Estimated Pulse Wave Velocity and All-Cause and Cardiovascular Mortality in the General Population.

Background: Carotid-femoral pulse wave velocity (cfPWV), acknowledged as a reliable proxy of arterial stiffness, is an independent predictor of cardiovascular (CV) events. Carotid-femoral PWV is considered the gold standard for the estimation of arterial stiffness. cfPWV is a demanding, time consuming and expensive method, and an estimated PWV (ePWV) has been suggested as an alternative method when cfPWV is not available. Our aim was to analyze the predictive role of ePWV for CV and all-cause mortality in the general population. Methods: In a stratified random sample of 1086 subjects from the general Croatian adult population (EH-UH study) (men 42.4%, average age 53 ± 16), subjects were followed for 17 years. ePWV was calculated using the following formula: ePWV = 9.587 - 0.402 × age + 4.560 × 10-3 × age2 - 2.621 × 10-5 × age2 × MBP + 3.176 × 10-3 × age × MBP - 1.832 × 10-2 × MBP. MBP= (DBP) + 0.4(SBP - DBP). Results: At the end of the follow-up period, there were 228 deaths (CV, stroke, cancer, dementia and degenerative diseases, COLD, and others 43.4%, 10.5%, 28.5%, 5.2%, 3.1%, 9.3%, respectively). In the third ePWV tercile, we observed more deaths due to CV disease than to cancer (20.5% vs. 51.04%). In a Cox regression analysis, for each increase in ePWV of 1 m/s, there was a 14% increase risk for CV death. In the subgroup of subjects with higher CV risk, we found ePWV to be a significant predictor of CV deaths (ePWV (m/s) CI 1.108; p < 0.029; HR 3.03, 95% CI 1.118-8.211). Conclusions: In subjects with high CV risk, ePWV was a significant and independent predictor of CV mortality.

Glomerular filtration rate is an independent prognostic factor in patients with B-large cell lymphoma.

Chronic kidney dysfunction is associated with increased mortality in multiple cancer types. Preliminary evidence suggests the same to be true for B-large cell lymphomas (B-LCL). To analyze the relationship of glomerular filtration rate (GFR) and outcome of B-LCL in detail we collected data on outcomes of 285 consecutive patients with newly diagnosed B-LCL treated at our institution with standard rituximab-containing regimens who did not have preexisting kidney disease or urinary tract obstruction at presentation. Median age was 59, range 18 to 87, 145 were male and 140 females. Forty-four had GFR < 60 mL/min, 123 had 60 to 90 mL/min, and 118 > 90 mL/min. Median follow-up of surviving patients was 49 months and estimated 3-year survival 76%. In univariate analysis age (P < .001), GFR (P = .014), stage (P < .001), performance status (P = .044), chemotherapy regimen (P < .01), and international prognostic index (IPI) (P < .001) were statistically significant prognostic factors. In multivariate analysis, age and GFR remained the only independent prognostic factors. Subtracting 1 from the IPI score of patients who had GFR > 90 mL/min and IPI > 1 resulted in a prognostic index that divides patients into 3 prognostic groups (low risk = 0-1, intermediate risk = 2-3 and high risk = 4-5) with an acceptable patient distribution frequency (38%, 39%, and 23%, respectively) and improved statistical significance and separation in comparison to IPI (5-year survival rates of 92%, 74%, and 42%, respectively). GFR is an important independent prognostic factor for B-LCL that should be taken into account in clinical decision making and data analysis and probably be incorporated in prognostic indices.

High prevalence of middle cerebral artery calcification is associated with cardiovascular mortality in hemodialyzed patients: an overlooked part of arterial tree?

