Determination of the Preferred Conditions for the Isolated Perfusion of Porcine Kidneys

2014 ◽  
Vol 54 (1-2) ◽  
pp. 44-54 ◽  
Author(s):  
Elina Mancina ◽  
Julia Kalenski ◽  
Pascal Paschenda ◽  
Christian Beckers ◽  
Christian Bleilevens ◽  
...  

Background: The isolated perfused porcine kidney (IPPK) model has been the method of choice for the early preclinical evaluation of kidney graft preservation techniques. The preferred reperfusion conditions have not yet been determined. Here, we examined the effects of pressure- or flow-controlled perfusion and oxygenation by pure oxygen or carbogen (95% O2/5% CO2) on normothermic reperfusion in the IPPK model. Methods: Porcine kidneys were cold-stored for 24 h in histidine-tryptophan-ketoglutarate solution and reperfused for 1 h with normothermic whole blood/Krebs-Henseleit buffer medium (20/80%). Kidneys (n = 5/group) were flow-controlled reperfused with pure oxygen (1 ml/min/g; Flow-O2) or pressure-controlled reperfused (85 mm Hg mean arterial pressure) and oxygenated with either pure oxygen (Pressure-O2) or carbogen (Pressure-O2/CO2). Renal function and damage were assessed during reperfusion and NGAL and HIF-1α levels were analyzed using an ELISA. Results: Pressure-O2 and Pressure-O2/CO2 were associated with significantly better renal hemodynamics and acid-base homeostasis compared to Flow-O2. Urine protein concentrations and the fractional excretion of sodium were lower with both Pressure-O2 and Pressure-O2/CO2 than with Flow-O2. NGAL and HIF-1α levels were also lower with Pressure-O2 and Pressure-O2/CO2 than with Flow-O2. Only Pressure-O2/CO2 could demonstrate a significantly increased urine production compared to Flow-O2. The structural integrity was well preserved in the Pressure-O2 and Pressure-O2/CO2 groups, whereas diffuse and global glomerular destruction was observed in the Flow-O2 group. Conclusion: In the IPPK model, the application of pressure-controlled reperfusion with carbogen oxygenation, and to a lesser extent with pure oxygen, maintained physiological renal function for 1 h, thus providing a reliable and reproducible ex vivo evaluation of kidney preservation quality.

2008 ◽  
Vol 295 (4) ◽  
pp. F1239-F1247 ◽  
Author(s):  
Alaa E. S. Abdel-Razik ◽  
Richard J. Balment ◽  
Nick Ashton

Urotensin II (UII) has been implicated widely in cardiovascular disease. The mechanism(s) through which it contributes to elevated blood pressure is unknown, but its emerging role as a regulator of mammalian renal function suggests that the kidney might be involved. The aim of this study was to determine the effect of UII on renal function in the spontaneously hypertensive rat (SHR). UII infusion (6 pmol·min−1·100 g body wt−1) in anesthetized SHR and control Wistar-Kyoto (WKY) rats produced marked reductions in glomerular filtration rate (ΔGFR WKY, n = 7, −0.3 ± 0.1 vs. SHR, n = 7, −0.6 ± 0.1 ml·min−1·100 g body wt−1, P = 0.03), urine flow, and sodium excretion rates, which were greater in SHR by comparison with WKY rats. WKY rats also showed an increase in fractional excretion of sodium (ΔFENa; +0.6 ± 0.1%, P = 0.02) in contrast to SHR in which no such change was observed (ΔFENa −0.6 ± 0.2%). Blockade of the UII receptor (UT), and thus endogenous UII activity, with urantide evoked an increase in GFR which was greater in SHR (+0.3 ± 0.1) compared with WKY rats (+0.1 ± 0.1 ml·min−1·100 g body wt−1, P = 0.04) and was accompanied by a diuresis and natriuresis. UII and UT mRNA expression were greater in the renal medulla than the cortex of both strains; however, expression levels were up to threefold higher in SHR tissue. SHR are more sensitive than WKY to UII, which acts primarily to lower GFR thus favoring salt retention in this model of hypertension.


2018 ◽  
Vol 132 (18) ◽  
pp. 2071-2085 ◽  
Author(s):  
Chuan Chuan Ren ◽  
Wen Zhu ◽  
Qing Wei Wang ◽  
Yu Tao Lu ◽  
Yan Wang ◽  
...  

