Arnošt Martínek

Acute kidney injury due to rhabdomyolysis and renal replacement therapy: a critical review

Rhabdomyolysis, a clinical syndrome caused by damage to skeletal muscle and release of its breakdown products into the circulation, can be followed by acute kidney injury (AKI) as a severe complication. The belief that the AKI is triggered by myoglobin as the toxin responsible appears to be oversimplified. Better knowledge of the pathophysiology of rhabdomyolysis and following AKI could widen treatment options, leading to preservation of the kidney: the decision to initiate renal replacement therapy in clinical practice should not be made on the basis of the myoglobin or creatine phosphokinase serum concentrations.

Quantiferon-CMV Test in Prediction of Cytomegalovirus Infection After Kidney Transplantation

Infection with cytomegalovirus (CMV) is a major cause of morbidity and mortality in immunosuppressed patients, including organ and bone marrow transplant recipients. The majority of CMV disease is caused by reactivation of alatent infection rather that by newly acquired virus. Many techniques have been currently available to aid in the diagnostics of CMV disease. In this report we performed a prospective evaluation of Quantiferon-CMV assay (Cellestis) to determine whether the test is predictive of CMV disease. CD8+ T-cell CMV-specific immunity was assessed in a longitudinal cohort of 14 kidney transplant recipients. According to our data, subjects with higher cellular immune response measured with Quantiferon test had a lower risk of manifestation of CMV infection than subjects with lower responses. Despite the small number of patients and large intra- and interindividual variability of the data in the study, we observed the Quantiferon-CMV assay to be a sensitive specific test to detect a virus-specific T-cell response. We propose that this assay in combination with viral DNA load estimates may prove to be useful to stratify patients at risk of CMV disease.

Cholesterol metabolism in active Crohn's disease

ZusammenfassungErniedrigte Cholesterin-Spiegel gelten als typisches Merkmal einer schweren Erkrankung und sind mit einer schlechten Prognose vergesellschaftet. Der Morbus Crohn ist eine entzündliche Erkrankung, die mit verschiedenen Störungen des Stoffwechsels einhergeht. In den vergangenen Dekaden haben verschiedene klinische Studien einen Zusammenhang zwischen dem Lipidstoffwechsel und der systemischen Entzündung etabliert. In unserer Studie haben wir nicht nur das Cholesterin-Profil (Cholesterin, LDL und HDL Cholesterin) im Plasma bestimmt, sondern auch Veränderungen im Cholesterin-Absorptions- beziehungsweise -Synthese-Prozess durch Bestimmung der Konzentrationen der Nicht-Cholesterin-Sterole im Serum untersucht. Die Plasmakonzentrationen des Gesamtcholesterins, des LDL- und HDL-Cholesterins sowie der Nicht-Cholesterin-Sterole (Squalene, Lathosterol, Campesterol, Sitosterol) wurden bei 24 Patienten mit aktivem Morbus Crohn in einer Zeitspanne von 28 Tagen erhoben. Die Plasmakonzentrationen des Gesamtcholesterins (p < 0,001) und des LDL-, und HDL-Cholesterins (p < 0,05) waren signifikant niedriger als die bei Kontrollpersonen erhobenen Werte. Im Vergleich zur Kontrolle hatten die Patienten mit aktivem Morbus Crohn signifikant niedrigere Plasmaspiegel von Lathosterol (p < 0,001) mit gleichzeitig nicht signifikant erhöhten Konzentrationen von Squalene. Die Campesterol-Plasmakonzentrationen waren signifikant (p < 0,001) erniedrigt. Sitosterol auch – aber nicht signifikant. Die aktive Phase des Morbus Crohn ist durch Veränderungen des Lipidstoffwechsels – vor allem von Cholesterin – gekennzeichnet. Unsere Ergebnisse zeigen Plasmakonzentrationen der Nicht-Cholesterin-Sterole außerhalb der Norm und sprechen dafür, dass die Cholesterin-Synthese und -Absorption beim aktiven Morbus Crohn verändert ist.SummaryHypocholesterolemia has been investigated as a typical feature of critical illness and is connected with poor prognosis. Crohns disease is an inflammatory process and is associated with several metabolic disturbances. In recent decades clinical studies have established a link between lipid metabolism and systemic inflammation. In our study we examined the serum profile of cholesterol (total cholesterol, LDL- and HDL-cholesterol) and changes in the cholesterol absorption/synthesis process by determination of plasma non-cholesterol sterol (squalene, lathosterol, campesterol, sitosterol) concentrations. Serum concentrations of total cholesterol, LDL- and HDL-cholesterol and non-cholesterol sterols were evaluated in 24 patients with active Crohns disease during a period of 28 days. We detected lower serum levels of total cholesterol (P < 0.001), LDL- and HDL-cholesterol (P < 0.05) in the patients with active Crohns disease than in the control group. In addition, the patients had significantly lower plasma levels of lathosterol (P < 0.001) and higher concentrations of squalene, although without significant differences. A significant decrease of campesterol plasma levels (P < 0.001) was detected, but lower plasma concentrations of sitosterol were without statistical significance. The active phase of Crohns disease is characterized by altered metabolism of lipids, mainly of cholesterol. Our results show abnormalities in plasma concentrations of non-cholesterol sterols and provide evidence that the process of cholesterol synthesis and absorption is altered in active Crohns disease.

