Úrsula Verdalles Guzmán

La calcifilaxis, caracterizada por la ulceracion isquemica de la piel secundaria a la calcificacion de las pequenas arteriolas subcutaneas, es una enfermedad poco frecuente pero con mal pronostico. Los pacientes con ERCT tienen un riesgo alto de calcificaciones patologicas debido a las alteraciones del metabolismo calcio-fosforo, pero solo un pequeno numero desarrollan esta enfermedad. Por ello es logico pensar que hay otros factores que condicionan el desarrollo de la calcifilaxis. Metodos: Con el fin de identificar estos posibles factores implicados en su genesis, hemos analizado de forma retrospectiva las caracteristicas de los 8 pacientes con ERCT que presentaron calcifilaxis en nuestro hospital entre de enero 2001 a diciembre 2006. Resultados: Los 8 pacientes eran mujeres con edad media de 68,5 ± 6,7 anos. Todas presentaban ERCT en hemodialisis periodica (HD) y en 6 casos la cacifilaxis aparecio en los primeros 4 meses del inicio del tratamiento con HD. Seis de las pacientes eran diabeticas tipo 2 y todas eran obesas (IMC > 25 kg/m2), 3 con obesidad grado 4 o morbida. Todas cumplian criterios de sindrome metabolico (APT III), habian sido hipertensas mal controladas y en un 75% de los casos recibian tratamiento con anticoagulantes cumarinicos por distintas causas. No presentaban alteraciones severas del metabolismo calcio-fosforo: todas tenian un producto CaxP < 55. En todos los casos se controlo estrictamente la Presion arterial (PA) con el tratamiento con HD manteniendo cifras medias de PA de 98,3 ± 22,7/60 ± 18,29 mmHg en el momento de la aparicion de los sintomas. La mayoria de las pacientes (7/8), presentaron las lesiones a nivel proximal en las zonas con mayor deposito graso como muslos y abdomen. El estudio histologico de las lesiones en todos los casos demostro calcificacion de pequenas arteriolas subcutaneas asociada a paniculitis y trombosis de pequenos vasos. La evolucion clinica fue mala ya que siete de las ocho pacientes murieron como consecuencia de una sepsis de origen cutaneo. La exeresis quirurgica de los nodulos no modifico la mala evolucion. En conclusion: La paniculitis calcificante en pacientes con ERCT es una enfermedad rara pero de mal pronostico y elevada mortalidad. El sexo mujer, la obesidad asociada a Diabetes y Sindrome metabolico, el tratamiento anticoagulante y el excesivo control de la presion arterial al inicio del tratamiento con HD pueden favorecer su aparicion incluso en ausencia de alteraciones relevantes del metabolismo Ca-P-PTH. Debido a la epidemia actual de DM, obesidad y sindrome metabolico es de esperar que el numero de pacientes con estas caracteristicas que desarrollen ERCT y calcifilaxis vaya en aumento.

INTRODUCTION: The aim of this study is to compare molecule removal and albumin leakage in postdilution online hemodiafiltration with different high-flux dialyzers. METHODS: We studied seven high-flux dialyzers (Polyflux 210H®, Evodial 2.2®, FxCordiax1000®, Elisio21H®, TS-2.1SL®, XevontaHi20®, VitaPES 210-HF®) in 6 patients. The reduction ratio (RR) of small- and middle-sized molecules was calculated. Dialysate samples were collected to estimate the albumin leakage. FINDINGS: Global differences between dialyzers were observed in the RR of ß2 microglobulin (P =0.003) and prolactin (P =0.013). The mean loss of albumin in the dialysate per session varied between 114 ± 67 mg (with Evodial 2.2) and 2621 ± 1363 mg per session (with XevontaHi20). We found global differences between dialyzers in total albumin loss (P = 0.05). DISCUSSION: We demonstrated that the performance of high-flux dialyzers was different among the types and that not all high-flux dialyzers should be considered equal.

