied with impaired antioxidant capacity. All patients responded to iron therapy with a significant increase in their serum ferritin, serum iron, hemoglobin, and red blood cells levels. However, iron treatment resulted in enhanced oxidative stress in plasma of HD patients, since significant increase in plasma MDA and CRD concentrations, together with a decrease in nonprotein SH groups levels were detected. Supplementation with iron did not significantly influence plasma SOD and GPX activities, nor did any of the red blood cell parameters tested. Our data show that, despite improvement in hematological parameters, an increase in iron stores due to supplementation could also contribute to increased free radical production in HD patients.

[Erythropoietin-beta in the treatment of anemia in patients with chronic renal insufficiency]. / Eritropoetin beta u lecenju anemije kod bolesnika sa hronicnom bubreznom insuficijencijom.

INTRODUCTION: Anemia is an early sign of chronic renal failure (CRF). Although multifactorial in origin, insufficient erythropoietin (EPO) synthesis is one of the most important factors. Other causes are: decreased erythrocyte survival (from 120 days to 70-80 days), chronic blood loss (mainly gastrointestinal and gynecological), inhibitors of erythropoiesis, inflammatory cytokines (IL-1, TNF-alpha, IFN-gamma) and malnutrition (folic acid, L-carnitine and vitamin B12 deficiency). Chronic blood loss may cause iron deficiency in about 25% of patients. Correlation between EPO level and glomerular filtration rate (GFR) is well preserved, but negative feed-back loop between hemoglobin and EPO is disturbed in patients with CRF. CONSEQUENCES OF GRF: The consequences of renal anemia are mainly cardiovascular; left ventricular hypertrophy (LVH) is often found at the start of dialytic therapy. Cardiovascular morbidity [especially LVH and congestive heart failure (CHF)] and mortality highly correlate with the degree of anemia. In addition, anemia affects patient rehabilitation and quality of life. It positively correlates with the degree of physical activity, sleep and general well-being. ERYTHROPOIETIN THERAPY: Optimization of erythropoietin therapy includes awareness of target hematocrit and hemoglobin, defining the renal anemia management period (RAMP), drug dosage and mode of application and significance of adjuvant therapy. Anemia should be treated early during the course of renal failure, even when GFR falls below 50 ml/min. According to dialysis outcomes quality initiative (DOQI) guidelines, target values are 0.33-0.36 L/L for hematocrit and 110-130 g/l for hemoglobin. Early administration is recommended especially in high-risk patients: the elderly, diabetics and those with coronary artery and peripheral artery diseases. EFFECTS OF EPO THERAPY: Individualization and close monitoring of therapy are very important and weekly rise in hematocrit (Ht) should not exceed 1%. More recent studies justify the normalization of Hb/Ht values--patients with normal Hb/Ht values have had the lowest mortality. In addition, normalization of Hb/Ht prevented LVH. Subcutaneous administration has priority compared to intravenous. Adjuvant therapy includes: iron, vitamin C and D, L-carnitine, folic acid, cytokines and growth factors. Intravenous iron administration has priority upon oral; target levels are 400-800 for ferritin um/ml and > 20 for transferrin saturation. Vitamin C (500 mg, after every hemodialysis) is very helpful in cases of functional iron deficiency. L-carnitine stabilizes the membrane of erythrocytes and prolongs their lives. Folic acid (10 mg/day) enhances response to EPO. Apart from correction of hematological parameters, erythropoietin therapy significantly improves left ventricular hypertrophy, quality of life, nutrition, sexual activity, carbohydrate and lipid metabolism, cognitive function and sleeping function. Given in predialysis period, it may slow progression of renal failure, prevents cardiovascular and overall morbidity and improves survival in dialysis population. CONCLUSION: The reasons for inadequate erythropoietin response are unrecognized bleeding, iron deficiency and infection/inflammation. Adverse events are very rare and predictable; they can be avoided with careful dosage and follow-up of patients. In conclusion, EPO-therapy is well established and efficient for renal anemia in dialysis and pre-dialysis patients.

[Acute kidney failure caused by poisoning]. / Akutna bubrezna insuficijencija kao posledica trovanja.

We present our experience in the treatment of acute renal failure (ARF) as a result of poisoning. The most frequent cause was acetic acid. Oligoanuric ARF was registered in 30 patients. In 34 patients peritoneal dialysis was applied for high values of serum urea and creatinine. The most frequent complications (oesophagitis, bleeding, mediastinitis, pneumonia, acute abdomen) were also the cause of death. After the treatment 31 patients were recovered with the mean creatinine clearance of 65.0 ae 27.7 ml/min. Ten patients died during the first 4 days of hospitalisation because of corrode effect of acid. This mortality of 24.4% is above the mean mortality registered for all ARF in our centre. In our opinion the treatment of ARF due to poisoning requires the team work of many specialists. Peritoneal dialysis is more advisable than haemodialysis because of bleeding tendency and intraabdominal monitoring.