Louise Roy

Predictors of clinical response to transjugular intrahepatic portosystemic shunt (TIPS) in cirrhotic patients with refractory ascites

Objective:Transjugular intrahepatic portosystemic shunt (TIPS) is used increasingly as a treatment for refractory ascites. The aim of the present study was to determine the prognostic value of different parameters in predicting a favorable evolution following TIPS in a cohort of 53 cirrhotic patients without organic renal disease and with refractory ascites.Methods:Patients were classified as good responders if they survived more than 6 months, without severe chronic hepatic encephalopathy and with good control of ascites. The prognostic value for a good outcome was evaluated using age, creatinine clearance, plasma renin activity, plasma aldosterone, and Pugh score.Results:Good control of ascites was obtained in 90%. The cumulative survival rate was 54% at 6 months, 48% at 1 yr, and 39% at 2 yr. The vast majority of patients died of complications of hepatic insufficiency. Severe chronic hepatic encephalopathy developed in 26%. Overall, a good clinical response was observed in 47%. Creatinine clearance was identified as the only pre-TIPS factor to be significantly and independently associated with a good clinical response to TIPS for refractory ascites. A good clinical response was observed in 57% of patients with a creatinine clearance >36 ml/min compared to 9% of those with a clearance <36 ml/min p < 0.01. This cutoff point in creatinine clearance had a sensitivity of 96% and a specificity of 36%; positive predictive and negative predictive values were 57% and 90%, respectively.Conclusions:TIPS might be useful for the treatment of refractory ascites in cirrhotic patients without severe renal function impairment. However, the TIPS usefulness still has to be demonstrated compared to large volume paracentesis or Leveen shunt. In patients with poor renal function or with liver failure after TIPS, liver transplantation should be considered.

Changes in plasma endothelin-1 and Big endothelin-1 induced by transjugular intrahepatic portosystemic shunts in patients with cirrhosis and refractory ascites

BACKGROUND/AIMS Endothelin-1 (ET-1) is a potent vasoconstrictor that may be involved in the pathogenesis of splanchnic and renal hemodynamic changes associated with portal hypertension. The aim of this study was to measure the concentration of ET-1 and of its precursor Big endothelin-1 (Big ET-1) in the systemic circulation as well as in the splanchnic and renal venous beds and to evaluate changes after the relief of portal hypertension following transjugular intrahepatic portosystemic shunt placement. METHODS Plasma concentrations of ET-1 and of Big ET-1 were measured in the vena cava, renal vein, hepatic vein and portal vein in ten patients with cirrhosis and refractory ascites before and 1-2 months after transjugular intrahepatic portosystemic shunt. The porto-caval gradient, creatinine clearance, plasma aldosterone and renin activity, as well as daily urinary sodium excretion were measured at the same time. RESULTS The plasma concentration of ET-1 and Big ET-1, respectively, in peripheral blood of normal volunteers were 0.28 +/- 03 and 3.95 +/- 0.34 pg/ml; the concentrations of both peptides were higher in patients with cirrhosis, both in vena cava (0.61 +/- 0.14 and 10.01 +/- 1.47 pg/ml), hepatic vein (0.62 +/- 0.13 and 13.93 +/- 1.77 pg/ml), portal vein (1.21 +/- 0.12 and 17.84 +/- 1.98 pg/ml) and renal vein (0.76 +/- 0.12 and 14.21 +/- 1.55 pg/ml). Moreover ET-1 and Big ET-1 concentrations were more elevated in the portal vein than in the vena cava (+98% and +70%) and slightly higher in the renal vein as compared to the vena cava (+25% and +42%). After transjugular intrahepatic portosystemic shunt, a rise in creatinine clearance and urinary sodium excretion (+49%; and +53%) was observed together with a marked reduction in plasma aldosterone and renin activity (-59% and -49%). ET-1 and Big ET-1 concentrations remained unchanged in the vena cava whereas a significant reduction of ET-1 and Big ET-1 occurred both in the portal vein (-43% and -44%) and in the renal vein (-53% and -29%). Portal vein and renal vein concentrations of both peptides became similar to vena cava levels. CONCLUSIONS Splanchnic and renal hemodynamic changes occurring in patients with cirrhosis and refractory ascites could be related to the production of ET-1 by splanchnic and renal vascular beds. This was abolished by transjugular intrahepatic portosystemic shunt, which could explain the exacerbation of systemic vasodilation and the improvement in renal perfusion observed after the procedure.

