*Csaba Kopitkó1, László Medve1, Tibor Gondos2
Renal blood supply and fluid therapy
1Dr. Kenessey Albert Hospital, Department of Anaesthesiology and Intensive Care Medicine, Balassagyarmat, Hungary
Head of the Faculty: Szabó Gèza, MD
2Department of Clinical Studies, Faculty of Health Sciences, Semmelweis University, Budapest, Hungary
Head of the Faculty: Zoltán Zsolt Nagy, MD, PhD
Summary
There are different underlying mechanisms of acute kidney injury (AKI) in various type of shock, but restoration of renal blood flow (RBF) is crucial in prevention of AKI. The first 24-48 hours of shock seem to be critical. Monitoring of global RBF and its intrarenal distribution is not possible in current clinical practice. The only way for optimization of renal blood supply is optimization of macrohemodynamics. In volume-responsive AKI, fluid therapy restores kidney function. Many clinical signs and parameters can be of use in determining the volume status. The accuracy of the assessment may be improved with the help of tools quantifying the clinical parameters (e.g. hypovolemic index – HVI). The basis of intravenous fluid therapy are crystalloids, and their effect is reported to be shorter than 120 min. Every form of hydroxyethyl starch has been shown to be harmful for patients at risk of impaired renal function. In sepsis, the boundary between volume-responsive and volume-unresponsive AKI is blurred. Fluid responsiveness can be lost in the course of AKI as early as on the first day of sepsis. According to the results of the ARDS Network study, the conservative approach in fluid therapy resulted in a shorter time of mechanical ventilation and did not affect the renal function, except for a slight increase of the serum creatinine level. Fluid overload is to be avoided, as renal venous and lymphatic congestion can limit the urine filtration rate, further worsening edema.
Introduction
Despite the development of renal replacement techniques, acute kidney injury (AKI) remains a poor prognostic factor in critically ill patients. AKI is diagnosed based on serum creatinine and urine output (table 1) (1). The optimization of renal blood supply can improve the outcome in patients suffering from AKI (2). The role of venous and lymphatic flow has been underlined in multiple studies on animal and human subjects concerning the pathophysiology of sepsis and cardiovascular disorders (3-8). Despite the availability of an increasing number of biomarkers for the early diagnosis of acute kidney injury, serum creatinine remains the widely available gold standard. In clinical setting, avoiding hypo- and hypervolemia and preserving renal blood flow remain the best preventive measures against AKI (9). The aim of this paper was to review the diagnostic and therapeutic options for AKI.
Tab. 1. Definition of acute kidney injury
| Class | Serum creatinine | Urine output |
| I | Increased to ≥ 0.3 mg/dl (≥ 26.4 μmol/l) or 1.5-2 times baseline | < 0.5 ml/kg/hour in > 6 hours |
| II | Increased to 2-3 times baseline | < 0.5 ml/kg/hour in > 12 hours |
| III | Increased to > 3 times baseline, or serum creatinine ≥ 4.0 mg/dl (≥ 354 μmol/l), or an acute rise ≥ 0.5 mg/dl (44 μmol/l) | < 0.3 ml/kg/hour over 24 hours or anuria lasting > 12 hours |
Pathophysiology of AKI
The renal blood flow (RBF) depends on cardiac output and renal vascular resistance. The underlying mechanism of AKI in different types of shock varies. The available data is based primarily on animal studies, as the continuous measurement of RBF in human is difficult to perform. In animal models, glomerular filtration rate (GFR) remains constant until RBF has decreased to 1-10% of the baseline, and the near-total occlusion of the renal artery for 2 hours results in a transient decline of renal function after the restoration of blood circulation (9-12). AKI is very rare in human survivors of cardiac arrest without shock, therefore, the coexistence of another disorder is necessary for the development of renal dysfunction (12).
Septic AKI can develop even in a hyperdynamic circulatory pattern, but low systemic blood flow aggravates this condition (13). A decrease in GFR in sepsis can develop as a result of the constriction of afferent arterioles, which lowers the filtration pressure, however, as recent studies underline, it is mainly caused by the dilation of efferent arterioles. Studies suggest that the first 24-48 hours of shock are critical for the renal function (13).
