Acute Kidney Injury- What Is It and How Do I Treat It?

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1 Acute Kidney Injury- What Is It and How Do I Treat It? Jayant Kumar, MD Renal Medicine Assoc., Albuquerque, NM Incidence of ARF in ICU Causes of ARF Non -ICU ICU 1

2 KDIGO criteria for AKI Increase in serum creatinine of 0.3 mg/dl within 48 hours Increase in serum creatinine of 1.5 times baseline within prior 7 days Urine volume <0.5 ml/kg/hour for more than 6 hours Complications of AKI Fluid overload or pre renal state Hyperkalemia Uremia : pericarditis, altered mental status Metabolic acidosis Distinction of Prerenal vs ATN Urinalysis. Fractional excretion of sodium and, to a lesser degree, the urine sodium concentration. Response to fluid repletion in patients who have evidence of volume depletion, which is the gold standard for the diagnosis prerenal disease. 2

3 Short-term outcomes The outcome of ATN is highly dependent on the severity of comorbid conditions. Uncomplicated ATN is associated with mortality rates of 7 to 23% Mortality of ATN in postoperative or critically ill patients with multisystem organ failure is high as 50 to 80%. Mortality rates increases with the number of failed organ systems Long-term outcomes Long-term outcomes of patients who survive are good. Of a population of 979 critically ill patients with ARF who required RRT (predominately patients with ATN), in-hospital mortality was 69%. Patients who survived to hospital discharge, 6-mo survival was 77%, 1-yr survival was 69%, and 5-yr survival was 50% 59% of surviving patients had no residual renal insufficiency, and only 10% required chronic dialysis therapy. Indications for RRT Pericarditis or pleuritis Progressive uremic encephalopathy or neuropathy (AMS, asterixis, myoclonus, seizures) Bleeding diathesis Fluid overload unresponsive to diuretics Metabolic disturbances refractory to medical therapy (hyperkalemia, metabolic acidosis, hyper- or hypocalcemia, hyperphosphatemia) Sepsis? Toxic overdose of a dialyzable drug 3

4 Goals of RRT Solute clearance Diffusive transport (based on countercurrent flow of blood and dialysate) Convective transport (solvent drag with ultrafiltration) Fluid removal Different modalities Peritoneal dialysis Intermittent hemodialysis Hemofiltration Continuous renal replacement therapy Hybrid methods like SLED Decision of modality determined by catabolic rate, hemodynamic stability, and whether primary goal is fluid or solute removal OUTCOMES : CRRT VS IHD Bellamo ET. AL. have found lower mortality in 24 ICU pt. with ARF treated with CAVHDF/CVVHDF vs IHD Pt. have median APACHE 2 score of Mortality was 49 % in CRRT vs 70 % in IHD. Limitations of study were CRRT was started earlier and patients have lower mean plasma urea. In comparison VAN Bomel Et.AL. have found no difference in mortality with CAVHDF VS IHD (57% VS 41% P=NS). But pt. in CRRT were more sicker. Mehta ET. AL have also found no difference and claims mortality is more associated with underlying disease than on renal failure. 4

5 Improved cardiovascular stability during CRRT therapy in critically ill patients with acute hepatic and renal failure In critically ill patients, in whom DO2(delivery of O2) is impaired, the use of continuous forms of renal replacement therapy is preferred for its improved cardiovascular tolerance compared with daily intermittent machine treatments. Davenport A Et. AL. Crit Care Med 1993 Mar;21(3): IHD VS CAVH/CAHD Thirty-two consecutive, critically ill, mechanically ventilated patients with combined acute hepatic and renal failure were randomized to treatment with either intermittent machine hemofiltration or (CAVH) or (CAVHD). During the first hour of treatment, there was a reduction in cardiac index of 15 +/- 2% during intermittent machine hemofiltration compared with no significant change during the continuous modes of treatment (CAVH/CAVHD) (3 +/- 3%; p <.05). Davenport A Et. AL. Crit Care Med 1993 Mar;21(3): IHD VS CAVH/CAHD This reduction in cardiac output during intermittent machine hemofiltration was associated with a maximum reduction in mean arterial pressure from 82 +/- 2 to 66 +/- 2 mm Hg (p <.001), a reduction in pulmonary artery occlusion pressure of 27 +/- 4%, tissue DO2 of 15 +/- 3%, and tissue oxygen uptake of 12 There was a maximum increase in intracranial pressure of 45 +/- 5% during the first hour of intermittent machine hemofiltration Davenport A Et. AL. Crit Care Med 1993 Mar;21(3):

