Role of insulin resistance in uric acid nephrolithiasis

Table 3 Pathophysiologic relationship between insulin resistance and uric acid stone formation

Ref.	Study Type	Year	n	Study population	Outcomes	Conclusion
Facchini et al[13]	Cross-sectional, single institution	1991	36	Healthy volunteers with varying degrees of IR	24H urine (pH, UA), UA clearance, steady-state plasma glucose, metabolic evaluation	As IR increases serum UA increases and urinary UA clearance decreases. Thus, increased serum UA concentration may be considered an additional trait of MetS
Cappuccio et al[14]	Cross-sectional, single institution	1993	568	Factory volunteers	Fasting spot urine (UA), fractional excretion of Na+, fasting blood analysis	The higher the serum UA level, the greater the amount of renal Na+ reabsorption. This phenomenon is consistent with hyperinsulinemia, and possibly IR, as insulin is known to increase renal sodium reabsorption
Pak et al[15]	Retrospective, single institution	2001	56	UA stone formers vs matched control with diet control	24H urine	UA stone formers have increased serum UA, decreased fractional excretion of urinary UA, and decreased urinary pH
Sakhaee et al[16]	Prospective, single institution	2002	70	Healthy vs stone formers (UA vs Calcium vs Mixed) with diet control	24H urine (pH, NH4+), fasting glucose	UA stone formers are more likely to have IR/DM. UA stone formation occurs due to impaired NH4+ excretion and urine acidification. Acid loading further decreases urinary pH in these patients as compared to non-UA stone formers/Controls
Abate et al[17]	Prospective, single institution	2004	68	Stone free patients vs UA stone formers with diet control	24H urine (pH, NH4+), glucose disposal rate	Acute hyperinsulinemia leads to elevated urinary pH and NH4+ excretion in normal insulin-sensitive subjects. Alternatively, IR is associated with low urinary pH and impaired NH4+ excretion and could be renal manifestations of IR causing UA stone formation
Maalouf et al[23]	Cross-sectional, single institution	2007	148	MetS vs No MetS (all stone free)	24H urine (pH, NH4+), Homeostasis model for IR, metabolic evaluation	Acidic urine is a feature of MetS and is associated with the degree of IR. As MetS traits increase, urine pH decreases
Bobulescu et al[24]	Prospective, single institution	2013	35	Matched patients with and without UA stones, matched non-stone forming diabetic controls	24H urine, urinary ammonium excretion	Both uric acid non-diabetic patients as well as DM non-stone forming patients had lower urinary pH as compared to matched non-stone forming non-diabetic controls
Cameron et al[25]	Prospective, single institution	2011	19	UA stone formers vs normal controls with diet control	24H urine, diurnal urinary pH	UA stone formers had decreased urinary pH with increased undissociated UA secretion compared to normal controls

IR: Insulin resistance; DM: Diabetes mellitus; UA: Uric acid; MetS: Metabolic syndrome.