on blood pressure Suggestions Proteinuria ACE inhibitor or ARB if urinary protein excretion of 0.5 to 1.0 g/day; increase dose to the extent that adverse events are acceptable to achieve urinary protein excretion of 1 g/day continues after 3 to 6 mo of proper supportive therapy (ACE inhibitor or ARB and blood-pressure control) and an eGFR of >50 ml/min/1.73 m2 Fish oil if urinary protein excretion of >1 g/day continues after 3 to 6 mo of proper supportive therapy Blood pressure: target is 1 g/day Rapidly declining eGFR Glucocorticoids and cyclophosphamide for crescentic IgA nephropathy (>50% glomeruli with crescents) with rapid deterioration in eGFR Supportive care if kidney biopsy shows acute tubular injury and intratubular erythrocyte casts Treatments without proven benefit Glucocorticoids with cyclophosphamide or azathioprine, unless crescentic IgA nephropathy with rapid deterioration in eGFR Immunosuppressive therapy with an eGFR of Section 1: Introduction and Methodology Kidney International Supplements (2012) 2, 13–18; doi:10.1038/kisup.2011.31 Chapter 1.1: Introduction The concept of acute renal failure (ARF) has undergone significant re-examination in recent years. Mounting evidence suggests that acute, relatively mild injury to the kidney or impairment of kidney function, manifest by changes in urine output and blood chemistries, portend serious clinical consequences.1–5 Traditionally, most reviews and textbook chapters emphasize the most severe reduction in kidney function, with severe azotemia and often with oliguria or anuria. It has only been in the past few years that moderate decreases of kidney function have been recognized as potentially important, in the critically ill,2 and in studies on contrast-induced nephropathy.4 Glomerular filtration rate and serum creatinine The glomerular filtration rate (GFR) is widely accepted as the best overall index of kidney function in health and disease. However, GFR is difficult to measure and is commonly estimated from the serum level of endogenous filtration markers, such as creatinine. Recently, Chertow et al. 1 found that an increase of serum creatinine (SCr) of 40.3 mg/dl (426.5 mmol/l) was independently associated with mortality. Similarly, Lassnigg et al. 3 saw, in a cohort of patients who underwent cardiac surgery, that either an increase of SCr X0.5 mg/dl (X44.2 mmol/l) or a decrease 40.3 mg/dl (426.5 mmol/l) was associated with worse survival. The reasons why small alterations in SCr lead to increases in hospital mortality are not entirely clear. Possible explanations include the untoward effects of decreased kidney function such as volume overload, retention of uremic compounds, acidosis, electrolyte disorders, increased risk for infection, and anemia.6 Although, these changes in SCr could simply be colinear with unmeasured variables that lead to increased mortality, multiple attempts to control for known clinical variables has led to the consistent conclusion that decreased kidney function is independently associated with outcome. Furthermore, more severe reductions in kidney function tend to be associated with even worse outcome as compared to milder reductions. Oliguria and anuria Although urine output is both a reasonably sensitive functional index for the kidney as well as a biomarker of tubular injury, the relationship between urine output and GFR, and tubular injury is complex. For example, oliguria may be more profound when tubular function is intact. Volume depletion and hypotension are profound stimuli for vasopressin secretion. As a consequence the distal tubules and collecting ducts become fully permeable to water. Concentrating mechanisms in the inner medulla are also aided by low flow through the loops of Henle and thus, urine volume is minimized and urine concentration maximized (4500 m Osmol/kg). Conversely, when the tubules are injured, maximal concentrating ability is impaired and urine volume may even be normal (i.e., nonoliguric renal failure). Analysis of the urine to determine tubular function has a long history in clinical medicine. Indeed, a high urine osmolality coupled with a low urine sodium in the face of oliguria and azotemia is strong evidence of intact tubular function. However, this should not be interpreted as ‘‘benign’’ or even prerenal azotemia. Intact tubular function, particularly early on, may be seen with various forms of renal disease (e.g., glomerulonephritis). Sepsis, the most common condition associated with ARF in the intensive-care unit (ICU)7 may alter renal function without any characteristic changes in urine indices.8,9 Automatically classifying these abnormalities as ‘‘prerenal’’ will undoubtedly lead to incorrect management decisions. Classification as ‘‘benign azotemia’’ or ‘‘acute renal success’’ is not consistent with available evidence. Finally, although severe oliguria and even anuria may result from renal tubular damage, it can also be caused by urinary tract obstruction and by total arterial or venous occlusion. These conditions will result in rapid and irreversible damage to the kidney and require prompt recognition and management. Acute tubular necrosis (ATN) When mammalian kidneys are subjected to prolonged warm ischemia followed by reperfusion, there is extensive necrosis destroying the proximal tubules of the outer stripe of the medulla, and the proximal convoluted