PURPOSE: We have analyzed markers of accelerated atherosclerosis like large artery stiffness, ankle-brachial index, carotid and vertebral duplex ultrasonography and their possible associations with the incidence of intracranial calcifications, clinical course of hemodialyzed patients, and cardiovascular mortality. METHODS: A computed tomographic scan of the head was performed for any neurological indication on 100 hemodialyzed patients. Eleven intracranial arteries were analyzed for calcification score, while internal carotid arteries and vertebral arteries were excluded in cerebral artery calcification score. As a control group for assessing intracranial calcifications, we have analyzed computed tomographic scans from diabetic patients who had an acute stroke. RESULTS: Deceased patients had significantly higher values of augmentation index and pulse wave velocity, lower ankle-brachial index, and higher internal carotid arteries peak systolic value than survived patients. Deceased patients had significantly higher number of calcified middle cerebral arteries as well as significantly higher intracranial artery calcification score and cerebral artery calcification score. Hemodialyzed patients had significantly higher both intracranial and cerebral artery calcification scores than diabetic control group. Age and calcified middle cerebral arteries had increased HR of 1.08 and 1.36 for cardiovascular mortality. CONCLUSION: This study showed that large artery stiffness and not the presence of peripheral arterial disease or carotid artery stenosis have the prognostic role of middle cerebral arteries' calcifications and cardiovascular mortality in hemodialyzed patients. The presence of middle cerebral arteries' calcifications diagnosed by a non-invasive method should be considered a marker of middle-sized conduit arteries atherosclerosis, subclinical brain damage, and future fatal cardiovascular events.

CHRONIC KIDNEY DISEASE IN RURAL POPULATION.

The aims of the study were to provide data on chronic kidney disease (CKD) prevalence in rural population and to analyze the association with cardiovascular risk factors and aging. A random sample of 2193 farmers (1333 female (F) and 860 male (M), mean age 50.61±17.12) were enrolled. Questionnaire and clinical examination were conducted. Participants provided a spot urine and fasting blood sample. Estimated glomerular filtration rate (eGFR) was estimated using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Subjects were classified according to the KDIGO guidelines. The overall prevalence of CKD (eGFR <60 mL/min/1.73 m2) was 8.83% (F vs. M 9.9% vs. 6.3%; p<0.001). Albuminuria (albumin-to-creatinine ratio >30 mg/g) was found in 8.45% (F vs. M p>0.05). Sharp increase in CKD prevalence was found to begin after the sixth decade (29.44% in subjects older than 65 years; F vs. M 30.9% vs. 26.8%; p<0.01). The strongest predictor factors for CKD were age >65 years (OR 22.12), hypertension (OR 6.53), albuminuria (OR 5.71), fasting blood glucose >7 mmol/L (OR 5.49), diabetes (OR 3.07), abdominal obesity (OR 2.05) and non-smoking (OR 0.41). In multivariate analysis, age (OR 1.13), female gender (OR 0.60) and diabetes (OR 1.75) were the independent predictor factors for CKD. In conclusion, CKD prevalence is high in rural population, being higher in women than in men. In both genders, eGFR significantly decreased with aging. Aging is a significant independent predictor of CKD.

Early biochemical markers in the assessment of acute kidney injury in children after cardiac surgery.

Our aim was to evaluate biochemical markers in plasma (NGAL, CysC) and urine (NGAL, KIM-1) in children's early onset of acute kidney injury after congenital heart defect surgery using cardiopulmonary bypass. This study prospectively included 100 children with congenital heart defects who developed AKI. Patients with acute kidney injury had significantly higher CysC levels 6 and 12 h after cardiac surgery and plasma NGAL levels 2 and 6 h after cardiac surgery. The best predictive properties for the development of acute kidney injury are the combination (+CysCpl or +NGALu) after 12 h and a combination (+CysCpl and +NGALu) 6 and 24 h after cardiac surgery. We showed that plasma CysC and urinary NGAL could reliably predict the development of acute kidney injury. Measurement of early biochemical markers in plasma and urine, individually and combination, may predict the development of cardiac surgery-associated acute kidney injury in children.

Lower number of plasma exchange sessions and glomerular filtration rate decline are associated with second relapses in patients with myasthenia gravis.

