Multimodality approach to treat calciphylaxis in end-stage kidney disease patients.

A multimodality approach has been proposed as an effective treatment for calciphylaxis in patients with end-stage kidney disease. In this retrospective study, we report the cases of 12 end-stage kidney disease patients from l'Hôtel-Dieu de Québec hospital (Canada) who were diagnosed with calciphylaxis between 2004 and 2012 and treated with a multimodality clinical approach including sodium thiosulfate (STS). Statistical analyses were performed to evaluate the impacts of patients characteristics, the different interventions as well as therapy regimen on the therapeutic response. The majority of patients (n = 9) were hemodialyzed. The patients-associated comorbidities were consistent with previously reported risk factors for calciphylaxis: Diabetes (n = 11), calcium-based phosphate binders use (n = 10), warfarin use (n = 9), obesity (n = 7), female gender (n = 8) and intravenous iron use (n = 8). STS was given for a median duration of 81 days. 75% of the patients had a response (total or partial) including a complete response in 42% of patients. One-year mortality rate was low (25%). STS was used during a mean duration of 83.33 ± 41.52 days and with a total cumulating dose of 1129.00 ± 490.58 g. The recorded mean time before a complete response was 102.20 days (51-143). Pain improvement occurred after a mean time of 8.67 ± 10.06 days. None of the studied factors was statistically associated with a complete or a partial response to the multimodality approach. Although our data have a limited statistical power, they support treating calciphylaxis with a multimodality approach including STS as its effects are independent from important clinical variables.

Sodium and urea excretion as determinants of urine output in autosomal dominant polycystic kidney disease patients on V2 receptor antagonists: impact of dietary intervention.

PURPOSE: Tolvaptan, a vasopressin V2 receptor antagonist, slows the decline in renal function in autosomal dominant polycystic kidney disease (ADPKD). However, it increases urine output such that patient adherence could be compromised. In a cohort of patients with ADPKD on tolvaptan, we aimed to identify the contribution of sodium and urea excretion rate to daily urine output, and to evaluate the effectiveness of dietary counseling on sodium and urea excretion rates. METHODS: Retrospective analysis of 30 ADPKD patients who underwent a single session of personalized dietary counseling to reduce sodium and protein intake before initiation of tolvaptan. Creatinine and 24-h urine were obtained regularly on treatment. Generalized estimation equations were used. RESULTS: Mean age and median eGFR were 44 ± 11 years and 52 (43-74) ml/min/1.73 m2. Tolvaptan increased diuresis from 2.5 to 5.2 l/day. After adjusting for the dose of tolvaptan, an increase in sodium and urea excretion rate by 50 mmol/day was associated with an estimated additional urine volume of 0.6 l/day (95% CI 0.4-0.8 l/day; P < 0.001) and 0.25 l/day (95% CI 0.11-0.39 l/day; P < 0.001), respectively. Dietary counseling resulted in a transient reduction of sodium excretion by 19 mmol/day during the first 4 months (P = 0.016) but resulted in a more sustained reduction in urea excretion by 69 mmol/day (P = 0.008). CONCLUSION: Both sodium and urea excretion rates contribute significantly to daily urine volume in patients treated with tolvaptan, and a single session of dietary counseling was transiently effective in reducing sodium intake but achieved a more sustained reduction in protein intake. Dietary counseling should be considered in the management of ADPKD patients treated by tolvaptan.

Changes in vascular accesses and in incidence rates of dialysis-related bloodstream infections in Québec, Canada, 2011-2017.

OBJECTIVE: Surveillance of dialysis-related bloodstream infections (DRBSIs) has been mandatory in Québec since April 2011. The aim of this study was to describe the epidemiology of DRBSIs in Québec. METHODS: Cohort study of prevalent patients undergoing chronic dialysis in the 36 facilities that participated without interruption in the provincial surveillance, between April 2011 and March 2017. Two indicators were analyzed: proportion of patient months dialyzed using a fistula (a patient month is a 28-day cycle during which an individual patient received dialysis) and incidence rate of DRBSI. Binomial and Poisson regression with generalized estimating equations were used to describe the evolution of indicators over time and to quantify the association between facilities' proportion of fistulas and their incidence rate. RESULTS: Globally, 42.6% of all patient months were dialyzed using a fistula, but there was a statistically significant decrease over time (46.2% in 2011-2012 to 39.3% in 2016-2017). Despite this decline in the use of fistulas, rates of DRBSIs have also decreased, going from 0.38 DRBSIs per 100 patient months in 2011-2012 to 0.23 DRBSIs per 100 patient months in 2016-2017. No association was found between facility use of fistulas and the rate of DRBSI. At the individual level, however, the DRBSI rate was 4.12 times higher for patients using a catheter. CONCLUSIONS: In Québec, the rate of DRBSIs has decreased over a 6-year period despite an increasing proportion of patients dialyzed by catheter.

