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  • Review Article
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Haemodialysis-induced hypoglycaemia and glycaemic disarrays

Nature Reviews Nephrology volume 11, pages 302–313 (2015)Cite this article

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Key Points

  • In patients with diabetes undergoing haemodialysis, both extremely high and low glycaemic levels are associated with increased morbidity and shortened survival owing to vascular and diabetic complications and malnutrition

  • Factors that are associated with an increased risk of hypoglycaemia in patients on haemodialysis include decreased renal gluconeogenesis, deranged metabolic pathways (including altered metabolism of medications) and decreased insulin clearance

  • Glucose loss to the dialysate and diffusion of glucose into erythrocytes during haemodialysis are also associated with haemodialysis-induced hypoglycaemia

  • Inclusion of glucose in the dialysate is important to prevent haemodialysis-induced hypoglycaemia; use of glucose-free or low-glucose dialysates should be avoided in patients with diabetes

  • After the completion of a haemodialysis session, a paradoxical hyperglycaemia may ensue via a mechanism similar to the Somogyi effect, together with insulin resistance and insulin removal by the dialyzer

  • Appropriate glycaemic control tailored for diabetic patients is required to avoid haemodialysis-induced hypoglycaemia and other glycaemic disarrays

Abstract

In patients with diabetes receiving chronic haemodialysis, both very high and low glucose levels are associated with poor outcomes, including mortality. Conditions that are associated with an increased risk of hypoglycaemia in these patients include decreased gluconeogenesis in the remnant kidneys, deranged metabolic pathways, inadequate nutrition, decreased insulin clearance, glucose loss to the dialysate and diffusion of glucose into erythrocytes during haemodialysis. Haemodialysis-induced hypoglycaemia is common during treatments with glucose-free dialysate, which engenders a catabolic status similar to fasting; this state can also occur with 5.55 mmol/l glucose-containing dialysate. Haemodialysis-induced hypoglycaemia occurs more frequently in patients with diabetes than in those without. Insulin therapy and oral hypoglycaemic agents should, therefore, be used with caution in patients on dialysis. Several hours after completion of haemodialysis treatment a paradoxical rebound hyperglycaemia may occur via a similar mechanism as the Somogyi effect, together with insulin resistance. Appropriate glycaemic control tailored for patients on haemodialysis is needed to avoid haemodialysis-induced hypoglycaemia and other glycaemic disarrays. In this Review we summarize the pathophysiology and current management of glycaemic disarrays in patients on haemodialysis.

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Figure 1
Figure 2: HbA1c levels and mortality in patients on dialysis.
Figure 3: Mechanisms of haemodialysis-induced hypoglycaemia and haemodialysis-associated hyperglycaemia in patients with diabetes.
Figure 4: Haemodialysis-associated hyperglycaemia in a 70-year-old man undergoing continuous glucose monitoring.
Figure 5: Daily profiles of plasma glucose levels in diabetic patients on haemodialysis.

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  • 27 April 2015

    In the PDF and html versions of this article originally published online, the author contributions were missing. This error has been corrected in print and online.

References

  1. Collins, A. J. et al. Excerpts from the US Renal Data System Annual Data Report. Am. J. Kidney Dis. 55, S1–S420 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  2. United States Renal Data System. 2014 Annual Data Report: epidemiology of kidney disease in the United States. usrds.org [online] (2014).

  3. Nakai, S. et al. Overview of regular dialysis treatment in Japan (as of 31 December 2011). Ther. Apher. Dial. 17, 567–611 (2013).

    Article  PubMed  Google Scholar 

  4. Monnier, L., Wojtusciszyn, A., Colette, C. & Owens, D. The contribution of glucose variability to asymptomatic hypoglycemia in patients with type 2 diabetes. Diabetes Technol. Ther. 13, 813–818 (2011).

    Article  CAS  PubMed  Google Scholar 

  5. Slinin, Y. et al. Management of hyperglycemia, dyslipidemia, and albuminuria in patients with diabetes and CKD: a systematic review for a KDOQI clinical practice guideline. Am. J. Kidney Dis. 60, 747–769 (2012).

    Article  PubMed  Google Scholar 

  6. Williams, M. E., Lacson, E. Jr, Teng, M., Ofsthun, N. & Lazarus, J. M. Hemodialyzed type I and type II diabetic patients in the US: characteristics, glycemic control, and survival. Kidney Int. 70, 1503–1509 (2006).