Monitoring and optimization of the renal blood flow
Arterial blood supply
In an ideal setting, the global and regional RBF of high-risk patients would be continuously monitored, preferably in a noninvasive way. There are several methods for measuring renal blood supply: non-imaging procedures (microsphere deposition, para-aminohippurate clearance, renal vein thermodilution, xenon washout technique, intravascular Doppler), nuclear techniques (scintigraphy, renal extraction of 51chromium-ethylenediaminetetraacetic acid, positron emission tomography), magnetic resonance imaging, and ultrasound imaging (Doppler and contrast-enhanced ultrasound). Unfortunately, these methods are either difficult (para-aminohippurate clearance), risky (renal vein thermodilution), inappropriate for human examination (intravascular Doppler), unavailable in critical care units (nuclear techniques and MRI), or do not provide the possibility of continuous observation of individual patients (15, 16).
Monitoring global RBF and its intrarenal distribution is not possible in current clinical practice. The decreased RBF may be either a cause or a consequence of AKI, e.g. due to venous congestion and elevated interstitial and intracapsular pressure. Dynamic parameters and tests, such as pulse pressure variation (PPV), systolic pressure variation (SPV), stroke volume variation (SVV) and the passive leg raising test are considered the most appropriate for assessing volume responsiveness, and therefore, intravascular hypovolemia (17-20). However, these methods have several limitations. For example, multiple conditions, including arrhythmia, respiratory effort due to an inadequate sedation of a mechanically ventilated patient, and a low tidal volume (< 6 ml/kg) may all result in erroneous results (21, 22).
The risk factors for AKI in surgical patients are listed in table 2. In surgical patients, the optimization of hemodynamic parameters prevents the development of AKI, but targeting for higher than normal values carries no further benefit (2, 9, 23-25).
Tab. 2. Risk factors for AKI in surgical patients
| Patient-related factors | Surgery-related factors |
severe cardiac or respiratory condition in patients aged > 70, with moderate functional limitation of one or more organ dysfunction
acute massive blood loss (> 2.5 l)
severe sepsis
shock or severe hypovolemia
respiratory failure (low paO2, SpO2, or PaO2/FiO2 or mechanical ventilation > 48 h)
acute intestinal failure
acute renal failure | extensive noncardiac surgery (e.g. oncological surgery involving bowel anastomosis, pneumonectomy, etc.)
major or combined cardiovascular surgery > 2 h
emergency surgery |
In all three studies conducted on patients with sepsis, increased RBF was observed (26-28). Nevertheless, due to the dilation of the efferent arterioles and the lack of effective filtration pressure, AKI is the leading cause of death in septical patients (13). However, maintaining mean arterial pressure (MAP) above 65-72 mm Hg, especially between the 6th and 24th hour of sepsis, decreases the incidence of AKI (9, 29-33). The Surviving Sepsis Campaign Guidelines suggest maintaining MAP ≥ 65 mm Hg as one of the hemodynamic targets in septic patients (34).
Fluid therapy
Traditionally, AKI is divided to prerenal, renal, and postrenal in origin, but this classification has little value in clinical practice. Currently, it is more common to refer to prerenal and renal AKI as volume-responsive and volume-unresponsive AKI, respectively. In volume-responsive AKI, fluid therapy restores kidney function and hemodynamic monitoring is not required. In some cases, although kidney function is not improved with fluid therapy, other systemic parameters, such as cardiac output and renal blood flow, improve. In these cases, the term ‘volume-responsive AKI’ is not appropriate. In other situations, renal function could potentially be volume-responsive, but the patient is not (e.g. due to heart failure with fluid overload) (33).