Acute effects of cinacalcet on arterial stiffness and ventricular function in hemodialysis patients: A randomized double-blinded crossover study.

BACKGROUND: Serum calcium concentration (Ca) plays an essential role in a vascular muscle tone and myocardial contractility. Previously, we showed that acutely lowering Ca by hemodialysis reduced arterial stiffness. Cinacalcet is a calcimimetic that lowers Ca and parathyroid hormone (PTH). The aim of the present study was to examine whether acute lowering of Ca by cinacalcet improves vascular stiffness and myocardial diastolic dysfunction. METHOD: This is a double-blinded randomized placebo-controlled crossover study that included 21 adult patients with end-stage kidney disease undergoing chronic hemodialysis. Subjects were assigned to placebo-cinacalcet (30 mg) or cinacalcet-placebo sequence. After each treatment period (7 days), aortic, brachial, and carotid stiffness were determined by examining carotid-femoral pulse wave velocity (cf-PWV), carotid-radial PWV (cr-PWV), and carotid distension. A central pulse wave profile was determined by radial artery tonometry and cardiac function was evaluated by echocardiography. RESULTS: Cinacalcet reduced PTH (483 [337-748] to 201 [71-498] ng/L, P < .001) and ionized Ca (1.11 [1.08-1.15] to 1.05 [1.00-1.10] mmol/L, P = .04). Cinacalcet did not reduced cf-PWV significantly (12.2 [10.4-15.4] to 12.2 [11.0-14.6] m/s, P = .16). After adjustments for mean blood pressure, sequence, carryover, and treatment effects, cf-PWV was not significantly lowered by cinacalcet (-0.35 m/s, P = .139). There were no significant changes in central blood pressures, brachial and carotid stiffness, and echocardiographic parameters. CONCLUSION: In this study, 30 mg daily cinacalcet for 1 week did not have any significant impact on peripheral and central blood pressures, arterial stiffness parameters, or cardiac function (NCT01250405).

Prediction and validation of the duration of hemodialysis sessions for the treatment of acute ethylene glycol poisoning.

The duration of hemodialysis (HD) sessions for the treatment of acute ethylene glycol poisoning is dependent on concentration, the operational parameters used during HD, and the presence and severity of metabolic acidosis. Ethylene glycol assays are not readily available, potentially leading to undue extension or premature termination of HD. We report a prediction model for the duration of high-efficiency HD sessions based retrospectively on a cohort study of 26 cases of acute ethylene glycol poisoning in 24 individuals treated by alcohol dehydrogenase competitive inhibitors, cofactors and HD. Two patients required HD for more than 14 days, and two died. In 19 cases, the mean ethylene glycol elimination half-life during high-efficiency HD was 165 minutes (95% confidence interval of 151-180 minutes). In a training set of 12 patients with acute ethylene glycol poisoning, using the 90th percentile half-life (195 minutes) and a target ethylene glycol concentration of 2 mmol/l (12.4 mg/dl) allowed all cases to reach a safe ethylene glycol under 3 mmol/l (18.6 mg/dl). The prediction model was then validated in a set of seven acute ethylene glycol poisonings. Thus, the HD session time in hours can be estimated using 4.7 x (Ln [the initial ethylene glycol concentration (mmol/l)/2]), provided that metabolic acidosis is corrected.

Phenytoin overdose treated with hemodialysis using a high cut-off dialyzer.

