Recent advances in the pathophysiology of nephrolithiasis

Abstract

Over the past 10 years, major progress has been made in the pathogenesis of uric acid and calcium stones. These advances have led to our further understanding of a pathogenetic link between uric acid nephrolithiasis and the metabolic syndrome, the role of Oxalobacter formigenes in calcium oxalate stone formation, oxalate transport in Slc26a6-null mice, the potential pathogenetic role of Randall's plaque as a precursor for calcium oxalate nephrolithiasis, and the role of renal tubular crystal retention. With these advances, we may target the development of novel drugs including (1) insulin sensitizers; (2) probiotic therapy with O. formigenes, recombinant enzymes, or engineered bacteria; (3) treatments that involve the upregulation of intestinal luminal oxalate secretion by increasing anion transporter activity (Slc26a6), luminally active nonabsorbed agents, or oxalate binders; and (4) drugs that prevent the formation of Randall's plaque and/or renal tubular crystal adhesions.

Figure 1

Physicochemical scheme for the development of uric acid stones.

Figure 2

Mechanisms of urinary acidification.

Figure 3. Acute acid loading

Previously published in Sakhaee et al.

Figure 4. Inpatient net acid excretion

Net acid excretion = NH₄ ⁺ + TA − (HCO₃⁻ + Cit).

Figure 5

Oxalate catabolism and energy conservation in Oxalobacter formigenes.

Figure 6. Oxalobacter formigenes in stool among patients with recurrent calcium oxalate kidney stones and non-stone formers

Previously published as a modification of information obtained from Kaufman et al.

Figure 7. Sites and characteristics of crystal deposition

A transmission electron micrograph showing a crystalline structure composed of concentric layers of crystalline material (light) and matrix protein (dark). Previously published in Evan et al.