6 Effect on Mortality CRRT VS INTERMITTENT HD Prospective study by Mehta Et.Al. 166 pt were randomized to intermittent HD VS CVVH in ICU. Principal outcome were ICU and in hosp. mortality, length of stay and recovery of renal function. Continues therapy were associated with an increase in ICU mortality (59.4%vs 41.5%p<0.002) and in hosp. mortality (65.5 % vs 47.6 % p<0.02) Mean ICU length was 16.5 days from time of nephrology consultation and recovery of renal functions was 34.9 and the did not show any difference. Higher APACHE 3 scores and OSF were associated with shorter length of stay secondary to increase mortality. MEHTA ET AL. CRRT VS IHD IN ARF KIDNEY INT. VOL CRRT VS INTERMITTENT HD CRRT was associated with high rates of renal recovery in surviving patients who received adequate trial of therapy with no cross over (92.3 vs 59.4). In addition patients who cross over from CRRT to IHD have higher rates of recovery than those who cross over from IHD to CRRT (15 pt cross over from IHD to CRRT and 17 cross over from CRRT to IHD). Cost of CRRT was $3946 vs $3077 for IHD. MEHTA ET AL. CRRT VS IHD IN ARF KIDNEY INT. VOL CRRT VS INTERMITTENT HD LOS was significantly reduced in patients using CRRT as initial therapy sec. to higher ICU mortality (CRRT 17.1 vs IHD 26.3 days P <0.001). CRRT resulted in lower solute level despite higher BUN levels at start of therapy Complete renal recovery was achieved more frequently in CRRT.This may be secondary to less hemodynamic insults,improved control of azotemia, clearance of middle molecule and reduction in pulmonary and myocardial and GI edema. MEHTA ET AL. CRRT VS IHD IN ARF KIDNEY INT. VOL

7 MEHTA ET AL. CRRT VS IHD IN ARF KIDNEY INT. VOL MEHTA ET AL. CRRT VS IHD IN ARF KIDNEY INT. VOL

8 Limitations Significant differences in groups in several covariates independently associated with mortality including gender, hepatic failure, APACHE II and III scores and number of failed organ systems in each instance biased in favor of intermittent HD. After adjustment of the imbalances in groups the odds of death with continuous therapy was 1.3, P=ns METHA ET. AL. RADOMIZED CLINICAL TRIAL OF CONTINUES VS INTERMITTENT HD IN ARF KIDNEY INT.2001 SEP ;60 (3): Limitations(Cont.) Study has limited statistical power as they assumed a mortality of 70% for control IHD patients. Mortality was infact %. The data showed an overall mortality of 50.6% considerably lower than % rates reported in most studies.this may be secondary to improved level of care of patients or patients with map <70mm were excluded. Mostly using CRRT in reality were excluded i.e. those with Map <70 mm. MEHTA ET AL. CRRT VS IHD IN ARF KIDNEY INT. VOL IHD VS CVVHD In ARF Paganini Et.Al. did a randomized controlled study of 80 critically ill patients with ARF. Pt were randomized after stratification by severity of illness to treatment with CVVHD or IHD. There was no sig. difference in survival or renal recovery. There were greater net volume removal in CVVHD. There were significant drop in mean BP for patients on IHD VS CVVHD but this did not lead to survival advantage. RANDOMIZED CONTROLLED TRIAL COMPARING IHD VS CVVHD IN ARF PAGNINI ET.AL. AJKD 2004 DEC.;44(6)

9 Systemic review : impact of dialytic modality on mortality Systemic review and meta-analysis of six eligible trials were done by Tonelli et.al., Univ. Of Alberta, Canada. He found no difference in relative risk of mortality and renal recovery associated with IHD vs CRRT. TONELLI M ET.AL. AJKD 2002 NOV;40 (5): VA Cooperative ATN study, 2008 Pavlesky, N Engl J Med July 3; 359(1):

