Ilan Szwarc

Cinacalcet chloride is efficient and safe in renal transplant recipients with posttransplant hyperparathyroidism.

Background. Persistent hyperparathyroidism (HPT) is observed in ∼50% of kidney transplant recipients one year after transplantation. It may result in hypercalcemia, hypophosphatemia, bone demineralization, vascular calcification, lithiasis, and participate in chronic allograft nephropathy. We evaluated the use of the calcimimetic cinacalcet chloride to correct chronic hypercalcemia in posttransplant HPT, in a prospective single-center study. Methods. Nine patients with persistent hypercalcemia (>2.6 mmol/L) and stable graft function were treated with cinacalcet (30 mg/day, thereafter adapted to obtain normal serum Ca levels) for six months. Their immunosuppressive schedule included mycophenolate mofetil (MMF), steroids, and cyclosporine A (4), tacrolimus (4), or sirolimus (2). Results. Serum Ca levels significantly decreased from 2.75±0.15 to 2.59±0.10, 2.42±0.29 and 2.44±0.25 mmol/L by one, two, and six months, respectively (P<0.02, Wilcoxon test for paired data, for all the data points). Parathyroid hormone (PTH) serum levels decreased from 171±102 to 134±63 pg/ml by two months (P<0.05) and stabilized thereafter (148±99 pg/ml at six months; NS). No changes in glomerular filtration rate (49.8±18.6 and 51.3±19 ml/min at initiation and six months, respectively) and no variation in serum concentration of the immunosuppressive drugs were observed. Three patients withdrew the treatment because gastrointestinal intolerance. Conclusion. Cinacalcet allows the correction of hypercalcemia with no interference in immunosuppressive treatment or renal function. However, whether the increased intolerance observed was due to the association of cinacalcet chloride with other drugs required in renal transplantation (e.g., MMF) needs to be assessed.

Does reduction in immunosuppression in viremic patients prevent BK virus nephropathy in de novo renal transplant recipients? A prospective study.

Background. BK virus nephropathy (BKVN) is a severe complication of renal transplantation, resulting in graft loss in >50% of cases. Because patients with BKV viremia are at high risk for developing BKVN, the aim of our study was to analyze whether early reduction of immunosuppression (IS) could prevent BKVN in viremic patients. Methods. BKV viruria was prospectively screened every 3 months by real-time polymerase chain reaction during the first year after transplantation in 123 consecutive renal transplant recipients. Plasma viral load was measured by polymerase chain reaction whenever viruria was positive; in viremic patients a graft biopsy was systematically performed and IS was reduced. Results. Viruria, viremia, and BKVN occurred in 48.8%, 10.5%, and 2.4% of patients, respectively. In the 13 patients with positive viremia, initial graft biopsy showed BKVN in two. After reduction of IS in patients without BKVN, viremia disappeared in 8 of 11, decreased in 2 of 11, and increased in one patient who eventually developed BKVN. In contrast, viremia remained positive in one patient with BKVN and disappeared in the second but renal function deteriorated in both of them. Initial viral load was higher in patients who developed BKVN. Conclusion. Reduction of IS is probably an effective therapeutic option to clear viremia and prevent BKVN in viremic renal transplant patients.

Monthly screening for BK viremia is an effective strategy to prevent BK virus nephropathy in renal transplant recipients

C. Alméras, F. Vetromile, V. Garrigue, I. Szwarc, V. Foulongne, G. Mourad. Monthly screening for BK viremia is an effective strategy to prevent BK virus nephropathy in renal transplant recipients.
Transpl Infect Dis 2011: 13: 101–108. All rights reserved

Outcome of renal transplant recipients admitted to an intensive care unit: a 10-year cohort study.

Background. Epidemiology and prognosis of severe complications related to renal transplantation requiring admission to intensive care unit (ICU) have not been assessed precisely. This study was undertaken to evaluate the outcome in this population and to identify the factors of prognosis. Methods. All records of adult renal transplant recipients admitted to our ICU from 1997 to 2007 were reviewed including transplant variables, clinical and biological parameters, use of mechanical ventilation, catecholamine support, or dialysis or both. Mortality was assessed and data were analyzed to identify predictive factors of outcome. Results. Twenty-seven women and 30 men, median age 54 years, were included in the study. Eighteen patients were oliguric, 35 were mechanically ventilated, 32 underwent hemodialysis, and 36 needed catecholamine. Twenty-three patients died (40.3%), a mortality significantly higher than in a matched by age and gravity scores control group of nontransplant ICU patients. By univariate analysis, survivors had a significantly lower ICU severity scores, a higher mean arterial pressure, a higher Glasgow Coma Score, a higher serum albumin, and a lower serum lactate on ICU admission. The need for catecholamine support, mechanical ventilation or dialysis or both during the ICU stay worsens the outcome significantly. Using the multivariate analysis, only the mean arterial pressure and the need for mechanical ventilation were predictive of mortality. Conclusion. The incidence of severe transplant-related complications requiring an admission to an ICU was at 16 of 1000 patients year with a mortality rate higher than the general ICU population (40% vs. 20%). These data suggest that immunosuppressive treatment of transplant patients with severe complications worsens significantly their outcome.

