Identifying risk factors in renal allografts before transplant: machine-measured renal resistance and posttransplant allograft survival

Enhancement of renal allograft function and survival in an era where expanded criteria donors are increasingly used requires validated selection criteria. The goal of this retrospective study was to evaluate the significance of pretransplant donor and allograft parameters to identify risk factors that can be used in a model to predict 1-year allograft outcomes. Donor demographic factors, donor type, and allograft parameters such as biopsy results and machine-measured renal resistance were correlated with 1-year graft outcome. The Kaplan-Meier method was used to estimate graft survival using the categorical predictors of donor type, donor age, and machine measured renal resistance at 1.5, 3, and 5 hours. The log-rank test was used to test the difference in survival curves between cohorts. The Cox regression analysis was used to estimate hazard ratios for machine-measured renal resistance, donor age, donor terminal creatinine level, donor's estimated glomerular filtration rate, cold ischemia time, and percent glomerulosclerosis. The data show that machine-measured renal resistance at 3 and 5 hours has a statistically significant inverse relationship to 1-year graft survival. All other risk factors had no correlation with 1-year graft survival. The machine-measured renal resistance at 3 hours is the earliest significant predictor of 1-year allograft outcome.     

Feasibility and correlation of standard 2D speckle tracking echocardiography and automated function imaging derived parameters of left ventricular function during dobutamine stress test

Speckle tracking echocardiography (STE) is a method of quantitative assessment of myocardial function complementary to ejection fraction and visual evaluation. Standard STE analysis, demands manual tracing of the myocardium whereas automated function imaging (AFI) offers more convenient (based on selection of three points) assessment of longitudinal strain. Nevertheless, feasibility and correlation between both methods were not thoroughly examined, especially during tachycardia at peak stage of dobutamine stress echocardiography (DSE). We performed DSE in 238 patients (pts) with recording of apical views during baseline (0) and peak (1) DSE and analyzed them by STE and AFI. According to angiography, 127/238 pts had significant (≥70 %) lesions in coronary arteries. We assessed correlations between STE and AFI derived peak systolic longitudinal strain values for global and regional parameters, feasibility, time of analysis and interobserver agreement. Global systolic longitudinal strain measured during baseline and peak stage of DSE by AFI showed very good correlation with standard STE parameters, with correlation coefficients r = 0.90 and r = 0.86 respectively (p < 0.0001). For regional parameters correlation coefficients ranged from 0.83 to 0.85 for baseline and from 0.70 to 0.79 for peak DSE. Both methods provided good and similar feasibility with only 1 % segments excluded from analysis at peak stage of DSE with shorter time and lower coefficient of variance offered by AFI. Global and regional longitudinal strain achieved by faster and less operator-dependent AFI method correlate well with standard more time-consuming STE analysis during baseline and peak stage of DSE.     

Combined thirty-day exposure to thioacetamide and choline-deprivation alters serum antioxidant status and crucial brain enzyme activities in adult rats

Choline (Ch) is an essential nutrient that seems to be involved in a wide variety of metabolic reactions and functions that affect the nervous system, while thioacetamide (TAA) is a well-known hepatotoxic agent. The induction of prolonged Ch-deprivation (CD) in rats receiving TAA (through the drinking water) provides an experimental model of mild progressive hepatotoxicity that could simulate commonly-presented cases in clinical practice. In this respect, the aim of this study was to investigate the effects of a 30-day dietary CD and/or TAA administration (300 mg/L of drinking water) on the serum total antioxidant status (TAS) and the activities of brain acetylcholinesterase (AChE), Na⁺,K⁺-ATPase and Mg²⁺-ATPase of adult rats. Twenty male Wistar rats were divided into four groups: A (control), B (CD), C (TAA), D (CD+TAA). Dietary CD was provoked through the administration of Ch-deficient diet. Rats were sacrificed by decapitation at the end of the 30-day experimental period and whole brain enzymes were determined spectrophotometrically. Serum TAS was found significantly lowered by CD (−11% vs Control, p < 0.01) and CD+TAA administration (−19% vs Control, p < 0.001), but was not significantly altered due to TAA administration. The rat brain AChE activity was found significantly increased by TAA administration (+11% vs Control, p < 0.01), as well as by CD+TAA administration (+14% vs Control, p < 0.01). However, AChE was not found to be significantly altered by the 30-day dietary CD. On the other hand, CD caused a significant increase in brain Na⁺,K⁺-ATPase activity (+16% vs Control, p < 0.05) and had no significant effect on Mg²⁺-ATPase. Exposure to TAA had no significant effect on Na⁺,K⁺-ATPase, but inhibited Mg²⁺-ATPase (−20% vs Control, p < 0.05). When administered to CD rats, TAA caused a significant decrease in Na⁺,K⁺-ATPase activity (−41% vs Control, p < 0.001), but Mg²⁺-ATPase activity was maintained into control levels. Our data revealed that an adult-onset 30-day dietary-induced CD had no effect on AChE activity. Treatment with TAA not only reversed the stimulatory effect of CD on adult rat brain Na⁺,K⁺-ATPase, but caused a dramatic decrease in its activity (−41%). Previous studies have linked this inhibition with metabolic phenomena related to TAA-induced fulminant hepatic failure and encephalopathy. Our data suggest that CD (at least under the examined 30-day period) is an unfavorable background for the effect of TAA-induced hepatic damage on Na⁺,K⁺-ATPase activity (an enzyme involved in neuronal excitability, metabolic energy production and neurotransmission).     