The aims were to determine the impact of dysphagia and glomerular filtration rate (GFR) in the prediction of myasthenia relapse and analyse whether different number of plasma exchange sessions could prolong the time before future relapse.This was a retrospective, longitudinal follow-up study with 60 enrolled patients. The patients were followed-up for a total of 50 months.Patients without relapses had significantly higher GFR and higher number of plasma exchange sessions when compared to patients with relapses. Mean time before next myasthenia relapse was significantly longer in patients with GFR ≥ 60 mL/min. Time before next and number of following myasthenia relapses were significantly higher in patients with symptoms of dysphagia.Decline in GFR levels is strongly associated with the presence of dysphagia and independently impacts the onset of myasthenia relapses. Timely initiation of plasmapheresis therapy and adequate hydration of patients with prolonged dysphagia should be one of the treatment goals for clinicians treating this disease.

The association of the decline in glomerular filtration rate with aggressive endometrial cancers.

PURPOSE: Most site-specific cancer incidence is increased with the decrease of glomerular filtration rate (GFR). We analyzed endometrial cancers depending on different type, staging, and histology grades. We hypothesized that patients with lower GFR levels have an increased risk for higher staging and histology grades of endometrial cancers. METHODS: Patients were divided into two subgroups regarding GFR; the first group with GFR < 60 ml/min and the second group with GFR > 60 ml/min and regarding different histology grades and cancer stages. Cancers were also divided by stages (1-4). Patients were followed up during 1 year through regular controls in the outpatient clinic and during that time cancer recurrence was recorded. RESULTS: GFR was the strongest predictor for higher cancer histology grade and higher cancer staging. Patients with reduced GFR had OR for higher histology grade and higher staging of 1.06 and 1.06. Traditional risk factors for endometrial cancer development were not associated with higher histology grade or higher cancer staging. CONCLUSION: Higher staging and histology grades in patients with endometrial cancers are associated with reduced GFR. Patients with mild-to-moderate CKD had significantly higher number of cancers with higher histology grades and higher stages than patients with mild or normal GFR category. Decline in GFR was independently associated with more aggressive cancers without other well-known risk factors for endometrial cancer development like age, menopause, diabetes, and obesity.

The association of preoperative reduced glomerular filtration rate with higher staging and histology grades in patients with urinary tract cancers.

PURPOSE: Studies have shown the increased incidence of urinary tract cancers which are associated with a decrease in glomerular filtration rate (GFR). We hypothesized that patients with GFR < 60 ml/min/1.73 m2 have an increased risk for higher staging and histology grades of cancers and, therefore, the increased risk for cancer recurrence and cancer-related death. METHODS: Retrospective clinical data and pathology reports were completed for 2116 patients. Patients were divided into two subgroups regarding GFR; the first group with GFR < 60 ml/min/1.73 m2 and the second group with GFR > 60 ml/min/1.73 m2 and regarding cancer recurrence. Cancers were also divided by stages (1-4) according to TNM classification. Patients were followed-up during 3 years. RESULTS: We have found significantly higher number of cancers with higher histology grades and higher staging in group of patients with GFR < 60 ml/min/1.73 m2 in all urinary tract localizations. GFR was the strongest predictor for higher cancer histology grade and only significant predictor for higher cancer staging. Patients with GFR < 60 ml/min/1.73 m2 had OR for higher histology grade, higher staging, and cancer recurrence of 10.7, 5.3, and 11.3 compared to patients with GFR > 60 ml/min. CONCLUSIONS: Higher staging and histology grades in patients with urinary tract cancers are associated with reduced GFR. Reduced GFR in these patients is a risk factor for cancer recurrence and cancer-related survival. Possible involvement of uremic toxins must be taken into account especially when cancers are predominantly located in estrogen sensitive organs. These patients should be intensively monitored and probably be more aggressively treated.

Acute Kidney Failure as a Single Complication of Varicella Virus Infection in an Adult Patient.