We describe the case of a 52-year-old man who presented after having ingested an unknown quantity of phenytoin. Peak phenytoin concentration was 51.2 mg/L (therapeutic range 10-20 mg/L). Five days after admission, the patient became comatose and was intubated. Because of persistent toxic phenytoin levels and unchanged clinical status for 12 days, hemodialysis (HD) was prescribed to enhance elimination of phenytoin. HD was performed using a Gambro TheraliteTM filter (Baxter International Inc., Deerfield, USA), a high cut-off filter that allows the removal of molecules of up to 45 kDa. Phenytoin concentration readily decreased during the 8-hour HD treatment from 38.9 mg/L to 27.8 mg/L (28.5% decrease); during HD, phenytoin half-life was 18.5h (compared to 1109.8h before HD and 56.3h after HD), phentyoin clearance averaged 80.1 mL/min and a total of 1.1 g of phenytoin was removed. Albumin removal from the Theralite filter was most important at the beginning of HD. The high clearance of phenytoin obtained with this filter was likely due to its high surface area rather than its capacity to remove the albumin-phenytoin complex.

Effectiveness of Haemodiafiltration with Heat Sterilized High-Flux Polyphenylene HF Dialyzer in Reducing Free Light Chains in Patients with Myeloma Cast Nephropathy.

INTRODUCTION: In cases of myeloma cast nephropathy in need of haemodialysis (HD), reduction of free light chains using HD with High-Cut-Off filters (HCO-HD), in combination with chemotherapy, may be associated with better renal recovery. The aim of the present study is to evaluate the effectiveness of haemodiafiltration (HDF) in reducing free light chain levels using a less expensive heat sterilized high-flux polyphenylene HF dialyzer (HF-HDF). METHODS: In a single-centre prospective cohort study, 327 dialysis sessions were performed using a 2.2 m2 heat sterilized high-flux polyphenylene HF dialyzer (Phylther HF22SD), a small (1.1m2) or large (2.1 m2) high-cut-off (HCO) dialyzer (HCOS and HCOL) in a cohort of 16 patients presenting with dialysis-dependent acute cast nephropathy and elevated free light chains (10 kappa, 6 lambda). The outcomes of the study were the mean reduction ratio (RR) of kappa and lambda, the proportion of treatments with an RR of at least 0.65, albumin loss and the description of patient outcomes. Statistical analysis was performed using linear and logistic regression through generalized estimating equation analysis so as to take into account repeated observation within subjects and adjust for session duration. RESULTS: There were no significant differences in the estimated marginal mean of kappa RR, which were respectively 0.67, 0.69 and 0.70 with HCOL-HD, HCOS-HDF and HF-HDF (P = 0.950). The estimated marginal mean of the proportions of treatments with a kappa RR ≥0.65 were 68%, 63% and 71% with HCOL-HD, HCOS-HDF and HF-HDF, respectively (P = 0.913). The estimated marginal mean of lambda RR were higher with HCOL-HDF (0.78), compared to HCOL-HD and HF-HDF (0.62, and 0.61 respectively). The estimated marginal mean proportion of treatments with a lambda RR ≥0.65 were higher with HCOL-HDF (81%), compared to 57% in HF-HDF (P = 0.042). The median albumin loss were 7, 21 and 63 g/session with HF-HDF, HCOL-HD and HCOL-HDF respectively (P = 0.044). Among survivors, 9 out of 10 episodes of acute kidney injuries became dialysis-independent following a median time of renal replacement therapy of 40 days (range 7-181). CONCLUSION: Therefore, in patients with acute dialysis-dependent myeloma cast nephropathy, in addition to chemotherapy, HDF with a heat sterilized high-flux polyphenylene HF dialyzer could offer an alternative to HCO dialysis for extracorporeal kappa reduction with lower albumin loss.

Prediction and validation of hemodialysis duration in acute methanol poisoning.

