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Diabetologia
Erschienen in: Diabetologia 9/2015

01.09.2015 | Review

Fructose and uric acid in diabetic nephropathy

verfasst von: Petter Bjornstad, Miguel A. Lanaspa, Takuji Ishimoto, Tomoki Kosugi, Shinji Kume, Diana Jalal, David M. Maahs, Janet K. Snell-Bergeon, Richard J. Johnson, Takahiko Nakagawa

Erschienen in: Diabetologia | Ausgabe 9/2015

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Abstract

Clinical studies have reported associations between serum uric acid levels and the development of diabetic nephropathy, but the underlying mechanisms remain elusive. There is evidence from animal studies that blocking uric acid production protects the kidney from tubulointerstitial injury, which may suggest a causal role for uric acid in the development of diabetic tubular injury. In turn, when fructose, which is endogenously produced in diabetes via the polyol pathway, is metabolised, uric acid is generated from a side-chain reaction driven by ATP depletion and purine nucleotide turnover. For this reason, uric acid derived from endogenous fructose could cause tubulointerstitial injury in diabetes. Accordingly, our research group recently demonstrated that blocking fructose metabolism in a diabetic mouse model mitigated the development of tubulointerstitial injury by lowering tubular uric acid production. In this review we discuss the relationship between uric acid and fructose as a novel mechanism for the development of diabetic tubular injury.
Literatur
1.
Maahs DM, Rewers M (2006) Editorial: Mortality and renal disease in type 1 diabetes mellitus–progress made, more to be done. J Clin Endocrinol Metab 91:3757–3759PubMedCrossRef
2.
Orchard TJ, Secrest AM, Miller RG, Costacou T (2010) In the absence of renal disease, 20 year mortality risk in type 1 diabetes is comparable to that of the general population: a report from the Pittsburgh Epidemiology of Diabetes Complications Study. Diabetologia 53:2312–2319PubMedCentralPubMedCrossRef
3.
Collins AJ, Foley RN, Chavers B et al (2012) United States Renal Data System 2011 annual data report: atlas of chronic kidney disease & end-stage renal disease in the United States. Am J Kidney Dis 59(1 Suppl 1):A7, e1–e420 PubMedCrossRef
4.
Bjornstad P, Cherney D, Maahs DM (2014) Early diabetic nephropathy in type 1 diabetes: new insights. Curr Opin Endocrinol Diabetes Obes 21:279–286PubMedCentralPubMedCrossRef
5.
6.
Maahs DM, Caramori L, Cherney DZ et al (2013) Uric acid lowering to prevent kidney function loss in diabetes: the preventing early renal function loss (PERL) allopurinol study. Curr Diab Rep 13:550–559PubMedCentralPubMedCrossRef
7.
8.
Lanaspa MA, Ishimoto T, Cicerchi C et al (2014) Endogenous fructose production and fructokinase activation mediate renal injury in diabetic nephropathy. J Am Soc Nephrol 25:2526–2538PubMedCrossRef
9.
Ficociello LH, Rosolowsky ET, Niewczas MA et al (2010) High-normal serum uric acid increases risk of early progressive renal function loss in type 1 diabetes: results of a 6-year follow-up. Diabetes Care 33:1337–1343PubMedCentralPubMedCrossRef
10.
Jalal DI, Rivard CJ, Johnson RJ et al (2010) Serum uric acid levels predict the development of albuminuria over 6 years in patients with type 1 diabetes: findings from the Coronary Artery Calcification in Type 1 Diabetes study. Nephrol Dial Transplant 25:1865–1869PubMedCentralPubMedCrossRef
11.
Bjornstad P, Snell-Bergeon JK, McFann K et al (2014) Serum uric acid and insulin sensitivity in adolescents and adults with and without type 1 diabetes. J Diabetes Complicat 28:298–304PubMedCentralPubMedCrossRef
12.
Hovind P, Rossing P, Tarnow L, Johnson RJ, Parving HH (2009) Serum uric acid as a predictor for development of diabetic nephropathy in type 1 diabetes: an inception cohort study. Diabetes 58:1668–1671PubMedCentralPubMedCrossRef
13.
Zoppini G, Targher G, Chonchol M et al (2012) Serum uric acid levels and incident chronic kidney disease in patients with type 2 diabetes and preserved kidney function. Diabetes Care 35:99–104PubMedCentralPubMedCrossRef
14.
Altemtam N, Russell J, El Nahas M (2012) A study of the natural history of diabetic kidney disease (DKD). Nephrol Dial Transplant 27:1847–1854PubMedCrossRef
15.
Miao Y, Ottenbros SA, Laverman GD et al (2011) Effect of a reduction in uric acid on renal outcomes during losartan treatment: a post hoc analysis of the reduction of endpoints in non-insulin-dependent diabetes mellitus with the Angiotensin II Antagonist Losartan Trial. Hypertension 58:2–7PubMedCrossRef
16.
Momeni A, Shahidi S, Seirafian S, Taheri S, Kheiri S (2010) Effect of allopurinol in decreasing proteinuria in type 2 diabetic patients. Iran J Kidney Dis 4:128–132PubMed
17.
Liu P, Chen Y, Wang B, Zhang F, Wang D, Wang Y (2014) Allopurinol treatment improves renal function in patients with type 2 diabetes and asymptomatic hyperuricemia: 3-year randomized parallel-controlled study. Clin Endocrinol. doi:10.​1111/​cen.​12673
18.
Iseki K, Ikemiya Y, Inoue T, Iseki C, Kinjo K, Takishita S (2004) Significance of hyperuricemia as a risk factor for developing ESRD in a screened cohort. Am J Kidney Dis 44:642–650PubMedCrossRef
19.
Sturm G, Kollerits B, Neyer U, Ritz E, Kronenberg F (2008) Uric acid as a risk factor for progression of non-diabetic chronic kidney disease? The Mild to Moderate Kidney Disease (MMKD) Study. Exp Gerontol 43:347–352PubMedCrossRef
20.
21.
Langford HG, Blaufox MD, Borhani NO et al (1987) Is thiazide-produced uric acid elevation harmful? Analysis of data from the Hypertension Detection and Follow-up Program. Arch Intern Med 147:645–649PubMedCrossRef
22.
Adamopoulos D, Vlassopoulos C, Seitanides B, Contoyiannis P, Vassilopoulos P (1977) The relationship of sex steroids to uric acid levels in plasma and urine. Acta Endocrinol (Copenh) 85:198–208
23.
Taniguchi A, Kamatani N (2008) Control of renal uric acid excretion and gout. Curr Opin Rheumatol 20:192–197PubMedCrossRef
24.
Iseki K, Oshiro S, Tozawa M, Iseki C, Ikemiya Y, Takishita S (2001) Significance of hyperuricemia on the early detection of renal failure in a cohort of screened subjects. Hypertens Res 24:691–697PubMedCrossRef
25.
Gilbert RE, Cooper ME (1999) The tubulointerstitium in progressive diabetic kidney disease: more than an aftermath of glomerular injury? Kidney Int 56:1627–1637PubMedCrossRef
26.
Ginevri F, Piccotti E, Alinovi R et al (1993) Reversible tubular proteinuria precedes microalbuminuria and correlates with the metabolic status in diabetic children. Pediatr Nephrol 7:23–26PubMedCrossRef
27.
28.
Rasch R, Dorup J (1997) Quantitative morphology of the rat kidney during diabetes mellitus and insulin treatment. Diabetologia 40:802–809PubMedCrossRef
29.
Verzola D, Bertolotto MB, Villaggio B et al (2004) Oxidative stress mediates apoptotic changes induced by hyperglycemia in human tubular kidney cells. J Am Soc Nephrol 15(Suppl 1):S85–S87PubMedCrossRef
30.
Kosugi T, Nakayama T, Heinig M et al (2009) Effect of lowering uric acid on renal disease in the type 2 diabetic db/db mice. Am J Physiol Ren Physiol 297:F481–F488CrossRef
31.
Kim SM, Choi YW, Seok HY et al (2012) Reducing serum uric acid attenuates TGF-beta1-induced profibrogenic progression in type 2 diabetic nephropathy. Nephron Exp Nephrol 121:e109–e121PubMedCrossRef
32.
Wang C, Pan Y, Zhang QY, Wang FM, Kong LD (2012) Quercetin and allopurinol ameliorate kidney injury in STZ-treated rats with regulation of renal NLRP3 inflammasome activation and lipid accumulation. PLoS ONE 7, e38285PubMedCentralPubMedCrossRef
33.
Verzola D, Ratto E, Villaggio B et al (2014) Uric acid promotes apoptosis in human proximal tubule cells by oxidative stress and the activation of NADPH oxidase NOX 4. PLoS One 9, e115210PubMedCentralPubMedCrossRef
34.
Golembiewska E, Ciechanowski K, Safranow K, Kedzierska K, Kabat-Koperska J (2005) Renal handling of uric acid in patients with type 1 diabetes in relation to glycemic control. Arch Med Res 36:32–35PubMedCrossRef
35.
Cook DG, Shaper AG, Thelle DS, Whitehead TP (1986) Serum uric acid, serum glucose and diabetes: relationships in a population study. Postgrad Med J 62:1001–1006PubMedCentralPubMedCrossRef
36.
Skeith MD, Healey LA, Cutler RE (1967) Urate excretion during mannitol and glucose diuresis. J Lab Clin Med 70:213–220PubMed
37.
Vuorinen-Markkola H, Yki-Jarvinen H (1994) Hyperuricemia and insulin resistance. J Clin Endocrinol Metab 78:25–29PubMed
38.
Muscelli E, Natali A, Bianchi S et al (1996) Effect of insulin on renal sodium and uric acid handling in essential hypertension. Am J Hypertens 9:746–752PubMedCrossRef
39.
Shichiri M, Iwamoto H, Marumo F (1990) Diabetic hypouricemia as an indicator of clinical nephropathy. Am J Nephrol 10:115–122PubMedCrossRef
40.
Golik A, Weissgarten J, Cotariu D et al (1993) Renal uric acid handling in non-insulin-dependent diabetic patients with elevated glomerular filtration rates. Clin Sci (Lond) 85:713–716
41.
Quinones Galvan A, Natali A, Baldi S et al (1995) Effect of insulin on uric acid excretion in humans. Am J Physiol 268:E1–E5PubMed
42.
List JF, Whaley JM (2011) Glucose dynamics and mechanistic implications of SGLT2 inhibitors in animals and humans. Kidney Int 79(Suppl 120):S20–S27CrossRef
43.
Freitas HS, Anhe GF, Melo KF et al (2008) Na+-glucose transporter-2 messenger ribonucleic acid expression in kidney of diabetic rats correlates with glycemic levels: involvement of hepatocyte nuclear factor-1α expression and activity. Endocrinology 149:717–724PubMedCrossRef
44.
Cherney DZ, Perkins BA, Soleymanlou N et al (2014) Sodium glucose cotransport-2 inhibition and intrarenal RAS activity in people with type 1 diabetes. Kidney Int 86:1057–1058PubMedCrossRef
45.
Skeith MD, Healey LA, Cutler RE (1970) Effect of phloridzin on uric acid excretion in man. Am J Physiol 219:1080–1082PubMed
46.
Musso G, Gambino R, Cassader M, Pagano G (2012) A novel approach to control hyperglycemia in type 2 diabetes: sodium glucose co-transport (SGLT) inhibitors: systematic review and meta-analysis of randomized trials. Ann Med 44:375–393PubMedCrossRef
47.
Lytvyn Y, Škrtić M, Yang GK, Yip PM, Perkins BA, Cherney DZ (2015) Glycosuria-mediated urinary uric acid excretion in patients with uncomplicated type 1 diabetes mellitus. Am J Physiol Ren Physiol 308:F77–F83CrossRef
48.
Augustin R, Carayannopoulos MO, Dowd LO, Phay JE, Moley JF, Moley KH (2004) Identification and characterization of human glucose transporter-like protein-9 (GLUT9): alternative splicing alters trafficking. J Biol Chem 279:16229–16236PubMedCrossRef
49.
Chino Y, Samukawa Y, Sakai S et al (2014) SGLT2 inhibitor lowers serum uric acid through alteration of uric acid transport activity in renal tubule by increased glycosuria. Biopharm Drug Dispos 35:391–404PubMedCentralPubMedCrossRef
50.
Kimura T, Takahashi M, Yan K, Sakurai H (2014) Expression of SLC2A9 isoforms in the kidney and their localization in polarized epithelial cells. PLoS ONE 9, e84996PubMedCentralPubMedCrossRef
51.
Ludvigson MA, Sorenson RL (1980) Immunohistochemical localization of aldose reductase. II. Rat eye and kidney. Diabetes 29:450–459PubMedCrossRef
52.
Terubayashi H, Sato S, Nishimura C, Kador PF, Kinoshita JH (1989) Localization of aldose and aldehyde reductase in the kidney. Kidney Int 36:843–851PubMedCrossRef
53.
Lanaspa MA, Sanchez-Lozada LG, Choi YJ et al (2012) Uric acid induces hepatic steatosis by generation of mitochondrial oxidative stress: potential role in fructose-dependent and -independent fatty liver. J Biol Chem 287:40732–40744PubMedCentralPubMedCrossRef
54.
Ghahary A, Luo JM, Gong YW, Chakrabarti S, Sima AA, Murphy LJ (1989) Increased renal aldose reductase activity, immunoreactivity, and mRNA in streptozocin-induced diabetic rats. Diabetes 38:1067–1071PubMedCrossRef
55.
Ghahary A, Chakrabarti S, Sima AA, Murphy LJ (1991) Effect of insulin and statil on aldose reductase expression in diabetic rats. Diabetes 40:1391–1396PubMedCrossRef
56.
Yamaoka T, Nishimura C, Yamashita K et al (1995) Acute onset of diabetic pathological changes in transgenic mice with human aldose reductase cDNA. Diabetologia 38:255–261PubMedCrossRef
57.
Tilton RG, Chang K, Nyengaard JR, Van den Enden M, Ido Y, Williamson JR (1995) Inhibition of sorbitol dehydrogenase. Effects on vascular and neural dysfunction in streptozocin-induced diabetic rats. Diabetes 44:234–242PubMedCrossRef
58.
Kawasaki T, Akanuma H, Yamanouchi T (2002) Increased fructose concentrations in blood and urine in patients with diabetes. Diabetes Care 25:353–357PubMedCrossRef
59.
Flath MC, Bylander JE, Sens DA (1992) Variation in sorbitol accumulation and polyol-pathway activity in cultured human proximal tubule cells. Diabetes 41:1050–1055PubMedCrossRef
60.
Sun W, Oates PJ, Coutcher JB, Gerhardinger C, Lorenzi M (2006) A selective aldose reductase inhibitor of a new structural class prevents or reverses early retinal abnormalities in experimental diabetic retinopathy. Diabetes 55:2757–2762PubMedCrossRef
61.
Hotta N, Kawamori R, Fukuda M, Shigeta Y (2012) Long-term clinical effects of epalrestat, an aldose reductase inhibitor, on progression of diabetic neuropathy and other microvascular complications: multivariate epidemiological analysis based on patient background factors and severity of diabetic neuropathy. Diabet Med 29:1529–1533PubMedCentralPubMedCrossRef
62.
Ohmura C, Watada H, Azuma K et al (2009) Aldose reductase inhibitor, epalrestat, reduces lipid hydroperoxides in type 2 diabetes. Endocr J 56:149–156PubMedCrossRef
63.
64.
Nakagawa T, Tuttle KR, Short RA, Johnson RJ (2005) Hypothesis: fructose-induced hyperuricemia as a causal mechanism for the epidemic of the metabolic syndrome. Nat Clin Pract Nephrol 1:80–86PubMedCrossRef
65.
Raivio KO, Becker A, Meyer LJ, Greene ML, Nuki G, Seegmiller JE (1975) Stimulation of human purine synthesis de novo by fructose infusion. Metab Clin Exp 24:861–869PubMedCrossRef
66.
67.
Nakagawa T, Hu H, Zharikov S et al (2006) A causal role for uric acid in fructose-induced metabolic syndrome. Am J Physiol Ren Physiol 290:F625–F631CrossRef
68.
Perez-Pozo SE, Schold J, Nakagawa T, Sanchez-Lozada LG, Johnson RJ, Lillo JL (2010) Excessive fructose intake induces the features of metabolic syndrome in healthy adult men: role of uric acid in the hypertensive response. Int J Obes 34:454–461CrossRef
69.
Nakayama T, Kosugi T, Gersch MS et al (2010) Dietary fructose causes tubulointerstitial injury in the normal rat kidney. Am J Physiol Ren Physiol 298:F712–F720CrossRef
70.
Doctor RB, Mandel LJ (1991) Minimal role of xanthine oxidase and oxygen free radicals in rat renal tubular reoxygenation injury. J Am Soc Nephrol 1:959–969PubMed
71.
Stirpe F, Della Corte E, Bonetti E, Abbondanza A, Abbati A, De Stefano F (1970) Fructose-induced hyperuricaemia. Lancet 2:1310–1311PubMedCrossRef
72.
Cox CL, Stanhope KL, Schwarz JM et al (2012) Consumption of fructose- but not glucose-sweetened beverages for 10 weeks increases circulating concentrations of uric acid, retinol binding protein-4, and gamma-glutamyl transferase activity in overweight/obese humans. Nutr Metab (Lond) 9:68CrossRef
73.
Choi JW, Ford ES, Gao X, Choi HK (2008) Sugar-sweetened soft drinks, diet soft drinks, and serum uric acid level: the Third National Health and Nutrition Examination Survey. Arthritis Rheum 59:109–116PubMedCrossRef
74.
Aoyama M, Isshiki K, Kume S et al (2012) Fructose induces tubulointerstitial injury in the kidney of mice. Biochem Biophys Res Commun 419:244–249PubMedCrossRef
75.
Gersch MS, Mu W, Cirillo P et al (2007) Fructose, but not dextrose, accelerates the progression of chronic kidney disease. Am J Physiol Ren Physiol 293:F1256–F1261CrossRef
76.
Cirillo P, Gersch MS, Mu W et al (2009) Ketohexokinase-dependent metabolism of fructose induces proinflammatory mediators in proximal tubular cells. J Am Soc Nephrol 20:545–553PubMedCentralPubMedCrossRef
77.
Glushakova O, Kosugi T, Roncal C et al (2008) Fructose induces the inflammatory molecule ICAM-1 in endothelial cells. J Am Soc Nephrol 19:1712–1720PubMedCentralPubMedCrossRef
78.
Shinozaki K, Kashiwagi A, Nishio Y et al (1999) Abnormal biopterin metabolism is a major cause of impaired endothelium-dependent relaxation through nitric oxide/O2 - imbalance in insulin-resistant rat aorta. Diabetes 48:2437–2445PubMedCrossRef
79.
Sanchez-Lozada LG, Lanaspa MA, Cristobal-Garcia M et al (2012) Uric acid-induced endothelial dysfunction is associated with mitochondrial alterations and decreased intracellular ATP concentrations. Nephron Exp Nephrol 121:e71–e78PubMedCentralPubMedCrossRef
80.
Tseng CH (2005) Correlation of uric acid and urinary albumin excretion rate in patients with type 2 diabetes mellitus in Taiwan. Kidney Int 68:796–801PubMedCrossRef
81.
Fukui M, Tanaka M, Shiraishi E et al (2008) Serum uric acid is associated with microalbuminuria and subclinical atherosclerosis in men with type 2 diabetes mellitus. Metabolism 57:625–629PubMedCrossRef
82.
Rosolowsky ET, Ficociello LH, Maselli NJ et al (2008) High-normal serum uric acid is associated with impaired glomerular filtration rate in nonproteinuric patients with type 1 diabetes. Clin J Am Soc Nephrol 3:706–713PubMedCentralPubMedCrossRef
83.
Behradmanesh S, Horestani MK, Baradaran A, Nasri H (2013) Association of serum uric acid with proteinuria in type 2 diabetic patients. J Res Med Sci 18:44–46PubMedCentralPubMed
84.
Chuengsamarn S, Rattanamongkolgul S, Jirawatnotai S (2014) Association between serum uric acid level and microalbuminuria to chronic vascular complications in Thai patients with type 2 diabetes. J Diabetes Complicat 28:124–129PubMedCrossRef
85.
Rodrigues TC, Maahs DM, Johnson RJ et al (2010) Serum uric acid predicts progression of subclinical coronary atherosclerosis in individuals without renal disease. Diabetes Care 33:2471–2473PubMedCentralPubMedCrossRef
86.
Bjornstad P, Maahs DM, Rivard CJ et al (2014) Serum uric acid predicts vascular complications in adults with type 1 diabetes: the coronary artery calcification in type 1 diabetes study. Acta Diabetol 51:783–791PubMedCrossRef
87.
Krolewski AS, Niewczas MA, Skupien J et al (2014) Early progressive renal decline precedes the onset of microalbuminuria and its progression to macroalbuminuria. Diabetes Care 37:226–234PubMedCentralPubMedCrossRef
Metadaten
Titel
Fructose and uric acid in diabetic nephropathy
verfasst von
Petter Bjornstad
Miguel A. Lanaspa
Takuji Ishimoto
Tomoki Kosugi
Shinji Kume
Diana Jalal
David M. Maahs
Janet K. Snell-Bergeon
Richard J. Johnson
Takahiko Nakagawa
Publikationsdatum
01.09.2015
Verlag
Springer Berlin Heidelberg
Erschienen in
Diabetologia / Ausgabe 9/2015
Print ISSN: 0012-186X
Elektronische ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-015-3650-4

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