Nonoliguric versus oliguric acute kidney injury

INTRODUCTION — The glomerular filtration rate (GFR) may fall to very low levels in patients with acute intrinsic kidney injury (AKI). However, a low GFR is not necessarily associated with a parallel reduction in urine output, which can vary from oliguria (<400 to 500 mL/day) to normal values (eg, 1 to 2 L/day) [1,2].

Although oliguria is common in patients with AKI, anuria (urine output <50 to 100 mL/day) is rare. Anuria is most often seen in two conditions: shock and complete bilateral urinary tract obstruction. Other, less common causes are the hemolytic-uremic syndrome, kidney cortical necrosis, bilateral renal arterial obstruction, and rapidly progressive (crescentic) glomerulonephritis, particularly antiglomerular basement membrane (GBM) antibody disease.

DETERMINANTS OF URINE OUTPUT — The difference in urine output between oliguric and nonoliguric acute kidney injury (AKI) may be due to one of two factors: Nonoliguric patients may have a higher glomerular filtration rate (GFR) than those with oliguria, and/or they may reabsorb less in the tubules. If, for example, the GFR falls to 7 L/day (equal to 5 mL/min), the urine output will be relatively normal at 1 to 2 L/day if only 5 to 6 L are reabsorbed.

Declines in urine output may not only be a result of AKI, but also predict its development. This was suggested in a retrospective analysis of 390 critically ill patients with septic shock [3]. Oliguria, defined as urine output <0.5 mL/kg per hour and observed within the first 12 hours following recognition of septic shock, was positively associated with the development of AKI (defined by a serum creatinine increment according to the Kidney Disease: Improving Global Outcomes [KDIGO] stage II criteria), need for kidney replacement therapy (KRT), and 28-day mortality (odds ratio [OR] 1.19, 95% CI 1.10-1.28). In this study, more than five hours of consecutive oliguria predicted subsequent AKI KDIGO stage II or greater with an accuracy of 82 percent [3].

Studies in animal models have shown that there is less morphologic and functional damage in nonoliguric compared with oliguric AKI [4]. There is also evidence in humans suggesting that the absence of oliguria in AKI generally reflects less severe disease [1,5-7]. The following observations from different studies are illustrative:

●One report noted a direct correlation between the urine flow rate and the residual GFR in patients with three to six days of AKI [5]. Oliguric patients generally had a GFR (measured by creatinine and inulin clearance) of <5 mL/min compared with 10 to 15 mL/min in patients with a urine volume of 50 to 100 mL/hour.

●In other studies, nonoliguric patients had a lower peak serum creatinine concentration (6 versus 9 mg/dL [528 versus 792 micromol/L]) than oliguric patients [1] and a lower incidence of requiring dialysis during the acute phase of the illness (28 versus 84 percent and 46 versus 82 percent in different studies) [1,6].

●In an analysis of an electronic database derived from patients admitted to the intensive care unit in one medical center, the relationship of absolute and relative serum creatinine increments and urine output decrements over a continuous spectrum of observation time intervals was evaluated [8]. Among 14,526 patients included in the analysis, oliguria <0.5 mL/kg per hour was associated with a sharp increase in the risk for mortality or the requirement for KRT. In addition, even higher urine output rates between 0.5 and 1 mL/kg per hour were associated with adverse clinical outcomes if they were observed over a prolonged time interval of 24 to 48 hours. Other studies in critically ill patients have shown similar results; mortality is higher in patients with oliguric AKI [9,10].

●Another, more recent analysis of electronic medical records underscored the prognostic importance of oliguria in addition to serum creatinine-based criteria for AKI in the clinical setting [11]. This analysis included data from 32,045 patients treated at a single center between 2000 and 2008, 74.5 percent of whom developed AKI according to the KDIGO staging criteria. The study showed that, while oliguria criteria alone were associated with only a 2.1 percent need for KRT and a 12.4 percent in-hospital mortality and serum creatinine increment criteria alone with 4.9 and 16.8 percent, respectively, patients who demonstrated a combination of oliguria and serum creatinine increment criteria experienced a need for KRT in 25 percent and in-hospital mortality in 32 percent of cases.

However, nonoliguric AKI is not necessarily associated with a better prognosis in all settings. In an observational study of patients with AKI who required dialysis, a higher urine volume was independently associated with increased time from admission to start of dialysis and higher in-hospital mortality (OR 3.8, 95% CI 1.1-12.8) [12]. Delay in initiation of dialysis, prompted by response to diuretic therapy and anticipation of recovery of kidney function, may be a contributing factor to the increase in mortality in patients with nonoliguric AKI.

OLIGURIA, POSITIVE FLUID BALANCE, AND INCREASED MORTALITY — Both oliguria and a positive fluid balance are independently associated with increased mortality in patients with acute kidney injury (AKI) in multiple prospective observational studies [13-20].

