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Review
. 2023 Mar 1;32(2):145-152.
doi: 10.1097/MNH.0000000000000859. Epub 2022 Dec 5.

Type 4 renal tubular acidosis and uric acid nephrolithiasis: two faces of the same coin?

Emmanuel A Adomako  1 , Naim M Maalouf  2
Affiliations
Review

Type 4 renal tubular acidosis and uric acid nephrolithiasis: two faces of the same coin?

Emmanuel A Adomako et al. Curr Opin Nephrol Hypertens. .

Abstract

Purpose of review: The present review summarizes findings of recent studies examining the epidemiology, pathophysiology, and treatment of type 4 renal tubular acidosis (RTA) and uric acid nephrolithiasis, two conditions characterized by an abnormally acidic urine.

Recent findings: Both type 4 RTA and uric acid nephrolithiasis disproportionately occur in patients with type 2 diabetes and/or chronic kidney disease. Biochemically, both conditions are associated with reduced renal ammonium excretion resulting in impaired urinary buffering and low urine pH. Reduced ammoniagenesis is postulated to result from hyperkalemia in type 4 RTA and from insulin resistance and fat accumulation in the renal proximal tubule in uric acid nephrolithiasis. The typical biochemical findings of hyperkalemia and systemic acidosis of type 4 RTA are rarely reported in uric acid stone formers. Additional clinical differences between the two conditions include findings of higher urinary uric acid excretion and consequent urinary uric acid supersaturation in uric acid stone formers but not in type 4 RTA.

Summary: Type 4 RTA and uric acid nephrolithiasis share several epidemiological, clinical, and biochemical features. Although both conditions may be manifestations of diabetes mellitus and thus have a large at-risk population, the means to the shared biochemical finding of overly acidic urine are different. This difference in pathophysiology may explain the dissimilarity in the prevalence of kidney stone formation.

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Conflict of interest statement

Conflicts of interest: There are no conflicts of interest.

Figures

Figure 1.
Figure 1.
Depiction of proximal tubule, thick ascending limb, and collecting duct function with emphasis on acid base response and uric acid stone formation. In the renal proximal tubule, intracellular hyperkalemia and free fatty excess reduce the production of ammonium from glutamine. In the urinary lumen, ammonia serves as a buffer and its deficiency leads to greater protonation of urate to insoluble uric acid. ENaC, Epithelial sodium channel; FFA, Free fatty acids; Gln,Glutamine; NHE3, Sodium-Hydrogen Exchanger 3; ROMK, renal outer medullary potassium channel; NKCC2, Na+/K+/2Cl− co-transporter
Figure 2.
Figure 2.
Similarities and differences in the clinical features of uric acid nephrolithiasis and type 4 renal tubular acidosis
See this image and copyright information in PMC

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