Introduction and Aims: There is no consensus on the best method to quantify hemodialysis and the optimal dosage of hemodialysis. Urea is the substance most often measured as a surrogate for the clearance of small molecules. In particular, Kt/ V, that is the dialyzer clearance of urea, multiplied by the length of the dialysis session, divided by the volume of distribution of urea, is the most widely accepted indicator of adequacy of hemodialysis. Most commonly Kt/V is estimated, by means of Daugirdas formula, from the values of BUN ( postdialysis/predialysis), ultrafiltration volume and postdialysis body weight. The aim of this study was to evaluate the possibility to calculate directly Kt/V as the total dialyzer urea clearance during the dialysis session, indexed for the volume of total body water of the patient, measured by means of electrical body impedance analysis (BIA). Methods: Seventy eigth patients (54 males), aged 34-86 years (mean 65.1), height 140-180 cm (mean 165), dry body weight 43-130 kg (mean 72.8), in maintenance hemodialysis treatment since 1-31 years (mean 6.5); 14 patients were diabetic. All patients were on a schedule of treatment with 3 dialysis (3h-4h15min length)/week, with bicarbonate dialysis (n=55), hemodiafiltration (n=16), or acetate free biofiltration (n=7). Different dialysis monitors were employed: Fresenius (n=37), Hospal (n=24), Gambro or others (n=17). BIA was measured using a single frequency tetrapolar impedance analyzer (ST-BIA, Akern, Firenze) at the end of the dialysys session. Total body water (TBW) was calculated from the values of resistance and reactance obtained with BIA, combined with body height and weight. Kt/VBIA was calculated as total blood clearance of urea during dialysis session over TBW. First, urea extraction ratio (UER) was calculated as ( predialysis-postdialysis)/predialysis values of urea, measured with standard auto-analyzer technique. The total volume of blood flow (QB, L) during dialysis was recorded from each monitor at the end of dialysis session. Then, Kt/V was calculated as: UER x QB / TBW; where UER x QB is the total dialyzer blood clearance of urea during the dialysis session. For comparison, Kt/V was calculated with the standard Daugirdas formula (spKt/V). Results: A very high correlation coefficient (r = 0.818) was found between the results of Kt/V measured with the two formulas. The slope was 1.13 x and the intercept non significantly different from 0. The mean difference sp Kt/V (Daugirdas) Kt/V ( present study) was -0.03, statistically not significant. The range of agreement ( 1.96 SD around the mean difference) between the two measurements was between -0.31 and + 0.37. The correlation between the two formulas was even better when clustering the patients in groups according to the model of dialysis monitor. In fact, correlation coefficient r ranged 0.853-0.912. This results indicate that the accuracy of the measurement of blood flow may be different according to the different monitors. Conclusions: It seems possible to assess the adequacy of dialysis from the direct calculation of Kt/V as total blood clearance of urea during dialysis session over total body water measured with BIA.