Body mass index and body size in early adulthood and risk of pancreatic cancer in a central European multicenter case-control study

The relationship between two measures of excess body weight, body mass index (BMI) and body size score, and risk of pancreatic cancer was examined among 574 pancreatic cancer cases and 596 frequency‐matched controls from the Czech Republic and Slovakia enrolled between 2004 and 2009. Analyses using multivariable logistic regression showed an increased risk of pancreatic cancer associated with elevated quartiles of BMI at ages 20 [fourth quartile: odds ratio (OR) = 1.79, 95% confidence interval (CI): 1.23, 2.61] and 40 (fourth quartile: OR = 1.57, 95% CI: 1.09, 2.27) compared to the lowest quartile. Consistent results were observed for body size score at ages 20 (high versus low: OR = 1.66, 95% CI: 1.08, 2.57) and 40 (medium versus low: OR = 1.36, 95% CI: 1.00, 1.86), but no association was found for BMI and body size score at 2 years before the interview. Stronger risk estimates for BMI were observed in males than females, particularly at age 20, but the analysis of body size yielded similar estimates by sex. When considering excess body weight at both ages 20 and 40 jointly, the highest risk estimates were observed among subjects with elevated levels at both time periods in the analysis of BMI (OR = 1.86, 95% CI: 1.32, 2.62) and body size (OR = 1.53, 95% CI: 1.09, 2.13). These findings, based on two different measures, provide strong support for an increased risk of pancreatic cancer associated with excess body weight, possibly strongest during early adulthood.

Acute kidney injury following acute pancreatitis: A review

UNLABELLED BACKROUND. Acute kidney injury (AKI) is a common serious complication of severe acute pancreatitis (SAP) and an important marker of morbidity and mortality in critically ill septic patients. AKI due to severe acute pancreatitis can be the result of hypoxemia, release of pancreatic amylase from the injured pancreas with impairment of renal microcirculation, decrease in renal perfusion pressure due to abdominal compartment syndrome, intraabdominal hypertension or hypovolemia. Endotoxins and reactive oxygen species (ROS) also play an important role in the pathophysiology of SAP and AKI. Knowledge of the pathophysiology and diagnosis of AKI following SAP might improve the therapeutic outcome of critically ill patients. METHODS AND RESULTS An overview of the pathophysiology, diagnosis and potential treatment options based on a literature search of clinical human and experimental studies from 1987 to 2013. CONCLUSIONS Early recognition of AKI and SAP in order to prevent severe complication like septic shock, intraabdominal hypertension or abdominal compartment syndrome leading to multiple organ dysfunction syndrome is a crucial tool of therapeutic measures in intensive care.

Vancomycin removal during low-flux and high-flux extended daily hemodialysis in critically ill septic patients

AIMS To determine the extent of vancomycin removal and vancomycin pharmacokinetics in septic patients with AKI using daily hemodialysis with polysulphone high-flux and low-flux membrane. METHODS Five patients received 6 h daily dialysis with low-flux polysulphone membrane, four patients with high-flux polysulphone membrane. Vancomycin was administered over the last hour of dialysis. The maintenance dose was adjusted based on pre-hemodialysis serum concentrations. Patients were followed up for two days. RESULTS Median percentage of vancomycin removal by low-flux membrane dialysis was 17% (8-38%) and by high-flux membrane dialysis was 31% (13-43%). Vancomycin clearance was only moderately higher in high-flux membrane dialysis (median 3.01 L/h, range 2.34-3.5 L/h) compared to low-flux dialysis (median 2.48 L/h, range 0.53-5.68 L/h) in the first day of the study. About two-fold higher vancomycin clearance in high-flux dialysis (median 3.62 L/h, range 1.37-5.07 L/h) was observed on the second day of the study than low-flux dialysis (median 1.74 L/h, range 0.75-30.94 L/h). CONCLUSIONS Both high-flux and low-flux membrane dialysis remove considerable amounts of vancomycin in critically ill septic patients with AKI. Application of vancomycin after each dialysis was required to maintain therapeutic concentrations.