10 VA cooperative ATN study, 2008 Pavlesky, N Engl J Med July 3; 359(1): Diagnosis and outcome of patients Treated with CRRT The most important factor contributing death was the underlying cause of ARF. Ultimate prognosis depends upon recovery of other organ systems not on ARF per se in patients with ARF and MOF. Lohr Et. Al. found that associated organ failure in the form of respiratory failure,gi dysfunction,chf,sepsis or hypotension were significantly associated with high mortality. Paganini Et.Al Seminar in nephrology vol 17 july Paganini Et.Al Seminar in nephrology vol 17 july

11 Choice of Dialytic Technique The choice of dialytic technique is dependent upon a variety of factors including availability, the expertise of the clinician, hemodynamic stability, and the degree to which solutes and/or fluid must be removed. Do what you know best Choice of Dialytic Technique: Rate of Solute Removal Solute removal occurs primarily by diffusion from the plasma into the dialysate during dialysis and, to a much lesser degree, by convection during ultrafiltration as solvent drag carries small and intermediate sized solutes with the water. Smaller solutes (such as urea and electrolytes) are removed in roughly the same concentration as the plasma with hemofiltration; as a result, the rate of solute clearance is equal to the ultrafiltration rate unless there is concurrent diffusive loss 11

12 Choice of Dialytic Technique: Rate of Solute Removal The rate of solute diffusion is determined by a number of factors including : The surface area and unit solute permeability of the dialysis membrane. The blood and dialysate flow rates which, if increased, maintain a maximum concentration gradient between these two compartments. The duration of dialysis. Choice of Dialytic Technique: Rate of Solute Removal In comparison, the rate of solute removal by ultrafiltration is influenced by: The transmembrane pressure gradient that provides the driving force for ultrafiltration. The surface area and unit water permeability of the dialysis membrane ultrafiltration. The duration of hemofiltration. The blood flow rate, which acts indirectly by moving nonfiltered plasma proteins away from the inner wall of the dialysis membrane; preventing local protein accumulation maintains water permeability. SLED The SLED/EDD technique offers every advantage of CRRT, but does not require any new equipment acquisition The 2008H hemodialysis machine can also be used. Thus, SLED/EDD is well suited for centers in which there is limited support for CRRT. The therapy can be applied to all patients in ARF requiring dialytic support who manifest intolerance to regular hemodialysis. 12

13 SLED Single center experience over 18 months since July 1998 with a hybrid technique named sustained low-efficiency dialysis (SLED), in which standard IHD equipment was used with reduced dialysate and blood flow rates. Sustained low-efficiency dialysis for critically ill patients requiring renal replacement therapy Marshall MR; Golper TA; Shaver MJ; Alam MG; Chatoth DK Kidney Int 2001 Aug;60(2): SLED (Cont.) Twelve-hour treatments were performed nocturnally, allowing unrestricted access to the patient for daytime procedures and tests. 145 SLED treatments were performed in 37 critically ill patients in whom IHD had failed or been withheld. Mean SLED treatment duration was 10.4 hours because 51 SLED treatments were prematurely discontinued sec. to hypotension or clotting. Marshall MR; Golper TA; Shaver MJ; Alam MG; Chatoth DK Sustained low-efficiency dialysis for critically ill patients requiring renal replacement therapy Kidney Int 2001 Aug;60(2): SLED (Cont.) Hemodynamic stability was maintained during most SLED treatments, allowing the achievement of prescribed ultrafiltration goals in most cases with an overall mean of only 240 ml per treatment. Mean delivered double-pool Kt/V of 1.36 per (completed) treatment. Observed hospital mortality was 62.2%, which was not significantly different from the expected mortality as determined from the APACHE II illness severity scoring system. CONCLUSIONS: SLED is a viable alternative to traditional continuous renal replacement therapies for critically ill patients in whom IHD has failed or been withheld. Marshall MR; Golper TA; Shaver MJ; Alam MG; Chatoth DK Sustained low-efficiency dialysis for critically ill patients requiring renal replacement therapy Kidney Int 2001 Aug;60(2):