    Article  CAS  PubMed  Google Scholar 

  7. Kalantar-Zadeh, K. et al. A1C and survival in maintenance hemodialysis patients. Diabetes Care 30, 1049–1055 (2007).

    Article  PubMed  Google Scholar 

  8. Ricks, J. et al. Glycemic control and cardiovascular mortality in hemodialysis patients with diabetes: a 6-year cohort study. Diabetes 61, 708–715 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Akmal, M. Hemodialysis in diabetic patients. Am. J. Kidney Dis. 38, S195–S199 (2001).

    Article  CAS  PubMed  Google Scholar 

  10. Jackson, M. A. et al. Hemodialysis-induced hypoglycemia in diabetic patients. Clin. Nephrol. 54, 30–34 (2000).

    CAS  PubMed  Google Scholar 

  11. Simic-Ogrizovic, S. et al. The influence of different glucose concentrations in hemodialysis solutions on metabolism and blood pressure stability in diabetic patients. Int. J. Artif. Organs 24, 863–869 (2001).

    Article  CAS  PubMed  Google Scholar 

  12. Sharma, R. & Rosner, M. H. Glucose in the dialysate: historical perspective and possible implications? Hemodial. Int. 12, 221–226 (2008).

    Article  PubMed  Google Scholar 

  13. Raimann, J. G. et al. Metabolic effects of dialyzate glucose in chronic hemodialysis: results from a prospective, randomized crossover trial. Nephrol. Dial. Transplant. 27, 1559–1568 (2012).

    Article  CAS  PubMed  Google Scholar 

  14. Jackson, M. A. et al. Occult hypoglycemia caused by hemodialysis. Clin. Nephrol. 51, 242–247 (1999).

    CAS  PubMed  Google Scholar 

  15. Burmeister, J. E., Scapini, A., da Rosa Miltersteiner, D., da Costa, M. G. & Campos, B. M. Glucose-added dialysis fluid prevents asymptomatic hypoglycemia in regular haemodialysis. Nephrol. Dial. Transplant. 22, 1184–1189 (2007).

    Article  CAS  PubMed  Google Scholar 

  16. Abe, M., Kaizu, K. & Matsumoto, K. Plasma insulin is removed by hemodialysis: evaluation of the relation between plasma insulin and glucose by using a dialysate with or without glucose. Ther. Apher. Dial. 11, 280–287 (2007).

    Article  CAS  PubMed  Google Scholar 

  17. Takahashi, A. et al. The mechanism of hypoglycemia caused by hemodialysis. Clin. Nephrol. 62, 362–368 (2004).

    Article  CAS  PubMed  Google Scholar 

  18. Wathen, R. L., Keshaviah, P., Hommeyer, P., Cadwell, K. & Comty, C. M. The metabolic effects of hemodialysis with and without glucose in the dialysate. Am. J. Clin. Nutr. 31, 1870–1875 (1978).

    Article  CAS  PubMed  Google Scholar 

  19. Borah, M. et al. Nitrogen balance during intermittent dialysis therapy of uremia. Kidney Int. 14, 491–500 (1978).

    Article  CAS  PubMed  Google Scholar 

  20. Ward, R. A., Shirlow, M. J., Hayes, J. M., Chapman, G. V. & Farrell, P. C. Protein catabolism during hemodialysis. Am. J. Clin. Nutr. 32, 2443–2449 (1979).

    Article  CAS  PubMed  Google Scholar 

  21. Ward, R. A., Wathen, R. L., Williams, T. E. & Harding, G. B. Hemodialysate composition and intradialytic metabolic, acid-base and potassium changes. Kidney Int. 32, 129–135 (1987).

    Article  CAS  PubMed  Google Scholar 

  22. Gutierrez, A., Bergstrom, J. & Alvestrand, A. Hemodialysis-associated protein catabolism with and without glucose in the dialysate fluid. Kidney Int. 46, 814–822 (1994).

    Article  CAS  PubMed  Google Scholar 

  23. Skutches, C. L. & Sigler, M. H. Plasma glucose turnover and oxidation during hemodialysis: nutritional effect of dialysis fluid. Am. J. Clin. Nutr. 65, 128–135 (1997).

    Article  CAS  PubMed  Google Scholar 

  24. Amiel, S. A., Sherwin, R. S., Simonson, D. C. & Tamborlane, W. V. Effect of intensive insulin therapy on glycemic thresholds for counterregulatory hormone release. Diabetes 37, 901–907 (1988).

