RESUMEN
BACKGROUND: Variation in residual volume between peritoneal dialysis dwells creates uncertainty in ultrafiltration determination, dialysis efficiency, and poses a risk of overfill if the residual volume is large. Measuring the dilution of a marker molecule during fluid fill offers a convenient approach, however, estimation accuracy depends on the choice of dilution marker. We here evaluate the feasibility of creatinine and urea as dilution markers compared to albumin-based residual volumes and three-pore model estimations. METHOD: This clinical, retrospective analysis comprises 56 residual volume estimations from 20 individuals, based on the dilution of pre-fill dialysate creatinine, urea and albumin concentrations during the dialysis fluid fill phase. Outcomes were compared individually. Bias induced by ultrafiltration, marker molecule mass-transfer and influence of fluid glucose contents was quantified using the three-pore model. Linear regression established conversion factors enabling conversion between the various marker molecules. RESULTS: Creatinine-based calculations overestimated residual volumes by 115â mL (IQR 89-149) in 1.5% dwells and 252â mL (IQR 179-313) in 4.25% glucose dwells. In hypertonic dwells, ultrafiltration was 52â mL (IQR 38-66), while intraperitoneal creatinine mass increased by 67% during fluid fill, being the leading cause of overestimation. Albumin-based volumes conformed strongly with three-pore model estimates. Correction factors effectively enabled marker molecule interchangeability. CONCLUSIONS: Mass-transfer of low molecular weight marker molecules is associated with residual volume overestimation. However, by applying correction factors, creatinine and urea dilution can still provide reasonable estimates, particularly when the purpose is to exclude the presence of a very large residual volume.
RESUMEN
The recently discovered selective glomerular hypofiltration syndromes have increased interest in the actual elimination of molecules in the human kidney. In the present study, a novel human model was introduced to directly measure the single-pass renal elimination of molecules of increasing size. Plasma concentrations of urea, creatinine, C-peptide, insulin, pro-BNP, ß2-microglobulin, cystatin C, troponin-T, orosomucoid, albumin, and IgG were analysed in arterial and renal venous blood from 45 patients undergoing Transcatheter Aortic Valve Implantation (TAVI). The renal elimination ratio (RER) was calculated as the arteriovenous concentration difference divided by the arterial concentration. Estimated glomerular filtration rate (eGFR) was calculated by the CKD-EPI equations for both creatinine and cystatin C. Creatinine (0.11 kDa) showed the highest RER (21.0 ± 6.3%). With increasing molecular size, the RER gradually decreased, where the RER of cystatin C (13 kDa) was 14.4 ± 5.3% and troponin-T (36 kDa) was 11.3 ± 4.6%. The renal elimination threshold was found between 36 and 44 kDa as the RER of orosomucoid (44 kDa) was -0.2 ± 4.7%. The RER of creatinine and cystatin C showed a significant and moderate positive linear relationship with eGFR (r = 0.48 and 0.40). In conclusion, a novel human model was employed to demonstrate a decline in renal elimination with increasing molecular size. Moreover, RERs of creatinine and cystatin C were found to correlate with eGFR, suggesting the potential of this model to study selective glomerular hypofiltration syndromes.
Asunto(s)
Creatinina , Cistatina C , Tasa de Filtración Glomerular , Riñón , Humanos , Cistatina C/sangre , Masculino , Creatinina/sangre , Femenino , Anciano , Riñón/metabolismo , Anciano de 80 o más Años , Troponina T/sangre , Microglobulina beta-2/sangre , Urea/sangre , Péptido Natriurético Encefálico/sangre , Péptido C/sangre , Insulina/sangre , Modelos Biológicos , Inmunoglobulina G/sangreRESUMEN
Introduction: In kidney transplantation (KT), the role of the intravascular innate immune system (IIIS) in response to ischemia-reperfusion injury (IRI) is not well-understood. Here, we studied parallel changes in the generation of key activation products of the proteolytic cascade systems of the IIIS following living donor (LD) and deceased donor (DD) transplantation and evaluated potential associations with clinical outcomes. Methods: In a cohort study, 63 patients undergoing LD (n = 26) and DD (n = 37) transplantation were prospectively included. Fifteen DD kidneys were preserved with hypothermic machine perfusion (HMP), and the remaining were cold stored. Activation products of the kallikrein-kinin, coagulation, and complement systems were measured in blood samples obtained systemically at baseline and locally from the transplant renal vein at 1, 10, and 30 minutes after reperfusion. Results: DD kidneys exhibited a prompt and interlinked activation of all 3 cascade systems of IIIS postreperfusion, indicating a robust and local thrombo-inflammatory response to IRI. In this initial response, the complement activation product sC5b-9 exhibited a robust correlation with other IIIS activation markers and displayed a strong association with short-term and mid-term (24-month) graft dysfunction. In contrast, LD kidneys did not exhibit this thrombo-inflammatory response. The use of HMP was associated with reduced thromboinflammation and preserved mid-term kidney function. Conclusion: Kidneys from DD are vulnerable to a prompt thrombo-inflammatory response to IRI, which adversely affects both short-term and long-term allograft function. Strategies aimed at minimizing graft immunogenicity prior to reperfusion are crucial to mitigate the intricate inflammatory response to IRI.