14 Table 1 Studies of sustained low-efficiency dialysis and extended nocturnal dialysis for treatment of patients with renal failure in the intensive care unit Fliser D and Kielstein JT (2006) Technology Insight: treatment of renal failure in the intensive care unit with extended dialysis Nat Clin Pract Neprol 2: doi: /ncpneph0060 Slow continuous ultrafiltration SCUF is designed to remove up to 6 to 7 L of fluid per day without requiring replacement fluid other than for hyperalimentation. Solute removal is minimal with this technique, being limited by the low ultrafiltration rate and lack of dialysis. Clearance of urea and other small solutes is equal to the ultrafiltration rate of approximately 4 to 5 ml/min. Thus, SCUF is not useful in patients who are uremic or hyperkalemic. SCUF without pump 14

15 SCUF- pump assisted SCUF (Cont.) Either arteriovenous or venovenous access can be used for SCUF. Practical goals are a UFR of 5 ml/min and a Qb of 80 ml/min. If necessary, the UFR can be increased by raising Qb or by adding suction to the filtrate drainage system. The Qb can be raised by increasing the systemic blood pressure or by inserting an extracorporeal blood pump into the circuit ge system. If the UFR is too rapid, ultrafiltration can be slowed by raising the level of the bag into which the ultrafiltrate drains. 15

16 SCUF (Cont.) Low Cardiac out put in CHF activate Renin angiotensin and stimulate Sympathetic nervous system with resultant accumulation of sodium and increased peripheral resistance. Some pt. with advanced CHF will not respond to diuretics. UF intermittently or SCUF breaks this cycle. SCUF (Cont.) Agostine Et.AL.randomized 16 pt. with CHF (NY class II and III) to UF liters for 3-4 hours or lasix 60mg IV followed by 1mg per min for 2 hours. Both treatments produced similar diuresis 3 months later RA pressure,pcwp and body wt. return to baseline in lasix group and they were still low in UF group. Suggest fluid removed by UF shifts the abnormal set point for fluid balance to a more physiological level despite comparable levels of vol. control. Continuous venovenous hemofiltration CVVH is similar to CAVH, except that an extracorporeal blood pump is required that allows the physician to control the flow rates within the system. The blood pump assures a fast and stable Qb that can be set for example, at approximately 250 ml/min. If the hematocrit is 33 percent, then the plasma flow rate will be 167 ml/min. A filtration fraction of 10 percent in this setting results in a UFR of 16.7 ml/min, which is equal to 1 L/h or 24 L/day (four times greater than that with SCUF). 16

17 Replacement, Pre vs Post dilution CVVH with post-dilution 17

18 PRISMA CVVHDF 18

19 CVVHDF with post-dilution Macias WL Et.Al. Am J Kidney Dis 1991 Oct;18(4):451-8 CVVHDF using regional citrate anticoagulation. ERA EDTA 2003; all rights reserved Cointault O et al. Nephrol. Dial. Transplant. 2004;19:

20 Continuous venovenous hemodialysis CVVHD combines the processes of diffusive and convective clearances. It utilizes a blood pump to maximize the delivery of blood to the extracorporeal device. Under routine operating conditions, the blood flow (Qb) varies from 150 to 300 ml/min and the dialysate flow (Qd) from 1 to 2 L/hour Nx Stage machine Antibiotic dosing in critically ill adult patients receiving CRRT 2005 by the Infectious Diseases Society of America Trotman R L et al. Clin Infect Dis. 2005;41:

21 Conclusion To minimize morbidity, dialysis should generally be started prior to the onset of complications due to renal failure. Sometimes one can also initiate renal replacement therapy in patients in whom excessive volume resuscitation is required (such as hepatic failure), even in the absence of significant azotemia. This is particularly relevant in patients demonstrating hemodynamic instability where volume removal must be performed slowly. Conclusion The apparent advantage of biocompatible dialysis membranes has led to our using them routinely in patients with acute renal failure. More intense delivered doses of dialysis appears to principally benefit patients with acute renal failure and illnesses of intermediate severity. Patients at either extremes of illness (severely ill or not very ill) have much less survival benefit with intense intermittent hemodialysis regimens. 21