Estimating the volume status of a patient is often not easy in clinical situations. Many clinical signs (increase in heart rate, decrease in systolic blood pressure, dry mucosa, altered mental status, muscular weakness, impaired speech, and decreased capillary refill time) and parameters (central venous pressure – CVP, global end-diastolic volume index – GEDVI, intrathoracic blood volume index – ITBVI, left and right ventricular end-diastolic area, systolic pressure variation – SPV, pulse pressure variation – PPV, stroke volume variation – SVV, etc.) can be of use in determining the volume status. The accuracy of the assessment may be improved with the help of tools quantifying the clinical parameters (e.g. hypovolemic index – HVI) (35).
The next issue is the amount and type of fluids (crystalloid vs. colloids, type of colloids, restricted vs. liberal fluid strategy) needed for the restoration of euvolemia. The effect of crystalloids is reported to be shorter than 120 min (36). Among colloids, 6% w/v hydroxyethyl starch results in a maximal hemodynamic response reflected in the improvement of several of hemodynamical parameters (MAP, CVP, cardiac index, GEDVI, Oxygen Delivery Index – DO2I, and Central Venous Oxygen Saturation – ScvO2).
In sepsis, the boundary between volume-responsive and volume-unresponsive AKI is blurred. Achieving the appropriate fluid balance can reverse AKI and normalize renal function. Fluid responsiveness can be lost in the course of AKI as early as on the first day of sepsis (16, 33). According to the results of the ARDS Network study, the conservative approach in fluid therapy (target CVP 9-13 instead of 15-18 mm Hg, and target pulmonary artery occlusion pressure – PAOP – 13-18 instead of 19-24 mm Hg) resulted in a shorter time of mechanical ventilation and did not affect the renal function, except for a slight increase in the serum creatinine level (38, 39). Several papers report that the positive fluid balance and fluid accumulation is a predictor of mortality and AKI (9, 40-44). The Sepsis Occurrence in Acutely Ill Patients trial (SOAP) reported fluid accumulation as an independent predictor of mortality, as well as of the length of ICU stay, duration of mechanical ventilation, and the need for renal replacement therapy (43). In the PICARD study (Program to Improve Care in Acute Renal Disease), increased mortality was observed in patients with a more than 10% increase in body water (9).
Moreover, fluid therapy causes hemodilution. Lower hematocrit results in lower amount of oxygen delivered to kidneys (36). What is more, crystalloid infusions may affect endothelial glycocalyx barrier by diluting the blood, predisposing to edema (45). Isotonic sodium chloride solution can cause renal vasoconstriction (11). This effect has not been observed during the use of balanced solutions (11). Intravenous fluid administration in septic AKI decreases glomerular oncotic pressure and increases chloride concentration on the level of macula densa, activating tubuloglomerular feedback mechanisms (11). Beneficial hemodynamic effects disappear after one hour. Every form of hydroxyethyl starch has been shown to be harmful for patients at risk of impaired renal function (11).
Vasopressors
To achieve the target blood pressure, vasopressors are often administered. In animal models, noradrenaline and phenylephrine increase MAP, as well as RBF and GFR (11,12). In Doppler flowmetry, it has been shown that norepinephrine increases both cortical and medullary renal blood flow (11). Similarly, noradrenaline administration after cardiac surgery seems to be beneficial in the prevention of AKI (12). In animal studies, the prevention of the dilatation of efferent arterioles with vasopressin resulted in a significantly higher urine output (11).
Conclusions
Nowadays, no clinical signs or measurable parameters are good and practical indicators of the autoregulation of renal vascular bed, therefore, it is clinically difficult to assess whether the autoregulation is still functional. Proper fluid and vasopressor therapy can prevent AKI and reduce costs. Fluid overload is to be avoided, as renal venous and lymphatic congestion can limit the urine filtration rate, further worsening edema. Further study is needed to create guidelines for the amount of fluids necessary to maintain adequate renal blood flow.
Piśmiennictwo
1. Mehta RL, Kellum JA, Shah SV et al.: Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury. Crit Care 2007; 11: R31.
2. Kirov MY, Kuzkov VV, Molnar Z: Perioperative haemodynamic therapy. Curr Opin Crit Care 2010; 16: 384-392.
3. Winton F: The influence of venous pressure on the isolated mammalian kidney. J Physiol 1931; 72: 49-61.
4. Bradley SE, Bradley GP: The Effect Of Increased Intra-Abdominal Pressure On Renal Function In Man. J Clin Invest 1947; 26: 1010-1022.