The duration of hemodialysis (HD) in methanol poisoning (MP) is dependent on the methanol concentration, the operational parameters used during HD, and the presence and severity of metabolic acidosis. However, methanol assays are not easily available, potentially leading to undue extension or premature termination of treatment. Here we provide a prediction model for the duration of high-efficiency HD in MP. In a retrospective cohort study, we identified 71 episodes of MP in 55 individuals who were treated with alcohol dehydrogenase inhibition and HD. Four patients had residual visual abnormality at discharge and only one patient died. In 46 unique episodes of MP with high-efficiency HD the mean methanol elimination half-life (T1/2) during HD was 108 min in women, significantly different from the 129 min in men. In a training set of 28 patients with MP, using the 90th percentile of gender-specific elimination T1/2 (147 min in men and 141 min in women) and a target methanol concentration of 4 mmol/l allowed all cases to reach a safe methanol of under 6 mmol/l. The prediction model was confirmed in a validation set of 18 patients with MP. High-efficiency HD time in hours can be estimated using 3.390 × (Ln (MCi/4)) for women and 3.534 × (Ln (MCi/4)) for men, where MCi is the initial methanol concentration in mmol/l, provided that metabolic acidosis is corrected.

Aortic-brachial stiffness mismatch and mortality in dialysis population.

We hypothesized that increased aortic stiffness (central elastic artery) combined with a decrease in brachial stiffness (peripheral muscular artery) leads to the reversal of the physiological stiffness gradient (ie, mismatch), promoting end-organ damages through increased forward pressure wave transmission into the microcirculation. We, therefore, examined the effect of aortic-brachial stiffness mismatch on mortality in patients in need of dialysis. In a prospective observational study, aortic-brachial arterial stiffness mismatch (pulse wave velocity ratio) was assessed using carotid-femoral pulse wave velocity divided by carotid-radial pulse wave velocity in 310 adult patients on dialysis. After a median follow-up of 29 months, 146 (47%) deaths occurred. The hazard ratio (HR) for mortality related to PWV ratio in a Cox regression analysis was 1.43 (95% confidence interval [CI], 1.24-1.64; P<0.001 per 1 SD) and was still significant after adjustments for confounding factors, such as age, dialysis vintage, sex, cardiovascular disease, diabetes mellitus, smoking status, and weight (HR, 1.23; 95% CI: 1.02-1.49). The HRs for changes in 1 SD of augmentation index (HR, 1.35; 95% CI, 1.12-1.63), carotid-femoral pulse wave velocity (HR, 1.29; 95% CI, 1.11-1.50), and carotid-radial pulse wave velocity (HR, 0.80; 95% CI, 0.67-0.95) were statistically significant in univariate analysis, but were no longer statistically significant after adjustment for age. In conclusion, aortic-brachial arterial stiffness mismatch was strongly and independently associated with increased mortality in this dialysis population. Further studies are required to confirm these finding in lower-risk groups.

The impact of warfarin on the rate of progression of aortic stiffness in hemodialysis patients: a longitudinal study.

BACKGROUND: Accelerated progression of aortic stiffness in patients with advanced chronic kidney disease is not well explained by the traditional cardiovascular risk factors. We hypothesized that vitamin K deficiency may result in an accelerated progression of aortic stiffness in the pro-calcifying uremic milieu. METHOD: Eighteen hemodialysis (HD) patients on warfarin were matched to 54 HD patients without warfarin (control). Aortic stiffness was determined by carotid-femoral pulse wave velocity (cf-PWV) at baseline and after a mean follow-up of 1.2 years. In the control group, spontaneous vitamin K deficiency was defined as proteins induced by vitamin K deficiency/absence-II >median. RESULTS: At baseline, clinical characteristics and cf-PWV were similar. Adjusted cf-PWV increased by 0.86 ± 1.87 m/s in control and by 2.24 ± 2.68 m/s in warfarin group (P = 0.024). After adjustments for confounders, warfarin therapy was independently associated with progression of aortic stiffness (P = 0.016). The rate of progression of aortic stiffness showed a linear trend in response to vitamin K status and warfarin therapy, suggesting that at least part of the effects are mediated through reduced availability of vitamin K. The unadjusted and adjusted hazard ratio (HR) of warfarin therapy on mortality were, respectively, 2.40 (P = 0.006) and 2.53 (P = 0.006). In a forward conditional Cox regression analysis, age, albumin, augmentation index (AIx) and a cf-PWV > 13.8 m/s at the time of follow-up (HR: 2.11, P = 0.05) were independent determinants of mortality, whereas warfarin use was not retained as an independent factor. Finally, control patients with poor vitamin K status had an intermediate survival as compared with controls with better vitamin K status and patients with warfarin (P = 0.01). CONCLUSION: This is the first study to show a temporal association between warfarin, functional vitamin K deficiency and progression of aortic stiffness in HD patients. These findings suggest that the net cardiovascular benefit of long-term warfarin therapy may need to be reevaluated in this population.

