Tubulointerstitial Disorders

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Renal disorders that affect the proximal and distal tubules and sometimes the tissue surrounding the tubules are termed tubulointerstitial disorders. These disorders, which include renal tubular acidosis, pyelonephritis, and drug-related nephropathies, may be acute or chronic in nature. Acute disease produces an abrupt onset of signs and symptoms, whereas chronic disorders result in fibrosis and atrophy of nephrons. Early signs of tubulointerstitial disorders include signs and symptoms of fluid and electrolyte imbalance such as nocturia, polyuria, and metabolic acidosis.

Figure 64-1 Renal tubular acidosis.

RENAL TUBULAR ACIDOSIS

Pathophysiology

Proximal tubular defects hinder bicarbonate reabsorption, whereas distal tubular defects result in a reduction of the secretion of metabolic acids. Both lead to metabolic acidosis, bone disease, renal calculi, and growth retardation in children.

Because the proximal tubules are where 90% to 95% of filtered bicarbonate is reabsorbed, defects affecting this area result in a loss of bicarbonate and sodium into the urine. Associated with the loss of bicarbonate and sodium is a reduction of serum bicarbonate levels, hypovolemia, increased aldosterone secretion, and hypokalemia. The distal tubules continue to function and excrete metabolic acids. Eventually, the proximal tubules regain enough function to reabsorb a small amount of bicarbonate.

Table 64-1 Types of Renal Tubular Acidosis

Type	Characteristics	Etiology
Type I (classic distal renal tubular acidosis)	Hypokalemic hyperchloremic metabolic acidosis Alkaline urine Hypercalciuria K excretion Hyperaldosteronism Renal calculi formation	Selective deficiency in hydrogen ion secretion of cells in the collecting tubules Autoimmune disease Drugs/toxins, i.e., amphotericin B
Type II (proximal renal tubular acidosis)	Hypokalemic hyperchloremic metabolic acidosis Bicarbonate is not reabsorbed by the proximal tubule Distal nephron tries to reabsorb some bicarbonate but becomes overwhelmed by the bicarbonate load and does not function adequately As bicarbonate is lost in the urine, the serum bicarbonate level falls and the distal nephron can again reabsorb some bicarbonate	Selective defects in the proximal tubule inhibit reabsorption of bicarbonate May be caused by carbonic anhydrase inhibitors Multiple myeloma Nephrotoxic drugs
Type IV^* (hyporeninemic [low levels of renin in plasma] hypoaldosteronemic renal tubular acidosis)	Most common form of renal tubular acidosis Hyperkalemic, hyperchloremic acidosis	Aldosterone deficiency— impairs distal nephron sodium reabsorption and potassium and hydrogen ion excretion Diabetic nephropathy Hypertensive nephrosclerosis Acquired immunodeficiency syndrome
^*A type III does not exist.