João Cruz

Renal Toxicity Mediated by Continuous Infusion of Recombinant lnterleukin-2

Interleukin-2 (IL-2), a potent lymphokine with antitumoral activity, was used in continuous intravenous infusion for 5 days (18,000,000 IU/m2/day) in 9 treatment cycles in 5 patients with metastatic colorectal carcinoma. During the infusion, patients received aggressive fluid replacement titrated by invasive hemodynamic monitoring, aiming at a stable central volemia. Body weight went up an average of 4.5 kg in 5 days, mean arterial blood pressure dropped slightly from day 1 to day 5 (105.4 +/- 11.6 to 86.1 +/- 12.5 mm Hg, p < 0.05), systemic vascular resistance decreased from 1304.7 +/- 242.1 to 871.7 +/- 237.2 dyn/s/cm-5 (p < 0.05), with stable pulmonary capillary wedge pressure, cardiac output and central venous pressure. The urinary output significantly dropped from 1.9 +/- 1.2 to 0.2 +/- 0.1 ml/min (p < 0.05) with very significant rises in serum creatinine from 76.0 +/- 28.3 to 242.2 +/- 144.9 mumol/l (0.86 +/- 0.32 to 2.47 +/- 1.64 mg/dl) and N-acetyl-beta-D-glucosaminidase urinary activity from 4.97 +/- 5.0 to 23.0 +/- 12.1 U/l, and significant decrement of creatinine clearance (1.86 +/- 0.65 to 0.29 +/- 0.27 ml/s or 111.5 +/- 38.9 to 17.1 +/- 16.6 ml/min) and urinary sodium (113.8 +/- 78.3 to 9.0 +/- 6.7 mmol/l). Urine sediment evolved from normal at day 1 to 9.0 +/- 3.7 epithelial cells/mm3 and 6.9 +/- 3.6 brown casts/mm3 (p = 0.001). We concluded that cancer treatment with IL-2 in continuous infusion, even with stable hemodynamics, induces an acute renal failure in most patients treated.

A Prospective Study on Incidence of Bacterial Infections in Portuguese Dialysis Units

Background: Viral infection has been the main epidemiologic concern in the hemodialysis unit; however, bacterial infection is responsible for more than 30% of all causes of morbidity and mortality in our patients, vascular access infection being the culprit in 73% of all bacteremias. Methods: A prospective multicenter cohort study of bacterial infections incidence, conducted from January to July 2004 in five hemodialysis units, to record and track bacterial infections, using a validated database from CDC’s Dialysis Surveillance Network Program. Results: 4,501 patient-months (P-M) were surveilled, being dialyzed through a native fistula (AVF) in 60.6%, a graft (PTFE) in 31.3%, a tunneled catheter (TC) in 7.6%, and a transient catheter (C) in 0.5%. As target events, we registered 166 hospitalizations – 3.7/100 P-M (2.2/100 P-M in patients with AVF, 4 in PTFE, 9.9 in TC, and 19 in C), and 182 intravenous antibiotic courses. Of these 182 antibiotic treatments, 47.8% included vancomycin, only 30% had blood cultures drawn pretreatment, and only 36% were positive. We recorded 98 infections at the vascular access site 2.18/100 P-M (0.95 in AVF, 1.6 in PTFE, 12.6 in TC, and 42.85 in C) and 2.13 infections/100 P-M at other sites. The isolated microorganisms were Staphylococcus epidermidis in 40.1%, Staphylococcus aureus in 30.1%, Pseudomonas in 13.3%, and Escherichia coli in 3.3%. Although we found a diversity of practice patterns, the number of target events (8.4/100 P-M) and the bacterial infections incidence (4.31/100 P-M) were remarkably homogeneous in the five centers. Conclusion: (1) High incidence of bacterial infections, causing major morbidity; (2) infectious risk is vascular access type-dependent, with dramatic rise in catheters; (3) underutilization of blood cultures to orient diagnosis and therapy, and (4) high rates of vancomycin prescription.

Efficacy of Percutaneous Transluminal Angioplasty on Dysfunctional Fistulae Because of Inflow Stenosis

