Role of bicarbonate supplementation on urine uric acid crystals and diabetic tubulopathy in adults with type 1 diabetes

Abstract

Uricosuria and crystallization are increasingly recognized risk factors for diabetic tubulopathy. This pilot clinical trial aimed to determine the acute effect of urinary alkalinization using oral sodium bicarbonate (NaHCO ) on UA crystals in adults with type 1 diabetes (T1D). Adults with T1D, ages 18 to 65 years (n = 45, 60% female, HbA1c, 7.5 ± 1.2%, 20.2 ± 9.3 years duration) without chronic kidney disease (eGFR ≥60 mL/min/1.73 m and albumin-to-creatinine ratio < 30 mg/g) received 2 doses of 1950 mg oral NaHCO over 24 hours. Fasting urine and serum were collected pre- and post-intervention. UA crystals were identified under polarized microscopy. Urine measurements included: osmolality, pH, UA, creatinine and kidney injury molecule-1 (KIM-1). NaHCO therapy increased mean ± SD urine pH from 6.1 ± 0.7 to 6.5 ± 0.7 (P < .0001). Prior to therapy, 31.0% of participants had UA crystals vs 6.7% post therapy (P = .005). Change in urine pH inversely correlated with change in urine KIM-1 (r:-0.51, P = .0003). In addition, change in urine UA over 24 hours correlated with change in urine KIM-1 (r:0.37, P = .01). In conclusion, oral NaHCO normalized urine pH and decreased UA crystals, and may hold promise as an inexpensive and safe tubulo-protective intervention in individuals with T1D.

Kidney Injury from Recurrent Heat Stress and Rhabdomyolysis: Protective Role of Allopurinol and Sodium Bicarbonate

“…The benefit of AP may be by blocking UA synthesis, whereas sodium BC appeared to facilitate urinary excretion of UA, therefore, reducing its systemic and renal concentrations. In this regard, there is evidence that BC supplementation reduced UA urine crystallization in diabetic patients along with tubular injury [13].…”

“…Both effects favor UA crystallization in kidney tubules inducing an inflammatory reaction and AP has also proved to attenuate the acute kidney damage caused by experimental rhabdomyolysis [12]. Likewise, bicarbonate (BC) therapy, by virtue of increasing urine pH, can reduce urate crystalluria that might be important in inducing local injury [13]. However, while urate crystalluria can activate inflammasomes [14], which has been regarded as a mechanism to induce inflammation, apoptosis and kidney injury in acute rhabdomyolysis [15], there is also some data that soluble UA can also activate inflammasomes and can also induce release of chemokines that can induce a local inflammatory response [14].…”

Fructose Increases Uric Acid Contributing to Metabolic Syndrome - Herbal, Nutritional and Dietary Strategies to Reduce Uric Acid

“…However, average weight in the lowest SUA quintile was only 69 kg, compared to the average weight for the study of 80 kg [81], so the nutritional status of the lowest SUA quintile in this study is open to question. Similarly, in a study of 45 Type 1 diabetics, ranging in age from 18 to 65 years, the fasting mean SUA value was 4.1 ± 0.9 mg/dl [82]. This low SUA value may reflect undernourishment in almost 50% of the study group, Additionally, it is possible that the low SUA indicates either a loss of kidney function or an early stage of chronic kidney disease [83].…”

“…Sodium bicarbonate (NaHCO 3 ) 2,000 mg twice daily has also been reported to increase urinary pH in diabetes type 1 adults and reduce uric acid crystallisation [82].…”

Hyperuricemia and Progression of Chronic Kidney Disease: A Review from Physiology and Pathogenesis to the Role of Urate-Lowering Therapy

“…Most of these diseases can be prevented by early administration of ULT [ 45 , 46 , 47 , 48 ]. Further studies suggested that intermittent uricosuria might result in tubular injury by both the direct toxic effects of urate crystals in tubules and the phenotypic transition of tubular cells induced by high concentrations of urate [ 7 , 11 , 49 ]. To date, it is believed that hyperuricemia is not only the result of renal impairment or sharing the risk factors with CKD, but also can be the cause of renal function impairment.…”