Paul Tam

A Randomized Controlled Trial Comparing Mupirocin and Polysporin Triple Ointments in Peritoneal Dialysis Patients: The MP3 Study

BACKGROUND AND OBJECTIVESnInfectious complications remain a significant cause of peritoneal dialysis (PD) technique failure. Topical ointments seem to reduce peritonitis; however, concerns over resistance have led to a quest for alternative agents. This study examined the effectiveness of applying topical Polysporin Triple ointment (P(3)) against mupirocin in a multi-centered, double-blind, randomized controlled trial.nnnDESIGN, SETTING, PARTICIPANTS, & MEASUREMENTSnPD patients routinely applied either P(3) or mupirocin ointment to their exit site. Patients were followed for 18 months or until death or catheter removal. The primary study outcome was a composite endpoint of exit-site infection (ESI), tunnel infection, or peritonitis.nnnRESULTSnSeventy-five of 201 randomized patients experienced a primary outcome event (51 peritonitis episodes, 24 ESIs). No difference was seen in the time to first event for P(3) (13.2 months; 95% confidence interval, 11.9-14.5) and mupirocin (14.0 months; 95% confidence interval, 12.7-15.4) (P=0.41). Twice as many patients reported redness at the exit site in the P(3) group (14 versus 6, P=0.10). Over the complete study period, a higher rate per year of fungal ESIs was seen in patients using P(3) (0.07 versus 0.01; P=0.02) with a corresponding increase in fungal peritonitis (0.04 versus 0.00, respectively; P<0.05).nnnCONCLUSIONSnThis study shows that P(3) is not superior to mupirocin in the prophylaxis of PD-related infections. Colonization of the exit site with fungal organisms is of concern and warrants further study. As such, the use of P(3) over mupirocin is not advocated in the prophylaxis of PD-related infections.

Improvement in eGFR in patients with chronic kidney disease attending a nephrology clinic

BackgroundThe adverse effects arising from late referral to a nephrologist of patients with chronic kidney disease (CKD) are well known. Retrospectively we examined the initial characteristics of patients referred in various stages of CKD to our nephrology division and tried to identify potential baseline factors associated with subsequent changes in estimated glomerular filtration rate (eGFR).Patients and methodsBetween September 1997 and June 2006 1,443 patients (909 male, 534 female) with CKD, with eGFRs ranging from 15 to 89xa0ml/min, were referred to our nephrology division and categorized using the National Kidney Foundation classification for CKD based on eGFR. The slope of eGFR change (ml/min−1/1.73/m2−1/year−1) was determined by linear regression analysis and the patients were divided into five groups: (1) significantly progressive slope (deterioration) (more negative than −5xa0ml/min/year); (2) mildly progressive slope (>−5 to ≤−1); (3) stable slope (>−1 to ≤+1); (4) mildly improved slope (>+1 to ≤+5), and (5) significantly improved slope (≥+5).ResultsAt the first nephrology referral, 5.8% of the patients were on CKD stage 2 (eGFR: 90–60xa0ml/m), 46.7% on CKD stage 3 (eGFR: 59–30xa0ml/m), and 47.5% on CKD stage 4 (eGFR: 29–15xa0ml/m) CKD. Significantly improved slope was detected in 48.2% of CKD stage 2 patients, 29.3% of CKD stage 3 patients, and only 14.7% of CKD stage 4 patients (Pxa0<xa00.05). Being in stage 4 or stage 3 versus being in stage 2 significantly reduced the likelihood of an improved slope in logistic regression analysis whereas age, gender, presence of hypertension, and diabetes mellitus did not reach the level of significance.ConclusionReferral to a nephrology clinic can lead not only to arrest of progression of CKD but also to regression/improvement. Early referral is a positive predictive factor for improvement in eGFR, which emphasizes the importance of such referral. The previously held idea that, once established, CKD progresses invariably is not valid anymore.

