Effect of 0.9% NaCl compared to plasma-lyte on biomarkers of kidney injury, sodium excretion and tubular transport proteins in patients undergoing primary uncemented hip replacement - a randomized trial.

BACKGROUND: Isotonic saline (IS) is widely used to secure perioperative cardiovascular stability. However, the high amount of chloride in IS can induce hyperchloremic acidosis. Therefore, IS is suspected to increase the risk of acute kidney injury (AKI). Biomarkers may have potential as indicators. METHODS: In a double-blinded, placebo-controlled study, 38 patients undergoing primary uncemented hip replacement were randomized to IS or PlasmaLyte (PL). Infusion was given during surgery as 15 ml/kg the first hour and 5 ml/kg the following two hours. Urinary samples were collected upon admission and the day after surgery. As surgery was initiated, urine was collected over the course of 4 h. Hereafter, another urine collection proceeded until the morning. Urine was analyzed for markers of AKI neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1). Arterious and venous blood samples for measurements of pH and plasma electrolytes including chloride (p-Cl) were collected as surgery was initiated, at the end of surgery and the following morning. RESULTS: IS induced an increase in p-Cl (111 ± 2 mmol/L after IS and 108 ± 3 after PL, p = 0.004) and a decrease in pH (7.39 ± 0.02 after IS and 7.43 ± 0.03 after PL, p = 0.001). Urinary NGAL excretion increased in both groups (ΔNGAL: 5.5 [4.1; 11.7] µg/mmol creatinine p = 0.004 after IS vs. 5.5 [2.1;9.4] µg/mmol creatinine after PL, p < 0.001). No difference was found between the groups (p = 0.839). Similarly, urinary KIM-1 excretion increased in both groups (ΔKIM-1: IS 115.8 [74.1; 156.2] ng/mmol creatinine, p < 0.001 vs. PL 152.4 [120.1; 307.9] ng/mmol creatinine, p < 0.001). No difference between the groups (p = 0.064). FENa increased (1.08 ± 0.52% after IS and 1.66 ± 1.15% after PL, p = 0.032). ENaC excretion was different within groups (p = 0.019). CONCLUSION: A significantly higher plasma chloride and a lower pH was present in the group receiving isotonic saline. However, u-NGAL and u-KIM-1 increased significantly in both groups after surgery despite absence of changes in creatinine. These results indicate that surgery induced subclinical kidney injury. Also, the IS group had a delayed sodium excretion as compared to the PL group which may indicate that IS affects renal sodium excretion differently from PL. TRIAL REGISTRATION: ClinicalTrials.gov Identifier:  NCT02528448 , 19/08/2015.

Effect of 3% saline and furosemide on biomarkers of kidney injury and renal tubular function and GFR in healthy subjects - a randomized controlled trial.

BACKGROUND: Chloride is speculated to have nephrotoxic properties. In healthy subjects we tested the hypothesis that acute chloride loading with 3% saline would induce kidney injury, which could be prevented with the loop-diuretic furosemide. METHODS: The study was designed as a randomized, placebo-controlled, crossover study. Subjects were given 3% saline accompanied by either placebo or furosemide. Before, during and after infusion of 3% saline we measured glomerular filtration rate (GFR), fractional excretion of sodium (FENa), urinary chloride excretion (u-Cl), urinary excretions of aquaporin-2 (u-AQP2) and epithelial sodium channels (u-ENaCγ), neutrophil gelatinase-associated lipocalin (u-NGAL) and kidney injury molecule-1 (u-KIM-1) as marker of kidney injury and vasoactive hormones: renin (PRC), angiotensin II (p-AngII), aldosterone (p-Aldo) and arginine vasopressin (p-AVP). Four days prior to each of the two examinations subjects were given a standardized fluid and diet intake. RESULTS: After 3% saline infusion u-NGAL and KIM-1 excretion increased slightly (u-NGAL: 17 ± 24 during placebo vs. -7 ± 23 ng/min during furosemide, p = 0.039, u-KIM-1: 0.21 ± 0.23 vs - 0.06 ± 0.14 ng/ml, p <  0.001). The increase in u-NGAL was absent when furosemide was given simultaneously, and the responses in u-NGAL were not significantly different from placebo control. Furosemide changed responses in u-KIM-1 where a delayed increase was observed. GFR was increased by 3% saline but decreased when furosemide accompanied the infusion. U-Na, FENa, u-Cl, and u-osmolality increased in response to saline, and the increase was markedly pronounced when furosemide was added. FEK decreased slightly during 3% saline infusion, but simultaneously furosemide increased FEK. U-AQP2 increased after 3% saline and placebo, and the response was further increased by furosemide. U-ENaCγ decreased to the same extent after 3% saline infusion in the two groups. 3% saline significantly reduced PRC, p-AngII and p-Aldo, and responses were attenuated by furosemide. p-AVP was increased by 3% saline, with a larger increase during furosemide. CONCLUSION: This study shows minor increases in markers of kidney injury after 3% saline infusion Furosemide abolished the increase in NGAL and postponed the increase in u-KIM-1. The clinical importance of these findings needs further investigation. TRIAL REGISTRATION: (EU Clinical trials register number: 2015-002585-23 , registered on 5th November 2015).