Congenital urinary tract obstruction is one of the most frequent malformations in fetuses or neonates, which usually causes profound impairment of renal function including reductions in both glomerular filtration rate (GFR) and tubular handling of water and solutes. Although obstruction can be released by surgical operation, the child will suffer from diuresis for sometime. It has been reported that erythropoietin (EPO) could prevent the down-regulation of aquaporin-2 (AQP2) and urinary-concentrating defects induced by renal ischemia/reperfusion (I/R) injury. However, whether EPO could promote the recovery of renal function and AQP2 expression after releasing of ureteral obstruction has not been reported yet. The purposes of the present study were to investigate the effects of EPO on renal function and AQP2 expression after release of bilateral ureteral obstruction (BUO-R) in rats. The results showed that EPO could promote interleukin (IL) 10 (IL-10) expression; inhibit tumor necrosis factor-α (TNF-α), IL-6, and inducible nitric oxide synthase (iNOS) expressions; reduce the fractional excretion of sodium (FENa) and plasma creatinine (CREA) and urea; and promote the recovery of water and salt handling and AQP2 expression in BUO-R rats, especially in the high dose of EPO-treated group rats. In conclusion, EPO could promote the recovery of renal function and AQP2 expression in BUO-R rats, which may partially associate with its anti-inflammation effect.


Author(s):  
Norbert Lameire ◽  
Raymond Vanholder ◽  
Wim Van Biesen

The prognosis of acute kidney injury (AKI) depends on early diagnosis and therapy. A multitude of causes are classified according to their origin as prerenal, intrinsic (intrarenal), and post-renal.Prerenal AKI means a loss of renal function despite intact nephrons, for example, because of volume depletion and/or hypotension.There is a broad spectrum of intrinsic causes of AKI including acute tubular necrosis (ATN), interstitial nephritis, glomerulonephritis, and vasculitis. Evaluation includes careful review of the patient’s history, physical examination, urinalysis, selected urine chemistries, imaging of the urinary tree, and eventual kidney biopsy. The history should focus on the tempo of loss of function (if known), associated systemic diseases, and symptoms related to the urinary tract (especially those that suggest obstruction). In addition, a review of the medications looking for potentially nephrotoxic drugs is essential. The physical examination is directed towards the identification of findings of a systemic disease and a detailed assessment of the patient’s haemodynamic status. This latter goal may require invasive monitoring, especially in the oliguric patient with conflicting clinical findings, where the physical examination has limited accuracy.Excluding urinary tract obstruction is necessary in all cases and may be established easily by renal ultrasound.Distinction between the two most common causes of AKI (prerenal AKI and ATN) is sometimes difficult, especially because the clinical examination is often misleading in the setting of mild volume depletion or overload. Urinary chemistries, like calculation of the fractional excretion of sodium (FENa), may be used to help in this distinction. In contrast to FENa, the fractional excretion of urea has the advantage of being rather independent of diuretic therapy. Response to fluid repletion is still regarded as the gold standard in the differentiation between prerenal and intrinsic AKI. Return of renal function to baseline or resuming of diuresis within 24 to 72 hours is considered to indicate ‘transient, mostly prerenal AKI’, whereas persistent renal failure usually indicates intrinsic disease. Transient AKI may, however, also occur in short-lived ATN. Furthermore, rapid fluid application is contraindicated in a substantial number of patients, such as those with congestive heart failure.‘Muddy brown’ casts and/or tubular epithelial cell casts in the urine sediment are typically seen in patients with ATN. Their presence is an important tool in the distinction between ATN and prerenal AKI, which is characterized by a normal sediment, or by occasional hyaline casts. There is a possible role for new serum and/or urinary biomarkers in the diagnosis and prognosis of the patient with AKI, including the differential diagnosis between pre-renal AKI and ATN. Further studies are needed before their routine determination can be recommended.When a diagnosis cannot be made with reasonable certainty through this evaluation, renal biopsy should be considered; when intrarenal causes such as crescentic glomerulonephritis or vasculitis are suspected, immediate biopsy to avoid delay in the initiation of therapy is mandatory.


2021 ◽  
Vol 89 (2) ◽  
pp. 98-106
Author(s):  
Nicolas M. Kouyoumdzian ◽  
Gabriel Kim ◽  
Gabriel D. Robbesaul ◽  
Paula D. Prince ◽  
Ana M. Puyó ◽  
...  