Survey of infection control practices in hemodialysis units: preventing vascular access-associated bloodstream infections.

OBJECTIVE: Despite surveillance, the Quebec Healthcare-Associated Infections Surveillance Program saw no improvement in vascular access-associated bloodstream infections in hemodialysis (HD). We aimed to determine the infection control measures recommended and implemented in Quebec's HD units, compliance of local protocols to infection control practice guidelines, and reasons behind the low prevalence of arteriovenous fistulas. METHODS: An online survey was elaborated on the basis of the Centers for Disease Control and Prevention (CDC) and National Kidney Foundation Kidney Disease Outcomes Quality Initiative guidelines. The questionnaire was validated (construct, content, face validity, and reliability) and sent to all HD units in Quebec (n = 40). Results were analyzed using descriptive statistics, linear regression, and Poisson regression. RESULTS: Thirty-seven (93%) of 40 HD units participated. Thirty (94%) of the 32 centers where central catheters are inserted have written insertion protocols. Compliance with practice guidelines is good, except for full-body draping during catheter insertion (79%) and ointment use at insertion site (3%). Prevention measures for catheter maintenance are in accordance with guidelines, except for skin disinfection with at least 0.5% chlorhexidine and 70% alcohol (67% compliance) and regular antiseptic ointment use at the insertion site (3%). Before fistula cannulation, skin preparation is suboptimal; forearm hygiene is performed in only 61% of cases. Several factors explain the low rate of fistulas, including patient preference (69%) and lack of surgical resources (39%; P = .01). CONCLUSIONS: Improvement in standardization of care according to practice guidelines is necessary. Fistula rate could be increased by improving access to surgical resources and patient education. Strategies are now being elaborated to address these findings.

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.

Active vitamin D and accelerated progression of aortic stiffness in hemodialysis patients: a longitudinal observational study.

BACKGROUND: We hypothesized that high-dose active vitamin D therapy in the form of alphacalcidol (α-calcidol), used to treat secondary hyperparathyroidism in chronic kidney disease, could lead to vascular calcification and accelerated progression of aortic stiffness. METHODS: We conducted an observational study in 85 patients on chronic hemodialysis, among which 70 were taking a weekly dose of α-calcidol of <2 µg and 15 were taking a weekly dose of ≥2 µg (pharmacological dose). Parathyroid hormone, 25-hydroxyvitamin D, fibroblast growth factor 23, and α-klotho were determined. Aortic stiffness was assessed by determination of carotid-femoral pulse wave velocity (cf-PWV) at baseline and after a mean follow-up of 1.2 years. A multivariable regression model was used to evaluate the impact of pharmacological dose of α-calcidol on the progression of aortic stiffness. RESULTS: At baseline, clinical, biological, and hemodynamic parameters were similar. At follow-up, cf-PWV increased more in patients with pharmacological dose of α-calcidol (0.583±2.291 m/s vs. 1.948±1.475 m/s; P = 0.04). After adjustment for changes in mean blood pressure and duration of follow-up, pharmacological dose of α-calcidol was associated with a higher rate of progression of cf-PWV (0.969 m/s; 95% confidence interval = 0.111-1.827; P = 0.03), and this association persisted after further adjustments for parameters of mineral metabolism. CONCLUSIONS: In this study, pharmacological dose of α-calcidol was associated with accelerated progression of aortic stiffness. This study suggest that the vascular safety of active vitamin D posology may need to be specifically addressed in the treatment of chronic kidney disease-related bone mineral disorder.

Determinants of progression of aortic stiffness in hemodialysis patients: a prospective longitudinal study.