[Renal side-effects of intraoperative and postoperative pain treatment with non-steroidal anti-inflammatory drugs]. / Renale sidevirkninger ved per- og postoperativ smertebehandling med ikkesteroide antiinflammatoriske farmaka.

Non-steroidal anti-inflammatory drugs (NSAID) are now commonly used in the treatment of postoperative pain. In normovolaemic conditions, prostaglandins do not seem to play a substantial role in maintaining renal function. However, numerous studies have shown that during activation of vasoconstrictor systems the synthesis of renal prostaglandins counteracts the vasoconstrictor effects and thereby maintains renal function. In animals, renal blood flow and GFR are markedly decreased when an NSAID is administered in the presence of renal hypoperfusion. Major surgery decreases renal function secondary to stimulation of the adrenosympathetic system and the renin-angiotensin system, and it has previously been demonstrated that maintenance of renal blood flow during laparotomy in dogs depends on an intact prostaglandin synthesis. Perioperative effects of NSAIDs are only sparsely investigated in humans, and studies on the effect on renal haemodynamics have not been presented. As in unanaesthetized volunteers, NSAID have been found to decrease the postoperative excretion of water, sodium and potassium. It therefore still remains unclarified whether general anaesthesia and surgery increase the risk of renal side effects of NSAIDs. Because of the potential risk of peri- and postoperative complications that may further deteriorate renal function, NSAIDs should not be used preoperatively, and not in patients in unstable haemodynamic states.

Weight gain during pregnancy does not influence the spread of spinal analgesia in the term parturient.

BACKGROUND: It is still controversial whether the spread of spinal anaesthesia in pregnancy is influenced by particular physique. Investigation was based on a clinical observation that parturients with a pronounced "pregnant" physique, e.g. generalised oedema and heavy abdomen, tended to develop more cephalad sensory blockades than parturients without these physical signs. Using weight gain during pregnancy as a measure for the physique at term, we aimed to determine whether this parameter influences the distribution of analgesia after subarachnoidal injection of plain bupivacaine. METHODS: Thirty women presenting for elective Caesarean section were studied. All the women received 13.5 mg plain bupivacaine via subarachnoid injection at the L2-3 interspace. Thirty minutes after the injection, while the women were in the supine position with a left lateral tilt on a horizontal operating table, the maximum cephalad extent of sensory analgesia (loss of sensation to sharpness of pinprick) was determined. RESULTS: Neither weight gain during pregnancy (6-22 kg, range), height (152-185 cm), weight (56-98 kg) nor body-mass index (20.2-31.8 kg/m2) correlated with the cephalad spread of sensory blockade. CONCLUSION: In parturients, weight gain during pregnancy, height, weight and body-mass index did not influence the extent of sensory analgesia after subarachnoidal administration of plain bupivacaine.