Generalized Seizure and Toxic Epidermal Necrolysis following Levofloxacin Exposure

OBJECTIVE: To report the case of a ciprofloxacin-allergic patient who developed a generalized tonic—clonic seizure and toxic epidermal necrolysis (TEN) following a single dose of levofloxacin. CASE SUMMARY: An 87-year-old white woman was admitted to the hospital following a transient episode of unresponsiveness that had been accompanied by flailing of her limbs. Approximately 4 hours earlier, she had developed a pruritic rash on her trunk and limbs, and 3 hours before this had taken a first dose of levofloxacin. The fluoroquinolone had been prescribed for treatment of an upper respiratory tract infection. She had developed a skin rash approximately 3 years earlier following ciprofloxacin prescribed for a urinary tract infection. On admission, the patient had a normal neurologic examination. She was mildly hypomagnesemic (serum magnesium 1.7 mg/dL), with no other electrolyte imbalances present. Skin biopsy confirmed TEN. The lesions progressed to involve 30% of the body surface area and were managed with polymyxin B and gramicidin cream. Levofloxacin was discontinued on admission, and no anticonvulsants were prescribed. The woman remained seizure-free at discharge one week later. DISCUSSION: Generalized tonic—clonic seizures are a rare complication of levofloxacin therapy. TEN following levofloxacin use has, to our knowledge, as of March 28, 2005, been previously reported only once. The seizure and TEN were probably induced by levofloxacin as corroborated by the Naranjo probability scale. We believe that the previous adverse dermatologic reaction to ciprofloxacin sensitized our patient to levofloxacin. CONCLUSIONS: These rare adverse reactions to levofloxacin, involving disparate organ systems, can occur simultaneously. A previous dematologic adverse reaction to a fluoroquinolone can sensitize a patient to more severe adverse reactions (with onset after only a single dose of the subsequent fluoroquinolone). Further fluoroquinolone use should be avoided in such patients.

Use of PTFE Stent Grafts for Hemodialysis-related Central Venous Occlusions: Intermediate-Term Results

PurposeTo assess the safety and effectiveness of a polytetrafluoroethylene (PTFE) encapsulated nitinol stents (Bard Peripheral Vascular, Tempe, AZ) for treatment of hemodialysis-related central venous occlusions.Materials and MethodsStudy design was a single-center nonrandomized retrospective cohort of patients from May 2004 to August 2009 for a total of 64 months. There were 14 patients (mean age 60 years, range 50–83 years; 13 male, 1 female). All patients had autogenous fistulas. All 14 patients had central venous occlusions and presented with clinical symptoms of the following: extremity swelling (14%, 2 of 14), extremity and face swelling (72%, 10 of 14), and face swelling/edema (14%, 2 of 14). There was evidence of access dysfunction with decreased access flow in 36% (5 of 14) patients. There were prior interventions or previous line placement at the site of the central venous lesion in all 14 patients. Results were assessed by recurrence of clinical symptoms and function of the access circuit (National Kidney Foundation recommended criteria).ResultsSixteen consecutive straight stent grafts were implanted in 14 patients. Average treated lesion length was 5.0xa0cm (range, 0.9–7xa0cm). All 14 patients had complete central venous occlusion (100% stenosis). The central venous occlusions were located as follows: right subclavian and brachiocephalic vein (21%, 3 of 14), right brachiocephalic vein (36%, 5 of 14), left brachiocephalic vein (36%, 5 of 14), and bilateral brachiocephalic vein (7%, 1 of 14). A total of 16 PTFE stent grafts were placed. Ten- or 12-mm-diameter PTFE stent grafts were placed. The average stent length was 6.1xa0cm (range, 4–8xa0cm). Technical (deployment), anatomic (<30% residual stenosis), clinical (resolution of symptoms), and hemodynamic (resolution of access dysfunction) success were 100%. At 3, 6, and 9xa0months, primary patency of the treated area and access circuit were 100% (14 of 14).ConclusionsThis PTFE encapsulated stent graft demonstrates encouraging intermediate-term patency results for central vein occlusions. Further prospective studies with long-term assessment and larger patient populations will be required.