    Article  CAS  PubMed  Google Scholar 

  25. Heller, S. R. & Cryer, P. E. Reduced neuroendocrine and symptomatic responses to subsequent hypoglycemia after 1 episode of hypoglycemia in non-diabetic humans. Diabetes 40, 223–226 (1991).

    Article  CAS  PubMed  Google Scholar 

  26. McCall, A. L. et al. Chronic hypoglycemia increases brain glucose transport. Am. J. Physiol. 251, E442–E447 (1986).

    CAS  PubMed  Google Scholar 

  27. DeFeo, P. et al. Modest decrements in plasma glucose concentration cause early impairment in cognitive function and later activation of glucose counterregulation in the absence of hypoglycemic symptoms in normal man. J. Clin. Invest. 82, 436–444 (1988).

    Article  CAS  Google Scholar 

  28. Heller, S. R. & Macdonald, I. A. Physiological disturbances in hypoglycemia: effect on subjective awareness. Clin. Sci. 81, 1–9 (1991).

    Article  CAS  PubMed  Google Scholar 

  29. Maran, A., Lomas, J., Macdonald, I. A. & Amiel, S. A. Lack of preservation of higher brain function during hypoglycemia in patients with intensively treated IDDM. Diabetologia 38, 1412–1418 (1995).

    Article  CAS  PubMed  Google Scholar 

  30. Bober, J. et al. Influence of glucose in dialyzing fluid on purine concentrations in hemodialyzed patients with chronic renal failure. Nephron Clin. Pract. 95, c31–c36 (2003).

    Article  CAS  PubMed  Google Scholar 

  31. Bober, J. et al. Does glucose present in the dialysate limit oxidative stress in patients undergoing regular hemodialysis? Blood Purif. 23, 219–225 (2005).

    Article  CAS  PubMed  Google Scholar 

  32. Henrich, W. L., Woodard, T. D. & McPhaul, J. J. Jr. The chronic efficacy and safety of high sodium dialysate: Double-blind, crossover study. Am. J. Kidney Dis. 2, 349–353 (1982).

    Article  CAS  PubMed  Google Scholar 

  33. Boden, G. Gluconeogenesis and glycogenolysis in health and diabetes. J. Investig. Med. 52, 375–378 (2004).

    Article  PubMed  Google Scholar 

  34. Gerich, J. E. Physiology of glucose homeostasis. Diabetes Obes. Metabol. 2, 345–350 (2000).

    Article  CAS  Google Scholar 

  35. Mather, A. & Pollock, C. Glucose handling by the kidney. Kidney Int. 79, S1–S6 (2011).

    Article  CAS  Google Scholar 

  36. Gerich, J. E., Meyer, C., Woerle, H. J. & Stumvoll, M. Renal gluconeogenesis: its importance in human glucose homeostasis. Diabetes Care 24, 382–391 (2001).

    Article  CAS  PubMed  Google Scholar 

  37. Meyer, C. et al. Renal substrate exchange and gluconeogenesis in normal postabsorptive humans. Am. J. Physiol. 282, E428–E434 (2002).

    CAS  Google Scholar 

  38. Peitzman, S. J. & Agarwal, B. N. Spontaneous hypoglycemia in end-stage renal failure. Nephron 19, 131–139 (1977).

    Article  CAS  PubMed  Google Scholar 

  39. Arem, R. Hypoglycemia associated with renal failure. Endocrinol. Metab. Clin. North Am. 18, 103–121 (1989).

    Article  CAS  PubMed  Google Scholar 

  40. Meyer, C., Woerle, H. J., Dostou, J. M., Welle, S. L. & Gerich, J. E. Abnormal renal, hepatic, and muscle glucose metabolism following glucose ingestion in type 2 diabetes. Am. J. Physiol. 287, E1049–E1056 (2004).

    CAS  Google Scholar 

  41. Stumvoll, M. et al. Human kidney and liver gluconeogenesis: evidence for organ substrate selectivity. Am. J. Physiol. 274, E817–E826 (1998).

    CAS  PubMed  Google Scholar 

  42. Rhee, C. M. et al. Updates on the management of diabetes in dialysis patients. Semin. Dial. 27, 135–145 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  43. Kalantar-Zadeh, K. et al. Burnt-out diabetes: impact of chronic kidney disease progression on the natural course of diabetes mellitus. J. Ren. Nutr. 19, 33–37 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  44. Kovesdy, C. P., Park, J. C. & Kalantar-Zadeh, K. Glycemic control and burnt-out diabetes in ESRD. Semin. Dial. 23, 148–156 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  45. Park, J., Lertdumrongluk, P., Molnar, M. Z., Kovesdy, C. P. & Kalantar-Zadeh, K. Glycemic control in diabetic dialysis patients and the burnt-out diabetes phenomenon. Curr. Diab. Rep. 12, 432–439 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Haneda, M. & Morikawa, A. Which hypoglycemic agents to use in type 2 diabetic subjects with CKD and how? Nephrol. Dial. Transplant. 24, 338–341 (2009).