&lt;b&gt;Introduction and Aims:&lt;/b&gt; Blood uremic toxin measurements are presumed to reflect extracellular fluid, on the assumption of a uniform distribution between its two compartments, plasma and interstitial fluid (ISF). ISF is however separated from plasma by microvascular pores; toxins may not necessarily circulate “freely”. Interstitial uremic composition may be particularly important due to proximity to cell metabolism, and a much larger, often expanded ISF volume in CKD. Little is known about ISF composition in CKD, owing to the difficulty of sampling the compartment. This study aimed to extract ISF and study its uremic composition in CKD patients, in steady states and during dialysis, in comparison to plasma. &lt;b&gt;Methods:&lt;/b&gt; A flow-variation microdialysis technique was modified and adapted to simultaneously sample subcutaneous ISF of urea, creatinine, phosphate and urate in CKD patients during, and off haemodialysis (HD). ISF concentrations of these toxins were compared to their plasma levels. Metabolomic and proteomic analyses of were performed on contemporaneous ISF and plasma samples, to characterise their uremic profiles. A novel microneedle was also developed and tested as a new means of sampling ISF in CKD patients. &lt;b&gt;Results:&lt;/b&gt; Microdialysis was performed on 24 subjects (4 controls, 13 CKD non HD, 7 HD). Although a good correlation was seen between plasma and ISF urea (r=0.98), creatinine (r=0.94), phosphate (r=0.74) and urate (r=0.82), paired analysis of the whole group showed significant differences between ISF and plasma for urea (p=0.01), creatinine (p=0.02) and urate (p=0.03), with slightly lower individual ISF levels. During HD, the ISF toxin decay curves lagged behind their plasma counterparts in most patients, indicating a disharmony between plasma and ISF toxin clearances. Metabolomics revealed over 6000 metabolites in ISF, with 33 peaks consistent with known small and protein-bound uremic toxins, and several unidentified peaks occurring more in ISF than plasma, and vice-versa. Larger hydrophobic metabolites like sphingolipids did not seem to circulate freely between the two compartments. Proteomics identified 354 proteins in ISF, with the uremic toxins beta-2 microglobulin, cystatin C and complement factor D seen in ISF, but not in plasma of some patients, and several others exhibiting a compartmental behaviour. The novel microneedles were successful in painlessly extracting ISF in 68.8% of oedematous CKD patients. &lt;b&gt;Conclusions:&lt;/b&gt; ISF is toxin rich, ideal for metabolomic and proteomic research in uremia, and may reveal earlier accumulation of toxins and possibly a sequestration of some larger toxins within the compartment. Even small toxins may show a differential compartmental distribution, enhanced by dialysis. Microneedles show great promise in minimally invasively sampling ISF, and may bridge the gap to better understanding of ISF uremic composition, with a likely significant impact on treatment delivery in CKD, and the assessment of its efficacy.

Objective: No consensus has been established which is the best fourth-line agent in patients with RHT. We previously demonstrated that bioimpedance-guided reduction of extracellular volumen with intensification of diuretic therapy can control BP in patients with RHT. To assess the effect of intensifying diuretic treatment with a loop diuretic (furosemide) or an aldosterone antagonist (spironolactone) on control of BP in patients with RHT. Design and method: Study population comprised 30 patients with RHT (mean of 4.1 ± 0.9 antihypertensive drugs/patient) who were divided into 2 treatment arms according to clinical criteria. Fifteen patients received furosemide 40 mg/day and 15 patients spironolactone 25 mg/day in combination with habitual medication. Ambulatory BP monitoring was performed baseline, 3 months, and 6 months. Results: Baseline BP was 162 ± 8/90 ± 6 mmHg, 70%men, age 63.3 ± 9.1 years, and 56.1% diabetic. Baseline glomerular filtration rate (eGFR-CKD-EPI) was 55.8 ± 16.5 mL/min/1.73m2. No significant differences were found between groups at baseline in age, gender, % diabetics, eGFR, BP, number of antihypertensive drugs, or aldosterone levels. At 6 months, systolic BP decreased 24 ± 9.2 mmHg (from 163.6 ± 8.6 to 139.6 ± 8.1 mmHg) in spironolactone group, compared with 13.8 ± 2.8 mmHg (from 162 ± 7.9 to 148 ± 6.4 mmHg) in furosemide group(p < 0.01). Diastolic BP fell 11 ± 8.1 mmHg in spironolactone group compared with 5.2 ± 2.2 mmHg in furosemide group (p < 0.01). Forty percent of patients in spironolactone group reached the BP target (<140/90 mmHg) at 6 months compared with only 13% in furosemide arm. No significant changes in eGFR in any group during follow up. A significant reduction in urinary albumin creatinine ratio (from 173 ± 268 to 14 ± 24 mg/g, p < 0.01) was observed in spironolactone group at 6 months, but not in furosemide group. Multiple regression analysis showed that only treatment with spironolactone was associated with control of BP < 140/90 mmHg at 6 months. No severe adverse events were recorded. Mild hyperkalemia was observed in 2 patients on spironolactone. Conclusions: Spironolactone is more effective than furosemide for control of BP in RHT patients, with positive added effect on albuminuria. Spironolactone is safe in patients with mild kidney impairment, although serum potassium should be closely monitored, especially in diabetics.