Introduction: The role of the chloride anion on the deleterious effects of excessive consumption of salt (NaCl) and whether its effects are independent each other of the presence of sodium remains to date, unknown and unclear. Objective: To demonstrate that both a chloride overload and a sodium overload in the diet produce deleterious effects, by different mechanisms, on systolic blood pressure (SBP), renal function and markers of oxidative stress in the kidney. Materials and Methods: Male Wistar rats were divided into four groups (n = 8 / group) and fed with different diets for three weeks: C: control (standard diet), and diets: NaCl: hypersodic-hyperchloric; Na: hypersodic without chloride and Cl: hyperchloric without sodium. Systolic blood pressure (SBP) and renal function were determined, and the production of thiobarbituric acid reactive species (TBARS) and the activity and expression of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) enzymes were evaluated in renal cortex tissue. Results: SBP increased (*) in the two groups fed with chloride. The fractional excretion of sodium and chloride increased (*) in the NaCl and Na groups. increased (*) in the renal cortex with the three diets. No changes were observed in the activity and expression of SOD and CAT. GPx activity increased (*) in the two groups that received chloride; (* p <0.05 vs C). Conclusion: Both sodium and chloride overload are associated with a higher oxidative state characterized by an increase in lipid peroxidation in the renal cortex. However, compared with Na group, only chloride overload is associated with higher GPx activity and hypertension without any changes in urinary chloride excretion, suggesting a higher renal pro-oxidant state in this experimental group.


1997 ◽  
Vol 115 (3) ◽  
pp. 1433-1439 ◽  
Author(s):  
Yara Marcondes Machado Castiglia ◽  
José Reinaldo Cerqueira Braz ◽  
Pedro Thadeu Galvão Vianna ◽  
Lino Lemonica ◽  
Luiz Antonio Vane

Our objective was to determine the effects of high-dose fentanyl on canine renal function (RF). We anesthetized with sodium pentobarbital (SP) 16 dogs, randomly divided into 2 groups: in G1, SP was given alone, and in G2, combined with 0.05 mg.kg-1 fentanyl. All animals were ventilated artificially and had catheterized left and right femoral veins and left femoral artery for fluid infusion, drug administration, blood collection, and hemodynamic measurement. Urine was collected throughout the experiment. Attributes of RF were studied. SP did not alter RF, which was significantly altered by fentanyl. In G2, slower heart rates, mean arterial pressure, creatinine clearance, urinary output, osmolar clearance and fractional excretion of sodium and potassium were observed. G1 had a behavior attributed to extracellular volume expansion and no RF alterations. In G2, we observed significant decreases in RF due to opioid-induced hemodynamic changes, not discarding the possible action of aldosterone.


2019 ◽  
Vol 20 (8) ◽  
pp. 1992 ◽  
Author(s):  
Abdelsalam Kasil ◽  
Sebastien Giraud ◽  
Pierre Couturier ◽  
Akbar Amiri ◽  
Jerome Danion ◽  
...  

Marginal kidney graft preservation in machine perfusion (MP) is well-established. However, this method requires improvement in order to mitigate oxidative stress during ischemia-reperfusion, by using oxygenation or an O2 carrier with anti-oxidant capacities (hemoglobin of the marine worm; M101). In our preclinical porcine (pig related) model, kidneys were submitted to 1h-warm ischemia, followed by 23 h hypothermic preservation in Waves® MP before auto-transplantation. Four groups were studied: W (MP without 100%-O2), W-O2 (MP with 100%-O2; also called hyperoxia), W-M101 (MP without 100%-O2 + M101 2 g/L), W-O2 + M101 (MP with 100%-O2 + M101 2 g/L) (n = 6/group). Results: Kidneys preserved in the W-M101 group showed lower resistance, compared to our W group. During the first week post-transplantation, W-O2 and W-M101 groups showed a lower blood creatinine and better glomerular filtration rate. KIM-1 and IL-18 blood levels were lower in the W-M101 group, while blood levels of AST and NGAL were lower in groups with 100% O2. Three months after transplantation, fractional excretion of sodium and the proteinuria/creatinuria ratio remained higher in the W group, creatininemia was lower in the W-M101 group, and kidney fibrosis was lower in M101 groups. We concluded that supplementation with M101 associated with or without 100% O2 improved the Waves® MP effect upon kidney recovery and late graft outcome.