Aortic stiffness is associated with increased cardiovascular mortality in patients with chronic kidney disease. However, the rate of progression of arterial stiffness and the role of cardiovascular risk factors in the progression of arterial stiffness has never been established in a longitudinal study. In a prospective, longitudinal, observational study, carotid-femoral pulse wave velocity and carotid-radial pulse wave velocity were assessed in 109 hemodialysis patients at baseline and after a mean follow-up of 1.2 years. We examined the impact of age, atherosclerotic cardiovascular disease, diabetes mellitus, dialysis vintage, and pentosidine (a well-characterized, advanced glycation end products) on the rate of progression of aortic stiffness. The annual rate of changes in carotid-femoral pulse wave velocity and carotid-radial pulse wave velocity were 0.84 m/s per year (95% confidence interval, 0.50-1.12 m/s per year) and -0.66 m/s per year (95% confidence interval, -0.85 to -0.47 m/s per year), respectively. Older subjects, and patients with diabetes mellitus or atherosclerotic cardiovascular disease had higher aortic stiffness at baseline, however, the rate of progression of aortic stiffness was only determined by plasma pentosidine levels (P=0.001). The degree of baseline aortic stiffness was a significant determinant of the regression of brachial stiffness (P<0.001) suggesting that the regression of brachial stiffness occurs in response to central aortic stiffness. These findings suggest that traditional cardiovascular risk factors may play some role in the progression of aortic stiffness before development of advanced chronic kidney disease, and that the enhanced rate of progression of aortic stiffness in chronic kidney disease patients on dialysis are probably determined by more specific chronic kidney disease-related risk factors such as advanced-glycation end products.

Gemella sanguinis endocarditis with c-ANCA/anti-PR-3-associated immune complex necrotizing glomerulonephritis with a 'full-house' pattern on immunofluorescence microscopy.

A 67-year-old man was evaluated for haematuria, with a rising creatinine level from 88 to 906 µmol/L and positive c-anti-neutrophil cytoplasm antibody (ANCA)/anti-proteinase 3 (anti-PR3). A kidney biopsy revealed necrotizing glomerulonephritis with a 'full-house' pattern on immunofluorescence microscopy. Echocardiography and blood cultures growing Gemella sanguinis diagnosed endocarditis. Dialysis was required for a month. Three months later, following valve replacement, glucocorticoids and 2 months of antibiotic therapy, the creatinine level decreased to 62 µmol/L and c-ANCA/anti-PR3 disappeared. This first case of c-ANCA/anti-PR3 positive glomerulonephritis with a 'full-house' immunofluorescence pattern due to bacterial endocarditis underlines the importance of ruling out infection with ANCA positivity or kidney biopsy suggestive of lupus nephritis.

Impact of dialysate calcium concentration on the progression of aortic stiffness in patients on haemodialysis.

BACKGROUND: Higher dialysate calcium (DCa) can result in an acute and transient increase in arterial stiffness. The aim of the present study is to evaluate the impact of DCa on the progression of arterial stiffness, calcium balance and bone metabolism in haemodialysis (HD) patients over a 6-month period. Method. We randomly assigned 30 patients on chronic HD to be dialysed with a DCa of 1.12 or 1.37 mmol/L for a period of 6 months. Aortic stiffness and brachial stiffness were respectively measured by carotid-femoral pulse wave velocities (cf-PWV) and carotid-radial pulse wave velocity (cr-PWV) at baseline and at 3 and 6 months. Central pulse pressure (PP) and augmentation index were determined by radial artery tonometry. Dialysis calcium balance and parathyroid hormone (PTH) were measured monthly. Procollagen type-1 amino-terminal propeptide (P1NP) and C-terminal telopeptide of type-I collagen (CTX) were measured as markers of bone formation and resorption, respectively. Data was analysed by linear mixed model. RESULTS: Twenty-seven patients (66 ± 13 years old) with a mean duration of HD of 5.8 ± 3.6 months completed the study. At baseline, the groups were similar with respect to age, serum levels of calcium, phosphate and PTH, blood pressure (BP), cf-PWV and cr-PWV. The cf-PWV at baseline and 3 and 6 months were, respectively, 13.4 ± 4.2, 14.7 ± 3.31 and 13.6 ± 2.5 m/s in the DCa 1.12 group and 14.6 ± 5.9, 15.8 ± 7.8 and 17.0 ± 7.0 m/s in the DCa 1.37 group. After correction for mean BP, cf-PWV increased with DCa 1.37 as compared to DCa 1.12 (Time-DCa interaction P = 0.002). However, there were no significant effects of DCa on progression of cr-PWV, central PP or augmentation index. During the intervention period, the mean PTH was slightly higher in the DCa 1.12 group as compared to the DCa 1.37 group (325 ± 185 versus 211 ± 128 ng/L, P = 0.054), and dialysis calcium balance was -8.1 ± 4.4 versus -0.2 ± 4.7 mmol/session, respectively, in groups with DCa 1.12 and DCa 1.37 (P = 0.0001). Treatment with DCa 1.12 mmol/L resulted in increasing levels of CTX as compared to DCa 1.37 (P = 0.02), whereas the P1NP levels did not change significantly in either group. CONCLUSIONS: In this study, aortic stiffness progressed with DCa 1.37, while it remained stable with DCa 1.12 over a 6-month period. These results suggest that higher DCa concentrations could be a risk factor for the progression of aortic stiffness in HD patients. In the context of limited oral calcium, the long-term safety of DCa 1.12 on bone metabolism remains to be established.