BACKGROUND: Varicella zoster virus (VZV) is distributed worldwide and is highly contagious. In adults and immunosuppressed patients of any age, the clinical course is much more severe. The most severe complications are pneumonia (the main cause of lethal outcomes in this infection), encephalitis, and very rarely Reye syndrome and hepatitis. CASE PRESENTATION: We present a 59-year-old man who came to the emergency department due to varicella and diarrhea. During initial evaluation acute kidney failure (AKF) was diagnosed, and the patient was admitted to the intensive care unit. Continuous renal replacement therapy was applied, and the patient was treated with acyclovir in adjusted doses; renal biopsy revealed acute tubular necrosis. Complete renal function recovery was established after 12 days. CONCLUSION: VZV infection occurs in a range of clinical scenarios, sometimes presenting only with mild symptoms, but in some other setting it can result in severe AKF even in healthy kidneys. Acute VZV infection can lead to isolated, clinically significant kidney failure. The administration of continuous renal replacement therapy and adjusted doses of acyclovir has a favorable effect on the course of the infection, with complete recovery of kidney function.

Consequence of Elevated Fibroblast Growth Factor 23 Levels in Acute Kidney Injury, Renal Recovery and Overall Survival in Intensive Care Unit Patients After Major Surgery.

The main goal of our study was to investigate the role of increased fibroblast growth factor 23 (FGF23) levels on renal recovery and overall survival. We conducted a prospective case-control cohort study, which included 121 adult cases who developed AKI after major surgical procedures. The subjects were followed-up until the last enrolled patient survived 180 days or until the time of death. Higher FGF23 levels positively correlated with serum creatinine levels (P < 0.05). Significantly higher number of patients without diuresis and with FGF23 ≤ 709 RU/mL survived when compared to patients without diuresis and with FGF23 ≥ 709 RU/mL (P < 0.001). FGF23 levels >709 RU/mL were a good predictive tool for overall mortality in a 6-month period (P < 0.05). This is the first study to analyze the impact of FGF23 values on short-term renal recovery and survival of patients with AKI after major surgery. The FGF23 increase related to AKI especially in more severe stages and in patients without diuresis is an independent risk factor for mortality.

Increased arterial stiffness - similar findings in patients with inflammatory bowel disease without prior hypertension or diabetes and in patients with well-controlled hypertension.

PURPOSE: Chronic inflammatory diseases are related with earlier onset of atherosclerosis. We hypothesized that inflammatory bowel disease patients with chronic, systemic inflammation have an increased arterial stiffness associated with the disease duration. Also, we wanted to compare arterial stiffness markers between inflammatory bowel disease and well-controlled hypertension patients. MATERIALS AND METHODS: A total of 89 inflammatory bowel disease patients (60 patients with Crohn's disease and 29 patients with ulcerative colitis, age range 20-64 years) without history of arterial hypertension or diabetes were enrolled and age matched with a control group of patients (73 patients, age range 25-69 years, 41 (56.1%) males) with known history of well-controlled arterial hypertension. We have used a noninvasive device that simultaneously measures brachial blood pressure and estimates PWV and AIx in inflammatory bowel disease and hypertension groups of patients. RESULTS: Patients with pathological PWV values were significantly older, had significantly longer duration of inflammatory bowel disease, higher values of serum cholesterol and HDL-cholesterol, and higher AIx (17.4% vs. 9.8%) (all p < .05). Higher PWV was associated with age and duration of inflammatory bowel disease in the linear regression model. PWV values were higher in hypertensive patients in the first two age quartiles while interestingly, in the last two quartiles, PWV was lower than in inflammatory bowel disease group of patients. CONCLUSIONS: Chronic subclinical inflammation is responsible for dyslipidemia and accelerated atherosclerosis which consequently alterates arterial elasticity. Inflammatory bowel disease and its duration should also be considered a risk factor for subclinical organ damage, as well as hypertension.

Role of Plasmapheresis in the Management of Acute Kidney Injury in Patients With Multiple Myeloma: Should We Abandon It?