5. Legrand M, Dupuis C, Simon C et al.: Association between systemic hemodynamics and septic acute kidney injury in critically ill patients: a retrospective observational study. Crit Care 2013; 17: R278.
6. Mullens W, Abrahams Z, Francis GS et al.: Importance of Venous Congestion for Worsening of Renal Function in Advanced Decompensated Heart Failure. J Am Coll Cardiol 2009; 53: 589-596.
7. Damman K, van Deursen VM, Navis G et al.: Increased Central Venous Pressure Is Associated With Impaired Renal Function and Mortality in a Broad Spectrum of Patients With Cardiovascular Disease. J Am Coll Cardiol 2009; 53: 582-588.
8. Kopitkó Cs, Medve L, Gondos T: Pathophysiology of renal blood supply. New Med 2016; 20: 27-29.
9. Teixera C, Garzotto F, Piccini P et al.: Fluid balance and urine volume are independent predictors of mortality in acute kidney injury. Crit Care 2013; 17: R14.
10. Bellomo R, Kellum JA, Ronco C: Acute Kidney Injury. Lancet 2012; 380: 756-766.
11. Prowle JR, Bellomo R: Sepsis-associated acute kidney injury: macrohemodynamic and microhemodynamic alterations in the renal circulation. Semin Nephrol 2015; 35: 64-74.
12. Prowle J, Bagshaw SM, Bellomo R: Renal blood flow, fractional excretion of sodium and acute kidney injury: time for a new paradigm? Curr Opin Crit Care 2012; 18: 585-592.
13. Langenberg C, Bellomo R, May C et al.: Renal blood flow in sepsis. Crit Care. 2005; 9: R363-374.
14. Wan L, Bagshaw SM, Langenberg C et al.: Pathophysiology of septic acute kidney injury: What do we really know? Crit Care Med 2008; 36: S198-S203.
15. Ricksten SE, Bragadottir G, Redfors B: Renal oxygenation in clinical acute kidney injury. Crit Care 2013; 17: 221.
16. Schneider AG, Goodwin MD, Bellomo R: Measurement of kidney perfusion in critically ill patients. Crit Care 2013; 17: 220.
17. Marik PE, Monnet X, Teboul JL: Hemodynamic parameters to guide fluid therapy. Ann Crit Care 2011; 1: 1.
18. Marik PE, Cavallazzi R, Vasu T, Hirani A: Dynamic changes in arterial waveform derived variables and fluid responsiveness in mechanically ventilated patients: A systematic review of the literature. Crit Care Med 2009; 37: 2642-2647.
19. DeBacker D, Heenen S, Piagnerelli M et al.: Pulse pressure variations to predict fluid responsiveness: influence of tidal volume. Intensive Care Med 2005; 31: 517-523.
20. Monet X, Rienzo M, Osman D et al.: Passive leg raising predicts fluid responsiveness in the critically ill. Crit Care Med 2006; 34: 1402-1407.
21. Teboul JL, Monnet X, Richard C: Arterial Pulse Pressure Variation During Positive Pressure Ventilation and Passive Leg Raising. In: Pinsky MR, Payen D (ed.): Functional Hemodynamic Monitoring. 1st ed., Springer-Verlag. Berlin 2004: 331-343.
22. Lamia B, Chemla D, Richard C, Teboul JL: Clinical review: Interpretation of arterial pressure wave in shock states. Crit Care 2005; 9: 601-606.
23. Brienza N, Giglio MT, Marucci M, Fiore T: Does perioperative hemodynamic optimization protect renal function in surgical patients? A meta-analytic study. Crit Care Med 2009; 37: 2079-2090.
24. Brienza N, Giglio MT, Marucci M: Preventing acute kidney injury after noncardiac surgery. Curr Opin Crit Care 2010; 16: 353-358.