Natural history of CKD stage 4 and 5 patients following referral to renal management clinic

BackgroundCKD patients referred to a renal management clinic are looked after by a multidisciplinary team whose care may improve outcome and delay the progression of kidney disease. This paper describes our experience and the results obtained in 940 patients with CKD stage 4 and 5 patients from two renal management clinics (RMC).Subjects and methodsWe collected and analyzed the data from 940 patients with CKD stage 4 and 5 at the RMCs of the Toronto General Hospital (TGH), University Health Network and The Scarborough General Hospital (TSH) from January 2000 to November 2007. Inclusion criteria for the study required at least three measurements of serum creatinine over a minimum follow-up of 6xa0months. We calculated the change of slope of the estimated GFR by linear regression analysis. The slopes were further subdivided into five groups: improved eGFR (eGFR slope ≥+5xa0ml/min/year); mild improvement (slope >+1 to <+5xa0ml/min/year); stable (slope <+1 to >−1xa0ml/min/year); slow progression (i.e., deterioration; slope <−1 to >−5xa0ml/min/year) and rapid progression (slope >−5xa0ml/min/year).ResultsDuring a median follow-up of 1.57xa0year (range 0.5–8.7xa0year) of stage 4 patients, eGFR improved in 10.6%, showed mild improvement in 24.2%, was stable in 27.5%, showed slow progression in 28.8% and rapid progression in 8.9% of patients. During a median follow-up of 1.4xa0year (range 0.5–8xa0year) of CKD stage 5 patients, eGFR improved in only 1.3%, showed mild improvement in 4.3%, remained stable in 35.6%; showed slow progression in 19.7% and rapid progression in 39.1%. Between the two hospitals (TGH and TSH) there was a statistically significant difference in the number of visits per year for CKD stage 4 patients during the first, second and third year. However, the number of visits per year had no effect on the rate of decline. On univariate analysis, factors predicting non-progression in eGFR slope were eGFR at referral, the use of ACE inhibitors-ARBs and absence of cardiovascular disease. However, in logistic multivariate regression analysis, after adjusting for confounding factors only the eGFR at referral and ACE inhibitors-ARBs were independent factors for non-progression in eGFR.Summary and conclusionsA significant percentage of CKD stage 4 patients attending a renal management clinic (RMC) showed non-progression or improvement in their kidney function. Although only few stage 5 CKD patients had improvement in their eGFR, 32% of them maintained their eGFR on conservative treatment for over 2xa0years delaying the initiation of dialysis.

Ultrahigh-Pressure Angioplasty versus the Peripheral Cutting Balloon™ for Treatment of Stenoses in Autogenous Fistulas: Comparison of Immediate Results:

Purpose To compare the immediate results of ultrahigh-pressure (UHP) balloons vs. peripheral cutting balloons (PCB) for the treatment of stenoses associated with autogenous fistulas using intra-access blood flow measurements. Materials and Methods This prospective randomized study consisted of 22 hemodialysis (HD) patients with autogenous fistulas who had decreased intra-access blood flow (<500 mL/min). All patients underwent a fistulogram and intraprocedural blood flow measurements. Patients were randomized once into two groups; one group undergoing UHP angioplasty and the second group undergoing PCB angioplasty. Randomization occurred once after the diagnostic fistulogram and each patient in each arm only underwent percutaneous transluminal angioplasty with either UHP or PCB. The study cohort consisted of 12 patients in the UHP group and 10 patients in the PCB group. Data collected included fistula anatomy, degree of stenosis, length of stenosis, balloon specifications and residual stenosis. Results The 22 study patients underwent 35 angioplasty procedures; 23 in the UHP group (12 patients) and 12 in the PCB group (10 patients). The technical success rate was 91%. The pre-intervention mean blood flow was 288 mL/min in the UHP group and 391 mL/min in the PCB group. The post-intervention mean blood flow was 613 mL/min in the UHP group and 606 mL/min in the PCB group. The mean increase in blood flow was 325.8 mL/min in the UHP group and 213 mL/min in the PCB group. This represents a relative mean increase in blood flow of 253% in the UHP group and 85% in the PCB group. An unpaired t-test showed there was no significant difference between the groups with respect to pre-flow, post-flow, and mean and relative mean increase in flow. There were two failures; one in the UHP group and one in the PCB group. There was one minor complication (2.8%) but no major complications. Conclusions In this small group of HD patients with autogenous fistulas our comparison of UHP to the PCB demonstrated that the immediate results, as determined by measurement of intra-access blood flow, were equivalent. Further long-term follow-up will be required to determine the longevity of these results

