The serum creatinine is a reasonable marker for creatinine clearance and GFR only in the steady state, that is, when the serum creatinine is neither increasing nor decreasing. In the steady state, the creatinine clearance (C_Cr) may be estimated from the serum creatinine (S_Cr) by the Cockroft-Gault equation:
Another equation derived as a result of the Modification of Diet in Renal Disease (MDRD) study has recently been validated as a more reliable predictor of GFR in some circumstances, such as chronic kidney diseases:
A GFR calculator utilizing this equation may be found at the website, http://www.nephron.com/cgi-bin/MDRD.cgi, and is also available on many “handheld” devices.

A rise in the blood urea nitrogen (BUN) and serum creatinine levels and development of oliguria (<400 mL per day) are the common clinical findings that suggest the presence of acute renal failure. However, the absence of oliguria does not exclude acute renal failure because the process may also be nonoliguric. In fact, 20% to 30% of patients with acute renal failure are nonoliguric (>400 mL per day).

In patients with acute renal failure, prerenal, postrenal, and intrarenal processes need to be considered. The respective causes of prerenal and postrenal azotemia as well as intrinsic renal disease are listed in Tables 9-1,9-2,9-3.

In hospitalized patients, the most common cause of acute renal failure (45%) is acute tubular necrosis, followed by prerenal azotemia and obstruction. Glomerulonephritis, vasculitis, interstitial nephritis, and atheroembolic
disease comprise most of the remaining causes. In contrast, acute renal failure in outpatients is most commonly due to prerenal azotemia (70%), followed by obstruction. Drug nephrotoxicity [e.g., aminoglycosides, angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), and nonsteroidal antiinflammatory drugs (NSAIDs)] accounts for most of the remaining cases.

The urinary findings that can be used to help differentiate between prerenal azotemia and intrarenal acute renal failure are listed in Table 9-4.

The various complications of acute renal failure are listed by category in Table 9-5.

Metabolic acidosis is a disorder that results from either the addition of hydrogen ion or the loss of bicarbonate, which, if unopposed, results in acidemia. However, metabolic acidosis is not defined either as a decrement in the serum bicarbonate level or as any given systemic arterial pH because, in the setting of mixed acid–base disorders. The serum bicarbonate level or pH, or both, may be normal or even elevated despite the presence of metabolic acidosis.

When metabolic acidosis develops, the decrease in pH activates carotid chemoreceptors and central nervous system receptors to stimulate ventilation. The increase in the minute ventilation lowers the partial pressure of carbon dioxide (Pco₂), thereby returning the pH toward normal.

Metabolic acidosis is broadly classified on the basis of the presence or absence of an increased anion gap. The anion gap (in millimoles per liter) is calculated using the following formula: plasma sodium – (plasma chloride + plasma bicarbonate). In most laboratories, a normal anion gap is considered to be 12 ± 2 mmol/L. A normal anion gap metabolic acidosis results from either the addition of hydrochloric acid or the loss of bicarbonate with the concomitant retention of chloride. Because chloride is retained and is included in the calculation, the anion gap metabolic acidosis is maintained in the normal range. An increased anion gap results from the addition of an exogenous or endogenous acid. The anions produced by these acids are not measured and chloride is not retained. The anion gap increases because bicarbonate is consumed to buffer the organic acid. For example, organic anion + H⁺ + NaHCO₃^– → H₂O + CO₂ + Na organic anion + organic acid. Because the organic anion is not measured or included in the calculation, the anion gap increases.

The various causes of metabolic acidosis with an increased anion gap are listed in Table 9-6.

The plasma osmolality is calculated using the following formula: Calculated osmolality = 2[Na] + [glucose]/18 + [BUN]/2.8 + [ethanol]/4.6. The osmolar gap is equal to the measured osmolality minus the calculated osmolality. A normal osmolar gap is less than 10 mOsm/kg. When the osmolar
gap is elevated in an acidemic patient, ethylene glycol or methanol intoxication must be strongly suspected.

The causes of metabolic acidosis with a normal anion gap are listed in Table 9-7.

On occasion, the UAG may help distinguish gastrointestinal loss from renal loss of HCO₃^– as the cause of hyperchloremic metabolic acidosis:
The UAG is an estimate of the urinary ammonium that is elevated in gastrointestinal HCO₃^– loss but low in distal RTA. UAG is a negative value if urine ammonium is high (as in diarrhea; average, -20 mEq/L), whereas it is positive if urine ammonium is low (as in distal RTA; average, +23 mEq/L).