An epidemic of Pneumocystis jiroveci pneumonia in a renal transplantation center: role of T-cell lymphopenia.

Although only 2 cases of Pneumocystis jiroveci pneumonia were observed in our center between 2004 and 2009, we diagnosed 9 cases in 2010. Each patient had been in contact in the hospital with at least 1 other patient suffering P jiroveci pneumonia. Genotyping of P jiroveci pneumonia strains demonstrates a total homogeneity of the DNA sequences in the 7 patients already analyzed. CD4+ lymphocyte count was significantly lower at M3 in P jiroveci pneumonia patients than in controls. Our clinical and molecular data confirm that interhuman transmission of P jiroveci is possible, particularly to lymphopenic transplant recipients.

Early high pulse pressure is associated with graft dysfunction and predicts poor kidney allograft survival.

Background. Pulse pressure (PP), which reflects the pulsatile component of the blood pressure (BP), is known as a major predictor of cardiovascular events and death. In the elderly and type 2 diabetic patients, PP is associated with low glomerular filtration rate and albuminuria. Because kidney allograft survival is closely related to BP levels, we investigated the impact of early high PP, systolic, diastolic, and mean arterial BP on kidney allograft survival. Methods. Renal hemodynamic and function studies using isotopic methods were prospectively performed in 493 renal transplant patients at 3 months posttransplantation to determine the impact of the different BP components on allograft survival using a proportional hazard model. Results. After a median follow-up of 6.3 years, 91 allografts were lost. High PP was associated with high systolic, diastolic, and mean arterial pressure, heart rate, recipient age, glycemia, and low glomerular filtration rate. Moreover, PP emerged as the strongest BP component influencing overall and death-censored kidney allograft survival. Conclusion. High PP is an early marker of poor allograft outcome that could be corrected by therapeutic intervention.

The use of SDS–PAGE scanning of spent dialysate to assess uraemic toxin removal by dialysis

Background. Uraemic toxins in the 8 to 60 kDa molecular weight range have been attracting increasing attention in dialysis therapy. However, there are no available standardized methods to evaluate their removal. Using new filtering membranes, we evaluated SDS–PAGE of spent dialysate to assess cut-off ranges and removal capacities into dialysate, while also measuring classical markers of dialyser function. Methods. Eighteen dialysis patients were washed out for 2 weeks with FX 100 (Helixone®), followed by randomization to Xevonta Hi 23 (Amembris®) or FX dialysers for 2 weeks, then crossed over for an additional 2 weeks, and finally placed on Xenium 210 (Purema®) for 2 weeks. SDS–PAGE scanning of the removed proteins contained in the spent dialysate was performed during all dialysis sessions. Total mass of urea, creatinine, total proteins, beta 2 microglobulin (β2m), retinol-binding protein (RBP) and albumin were measured. The reduction rates of serum urea, creatinine, β2m, leptin, RBP, alpha 1-antitrypsin, albumin and total proteins were also determined. Results. SDS–PAGE scanning identified four major protein peaks (10–18, 20–22.5, 23–30 and 60–80 kDa molecular weight) and showed clear differences in the amounts of removed proteins between the dialysers, particularly in the 20–22.5, 23–30 and 60–80 kDa ranges. Total mass of removed β2m, RBP and albumin were in agreement with SDS–PAGE, while serum assays showed differing results. Conclusions. SDS–PAGE scanning provided a good characterization of protein patterns in the spent dialysate; it extended and agreed with protein determinations and allowed a better assessment of dialyser performance in removing 10 to 80 kDa molecular weight substances. It also identified differences between the three mainly filtrating polysulfone dialysers that were not detected with blood measurements.