The aim of the current study was to determine whether plasmapheresis in combination with chemotherapy could significantly remove free light chains (FLC) in multiple myeloma (MM) patients with acute kidney injury (AKI) and therefore improve renal recovery and patient survival. During the study period, 29 patients with MM and AKI presented to our unit and were treated with two different therapy modalities (plasmapheresis with chemotherapy or bortezomib). At the end of treatment, a significant decrease of FLCs was present in the group treated with plasmapheresis compared to the bortezomib group. Patients treated with plasmapheresis had similar survival compared to patients treated with bortezomib. There was a significantly higher decrease of FLCs and longer survival in patients treated with three or more plasmapheresis sessions than in patients treated with two plasmapheresis sessions. Plasmapheresis therapy still remains a useful and effective method in the treatment of AKI in MM patients. Plasmapheresis significantly reduces FLCs compared to bortezomib especially with higher number of plasma exchange sessions but it must be combined with other chemotherapy agents in order to prolong renal recovery and therefore patient survival.

The incidence of urinary tract cancers is related to preserved diuresis: a single-center report.

PURPOSE: Residual diuresis progressively decreases with longer dialysis vintage, and higher incidence of renal and urinary tract cancers was often observed in hemodialyzed patients compared to the general population so we hypothesized that patients without preserved residual diuresis have higher risk of renal and urinary tract cancers than patients with preserved residual diuresis. METHODS: Retrospective clinical data and pathology reports were completed for 307 uremic patients undergoing chronic hemodialysis. Patients were divided into two subgroups regarding residual diuresis: the first group with residual diuresis < 500 mL, 133 of 173 (76.8%) patients from this group were completely anuric, and the second group with 134 patients with residual diuresis > 500 mL. RESULTS: Site- and type-specific cancers in our population of ESRD patients were all localized in estrogen-positive receptor organs. The increased risk of all types of urinary tract cancers occurred in the whole group, men and women, when compared to general population. There were a significantly higher number of patients with all types of cancers in the group with residual diuresis < 250 mL compared to patients with residual diuresis > 500 mL. Importantly, all urinary tract cancers were present in patients with residual diuresis < 500 mL. CONCLUSION: Higher incidence of urinary tract cancers found in ESRD patients undergoing chronic hemodialysis is associated with lost residual diuresis. Residual diuresis in these patients might be considered a risk marker for future urinary tract cancers as well as already established markers.

Continuous Veno-Venous Hemofiltration Improves Survival of Patients With Congestive Heart Failure and Cardiorenal Syndrome Compared to Slow Continuous Ultrafiltration.

Continuous veno-venous hemofiltration (CVVH) could modulate the inflammatory response by removal of circulating cytokines and therefore improve cardiac function in patients with heart failure (HF). We hypothesized that patients with developed cardiorenal syndrome and treated with CVVH have lower risk for mortality than other patients treated with slow continuous ultrafiltration (SCUF). This was a prospective, longitudinal follow-up study for 24 months duration. In total, 120 patients were recruited from the intensive care units. Only patients with cardiorenal syndrome type 1 and 2 were enrolled. 54 CVVH and 23 SCUF patients survived. Mean survival time was longer in CVVH group with cardiomyopathy than in the SCUF group. When we compared patients with cardiomyopathy and hourly urine output <10 mL/h, mean survival time was significantly longer in patients treated with CVVH. This is the first study to analyze the impact of different CRRT modalities (CVVH vs. SCUF) on survival of patients with HF and who developed cardiorenal syndrome. Better survival in patients treated with CVVH, which is mostly pronounced in patients with cardiomyopathy, is a consequence of a better preserved hourly urine output. Longer survival in patients with cardiomyopathy is most probably related to cytokine removal by CVVH with smaller UF rates and longer duration of each treatment. Slow continuous ultrafiltration remains the method of choice in patients with HF and preserved renal function but in cases of developed cardiorenal syndrome is much inferior to CVVH.

Chronic dietary exposure to aristolochic acid and kidney function in native farmers from a Croatian endemic area and Bosnian immigrants.