Principles and Operational Parameters to Optimize Poison Removal with Extracorporeal Treatments

A role for nephrologists in the management of a poisoned patient involves evaluating the indications for, and methods of, enhancing the elimination of a poison. Nephrologists are familiar with the various extracorporeal treatments (ECTRs) used in the management of impaired kidney function, and their respective advantages and disadvantages. However, these same skills and knowledge may not always be considered, or applicable, when prescribing ECTR for the treatment of a poisoned patient. Maximizing solute elimination is a key aim of such treatments, perhaps more so than in the treatment of uremia, because ECTR has the potential to reverse clinical toxicity and shorten the duration of poisoning. This manuscript reviews the various principles that govern poison elimination by ECTR (diffusion, convection, adsorption, and centrifugation) and how components of the ECTR can be adjusted to maximize clearance. Data supporting these recommendations will be presented, whenever available.

Successful treatment of lithium toxicity with sodium polystyrene sulfonate: a retrospective cohort study

Context. Lithium (Li) is a first-line treatment for bipolar disorder but has a narrow therapeutic index. Treatment of Li toxicity includes supportive measures and hemodialysis in severe cases, but this modality is not always immediately available. Sodium polystyrene sulfonate (SPS, Kayexalate™), a cation exchanger, has been promising in animal models and human reports to reduce absorption and enhance elimination of Li. Material and methods. A retrospective cohort study was conducted. All cases of chronic Li intoxication were reviewed in two adult-care hospitals from 2000 to 2009. A group comparison and a within-patient comparison were performed to compare the effect of SPS on the median Li half-life (T1/2). For this study, at least three serum Li levels were required for T1/2 calculations. Results. Forty-eight patients met inclusion requirements, 12 of whom had taken SPS. Median Li T1/2 in the treated and control groups was 20.5 and 43.2 hours, respectively (p = 0.0006). In the 12 treated patients, Li T1/2 during SPS was on average 48.9% shorter than without SPS. Furthermore, in one subject in whom urinary Li data were available, Li clearance with SPS was superior to Li renal clearance. Prolonged constipation was noted in one patient whereas mild hypokalemia was noted in six patients treated with SPS. Conclusion. This study shows that SPS reduced Li T1/2 and suggests that SPS is capable of promoting Li elimination in chronic intoxications. These results warrant a prospective trial looking at the use of SPS in the treatment of Li overdose as an adjunct to supportive measures and hemodialysis.

Adherence to antihypertensive agents improves risk reduction of end-stage renal disease

Uncontrolled hypertension is associated with an increased risk of end-stage renal disease (ESRD). Intensified blood pressure control may slow progression of chronic kidney disease; however, the impact of antihypertensive agent adherence on the prevention of ESRD has never been evaluated. Here we assessed the impact of antihypertensive agent adherence on the risk of ESRD in 185,476 patients in the RAMQ databases age 45 to 85 and newly diagnosed/treated for hypertension between 1999 and 2007. A case cohort study design was used to assess the risk of and multivariate Cox proportional models were used to estimate the adjusted hazard ratio of ESRD. Adherence level was reported as a medication possession ratio. Mean patient age was 63 years, 42.2% male, 14.0% diabetic, 30.3% dyslipidemic, and mean follow-up was 5.1 years. A high adherence level of 80% or more to antihypertensive agent(s) compared to a lower one was related to a risk reduction of ESRD (hazard ratio 0.67; 95% confidence intervals 0.54-0.83). Sensitivity analysis revealed that the effect is mainly in those without chronic kidney disease. Risk factors for ESRD were male, diabetes, peripheral artery disease, chronic heart failure, gout, previous chronic kidney disease, and use of more than one agent. Thus, our study suggests that a better adherence to antihypertensive agents is related to a risk reduction of ESRD and this adherence needs to be improved to optimize benefits.