Consequences of increasing convection onto patient care and protein removal in hemodialysis

Introduction Recent randomised controlled trials suggest that on-line hemodiafiltration (OL-HDF) improves survival, provided that it reaches high convective volumes. However, there is scant information on the feasibility and the consequences of modifying convection volumes in clinics. Methods Twelve stable dialysis patients were treated with high-flux 1.8 m2 polysulphone dialyzers and 4 levels of convection flows (QUF) based on GKD-UF monitoring of the system, for 1 week each. The consequences on dialysis delivery (transmembrane pressure (TMP), number of alarms, % of achieved prescribed convection) and efficacy (mass removal of low and high molecular weight compounds) were analysed. Results TMP increased exponentially with QUF (p<0.001 for N >56,000 monitoring values). Beyond 21 L/session, this resulted into frequent TMP alarms requiring nursing staff interventions (mean ± SEM: 10.3 ± 2.2 alarms per session, p<0.001 compared to lower convection volumes). Optimal convection volumes as assessed by GKD-UF-max were 20.6 ± 0.4 L/session, whilst 4 supplementary litres were obtained in the maximum situation (24.5 ± 0.6 L/session) but the proportion of sessions achieving the prescribed convection volume decreased from 94% to only 33% (p<0.001). Convection increased high molecular weight compound removal and shifted the membrane cut-off towards the higher molecular weight range. Conclusions Reaching high convection volumes as recommended by the recent RCTs (> 20L) is feasible by setting an HDF system at its optimal conditions based upon the GKD-UF monitoring. Prescribing higher convection volumes resulted in instability of the system, provoked alarms, was bothersome for the nursing staff and the patients, rarely achieved the prescribed convection volumes and increased removal of high molecular weight compounds, notably albumin.

Use of spent dialysate analysis to estimate blood levels of uraemic solutes without blood sampling: urea

BACKGROUND Urea kinetic modelling-based methods are widely used to assess dialysis efficacy. However, they require blood sampling and are susceptible to a number of errors, mainly from the calculated parameters (particularly V). Spent dialysate determinations have been used and have been shown to be reliable and simple to use. In this study, we associated dialysate-based and clearance determinations along with Kt/V to estimate blood urea levels. METHODS Urea kinetic modelling, continuous sampling of spent dialysate and ionic dialysance were determined in 18 stable dialysis patients during 126 dialysis sessions. Mean blood urea levels were estimated as follows: mean urea level = spent dialysate - urea mass/(dialysance T). Blood urea levels before and after dialysis were calculated based on the same determinations and extended formulae. RESULTS Estimated mean urea level was significantly correlated with measured mean blood urea level (R(2) = 0.957; P < 0.0001), and Bland and Altman analysis showed significant agreement between estimated and measured levels. Estimated and measured blood urea levels were also correlated before and after dialysis (R(2) = 0.972 , P < 0.0001 and R(2) = 0.903 , P < 0.0001, respectively), with good agreement for both blood urea before and after dialysis and their respective estimates. CONCLUSIONS Blood urea levels may be reliably estimated from the total mass of urea removed in the dialysate and the dialysance measured during dialysis. Coupling both measurements allows a precise monitoring of dialysis efficacy and a specific evaluation of the patients urea metabolism status. Technical dysfunctions and patient variations may be easily identified using this approach without blood sampling.

Early changes in body weight and blood pressure are associated with mortality in incident dialysis patients

Abstract Background While much research is devoted to identifying novel biomarkers, addressing the prognostic value of routinely measured clinical parameters is of great interest. We studied early blood pressure (BP) and body weight (BW) trajectories in incident haemodialysis patients and their association with all-cause mortality. Methods In a cohort of 357 incident patients, we obtained all records of BP and BW during the first 90 days on dialysis (over 12 800 observations) and analysed trajectories using penalized B-splines and mixed linear regression models. Baseline comorbidities and all-cause mortality (median follow-up: 2.2 years) were obtained from the French Renal Epidemiology and Information Network (REIN) registry, and the association with mortality was assessed by Cox models adjusting for baseline comorbidities. Results During the initial 90 days on dialysis, there were non-linear decreases in BP and BW, with milder slopes after 15 days [systolic BP (SBP)] or 30 days [diastolic BP (DBP) and BW]. SBP or DBP levels at dialysis initiation and changes in BW occurring in the first month or during the following 2 months were significantly associated with survival. In multivariate models adjusting for baseline comorbidities and prescriptions, higher SBP value and BW slopes were independently associated with a lower risk of mortality. Hazard ratios of mortality and 95% confidence intervals were 0.92 (0.85–0.99) for a 10 mmHg higher SBP and 0.76 (0.66–0.88) for a 1 kg/month higher BW change on Days 30–90. Conclusions BW loss in the first weeks on dialysis is a strong and independent predictor of mortality. Low BP is also associated with mortality and is probably the consequence of underlying cardiovascular diseases. These early markers appear to be valuable prognostic factors.