The following findings are illustrative:

●In a study of critically ill patients that included 1120 patients with AKI, oliguric patients had a greater mean positive fluid balance than nonoliguric patients (620 versus 270 mL) and a significantly higher 60-day mortality rate (41 versus 33 percent) [13].

●In a cohort of 1453 patients enrolled in the Randomized Evaluation of Normal versus Augmented Level renal replacement therapy trial, the mean daily fluid balance was +560 mL/day among nonsurvivors compared with -234 mL/day among survivors [15]. A negative mean daily fluid balance was independently associated with a significantly lower risk of death at 90 days (odds ratio [OR] 0.32, 95% CI 0.24-0.43).

●In the Fluids and Catheters Treatment Trial, 306 of 1000 patients developed AKI [16]. Among these patients, positive fluid balance was associated with an increased adjusted 60-day mortality (OR 1.6 per L/day, 95% CI 1.3-2.0).

●A retrospective analysis from a single center evaluated 15,395 patients who were transferred from an intensive care unit to a regular medical or surgical ward [17]. The adjusted hazard ratio for 90-day mortality was higher in the fourth (median +7.6 liters) compared with the first (-1.5 liters) quartile of fluid balance (adjusted hazard ratio 1.35, 95% CI 1.13-1.61). These results were driven by patients suffering from congestive heart failure, AKI, or kidney function impairment. [18,19]

An individualized approach is appropriate that combines accurate assessment of the effective volume status and the hemodynamic and urine output response to fluid bolus administration. The immediate physiologic benefits of volume expansion in patients with circulatory failure and volume depletion should not be overlooked. This was demonstrated in a study of 49 critically ill patients with hypotension, need for vasopressors, oliguria, or reduced central or mixed venous oxygen saturation who were compared with 39 control subjects [21]. Fluid administration resulted in a small but consistent decrease in Doppler sonographically measured resistivity index (RI) in renal interlobar arteries and increases in mean arterial pressure and urine output. The increase in urine output was predicted by changes in RI, but not changes in mean arterial pressure in this analysis.

LIMITED ROLE OF DIURETICS — The main indication for diuretic therapy in patients with acute kidney injury (AKI) is short-term treatment for volume control. However, such use should not postpone the initiation of dialysis, if required [22]. (See "Overview of the management of acute kidney injury (AKI) in adults", section on 'Role of diuretics'.)

In a small, blinded, placebo-controlled trial of 73 adults with AKI admitted to the intensive care unit, furosemide did not impact the trajectory of AKI or reduce the need for kidney replacement therapy [23]. Furthermore, patients in the intervention group were more likely to suffer from electrolyte abnormalities. This trial is consistent with a large observational study of patients admitted to five adult intensive care units, which found that loop diuretic use in patients with AKI was not associated with the progression of AKI [24]. On the other hand, another observational study of critically ill patients with AKI reported an association between furosemide administration and improved short-term survival and recovery of kidney function [25]. However, in the latter observational study furosemide was used more frequently in surgical patients and in patients with milder AKI. In addition, patients with a urinary response to diuretic administration may have less severe AKI, as demonstrated by the furosemide stress tests in multiple studies [26,27]. (See "Overview of the management of acute kidney injury (AKI) in adults", section on 'Hypervolemia with pulmonary edema'.)

The 2012 Kidney Disease: Improving Global Outcomes (KDIGO) guidelines and other reviews concluded that loop diuretics should not be used to prevent AKI or as a possible therapy for established AKI [22,28]. The KDIGO guidelines also concluded that mannitol is not scientifically justified in an attempt to prevent AKI [28]. The supportive data are discussed elsewhere. (See "Possible prevention and therapy of ischemic acute tubular necrosis", section on 'Experimental and unproven measures for the prevention of ischemic ATN'.)

SUMMARY AND RECOMMENDATIONS

●Acute kidney injury (AKI) and urine output – The decrease in glomerular filtration rate (GFR) that occurs in AKI is not always associated with a reduction in urine output. Urine output can vary from oliguric levels (<400 to 500 mL/day) to relatively normal values. Anuria (urine output <50 to 100 mL/day) is relatively rare, however. (See 'Introduction' above.)

●Determinants of urine output – The difference in urine output between oliguric and nonoliguric AKI may be due to variations in GFR or in the rate of tubular reabsorption. Animal and human studies suggest that less severe injury is present in nonoliguric compared with oliguric subjects. (See 'Determinants of urine output' above.)

●Limited role of diuretics – The main indication for diuretic therapy in patients with AKI is short-term treatment for volume control. However, such use should not postpone the initiation of dialysis, if required. The use of diuretics to increase urine output in patients with established oliguric AKI does not shorten the duration of kidney failure, decrease the requirement for dialysis, or improve survival. Among patients with oliguria and established AKI, diuretics should not be used as a possible therapy of AKI. (See 'Limited role of diuretics' above.)