Liver blood flow in chronic hemodialysis patients

The purpose of this study was to assess liver blood flow and cardiac output in chronic hemodialysis patients (n = 7) before and after a hemodialysis session, and to compare it to normal volunteers (n = 11). We used the hepatic clearance of sorbitol to calculate liver blood flow and echocardiograms to evaluate cardiac output. The latter was higher in hemodialysis patients (predialysis 4.7 +/- 1.8 liters/min, postdialysis 4.5 +/- 0.9 liters/min) compared to normal subjects (3.8 +/- 0.9 liters/min, p = 0.09 and p = 0.05). Hepatic blood clearance of sorbitol was similar in hemodialysis patients before and after dialysis (1,610 +/- 266 and 1,541 +/- 415 ml/min) as well as in normal volunteers (1,565 +/- 313 ml/min). The hepatic extraction ratio of sorbitol is slightly decreased in hemodialysis patients (n = 3) (0.87 +/- 0.03) compared to values reported in the literature for healthy subjects. We conclude that liver blood flow is not significantly altered in hemodialysis patients.

Epidural blood patch in a seven-year-old child

We present an unusual case of postoperative headache in a child after an epidural block. A seven-year-old girl (ASA 1) was scheduled to undergo a urological procedure under general anaesthesia combined with an epidural technique for intra- and postoperative analgesia. Although there was no evidence of durai puncture when the block was performed, the patient developed a headache postoperatively. The headache, which was accompanied by neck pain, appeared in the sitting or standing position and was relieved by decubitus. According to the mother, her child had never complained of those symptoms in the past. After independent evaluation by an anaesthetist and a neurologist, a postdural puncture headache (PDPH) was considered the most likely diagnosis. As oral analgesics failed to provide relief, an epidural blood patch (EBP) using 10 ml autologous blood was performed under light sedation. This was followed by resolution of the symptoms. Epidural injections of opioids and local anaesthetics are becoming increasingly popular for pain management in children. This implies that there may be an increasing number of unintentional durai punctures that may result in more PDPHs in children. Epidural blood patches are effective in treating PDPHs in adults but their use has been reported very rarely in children. Resolution of the patient’s symptoms following EBP supported the diagnosis while illustrating that EBP can be useful in the treatment of PDPH in children.RésuméNous rapportons un cas inhabituel de céphalées survenues en période postopératoire chez une enfant après une technique péridurale. Une patiente de sept ans a été admise pour subir une chirurgie urologique sous anesthésie générale combinée à une péridurale. Au cours de la période postopératoire, la patiente a développé une céphalée sans qu’il n’y ait eu aucune évidence de ponction de dure-mère lors de la technique péridurale. Les céphalées, associées à des cervicalgies, étaient de nature positionnelle: aggravées par la position verticale et soulagées par le décubitus. Selon la mère, sa fille ne se serait jamais plainte de céphalées dans le passé. Une anesthésiste et un neurologue, après avoir chacun évalué la patiente de façon indépendante, ont retenu la céphalée post-ponction de dure-mère (CPPDM) comme étant le diagnostic le plus probable. Devant l’inefficacité des analgésiques oraux, une injection péridurale de sang autologue (IPSA) de 10 ml a été pratiquée sous sédation légère. Par la suite, la patiente a noté la disparition de ses symptômes. L’utilisation d’anesthésiques locaux et de narcotiques par voie péridurale pour le contrôle de la douleur connaît une popularité croissante en pédiatrie. Ceci implique une augmentation des ponctions de dure-mère accidentelles et la possibilité d’une incidence accrue de CPPDM dans ce groupe d’âge. L’efficacité de l’IPSA dans le traitement des CPPDM a été bien démontrée chez l’adulte mais n’a été rapportée que très rarement chez l’enfant. La résolution des symptômes de cette patiente suite à l’IPSA a confirmé notre diagnostic en plus d’illustrer son utilité dans le traitement de la CPPDM dans la population pédiatrique.

