FLUID, ELECTROLYTE AND ACID-BASE DISORDERS ASSOCIATED WITH

ANTIBIOTIC THERAPY.
Paul C. Auguin*, Joju Sebastian C, Parul Elsa Thomas, Swathy Pradeep.
KEYPOINTS

INTRODUCTION

Antibiotics are among the most frequently prescribed drugs in medicine. Their use is often limited by associated renal toxic effects.
The most common manifestation of these toxic effects is increased glomerular filtration rate. There needs a real focus on antibiotic-associated
fluid, electrolyte and acid-base disorders that do not greatly reduce glomerular filtration.
Renal tubules can be affected by antibiotics at various locations. In the proximal tubule, toxic effects of tetracyclines and
aminoglycosides can result in complete proximal tubular dysfunction, known as the Fanconi syndrome. Aminoglycosides (and Capreomycin)
can also affect the loop of Henle and lead to Bartter-like syndrome. In the collecting ducts, the disorders include hyponatremia, hypokalemia,
hyperkalemia, renal tubular acidosis, and nephrogenic diabetes insipidus caused by trimethoprim, amphotericin B, penicillins, ciprofloxacin,
demeclocycline and various antitubercular agents. Thus, early recognition and correction of their harmful renal and electrolyte effects are
required.
Here we describe the mechanisms that disrupt renal tubular function, integrated with the physiology of each successive nephron
segment; the receptors, transporters, channels or pores that are affected by antibiotics. This can pave the way for pathophysiology-directed
treatment of these disorders.

Renal tubular function can be affected by antibiotic treatment without a concurrent

reduction in glomerular reduction rate.

Hypokalemia is a frequent complication of antimicrobial therapy.

Treatment with aminoglycosides can affect renal tubular function in several ways
and can lead to hypokalemia, as well as acidosis and alkalosis.

If unexpected disturbances in electrolyte and/or acid-base balance occur in a

patient, their prescribed medications should be carefully checked.

FLUID, ELECTROLYTE AND ACID-BASE DISTURBANCES CAUSED BY

ANTIBIOTIC TREATMENT.

DIAGNOSITIC FEATURES AND TREATMENT OF ANTIBIOTICASSOCIATED RENAL-TUBULE DISORDERS.

ANTIBIOTICS AND RELEVANT
DISORDERS.

DIAGNOSTIC FEATURES.

TREATMENT.

AMINOGLYCOSIDES AND TETRACYCLINES.

Proximal RTA or Fanconi
Syndrome.

Non-anion-gap metabolic acidosis,

hypokalemia with or without
hypouricemia, hypophosphatemia,
glucosuria, tubular proteinuria.

Supplementation of potassium,
bicarbonate and/or phosphate.

Bartter-like syndrome.

Hypokalemia, metabolic alkalosis,

hypomagnesemia, hypocalcemia
natriuresis.

Supplementation of potassium,
magnesuim and/or calcium, isotonic
saline.

AMPHOTERICIN B

Figure 1 :Antibiotics that affect proximal tubule cells.

Gentamicin enters the cell through megalincubulin system, while tetracyclines enter via apical or
basolateral organic anion transporters. Gentamycin and
tetracyclines can impair the function of mitochondrial
ribosomes and interfere with the conversion of ADP to
ATP. Consequently, these antibiotics inhibit the Na++K++
ATPase pump, which is dependent on ATP, and also
indirectly inhibits NHE-3 and other sodium-dependent
solute transporters, including transporters for uric acid,
amino acids and glucose.

Figure 3 : Antibiotics that affect Collecting duct

principal cells.
Trimethoprim blocks ENaCs similarly to
Amiloride, which causes Na++ wasting, reduced
kaliuresis, and distal renal tubular acidosis (because
H++ excretion decreases). Penicillin acts as a non
reabsorbable anion that maintains the luminal
negative charge if aldosterone-driven Na++
reabsorption is increased. This negative charge
stimulates K++ secretion and may cause hypokalemia.
Demeclocycline and Amphotericin B both
cause nephrogenic diabetes insipidus, by inhibiting
vasopressin-stimulated
V2-AQP2
signaling.
Amphotericin B creates pores in cell membranes;
once inside, it inhibits G55 proteins and/or adenylate
cyclase. These pores leak K++, which induces
hypokalemia. Demeclocycline enters the cell via
hOAT1 or hOAT3 and probably disrupts
vasopressin-aquaporin signaling.

Distal RTA.

Non-anion-gap metabolic acidosis,

hypokalemia.

Supplementation of bicarbonate
and/or potassium.

Hypokalemia.

Urinary potassium loss.

Supplementation of potassium,
amiloride, spironolactone.

Hyperkalemia.

Potassium shift out of cells (no

specific diagnostic test available).

Calcium (with arrhythmia), glucoseinsulin, cation-exchange resin,

isotonic saline.

TRIMETHOPRIM
ENaC blockade.

Hyperkalemia with or without

hyponatremia.

Isotonic saline, alkalization of the

urine.

Distal RTA.

Non-anion-gap metabolic acidosis.

Bicarbonate.

PENICILLIN.
Hypokalemia.

Typically low urine chloride and

high urine potassium.

Potassium supplementation.

Hyperkalemia.

High potassium in drug in patient

with impaired kaliuresis.

Calcium (with arrhythmia), glucoseinsulin, cation-exchange resin,

isotonic saline.

Pyroglutamic acidosis.

High-anionic-gap metabolic
acidosis.

Discontinuation of the drug.

TETRACYCLINES AND LINEZOLID.

Lactic acidosis.

Figure 2 : Antibiotics that affect the Thick Ascending

limb of the loop of Henle.
Gentamicin, other aminoglycosides and
Capreomycin can stimulate the CaSR. This
stimulation can disrupt electrolyte transport via
inhibition of four different pathways that involve
NKCC2, ROMK, K++ATPase and/or paracellular
diffusion. Inhibition of these transport mechanisms
2+
leads to increased urinary excretion of Na++, K++, Mg2+
2+, and associated electrolyte disorders.
and Ca2+,
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High-anionic-gap metabolic acidosis Discontinuation of the drug.

with elevated lactate.

Figure 4 : Antibiotics that affect collecting duct intercalated cells.

Amphotericin B can create pores in the cell membrane. These pores
allow a back flux of H++ into the cell, which inhibits urinary H++ excretion and
therefore, results in distal renal tubular acidosis.

CONCLUSION

Several groups of patients are at a risk of developing renal side effects of antimicrobial agents,
including those with an impairment of renal function or volume depletion. Most of the adverse effects are
dose-dependent and quite frequent; as a result of which, there requires close monitoring of serum
electrolyte composition and acid-base balance during the treatment of infections.
Dose adjustment and therapeutic drug monitoring are imperative. Thus, in caring for these patients,
decision should be made on whether the characteristics of the infection for which the antibiotics are given
outweigh the adverse effects caused by the treatment.