Low-Sodium Versus Standard-Sodium Peritoneal Dialysis Solution in Hypertensive Patients: A Randomized Controlled Trial

BACKGROUNDnPeritoneal dialysis (PD) solutions with reduced sodium content may have advantages for hypertensive patients; however, they have lower osmolarity and solvent drag, so the achieved Kt/Vurea may be lower. Furthermore, the increased transperitoneal membrane sodium gradient can influence sodium balance with consequences for blood pressure (BP) control.nnnSTUDY DESIGNnProspective, randomized, double-blind clinical trial to prove the noninferiority of total weekly Kt/Vurea with low-sodium versus standard-sodium PD solution, with the lower confidence limit above the clinically accepted difference of -0.5.nnnSETTING & PARTICIPANTSnHypertensive patients (≥ 1 antihypertensive drug, including diuretics, or office systolic BP ≥ 130 mmHg) on continuous ambulatory PD therapy from 17 sites.nnnINTERVENTIONn108 patients were randomly assigned (1:1) to 6-month treatments with either low-sodium (125 mmol/L of sodium; 1.5%, 2.3%, or 4.25% glucose; osmolarity, 338-491 mOsm/L) or standard-sodium (134 mmol/L of sodium; 1.5%, 2.3%, or 4.25% glucose; osmolarity, 356-509 mOsm/L) PD solution.nnnOUTCOMESnPrimary end point: weekly total Kt/Vurea; secondary outcomes: BP control, safety, and tolerability.nnnMEASUREMENTSnTotal Kt/Vurea was determined from 24-hour dialysate and urine collection; BP, by office measurement.nnnRESULTSnTotal Kt/Vurea after 12 weeks was 2.53 ± 0.89 in the low-sodium group (n = 40) and 2.97 ± 1.58 in the control group (n = 42). The noninferiority of total Kt/Vurea could not be confirmed. There was no difference for peritoneal Kt/Vurea (1.70 ± 0.38 with low sodium, 1.77 ± 0.44 with standard sodium), but there was a difference in renal Kt/Vurea (0.83 ± 0.80 with low sodium, 1.20 ± 1.54 with standard sodium). Mean daily sodium removal with dialysate at week 12 was 1.188 g higher in the low-sodium group (P < 0.001). BP changed marginally with standard-sodium solution, but decreased with low-sodium PD solution, resulting in less antihypertensive medication.nnnLIMITATIONSnBroader variability of study population than anticipated, particularly regarding residual kidney function.nnnCONCLUSIONSnThe noninferiority of the low-sodium PD solution for total Kt/Vurea could not be proved; however, it showed beneficial clinical effects on sodium removal and BP.