Effect of cinacalcet availability and formulary listing on parathyroidectomy rate trends

BackgroundRecent trends in parathyroidectomy rates are not known. Our objective was to investigate the trend in parathyroidectomy rates between 2001 and 2010, and to evaluate if the availability and reimbursement of cinacalcet modified that trend.MethodsUsing a provincial administrative database, we included all adult patients receiving chronic dialysis treatments between 2001 and 2010 (incident and prevalent) in a time series analysis. The effect of cinacalcet availability on parathyroidectomy bimonthly rates was modeled using an ARIMA intervention model using different cut-off dates: September 2004 (Health Canada cinacalcet approval), January 2005, June 2005, January 2006, June 2006 (date of cinacalcet provincial reimbursement), and January 2007.ResultsA total of 12 795 chronic dialysis patients (mean age 64 years, 39% female, 82% hemodialysis) were followed for a mean follow-up of 3.3 years. During follow-up, 267 parathyroidectomies were identified, translating to an average rate of 7.0 per 1000 person-years. The average parathyroidectomy rate before cinacalcet availability was 11.4 /1000 person-years, and 3.6 /1000 person-years after cinacalcet public formulary listing. Only January 2006 as an intervention date in the ARIMA model was associated with a change in parathyroidectomy rates (estimate: -5.58, p = 0.03). Other intervention dates were not associated with lower parathyroidectomy rates.ConclusionsA reduction in rates of parathyroidectomy was found after January 2006, corresponding to cinacalcet availability. However, decreased rates may be due to other factors occurring simultaneously with cinacalcet introduction and further studies are needed to confirm these findings.

Irreversible Renal Failure Associated with Triamterene

A 66-year-old man was admitted with acute oliguric renal failure. The patient was known to have chronic heart failure (ejection fraction 13%) and his medication included furosemide, digoxin and triamterene. Physical examination was unremarkable, and blood pressure was 170/80 mm Hg. Serum creatinine was 1,173 mumol/l. Renal ultrasound, CT scan and angiogram were normal. Despite correction of potential reversible factors and discontinuation of triamterene, renal function did not improve. Renal biopsy showed tubular obstruction with deposition of birefringent crystals and interstitial lymphocytic infiltration; the crystals emitted a blue autofluorescence at 425 nm, typical of triamterene. Renal tissue contained large amounts of triamterene (6.44 mg/g kidney at the initial biopsy and 400 micrograms/g kidney 5 months later). Triamterene has been previously reported to cause acute reversible renal failure, but to our knowledge, this is the first case of irreversible renal failure due to intratubular obstruction by triamterene crystal deposition.

A stepwise approach for the management of poisoning with extracorporeal treatments.

The use of an extracorporeal treatment (ECTR) in a poisoned patient may be life‐saving in a limited number of scenarios. The decision‐processes surrounding the use of ECTR in poisoning is complex: most nephrologists are not trained to assess a poisoned patient while clinical toxicologists rarely prescribe ECTRs. Deciding on which ECTR is most appropriate for a poison requires a good understanding of the poisons physicochemical and pharmacokinetic properties. Further, a detailed understanding of the capabilities and limitations of the different ECTRs can be useful to select the most appropriate ECTR for a given clinical situation. This manuscript provides a stepwise approach to assess the usefulness of ECTRs in poisoning.