Use of lamotrigine in glossopharyngeal neuralgia: a case report

We describe a case of a patient with glossopharyngeal neuralgia (refractory to treatment with carbamazepine, amytriptyline, diazepam, and indomethacin) treated with lamotrigine as monotherapy, the first described, who responded completely to the therapy and did not complain of side effects. The complete analgesic effect was reached at the lamotrigine daily dose of 200 mg per day and was maintained at that dose for additional 6 months, with the blood concentration within the reference range.     

Experimentally-induced Wernicke’s encephalopathy modifies crucial rat brain parameters: the importance of Na+,K+-ATPase and a potentially neuroprotective role for antioxidant supplementation

Wernicke’s encephalopathy (WE) is a serious neuropsychiatric syndrome caused by chronic alcoholism and thiamine (T) deficiency. Our aim was to shed more light on the pathophysiology of WE, by introducing a modified in vivo experimental model of WE and by focusing on changes provoked in the total antioxidant status (TAS) and three crucial brain enzyme activities in adult rats. Rats were placed on ethanol (EtOH) consumption (20 %?v/v) for a total of 5 weeks. By the end of the third week, rats were fed a T-deficient diet (TDD) and were treated with pyrithiamine (PT; 0.25 mg/kg) for the remaining 2 weeks. Following the induction of WE symptomatology, rats were treated with three consecutive (every 8 h) injections of saline or T (100 mg/kg) and were sacrificed. Brain homogenates were generated and used for spectrophotometrical evaluation of TAS and enzymatic activities. Additionally, in vitro experiments were conducted on brain homogenates or pure enzymes incubated with T or neuromodulatory antioxidants. Pre-exposure to EtOH provided a successful protocol modification that did not affect the expected time of WE symptomatology onset. Administration of T ameliorated this symptomatology. WE provoked oxidative stress that was partially limited by T administration, while T itself also caused oxidative stress to a smaller extent. Brain acetylcholinesterase (AChE) was found inhibited by WE and was further inhibited by T administration. In vitro experiments demonstrated a potential neuroprotective role for L-carnitine (Carn). Brain sodium-potassium adenosine triphosphatase (Na⁺,K⁺-ATPase) activity was found increased in WE and was reduced to control levels by in vivo T administration; this increase was also evident in groups exposed to PT or to TDD, but not to EtOH. In vitro experiments demonstrated a potential neuroprotective role for this Na⁺,K⁺-ATPase stimulation through T or L-cysteine (Cys) administration. Brain magnesium adenosine triphosphatase (Mg²⁺-ATPase) activity was found decreased by prolonged exposure to EtOH, but was not affected by the experimental induction of WE. Our data suggest that T administration inhibits AChE, which is also found inhibited in WE. Moreover, increased brain Na⁺,K⁺-ATPase activity could be a marker of T deficiency in WE, while combined T and antioxidant co-supplementation of Cys and/or Carn could be neuroprotective in terms of restoring the examined crucial brain enzyme activities to control levels.     

Cytomegalovirus infection in renal transplant recipients

Cytomegalovirus (CMV) belongs to the family of human herpes viruses. It is also known as the human herpes virus 5 (HHV-5). In immunocompromised host it becomes significant pathogen, causing the spectrum of different symptoms and affecting different tissues and organs. Epidemiologic forms of CMV infection include primary infection, reactivation or secondary infection, and superinfection or reinfection. CMV infection has direct and indirect effects. Direct effects occur at the time of highest viraemia with severe clinical presentation. To the contrast, indirect effects occur at the time of asymptomatic viraemia as the consequence of immunologic response. Indirect effects are mediated by cytokines, chemokines and growth factors. Diagnosis of CMV infection is based on virus detection in body fluids and tissues. There are several diagnostic methods for detection of CMV, and their use is primarily determined by the possibilities of the specific transplantation center. Regarding the risk of CMV infection, several categories of renal transplant recipients may be identified. The main factor for estimation of risk for development of CMV infection is donor and recipient serological status. The highest risk is associated with combination of CMV seropositive donor and CMV seronegative recipient (D+/R-). CMV infection was often fatal before introduction of potent antiviral drugs in therapeutic protocols. Contemporary treatment has significantly decreased mortality rate from the CMV infection. Several drugs are used for prevention and treatment of CMV infection: hyper immune gamma globulin, gancyclovir, valgancyclovir, valacyclovir and acyclovir, depending on the kind of treatment (prophylaxis or preemptive treatment). In the case of CMV disease, the best results may currently be achieved with the combination of hyper immune gamma globulin and intravenous gancyclovir.     

The role of nephrologist in treatment of multiple myeloma

Multiple myeloma (MM) is malignant disease caused by proliferation of malignant clone of terminally differentiated plasma-cells. Clinical features may include symptoms of bone disease, unexplained back-pain, fractures, anaemia, kidney failure, oedema, hypercalcaemia, bacterial infections, impaired hemostasis, peripheral neuropathy and hyperviscosity. Impairment of renal function occurs in 50% of patients with different forms of kidney disease. Majority of patients have precipitation of monoclonal immunoglobulins or their fragments in kidney. Hypercalcemia, dehydration, infections and nephrotoxic drugs contribute to development of kidney injury. Treatment consists of chemotherapy for primary disease, with plasma exchange in cases of hyperviscosity. Supportive treatment should include rehydration, treatment of hyperuricemia and hypercalcaemia. Patients with end-stage renal disease could be treated with peritoneal dialysis or haemodialysis. Renal transplantation is rarely offered to this group of patients.