Gentamicin pharmacokinetics during continuous venovenous hemofiltration in critically ill septic patients

Abstract Objective: Current dosing recommendations for administration of gentamicin to septic patients with acute kidney injury (AKI) on continuous venovenous hemofiltration (CVVH) at a filtration rate of 45 ml/kg/h are missing. Aim: To describe gentamicin pharmacokinetics and to find an optimal dosing regimen in patients on CVVH. Methods: Seven adult patients were included. Patients received loading dose of 240 mg followed by application of maintenance dose every 24 hours. Maintenance dose was adjusted according to gentamicin Cmax/MIC ratio and drug levels simulation using a pharmacokinetic programme. Results: Median total clearance (0·59–0·79 ml/min/kg) was similar to patients with normal renal function; median volume of distribution was higher than observed in non-septic patients (about 0·5 l/kg versus 0·25 l/kg). Patients with diuresis required an increase of gentamicin dose to reach Cmax/MIC ratio. Conclusion: Septic patients with AKI on CVVH (45 ml/kg/h) require a loading dose of 240 mg, followed by therapeutic drug monitoring to optimize maintenance dose.

Vancomycin pharmacokinetics during high-volume continuous venovenous hemofiltration in critically ill septic patients.

AIMS To assess the influence of continuous venovenous hemofiltration (CVVH) at a filtration rate of 45 mL/kg/h on vancomycin pharmacokinetics in critically ill septic patients with acute kidney injury (AKI). METHODS Seventeen adult septic patients with acute kidney injury treated with CVVH and vancomycin were included. All patients received first dose of 1.0 g intravenously followed by 1.0 g/12 h if not adjusted. In sixteen patients vancomycin was introduced on the day of the start of CRRT therapy. Blood samples and ultrafiltrates were obtained before and 0.5, 1, 6 and 12 h after vancomycin administration. RESULTS On the first day, the median total vancomycin clearance (Cltot) was 0.89 mL/min/kg (range 0.31 - 2.16). CRRT clearance accounted for around 50-60% of the total clearance of vancomycin found in a population with normal renal function (0.97 mL/min/kg). Vancomycin serum concentrations after the first dose were below the required target of 10 mg/L as early as 6 h in 10 patients, AUC0-24/MIC ≥ 400 ratio was achieved in 10 patients on the first day. CONCLUSIONS CVVH at a filtration rate of 45 mL/kg/h leads to high and rapid extracorporeal removal of vancomycin in critically ill patients. Due to the rapid change in patient clinical status it was impossible to predict a fixed dosage regimen. We recommend blood sampling as early as 6 h after first vancomycin dose with maintenance dose based on vancomycin serum level monitoring.

Renal cell carcinoma: Review of etiology, pathophysiology and risk factors.

BACKGROUND AND AIMS The global incidence of renal cell cancer is increasing annually and the causes are multifactorial. Early diagnosis and successful urological procedures with partial or total nephrectomy can be life-saving. However, only up to 10% of RCC patients present with characteristic clinical symptoms. Over 60% are detected incidentally in routine ultrasound examination. The question of screening and preventive measures greatly depends on the cause of the tumor development. For the latter reason, this review focuses on etiology, pathophysiology and risk factors for renal neoplasm. METHODS A literature search using the databases Medscape, Pubmed, UpToDate and EBSCO from 1945 to 2015. RESULTS AND CONCLUSIONS Genetic predisposition/hereditary disorders, obesity, smoking, various nephrotoxic industrial chemicals, drugs and natural/manmade radioactivity all contribute and enviromental risks are a serious concern in terms of prevention and the need to screen populations at risk. Apropos treatment, current oncological research is directed to blocking cancer cell division and inhibiting angiogenesis based on a knowledge of molecular pathways.

Total and High Molecular Weight Adiponectin Levels and Prediction of Cardiovascular Risk in Diabetic Patients

The study aimed at assessing the potential use of lower total and HMW adiponectin levels for predicting cardiovascular risk in patients with type 2 diabetes mellitus (T2DM). Concentrations of total adiponectin or high molecular weight (HMW) adiponectin decrease in association with the development of metabolic dysfunction such as obesity, insulin resistance, or T2DM. Increased adiponectin levels are associated with a lower risk for coronary heart disease. A total of 551 individuals were assessed. The first group comprised metabolically healthy participants (143 females, and 126 males) and the second group were T2DM patients (164 females, and 118 males). Both total adiponectin and HMW adiponectin in diabetic patients were significantly lower when compared with the group of metabolically healthy individuals. There was a weak monotonic correlation between HMW adiponectin levels and triglycerides levels. Binary logistic regression analysis, gender adjusted, showed a higher cardiovascular risk in diabetic persons when both total adiponectin (OR = 1.700) and HMW adiponectin (OR = 2.785) levels were decreased. A decrease in total adiponectin levels as well as a decrease in its HMW adiponectin is associated with a higher cardiovascular risk in individuals with T2DM. This association suggests that adiponectin levels may be potentially used as an epidemiological marker for cardiovascular risk in diabetic patients.