Abstract
IntroductionThe aim of the study was to evaluate some of the underlying pathomechanisms of hydroxyethylstarch (HES) induced adverse effects on renal function using 24 porcine kidneys in an isolated perfusion model over six hours.MethodsInfusion of either 10% HES 200/0.5, 6% HES 130/0.42 or Ringer's lactate (RL) was performed to achieve an haematocrit of 20% in eight kidneys from four animals per group. Physiological and pathophysiological parameters were determined (including N-acetyl-beta-aminoglucosidase as a marker for lysosomal tubular damage). Histological investigations and immunohistological stainings of the kidneys were performed.ResultsInitially after haemodilution, HES 130/0.42 and HES 200/0.5 reduced urine output compared with RL (P < 0.01). After six hours, N-acetyl-beta-aminoglucosidase was significantly higher in HES 200/0.5 (81 ± 23 U/L) compared with HES 130/0.42 (38 ± 12 U/L) and RL (21 ± 13 U/L; P < 0.001). Osmotic nephrosis-like lesions (OL) of the tubuli were present in all groups showing a significantly lower number of OL in RL (1.1 ± 0.4; P = 0.002) compared with both HES groups (HES 200/0.5 = 2.1 ± 0.6; HES 130/0.42 = 2.0 ± 0.5). Macrophage infiltration was significantly higher in HES 200/0.5 compared with HES 130/0.42 (1.3 ± 1.0 vs. 0.2 ± 0.04; P = 0.044). There was a significant increase in interstitial cell proliferation in the HES 200/0.5 group vs. HES 130/0.42 (18.0 ± 6.9 vs. 6.5 ± 1.6; P = 0.006) with no significant difference in RL (13.5 ± 4.0).ConclusionsWe observed impaired diuresis and sodium excretion by HES and identified renal interstitial proliferation, macrophage infiltration and tubular damage as potential pathological mechanisms of HES-induced adverse effects on renal function using an isolated porcine renal perfusion model. Furthermore, we demonstrated that 10% HES 200/0.5 had more of a pro-inflammatory effect compared with 6% HES 130/0.42 and caused more pronounced tubular damage than 6% HES 130/0.42 and RL. OL were present in all groups, but to a lesser degree after RL administration.
Highlights
The aim of the study was to evaluate some of the underlying pathomechanisms of hydroxyethylstarch (HES) induced adverse effects on renal function using 24 porcine kidneys in an isolated perfusion model over six hours
We demonstrated that 10% hydroxyethyl starch (HES) 200/0.5 had more of a pro-inflammatory effect compared with 6% HES 130/ 0.42 and caused more pronounced tubular damage than 6% HES 130/0.42 and Ringer's lactate (RL)
Mean sodium transport over time was significantly lower in the HES 130/ 0.42 (-4.1 ± 0.8 mmol/minute/g) and HES 200/0.5 (-0.3 ± 0.2 mmol/minute/g) groups compared with RL (-13.9 ± 4.8 mmol/ minute/g; P < 0.01; Table 2)
Summary
The aim of the study was to evaluate some of the underlying pathomechanisms of hydroxyethylstarch (HES) induced adverse effects on renal function using 24 porcine kidneys in an isolated perfusion model over six hours. It has been shown that early goal-directed fluid resuscitation in patients with severe sepsis and septic shock is associated with improved outcome [2]. ANOVA: analysis of variance; Beta-NAG: N-acetyl-beta-aminoglucosidase; ClCrea: creatinine clearance; COP: colloid osmotic pressure; ECG: echocardiography; ED-1: marker for macrophage infiltration; H&E: haematoxylin and eosin; HES: hydroxyethyl starch; IOPS: isolated organ perfusion system; NaCl: sodium chloride; OL: osmotic nephrosis-like lesions; PaCO2: partial pressure of arterial carbon dioxide; PaO2: partial pressure of arterial oxygen; PCNA: proliferating nuclear antigen; PCrea: serum creatinine concentration; pc/vf: positive cells/visual field; RL: Ringer's lactate; UCrea: urine creatinine concentration; UVol: urine volume during the collection period; VRS: volume replacement solution. Either colloids or crystalloids for fluid replacement in patients with sepsis or septic shock [3]. Hydroxyethylstarch (HES) solutions are one group of volume replacement solutions (VRS) that can be trialled in the haemodynamically unstable patient, and recent developments include the introduction of new formulations and newly available HES products
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