BACKGROUND AND OBJECTIVES: Improvements in agricultural practices in Croatia have reduced exposure to consumption of aristolochic acid-contaminated flour and development of endemic (Balkan) nephropathy. Therefore, it was hypothesized that Bosnian immigrants who settled in an endemic area in Croatia 15-30 years ago would be at lower risk of developing endemic nephropathy because of reduced exposure to aristolochic acid. To test this hypothesis, past and present exposure to aristolochic acid, proximal tubule damage as a hallmark of endemic nephropathy, and prevalence of CKD in Bosnian immigrants were analyzed. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In this cross-sectional observational study from 2005 to 2010, 2161 farmers were divided into groups: indigenous inhabitants from endemic nephropathy and nonendemic nephropathy villages and Bosnian immigrants; α-1 microglobulin-to-creatinine ratio >31.5 mg/g and eGFR<60 ml/min per 1.73 m(2) were considered to be abnormal. RESULTS: CKD and proximal tubule damage prevalence was significantly lower in Bosnian immigrants than inhabitants of endemic nephropathy villages (6.9% versus 16.6%; P<0.001; 1.3% versus 7.3%; P=0.003, respectively); 20 years ago, Bosnian immigrants observed fewer Aristolochia clematitis in cultivated fields (41.9% versus 67.8%) and fewer seeds among wheat seeds (6.1% versus 35.6%) and ate more purchased than homemade bread compared with Croatian farmers from endemic nephropathy villages (38.5% versus 14.8%, P<0.001). Both Croatian farmers and Bosnian immigrants observe significantly fewer Aristolochia plants growing in their fields compared with 15-30 years ago. Prior aristolochic acid exposure was associated with proximal tubule damage (odds ratio, 1.64; 95% confidence interval, 1.04 to 2.58; P=0.02), whereas present exposure was not (odds ratio, 1.31; 95% confidence interval, 0.75 to 2.30; P=0.33). Furthermore, immigrant status was an independent negative predictor of proximal tubule damage (odds ratio, 0.40; 95% confidence interval, 0.19 to 0.86; P=0.02). CONCLUSIONS: Bosnian immigrants and autochthonous Croats residing in endemic areas are exposed significantly less to ingestion of aristolochic acid than in the past. The prevalence of endemic nephropathy and its associated urothelial cancers is predicted to decrease over time.

[Salt--hidden poison in everyday meal]. / Kuhinjska sol--skriveni otrov u svakodnevnoj hrani.

A large number of epidemiologic, evolutionary and clinical studies have confirmed that table salt is a significant factor in determining the blood pressure (BP) level, and thereby in the prevalence of arterial hypertension (AH). It has been observed in epidemiologic studies that BP increases with age only if accompanied by excessive table salt intake. In addition to affecting BP, increased salt intake independently contributes to target organ damage. Correlation has also been observed between coronary artery disease, left ventricular hypertrophy, cerebrovascular insult, microalbuminuria. Table salt, i.e. NaCl, is directly involved in the process of atherothrombogenesis by changing the relation between vasoactive factors in the blood vessel wall, by affecting the expression of receptor for angiotensin II and, which is particularly important, by elevating platelet aggregability. From clinical and public health aspects, the data obtained in interventional studies are particularly important, as well as those that apparently confirm the benefit of restricting NaCl intake. This benefit is manifested not only in decreased BP and reduction in cardiovascular morbidity and mortality, but also in improved total health as it is known that excessive table salt intake is also a risk factor for osteoporosis, nephrolithiasis, gastric and nasopharyngeal carcinoma, etc. Although there were some studies that raised doubt about the fact that reduced table salt intake could be harmful due to activation of counter-regulative mechanisms, a substantially higher number of authors demonstrated that moderate intake reduction was not associated with the increased risk but rather the contrary. Table salt intake restriction should be performed as part of other lifestyle changes, primarily weight loss and increased physical activity. During NaCl intake reduction, it is necessary to pay attention to other electrolytes and microelements that are also important stones in the mosaic of healthy living. Gooverment authorities and food manufacturers bear heavy responsibility as ready or half-cooked food accounts for over 70% of NaCl intake into the body.