Linezolid-associated acute interstitial nephritis and drug rash with eosinophilia and systemic symptoms (DRESS) syndrome.

Linezolid is a recent addition to the antibiotic armamentarium against Gram-positive bacteria, including multiresistant staphylococci and enterococci. Linezolid is relatively well tolerated and is not believed to be nephrotoxic. However, we report the case of an 88-year-old woman who was treated for prosthetic joint infection and methicillin-resistant Staphylococcus aureus bacteremia with vancomycin followed by linezolid therapy. On day 7 of linezolid treatment, the patient developed severe pruritus, macular rash, facial edema, eosinophilia, marked increase in serum creatinine level, and mild hepatitis. Renal biopsy showed acute interstitial nephritis with eosinophilic cells. Discontinuation of linezolid and a short course of prednisone led to rapid improvement of renal function. This case of linezolid-associated acute interstitial nephritis within the context of a drug rash with eosinophilia and systemic symptoms (DRESS) syndrome in a patient treated with linezolid raises concerns about the presumed renal safety of this drug. Clinicians should be aware of this potential life-threatening adverse reaction and monitor kidney function while patients are using linezolid.

Effects of acute variation of dialysate calcium concentrations on arterial stiffness and aortic pressure waveform.

BACKGROUND: Abnormal mineral metabolism in chronic kidney disease plays a critical role in vascular calcification and arterial stiffness. The impact of presently used dialysis calcium concentration (D(Ca)) on arterial stiffness and aortic pressure waveform has never been studied. The aim of the present study is to evaluate, in haemodialysis (HD) patients, the impact of acute modification of D(Ca) on arterial stiffness and central pulse wave profile (cPWP). Method. A randomized Latin square cross-over study was used to evaluate the three different concentrations of D(Ca) (1.00, 1.25 and 1.50 mmol/L) during the second HD of the week for 3 consecutive weeks. Subjects returned to their baseline D(Ca) for the following two treatments, allowing for a 7-day washout period between each experimental HD. cPWP, carotido-radial (c-r) and carotido-femoral (c-f) pulse wave velocities (PWV), plasma level of ionized calcium (iCa) and intact parathyroid hormone (PTH) were measured prior to and immediately after each experimental HD session. Data were analysed by the general linear model for repeated measures and by the general linear mixed model. RESULTS: Eighteen patients with a mean age of 48.9 +/- 18 years and a median duration of HD of 8.7 months (range 1-87 months) completed the study. In post-HD, iCa decreased with D(Ca) of 1.00 mmol/L (-0.14 +/- 0.04 mmol/L, P < 0.001), increased with a D(Ca) of 1.50 mmol/L (0.10 +/- 0.06 mmol/L, P < 0.001) but did not change with a D(Ca) of 1.25 mmol/L. Tests of within-subject contrast showed a linear relationship between higher D(Ca) and a higher post-HD Deltac-f PWV, Deltac-r PWV and Deltamean BP (P < 0.001, P = 0.008 and P = 0.002, respectively). Heart rate-adjusted central augmentation index (AIx) decreased significantly after HD, but was not related to D(Ca). The timing of wave refection (Tr) occurred earlier after dialysis resulting in a linear relationship between higher D(Ca) and post-HD earlier Tr (P < 0.044). In a multivariate linear-mixed model for repeated measures, the percentage increase in c-f PWV and c-r PWV was significantly associated with the increasing level of iCa, whereas the increasing level of DeltaMBP was not significant. In contrast, the percentage decrease in Tr (earlier wave reflection) was determined by higher DeltaMBP and higher ultrafiltration, whereas the relative change in AIx was inversely determined by the variation in the heart rate and directly by DeltaMBP. CONCLUSION: We conclude that D(ca) and acute changes in the serum iCa concentration, even within physiological range, are associated with detectable changes of arterial stiffness and cPWP. Long-term studies are necessary to evaluate the long-term effects of D(Ca) modulation on arterial stiffness.

