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Renal Tubular Defects 

Renal Tubular Defects
Chapter:
Renal Tubular Defects
Author(s):

Matthew McGuire

, and Subramaniam Pennathur

DOI:
10.1093/med/9780190862800.003.0040
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date: 04 December 2020

  1. A. Introduction

    1. a. Renal tubular defects are both congenital and acquired diseases of the kidney that affect the tubules to a greater extent than the glomeruli.

    2. b. The defects may be anatomic or physiologic.

      1. i. Diseases that cause anatomic defects are usually hereditary and include polycystic renal disease, medullary sponge kidney, and medullary cystic disease. Anatomic defects can be diagnosed by intravenous pyelography or ultrasound.

      2. ii. Diseases that cause physiologic defects in tubular transport usually present as polyuria, electrolyte imbalance, and/or a nongap metabolic acidosis. This chapter focuses on the physiologic defect of renal tubular acidosis (RTA).

  2. B. Renal Tubular Acidosis

    1. a. Definition. RTA results from a net decrease in tubular hydrogen secretion or bicarbonate reabsorption, causing a nongap (or hyperchloremic) metabolic acidosis.

    2. b. Diagnosis. When encountering a nongap metabolic acidosis, the physiologic defect is invariably one of two things: (1) a defect in acid secretion or (2) a loss of bicarbonate/defect in bicarbonate reabsorption. Usually this is apparent from the history; however, there are times when the history is unclear or there are numerous problems at once, and in these instances the urine anion gap (UAG) can help determine whether the kidney is excreting acid as it should be.

      1. i. Measurement of the UAG can be helpful to distinguish between defects in acid secretion or bicarbonate loss/reabsorption:

        • UAG = (urine Na + urine K) – urine Cl

        • The UAG is an indirect measurement of urinary ammonium excretion. Ammonium chloride (NH4Cl) is normally excreted by the kidneys in response to acidosis. A positive UAG in a patient with nongap acidosis represents a renal defect in acid secretion.

    3. c. Classification. Most patients with a nongap metabolic acidosis who do not have diarrhea or an anatomic gastrointestinal abnormality will have one of the three types of RTA (Table 40.1).

      Table 40.1 Overview of Renal Tubular Acidosis

      Type 1 (Distal)

      Type 2 (Proximal)

      Type 4

      Defect

      Decrease in hydrogen secretion

      Decrease in bicarbonate reabsorption

      Aldosterone deficiency or resistance

      Serum [K+]

      Decreased

      Decreased

      Increased

      Urinary pH

      >5.3

      <5.3 (>5.3 with base load)

      <5.3

      Major causes

      Amphotericin toxicity, hyperparathyroidism, obstructive uropathy, sickle cell anemia, cirrhosis

      Fanconi’s syndrome, drugs, Wilson’s disease, vitamin D deficiency, amyloidosis, multiple myeloma, renal transplantation

      Diabetes mellitus, nephrosclerosis from hypertension, chronic kidney disease, chronic interstitial nephritis, Addison’s disease, angiotensin-converting enzyme inhibitors, heparin

      Treatment

      Bicarbonate and K+

      Bicarbonate and K+*

      Mineralocorticoids and potassium restriction

      * But not in Fanconi’s syndrome.

      1. i. Type 1 (distal) RTA occurs as a result of defective hydrogen ion secretion; therefore, urinary pH will be elevated. Hypokalemia results when potassium is excreted instead of H+ cations. (Usually, Na+ is reabsorbed, and H+ is excreted to some degree; however, H+ secretion does not occur effectively in type 1 RTA, so K+ is secreted to maintain electroneutrality leading to hypokalemia).

      2. ii. Type 2 (proximal) RTA occurs as a result of decreased bicarbonate reabsorption in the proximal tubule. Initially, the urinary pH will be elevated because of bicarbonate loss. However, with continued bicarbonate loss, the serum bicarbonate and, thus, the urine bicarbonate concentrations decrease. As the filtered load of bicarbonate drops, all urine bicarbonate can be reabsorbed by the distal tubule, and urinary pH falls. Hypokalemia occurs as potassium secretion is enhanced to accompany the bicarbonate excreted in the urine (the body always tries to retain electroneutrality).

      3. iii. Type 4 RTA is caused by a reduction of distal tubular electronegativity. This is usually caused by aldosterone deficiency or resistance whereby a lack of aldosterone action causes a decrease in distal sodium reabsorption, leading to decreased tubular electronegativity, decreased drive for both H+ and K+ secretion, and acidosis and hyperkalemia. Relative hypoaldosteronism from hyporeninemic states can occur in diabetic nephropathy, hypertensive nephropathy, tubulointerstitial diseases, and AIDS. It should be noted that hyperkalemia in and of itself decreases ammonium excretion and can play a role in propagation of the acidosis.

Suggested Further Readings

Santos F, Ordóñez FA, Claramunt-Taberner D, Gil-Peña H. Clinical and laboratory approaches in the diagnosis of renal tubular acidosis. Pediatr Nephrol 2015;30:2099–107.Find this resource:

Sharma S, Gupta A, Saxena S. Comprehensive clinical approach to renal tubular acidosis. Clin Exp Nephrol 2015;19:556–61.Find this resource: