Renal Urate Transport
Serum uric acid is determined by a balance between production and renal excretion. Luminal reabsorption of urate by the proximal tubule from the glomerular ultrafiltrate involves coupling between sodium-anion cotransport and urate-anion exchange. Apical sodium-coupled cotransport of lactate, ketoacids, nicotinate, and pyrazinoate increases intracellular levels of these anions in proximal tubular cells, stimulating the apical absorption of luminal urate via anion exchange. Hyperuricemia occurs when plasma levels of these anions increase; for example, hyperuricemia is a well-recognized concomitant of lactic acidosis and ketoacidosis. Relevant developments in the molecular and renal physiology of urate homeostasis are reviewed.
Available from: Yuqing Chen
- "It is well known that renal handling of uric acid excretion is a major denominator of plasma uric acid levels in adults with hyperuricemia [5-7]. Renal uric acid excretion is regulated by multiple factors such as glomerular filtration rate, tubular re-absorption and excretion [5,7]. "
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ABSTRACT: Hyperuricemia appeared to be a common symptom in IgA nephropathy (IgAN), even in those with normal eGFR. IgAN was characterized by variation of pathological features, especially variable tubulointerstitial lesions. Since tubular reabsorption and excretion appeared to be more important in determination of plasma uric acid levels in persons without obvious decrease of glomerular filtration rate, we took advantage of our IgAN cohort to investigate whether plasma uric acid level associated with tubular interstitial lesions, and could be considered as a maker for tubular interstitial lesions, especially at early stage with normal eGFR.
623 IgAN patients were involved in the present study. Morphological changes were evaluated with Oxford classification scoring system as well as Beijing classification system of IgAN. Statistical analysis was done with SPSS 13.0.
We found that plasma uric acid level associated with percentage of interstitial fibrosis/tubular atrophy. Higher plasma uric acid levels indicated higher tubulointerstitial scores, either with Oxford system (P = 0.012) or with Beijing classification system (P = 4.8*10-4) in the whole cohort. We also found that in the subgroup of 258 IgAN cases with normal baseline eGFR (eGFR > =90 ml/min/1.73 M2), higher plasma uric acid associated with more severe tubulointerstitial lesions with Beijing scoring system (P = 3.4*10-5). The risk of having more than 10% tubulointerstitial lesions in patients with hyperuricemia increased 58% compared with normal uric acid level. In subgroup with normal eGFR, only hyperuricemia predicted tubulointerstitial leisions, and the risk of having more tubulointerstitial changes increased 100%. Among these patients, hyperuricemia was associated with more tubulointerstitial lesions with a specificity of 60.3%. Specificity increased to 65% among those patients with eGFR > =90 ml/min/1.73 m2.
Plasma uric acid levels indicate tubular interstitial lesions in IgAN and hyperuricemia may be considered as a marker for tubulointerstitial lesions.
BMC Nephrology 01/2014; 15(1):11. DOI:10.1186/1471-2369-15-11 · 1.69 Impact Factor
Available from: Rebecca Rosenwasser
- "Decreases in serum uric acid by SGLT2 inhibitors might be of importance given mounting evidence of the relationship between uric acid levels and CV disease.3,70 The exact mechanism by which SGLT2 inhibition and uric acid reduction are related is unknown, but may involve a direct effect on renal uric acid transport or an indirect effect secondary to corresponding decreases in sodium reabsorption in the proximal tubule.71,72 Serum concentration of uric acid parallels sodium absorption by the kidney, therefore when SGLT2 inhibitors inhibit both sodium and glucose reabsorption, the outcome is excretion of uric acid.72 "
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ABSTRACT: Diabetes remains a burgeoning global problem, necessitating ongoing efforts on the part of pharmaceutical and device manufacturers, patients, and society to curb the frightening trends in morbidity and mortality attributable to the malady. Since 1835 when phlorizin was discovered, sodium glucose co-transporter 2 (SGLT-2) inhibitors have rested tantalizingly on the horizon, promising a more physiological approach to glucose control. These agents lower glucose by enhancing its excretion by blocking reabsorption in the renal tubules, thus eliminating glucose from the body along with the molecules' attendant effects on caloric balance, plasma osmolality, and lipids. Consequently, SGLT-2 inhibitors improve glucose control to an extent comparable to other hypoglycemic agents while simultaneously reducing body weight, blood pressure, and cholesterol - an admirable portfolio. One agent, canagliflozin, has recently been approved by the US Food and Drug Administration (FDA) and two other agents have progressed through Phase III trials, including dapagliflozin and empagliflozin. Collectively, when used as monotherapy, these agents have demonstrated reductions in hemoglobin A1c (HbA1c), body weight, and blood pressure of -0.34% to -1.03%, -2.0 to -3.4 kg, and -1.7 to -6.4 mmHg/-0.3 to -2.6 mmHg (systolic blood pressure/diastolic blood pressure), respectively. SGLT-2 inhibitors have been well tolerated, with hypoglycemia (0.9% to 4.3%) occurring infrequently in clinical trials. Safety signals related to breast and bladder cancer have arisen with dapagliflozin, though these are unsubstantiated and likely ascribed to the presence of preexisting cancer. As these agents emerge, clinicians should embrace the addition to the formulary for treating type 2 diabetes, but must also weight the risk-benefit of this new class in deciding which patient types are most likely to benefit from their novel mechanism of action.
Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy 11/2013; 6:453-467. DOI:10.2147/DMSO.S34416
Available from: Erick Prado de Oliveira
- "In this phase, the renal excretion of urate follows the limiting factors that accompany renal diseases (glomerular and medullary). The urate renal excretion phase is that of post-secretory resorption . "
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ABSTRACT: High plasma uric acid (UA) is a precipitating factor for gout and renal calculi as well as a strong risk factor for Metabolic Syndrome and cardiovascular disease. The main causes for higher plasma UA are either lower excretion, higher synthesis or both. Higher waist circumference and the BMI are associated with higher insulin resistance and leptin production, and both reduce uric acid excretion. The synthesis of fatty acids (tryglicerides) in the liver is associated with the de novo synthesis of purine, accelerating UA production. The role played by diet on hyperuricemia has not yet been fully clarified, but high intake of fructose-rich industrialized food and high alcohol intake (particularly beer) seem to influence uricemia. It is not known whether UA would be a causal factor or an antioxidant protective response. Most authors do not consider the UA as a risk factor, but presenting antioxidant function. UA contributes to > 50% of the antioxidant capacity of the blood. There is still no consensus if UA is a protective or a risk factor, however, it seems that acute elevation is a protective factor, whereas chronic elevation a risk for disease.
Diabetology and Metabolic Syndrome 04/2012; 4(1):12. DOI:10.1186/1758-5996-4-12 · 2.17 Impact Factor
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