Association of urinary excretion rates of uric acid with biomarkers of kidney injury in patients with advanced chronic kidney disease.

BACKGROUND: The potential influence of hyperuricemia on the genesis and progression of chronic kidney disease (CKD) remains controversial. In general, the correlation between blood levels of uric acid (UA) and the rate of progression of CKD is considered to be modest, if any, and the results of relevant trials oriented to disclose the effect of urate-lowering therapies on this outcome have been disappointing. Urinary excretion rates of UA could reflect more accurately the potential consequences of urate-related kidney injury. METHOD: Using a cross-sectional design, we investigated the correlation between different estimators of the rates of urinary excretion of UA (total 24-hour excretion, mean urinary concentration, renal clearance and fractional excretion)(main study variables), on one side, and urinary levels of selected biomarkers of kidney injury and CKD progression (DKK3, KIM1, NGAL, interleukin 1b and MCP)(main outcome variables), in 120 patients with advanced CKD (mean glomerular filtration rate 21.5 mL/minute). We took into consideration essential demographic, clinical and analytic variables with a potential confounding effect on the explored correlations (control variables). Spearman's rho correlation and nonlinear generalized additive regression models (GAM) with p-splines smoothers were used for statistical analysis. MAIN RESULTS: Multivariate analysis disclosed independent correlations between urinary UA concentrations, clearances and fractional excretion rates (but not plasma UA or total 24-hour excretion rates of UA), on one side, and the scrutinized markers. These correlations were more consistent for DKK3 and NGAL than for the other biomarkers. Glomerular filtration rate, proteinuria and treatment with statins or RAA axis antagonists were other independent correlates of the main outcome variables. CONCLUSIONS: Our results support the hypothesis that urinary excretion rates of UA may represent a more accurate marker of UA-related kidney injury than plasma levels of this metabolite, in patients with advanced stages of CKD. Further, longitudinal studies will be necessary, to disclose the clinical significance of these findings.

Influencia del volumen peritoneal residual en los resultados de la prueba de equilibrio peritoneal. Estudio prospectivo / Influence of peritoneal residual volume on the results of the peritoneal equilibration test. Prospective study

Introducción y objetivos: La categorización de la capacidad de ultrafiltración durante la prueba de equilibrio peritoneal (PEP) es parte habitual de la monitorización del funcionalismo peritoneal en pacientes tratados con diálisis peritoneal (DP). La estimación del volumen residual (Vr) tras el cambio previo (Vrpre) y el de la propia PEP (Vrpost) podría ayudar a mejorar la precisión de la prueba. Método: Siguiendo un diseño prospectivo, estimamos el Vrpre y Vrpost en 116 pacientes incidentes o prevalentes en DP que fueron sometidos a una o dos (n=27) PEP con solución de glucosa al 3,86/4,25% y drenaje completo a los 60 minutos. Valoramos la consistencia del Vr comparando Vrpre y Vrpost y también estos parámetros en PEP sucesivas. Analizamos la posible influencia de factores demográficos y clínicos en la cuantía del Vr, así como el impacto de la corrección para Vr de la ultrafiltración durante la PEP sobre la categorización de la capacidad de ultrafiltración. Resultados: El Vrpost fue mayor que el Vrpre, por lo que la ultrafiltración corregida para Vr fue signficativamente mayor que la calculada por procedimiento estándar (494 vs. 449mL, p<0,0005). Resultó notable la escasa concordancia de estimaciones sucesivas (Vrpre vs Vrpost y PEP sucesivas) del Vr. Asimismo, ningún parámetro demográfico o clínico escrutado mostró asociación con la magnitud del Vr. Tan solo un 12,9% de los pacientes presentó una desviación clínicamente significativa (>200mL) de la ultrafiltración corregida para Vr frente al valor estándar. Sin embargo, un 21,1% de los pacientes que cumplían criterio de fallo de ultrafiltración por método estándar, no lo hacían si se aplicaba la corrección para Vr. (AU)

Background: Categorization of the capacity of ultrafiltration during a peritoneal equilibration test (PET) is a usual step during the monitoring of peritoneal transport characteristics of peritoneal dialysis (PD) patients. Quantifying the peritoneal residual volume (Vr) after the dwell preceding the PET (Vrpre) and at the end of the test (Vrpost) could help to improve the accuracy of the estimation of this variable. Method: Following a prospective design, we calculated Vrpre and Vrpost in 116 patients, incident or prevalent on DP, who underwent one or two (n=27) PET with 3.86/4.25% glucose-based PD solutions and complete drainage at 60min. We evaluated the consistency of Vr by comparing Vrpre and Vrpost, as also these two parameters in repeated tests. We scrutinized potential associations between demographic and clinical factors, on one side, and the amount of Vr on the other, as also the impact of correcting ultrafiltration during PET for Vr on the categorization of the capacity of ultrafiltration. Results: As a mean, Vrpost was larger than Vrpre. Consequently, correction of ultrafiltration for Vr resulted in significantly higher values than those obtained according to the standard procedure (494 vs 449mL, p<0.0005). We disclosed marked inconsistencies for different estimations of Vr in the same patients (Vrpre vs Vrpost and repeated PET studies). Moreover, no demographic or clinical variable was able to predict the amount of Vr. We observed a significant deviation (>200mL) between both methods of estimation of the capacity of utrafiltration in only 12.9% of the patients. However, 21.1% of the patients categorized as cases of ultrafiltration failure according to the standard procedure did not maintain this condition after correction for Vr. (AU)

Low Incidence of Acute Antibody-Mediated Rejection after HLA Desensitization in Living Donor Kidney Transplant Recipients.

Desensitization allows the performance of human leukocyte antigen (HLA)-incompatible transplants. However, the incidence of acute rejection (AR) is high. This study aims to analyze the incidence of AR after transplantation with HLA-incompatible living donors in patients who underwent desensitization. Patients were immunosuppressed with tacrolimus, mycophenolic acid derivatives, and steroids after being desensitized with rituximab, plasma exchange, and/or immunoadsorption with specific cytomegalovirus immunoglobulins. A negative complement-dependent cytotoxicity or flow cytometry crossmatch and a donor-specific antibody titer < 1000 mean fluorescence intensity (MFI) were used to determine desensitization efficacy. A total of 36 patients underwent desensitization, and 27 (75%) were transplanted. After a follow-up of 58 ± 58 months (Min−Max: 0.13−169.5), five episodes of AR occurred: two antibody-mediated and three T-cell-mediated. No differences were found in baseline calculated panel-reactive antibodies (cPRA), class I or II MFI, number of antibodies, or Relative Intensity Scale (RIS) between AR and non-AR patients. Patients with antibody-mediated AR had higher cPRA (NS), MFI class I (p = 0.07) and class II (p = 0.006), and RIS (p = 0.01). The two patients with antibody-mediated AR and one patient with T-cell-mediated AR lost their grafts. In conclusion, the incidence of acute antibody-mediated rejection after desensitization was 7.4%, which occurred early post-transplantation in patients with high MFI and was associated with early graft loss.