The impact of arteriovenous fistulas on aortic stiffness in patients with chronic kidney disease.

BACKGROUND: The creation of arteriovenous fistulas (AVF) in patients with advanced chronic kidney disease (CKD) has been shown to have adverse effects on their central pulse wave profile suggesting a likely increase in arterial stiffness. The aim of the present study was to directly evaluate the effect of AVF on arterial stiffness. Method. Thirty-one stage-5 CKD patients underwent haemodynamic assessment prior to and 3 months after creation of AVF. Haemodynamic assessment included measurement of blood pressure (BP), central and carotidal pulse wave profile analysis, and carotido-femoral and carotido-radial pulse wave velocities (PWV). Pre-AVF and post-AVF haemodynamic parameters were compared using the Wilcoxon signed-rank test or the paired Student t-test as appropriate. Pearson correlations, single and multiple linear regressions, were used to determine the association between variables. RESULTS: After creation of AVF, peripheral and central BPs decreased without significant change in heart rate (HR) or pulse pressure. Carotido-femoral PWV ((c-f)PWV) fell from 13.2 +/- 4.1 to 11.7 +/- 3.1 m/s (P < 0.001). There was an increase in the central augmentation index (20.8% +/- 11.5 versus 23.7% +/- 11.6, P = 0.07) of borderline significance, and a significant reduction in the subendocardial viability ratio (153% +/- 34 versus 143% +/- 32, P < 0.05), which was mainly the result of a decrease in the diastolic pressure time index (DPTI) without any significant change in the diastolic duration. The reduction of (c-f)PWV was explained by changes in mean BP and HR (R(2) = 0.29). The reduction in DPTI was related to changes in central diastolic BP and changes in end-systolic BP (adjusted R(2) = 0.87). The significant improvement in aortic stiffness was mostly the result of the relative reduction of (c-f)PWV in the subgroup of patients with baseline (c-f)PWV above the median value of 13 m/s. CONCLUSION: The creation of AVF is associated with a passive improvement of aortic stiffness especially in patients with stiffer arteries. This improvement in arterial stiffness could potentially be beneficial to the cardiovascular system despite an associated deterioration in the aortic pulse wave profile.

Impact of age on glomerular filtration estimates.

BACKGROUND: Glomerular filtration decreases progressively with age in adults. Predictive equation should have proper modelling to adequately account for normal senescence. METHODS: Corrected 24-h creatinine clearances (CCLs) were measured in a cohort of 773 outpatients from 18 to 90 years old. Multiple linear regression was used to model the effect of age on glomerular filtration. Comparisons were made with the simplified MDRD and the MAYO equations. Impact of the derived equation was tested in a second cohort of 7551 patients with normal serum creatinine. RESULTS: While all equations show declining function with age, our results suggest that the GFR reduction is progressive after the age of 30 and continue to decline steadily after the age of 60. This leads to a convex curve in the multiple regression analysis that is best fitted by an equation including the quadratic term (age(2)). In contrast, the MDRD equation produces a faster decrease in early adulthood and a flatter curve after the age of 60 while the MAYO equation produces a more linear effect. MDRD results in the normal range are lower than those estimated by the MAYO equation. These equations, as applied on an independent cohort of 7551 normal outpatients from 18 to 102 years, produce different profile of evolution of GFR with age. CONCLUSIONS: Inclusion of a quadratic term for age in the formula estimating GFR results in better modelling of the natural decline of renal function associated with ageing. Furthermore, as GFR steadily declines after the age of 30, a single cut-off value of GFR normality for all ages leads to underdiagnosis of young adults and over diagnosis of elderly individuals. Guidelines should take into account the observed reduction of kidney function with age in normal population for optimal evaluation of eGFR.