Purpose Autogenous fistulas are the preferential vascular access for hemodialysis. The aim of this retrospective study was to determine the efficacy of angioplasty for dysfunctional fistulas because of inflow dysfunction. Methods We reviewed all the angiographic procedures performed on our institution between April 2007 and April 2009. Procedures performed in dysfunctional fistulas because of inflow stenoses were analyzed. Fistulas with stenoses out of these areas were excluded. The following data were collected: patient age and sex, fistula age at the time of intervention, location of fistula, number and location of stenosis, angiography referral criteria, clinical findings (presence or absence of thrills, bruits and pulsatility) and date of reintervention or failure. Results During the study period 215 fistulas were submitted to angiography of which, seventy-one presented inflow stenosis (33%). Mean follow-up was 21.72±9.26 months, and average age was 7.03 months. Two groups were considered: 31 fistulas comprising ≤6 months old, and 40 fistulas >6 months old. Primary patency rates±SE for older fistulas at 6, 12, 18 and 24 months, respectively, was 91.3%± 0.04%, 80.7%± 0.07%, 53.8% ±0.10% and 34.2±0.1%. versus 91.7±0.08%, 57.1 ±0.14%, 23±0.14%, 11.4%± 0.1% for younger fistulas (P=0.04). Fistulas ≤6 months old and multiple stenosis were associated with a poorer primary patency rate (P=0.005). Conclusions Inflow stenosis is frequently associated with fistula dysfunction. In this study we only analyzed AVF with inflow stenosis and we have shown that angioplasty can have great patency results, particularly for single lesions in matured fistulas.

Lemmel’s Syndrome: A Rare Cause of Cholestasis

performed to exclude peri-ampullary tumor. The biopsy did not reveal tumor cells. A diagnostic of Lemmel’s syndrome (i.e., juxtampullary duodenal diverticulum compressing the intrapancreatic bile duct resulting in obstructive jaundice in the absence of cholelithiasis or other detectable obstacles) was done. Duodenum diverticula are most frequently asymptomatic.1,2 Lemmel’s syndrome was first described in 1934,3 but to date, very few cases have been published. The diagnosis is confirmed by imaging, including barium meal, EUS, endoscopic retrograde cholangiopancreatography, CT or magnetic resonance cholangiopancreatography.4,5 Lemmel’s Syndrome: A Rare Cause of Cholestasis

Does pre- and post-angioplasty Doppler ultrasound evaluation help in predicting vascular access outcome?

Background Kidney Disease – Improving Global Outcomes (KDIGO) recommends post-percutaneous transluminal angioplasty (PTA) <30% residual stenosis (RS) and hemodynamic parameters improvement. Primary end point: how post-PTA access blood flow (ABF) improvement predicts vascular access (VA) outcome. Secondary: compare Doppler ultrasound (DU) and angiography diagnostic accuracy; determine how other factors predict outcome. Methods Eighty patients. DU evaluation performed pre- and post-PTA. Several parameters recorded. Secondary patency verified after 6 months. Results Initial ABF 537 ± 248 mL/min; final ABF 1013 ± 354 mL/min. Number and location of stenosis was highly correlated between DU and angiography (p<0.001); central vessels mismatching. First semester overall survival was 63%; significantly better for fistulas (76%) than grafts (51.7%), p 0.044. Final RS>30% associated to better survival, p 0.038. Initial ABF<500 mL/min and multiple stenosis did not affect outcome (p>0.05). A >2-fold ABF increase had no significant impact on fistulas (p>0.05) but was significantly associated with worst outcomes in grafts (23.1% vs. 73.5%, p 0.009). Grafts had lower survival (HR 3.3, p 0.034). Conclusions Although less accurate for central lesions, DU has a key role on VA surveillance, allowing a morphologic and hemodynamic assessment. Angioplasty is effective in preserving VA; however, it may increase restenosis due to accelerated neointimal hyperplasia. Current parameters are not useful. Trials addressing this issue are needed.

Geographical variability of patient characteristics and treatment patterns affect outcomes for incident hemodialysis patients.

BACKGROUND Geographical differences in disease prevalence and mortality have been described in the general population and in chronic kidney disease patients in Europe. In this secondary analysis of the Membrane Permeability Outcome (MPO) study, we addressed differences in patient and treatment patterns, and whether these affect patient outcomes. METHODS Participating countries were grouped according to geographical location; thus study centers in France, Greece, Italy, Portugal and Spain were allocated to southern Europe (n=499), and those in all other countries (Belgium, Germany, Poland and Sweden) to northern Europe (n=148). Descriptive analysis of patient and treatment patterns at study start, as well as survival analysis, was performed. RESULTS In patients from the northern European countries, a higher prevalence of diabetes mellitus and of cardiovascular disease was observed than in those from southern Europe (diabetes 35.1% vs. 21.0%, p=0.0007; cardiovascular disease 40.5% vs. 22.8%, p<0.0001). In northern Europe, 23% of patients started hemodialysis with a catheter for vascular access, while in southern European centers, only 13% did so (p=0.0042). Kaplan-Meier survival analysis revealed a lower probability for both all-cause and cardiovascular mortality in southern Europe (log-rank test p<0.001). In a Cox proportional hazards model, a higher mortality risk was estimated for the northern European patients after adjustment for age, sex, membrane permeability, comorbidity index and vascular access (hazard ratio = 1.831; 95% confidence interval, 1.282-2.615; p=0.0009). CONCLUSIONS Our study patients from northern Europe showed a higher risk profile than those from southern Europe. However, only some of the factors can be modified in attempts to lower the mortality risk in this geographical area.