25. Pearse RM, Dawson D, Fawcett J et al.: Early goal-directed therapy after major surgery reduces complications and duration of hospital stay. A randomised, controlled trial. Crit Care 2005; 9: R687-R693.
26. Brenner M, Schaer GL, Mallory DL et al.: Detection of renal blood flow abnormalities in septic and critically ill patients using a newly designed indwelling thermodilution renal vein catheter. Chest 1990; 98: 170-179.
27. Lucas CE, Rector FE, Werner M, Rosenberg IK: Altered renal homeostasis with acute sepsis. Clinical significance. Arch Surg 1973; 106: 444-449.
28. Rector F, Goyal S, Rosenberg IK, Lucas CE: Sepsis: a mechanism for vasodilatation in the kidney. Ann Surg 1973; 178: 222-226.
29. Dünser MW, Takala J, Ulmer H et al.: Arterial blood pressure during early sepsis and outcome. Intensive Care Med 2009; 35: 1225-1233.
30. Asfar P, Teboul JL, Radermacher P: High versus low blood-pressure target in patients with septic shock. NEJM 2014; 370: 1583-1593.
31. Varpula M, Tallgren M, Saukkonen K et al.: Hemodynamic variables related to outcome in septic shock. Intensive Care Med 2005; 31: 1066-1071.
32. Badin J, Boulain T, Ehrmann S et al.: Relation between mean arterial pressure and renal function in the early phase of shock: a prospective, explorative cohort study. Crit Care 2011; 15: R135.
33. Himmelfarb J, Joannidis M, Molitoris B et al.: Evaluation and initial management of acute kidney injury. Clin J Am Soc Nephrol 2008; 3: 962-967.
34. Dellinger RP, Levy MM, Rhodes A et al.: Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock, 2012. Intensive Care Med 2013; 39: 165-228.
35. Bardossy G, Halasz G, Gondos T: The diagnosis of hypovolemia using advanced statistical methods. Computers in Biology and Medicine 2011; 41: 1022-1032.
36. Gondos T, Marjanek Zs, Ulakcsai Zs et al.: Short-term effectiveness of different volume replacement therapies in postoperative hypovolaemic patients. Eur J Anaesthesiol 2010; 27: 794-800.
37. Levy MM, Macias WL, Vincent JL et al. : Early changes in organ function predict eventual survival in severe sepsis. Crit Care Med 2005; 33: 2194-2201.
38. Stewart RM, Park PK, Hunt JP et al.: NIH NHLBI ARDS Clinical Trials Network. Less is more: Improved outcomes in surgical patients with conservative fluid administration and central venous catheter monitoring. J Am Coll Surg 2009; 208: 725-737.
39. Rosenberg AL, Dechert RE, Park PK, Bartlett RH: Review of a large clinical series: association of cumulative fluid balance on outcome in acute lung injury: a retrospective review of the ARDSnet tidal volume study cohort. J Intensive Care Med 2009; 24: 35-46.
40. Bouchard J, Soroko SB, Chertow GM et al.: Fluid accumulation, survival and recovery of kidney function in critically ill patients with acute kidney injury. Kidney Int 2009; 76: 422-427.
41. Heung M, Wolfgram DF, Kommareddi M et al.: Fluid overload at initiation of renal replacement therapy is associated with lack of renal recovery in patients with acute kidney injury. Nephrol Dial Transplant 2012; 27: 956-961.
42. Vaara ST, Korhonen AM, Kaukonen KM et al.: Fluid overload is associated with an increased risk for 90-day mortality in critically ill patients with renal replacement therapy: data from the prospective FINNAKI study. Crit Care 2012; 16: R197.
43. Vincent JL, Yasser S, Sprung CL et al.: Sepsis in European intensive care units: Results of the SOAP study. Crit Care Med 2006; 34: 344-353.
44. Lees N, Hamilton M, Rhodes A: Clinical review: goal-directed therapy in high risk surgical patients. Crit Care 2009; 13: 231.
45. Guidet B, Ait-Oufella H. Fluid resuscitation should respect the endothelial glycocalyx layer. Crit Care. 2014; 18: 707.