RTA is one of the common causes of metabolic acidosis with a normal anion gap. Proximal RTA results from a failure to resorb the normal amount of bicarbonate in the proximal tubule, whereas distal RTA results from a defect in hydrogen ion secretion in the distal tubule. These two forms of RTA can be differentiated by determining the urine pH during systemic acidosis. In proximal RTA, when the serum bicarbonate, and therefore the filtered
bicarbonate level, is lowered to one that allows for proximal reabsorption of all the filtered bicarbonate, the urine can be maximally acidified (pH <5.4) as there is no increased distal delivery of unreabsorbed bicarbonate. In contrast, in distal RTA, the urine cannot be maximally acidified (pH >5.4) independent of the serum bicarbonate concentration.

Metabolic alkalosis is a disorder that results from either the loss of hydrogen ions or the addition of bicarbonate, which, if unopposed, results in alkalemia. Metabolic alkalosis is not defined either as an increment in the serum bicarbonate concentration or as a given systemic arterial pH because, in the setting of mixed acid–base disorders. The serum bicarbonate level or the pH, or both, could be either normal or even decreased in the presence of metabolic alkalosis.

Pathophysiologically, the development of metabolic alkalosis involves two phases (see Fig. 9-1). The first involves the generation of metabolic alkalosis. As follows from the definition just given, metabolic alkalosis can be generated as a result of either a net loss of hydrogen ions from the extracellular fluid, most commonly from either the upper gastrointestinal tract or more rarely through the kidneys, or from the net addition of bicarbonate or substances that generate bicarbonate (e.g., lactate, citrate, and acetate). In addition, the
loss of fluid having high concentrations of chloride and low concentrations of bicarbonate, as occurs with diuretic use and certain gastrointestinal tract diseases such as villous adenoma, generates a metabolic alkalosis.

The kidney provides the corrective response to metabolic alkalosis by excreting excess bicarbonate. When the serum bicarbonate level exceeds 28 mEq/L, the anion appears in the urine, thereby preventing a further increase in its concentration. The maintenance of alkalosis therefore requires an alteration in renal bicarbonate reabsorption. Several factors constrain the kidney’s ability to excrete bicarbonate and are important in the maintenance phase of metabolic alkalosis. Probably, the most important factor in this regard is extracellular fluid volume depletion, which serves to stimulate increased sodium resorption and bicarbonate reclamation in the proximal tubule. A decrement in GFR with a decrease in bicarbonate filtration contributes to the maintenance of the metabolic alkalosis. Another important factor in the maintenance of metabolic alkalosis is the chloride concentration. When the plasma bicarbonate concentration rises, the chloride concentration must fall. Because chloride is the only anion other than bicarbonate that can accompany sodium resorption, bicarbonate resorption is enhanced in its absence. Therefore, chloride must exist in sufficient quantity to allow for bicarbonate excretion. The hormone aldosterone stimulates the exchange of sodium reabsorption for hydrogen or potassium ion secretion in the distal tubule. With
the secretion of hydrogen ions, bicarbonate generation occurs in the plasma. Potassium ion depletion directly enhances bicarbonate reabsorption. An elevation in the Pco₂ also stimulates bicarbonate reabsorption, and is important in the compensatory mechanism that keeps respiratory acidosis in check.

Metabolic alkalosis can be divided into two groups: NaCl responsive and NaCl resistant. The former is found in alkalemic patients who are volume depleted, and the latter in those with volume expansion. The most useful laboratory test for differentiating between the two groups is a spot urine chloride determination done before the initiation of therapy. In NaCl-responsive states, the urine chloride concentration is usually less than 20 mEq/L, and frequently even less than 10 mEq/L; in NaCl-resistant states, the urine chloride level exceeds 20 mEq/L. However, although metabolic alkalosis is routinely divided into these two categories, there are several disorders that are unclassified.

The causes of NaCl-responsive metabolic alkalosis are listed in Table 9-9.

The causes of NaCl-resistant metabolic alkalosis are listed in Table 9-10.

The unclassified causes of metabolic alkalosis are listed in Table 9-11.

When metabolic alkalosis develops, the alkalemia is sensed by chemoreceptors in the respiratory system. This leads to hypoventilation and an increase
in Pco₂. As a general rule, the Δ Pco₂ (mm Hg) = 0.25 – 1.0 M × [HCO₃^–] mEq/L, where Δ Pco₂ is the change in the Pco₂. However, this hypoventilatory response is not as efficient as the hyperventilatory responses that accompany a metabolic acidosis.