Aluminum toxicokinetics in peritoneal dialysis patients

Context. Despite the risk of aluminum (Al) toxicity in dialysis patients, little is known about its toxicokinetics (TK) in this population. A national contamination of dialysate solutions with Al provided the opportunity to study Al TK in peritoneal dialysis (PD) patients and to better understand the influence of covariates on its disposition. Methods. Al levels in serum and dialysate as well as other laboratory values were collected prospectively from 83 PD patients after correction of Al contamination. Population TK analyses were conducted with NONMEM VI using standard model discrimination criteria. Covariate analyses were also performed using stepwise forward regression followed by backward deletion. Results. After correction of Al exposure, serum levels declined in a biphasic manner, which was captured by the TK model. The TK of Al were best described by a 2-compartment model with linear elimination. Total creatinine clearance was a significant covariate for total clearance (CL). Mean parameter estimates for volume of central compartment (V1), CL, volume of peripheral compartment (V2), volume of distribution at steady-state (Vss), and intercompartmental clearance (Q) were 168 L, 8.99 L/day, 12 000 L, 12 168 L, and 4.93 L/day, respectively. Inter-individual variability for CL and V2 were 22.6 and 51.1%, respectively. Al distributional half-life was 8.5 days, while the terminal elimination half-life was 7.2 years. This model confirms that the large Vss reflects the widespread distribution of Al in bone, lungs, liver, and other tissues. Conclusion. This study describes the first population Al TK model in a large group of PD patients, which includes a covariate effect. The model confirms the extensive half-life and tissue distribution of Al in a dialysis-dependent population.

Recanalization of chronic refractory central venous occlusions utilizing a radiofrequency guidewire perforation technique.

Purpose To assess the technical success rate and safety of radiofrequency perforation guidewire (RF) technology for the recanalization of refractory chronic central venous occlusions in symptomatic hemodialysis patients with failed conventional endovascular methods. Methods This single center retrospective cohort of hemodialysis patients comprised of six men (mean age 67 years, range 55 to 80) with autogenous fistulae, who had already undergone failed conventional endovascular methods. These patients underwent the RF perforation technique from December 2006 to January 2010. Results Three patients were successfully treated using the RF perforation technique, after which they had PTFE stent grafts placed at the site of occlusion. There was no recurrence of clinical symptoms. In the remaining three patients, the procedure was terminated after multiple unsuccessful attempts. There were no complications. Conclusions The RF perforation technique is a potential alternative technology for recanalization of refractory chronic central venous occlusions in hemodialysis patients in the setting of failed conventional endovascular recanalization techniques.

Variability in CKD stage in outpatients followed in two large renal clinics: implications for CKD trials and the status of current knowledge of patterns of CKD to ESRD progression: response to Dr. Onuigbo

Editor, We thank Dr. Onuigbo for his comments concerning our report on glomerular filtration rate (GFR) stage variability in patients with chronic kidney disease [1]. Dr. Onuigbo supports the notion that medication changes, and in particular changes in inhibitors of the renin–angiotensin–aldosterone system, contribute to the observed variation in renal function between office visits. He also finds very interesting the observation that a sizeable minority of patients with early stages of CKD or those who had been found to have stable or even improving renal function (during the initial observation period of 1.1 year) still went on to require hemodialysis at a mean follow-up of 2.3 years later. He suggests that these patients have the syndrome of rapid-onset end-stage renal disease. The use of medications such as renin–angiotensin– aldosterone blockers can certainly contribute to the observed variability in GFR stages in our patients. In addition, the use of other antihypertensive medications (including diuretics) can also lead to changes in GFR. Proteinuria rates, genetic factors, other environmental factors including interval development of acute kidney injury, and control of relevant disease states all contribute to renal disease, and it is perhaps not surprising that GFR declines are often not linear or necessarily progressive [2–5]. Others have reported on this ‘noise’ in GFR and on the fact that additional tools are urgently required to further refine the estimates of renal disease and progression rates beyond simple GFR values [3–5]. The main objective of our study was to describe GFR variability in stable outpatients with chronic kidney disease. The underlying premise was that GFR variability pattern, similar to cross-sectional or initial eGFR values, or to proteinuria rates, may be another important dimension that independently influences important renal outcomes such as end-stage renal disease or death. Only a larger prospective study could confirm or refute this hypothesis.