2020 ◽  
Vol 21 (21) ◽  
pp. 8156
Author(s):  
Sebastien Giraud ◽  
Raphaël Thuillier ◽  
Jérome Cau ◽  
Thierry Hauet

Oxidative stress is a key element of ischemia–reperfusion injury, occurring during kidney preservation and transplantation. Current options for kidney graft preservation prior to transplantation are static cold storage (CS) and hypothermic machine perfusion (HMP), the latter demonstrating clear improvement of preservation quality, particularly for marginal donors, such as extended criteria donors (ECDs) and donation after circulatory death (DCDs). Nevertheless, complications still exist, fostering the need to improve kidney preservation. This review highlights the most promising avenues of in kidney perfusion improvement on two critical aspects: ex vivo and in vitro evaluation.


1972 ◽  
Vol 50 (7) ◽  
pp. 662-673 ◽  
Author(s):  
D. R. Wilson

The effect of unilateral papillectomy on renal function in the rat was compared with the effect of partial nephrectomy which produced a similar decrease in glomerular filtration rate (G.F.R.) in the presence of an intact papilla. Under hydropenic conditions the kidney with papillectomy had a higher urine flow rate, sodium excretion rate, fractional sodium excretion, and osmolar clearance, while urine osmolality was lower. After an acute saline load the differences in sodium and water excretion disappeared, and fractional excretion of sodium and water were significantly higher in both types of kidney damage than in the contralateral control kidney. Free water reabsorption was lower in the papillectomized kidney after saline loading. Thus removal of the papilla resulted in abnormalities in the renal handling of salt and water which varied with the state of hydration of the animal and which were distinct from the effects of a reduction in G.F.R. by partial nephrectomy. It was concluded that the site of nephron loss, whether mainly in the renal medulla or in the cortex, may be another factor, in addition to G.F.R. and tubular reabsorption, which influences sodium and water excretion by the moderately damaged kidney.


2016 ◽  
Vol 57 (1-2) ◽  
pp. 10-21 ◽  
Author(s):  
Julia Kalenski ◽  
Elina Mancina ◽  
Pascal Paschenda ◽  
Christian Beckers ◽  
Christian Bleilevens ◽  
...  

Background/Aim: The global shortage of donor organs for transplantation has necessitated the expansion of the organ pool through increased use of organs from less ideal donors. Venous systemic oxygen persufflation (VSOP) and oxygenated machine perfusion (OMP) have previously demonstrated beneficial results compared to cold storage (CS) in the preservation of warm-ischemia-damaged kidney grafts. The aim of this study was to compare the efficacy of VSOP and OMP for the preservation of warm-ischemia-damaged porcine kidneys using the recently introduced Ecosol preservation solution compared to CS using Ecosol or histidine-tryptophan-ketoglutarate solution (HTK). Materials and Methods: Kidneys from German Landrace pigs (n = 5/group) were retrieved and washed out with either Ecosol or HTK after 45 min of clamping of the renal pedicle. As controls, kidneys without warm ischemia, cold stored for 24 h in HTK, were employed. Following 24 h of preservation by VSOP, OMP, CS-Ecosol, or CS-HTK, renal function and damage were assessed during 1 h using the isolated perfused porcine kidney model. Results: During reperfusion, urine production was significantly higher in the VSOP and OMP groups than in the CS-HTK group; however, only VSOP could demonstrate lower urine protein concentrations and fractional excretion of sodium, which did not differ from the non-warm-ischemia-damaged control group. VSOP, CS-Ecosol, and controls showed better maintenance of the acid-base balance than CS-HTK. Reduced lipid peroxidation, as reflected in postreperfusion tissue thiobarbituric acid-reactive substance levels, was observed in the VSOP group compared to the OMP group, and the VSOP and CS-Ecosol groups had concentrations similar to the controls. The ratio of reduced to oxidized glutathione was higher in the VSOP, OMP, and CS-Ecosol groups than in the CS-HTK group and controls, with a higher ratio in the VSOP than in the OMP group. Conclusion: VSOP was associated with mitigation of oxidative stress in comparison to OMP and CS. Preservation of warm-ischemia-damaged porcine kidneys by VSOP was improved compared to OMP and CS, and was comparable to preservation of non-warm-ischemia-damaged cold-stored kidneys.


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