    Article  PubMed  Google Scholar 

  47. Holstein, A., Plaschke, A., Hammer, C. & Egberts, E. H. Characteristics and time course of severe glimepiride- versus glibenclamide-induced hypoglycemia. Eur. J. Clin. Pharmacol. 59, 91–97 (2003).

    Article  CAS  PubMed  Google Scholar 

  48. Yale, J. F. Oral antihyperglycemic agents and renal disease: new agents, new concepts. J. Am. Soc. Nephrol. 16, 7–10 (2005).

    Article  CAS  Google Scholar 

  49. Abe, M., Okada, K. & Soma, M. Antidiabetic agents in patients with chronic kidney disease and end-stage renal disease on dialysis: metabolism and clinical practice. Curr. Drug Metab. 12, 57–69 (2011).

    Article  CAS  PubMed  Google Scholar 

  50. Kidney Disease Outcomes Quality Initiative (KDOQI). Clinical practice guidelines and clinical practice recommendations for diabetes and chronic kidney disease. Am. J. Kidney Dis. 49, S62–S73 (2007).

  51. Snyder, R. W. & Berns, J. S. Use of insulin and oral hypoglycemic medications in patients with diabetes mellitus and advanced kidney disease. Semin. Dial. 17, 365–370 (2004).

    Article  PubMed  Google Scholar 

  52. Tuttle, K. R. et al. Diabetic kidney disease: a report from an ADA Consensus Conference. Am. J. Kidney Dis. 64, 510–533 (2014).

    Article  PubMed  Google Scholar 

  53. Schernthaner, G., Ritz, E. & Schernthaner, G. H. Strict glycaemic control in diabetic patients with CKD or ESRD: beneficial or deadly? Nephrol. Dial. Transplant. 25, 2044–2047 (2010).

    Article  PubMed  Google Scholar 

  54. Flynn, C. & Bakris, G. L. Noninsulin glucose-lowering agents for the treatment of patients on dialysis. Nat. Rev. Nephrol. 9, 147–153 (2013).

    Article  CAS  PubMed  Google Scholar 

  55. National Kidney Foundation. KDOQI clinical practice guideline for diabetes and CKD: 2012 update. Am. J. Kidney Dis. 60, 850–886 (2012).

  56. Kalantar-Zadeh, K., Uppot, R. N. & Lewandrowski, K. B. Case 23–2013. A 54-year-old woman with abdominal pain, vomiting, and confusion. N. Engl. J. Med. 369, 374–382 (2013).

    Article  CAS  PubMed  Google Scholar 

  57. Grey, A. B. Skeletal toxicity of thiazolidinediones. Ann. Intern. Med. 148, 563 (2008).

    Article  PubMed  Google Scholar 

  58. Abe, M., Kikuchi, F., Kaizu, K. & Matsumoto, K. Combination therapy of pioglitazone with voglibose improves glycemic control safely and rapidly in Japanese type 2-diabetic patients on hemodialysis. Clin. Nephrol. 68, 287–294 (2007).

    Article  CAS  PubMed  Google Scholar 

  59. Ito, M. et al. The dipeptidyl peptidase-4 (DPP-4) inhibitor vildagliptin improves glycemic control in type 2 diabetic patients undergoing hemodialysis. Endocr. J. 58, 979–987 (2011).

    Article  CAS  PubMed  Google Scholar 

  60. Kume, S. et al. Efficacy and tolerability of vildagliptin in type 2 diabetic patients on hemodialysis. J. Diabetes Investig. 3, 298–301 (2012).

    Article  CAS  PubMed  Google Scholar 

  61. Fujii, Y. et al. The dipeptidyl peptidase-4 inhibitor alogliptin improves glycemic control in type 2 diabetic patients undergoing hemodialysis. Expert Opin. Pharmacother. 14, 259–267 (2013).

    Article  CAS  PubMed  Google Scholar 

  62. The Diabetes Control and Complication Trial (DCCT) Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N. Engl. J. Med. 329, 977–986 (1993).

  63. The Diabetes Control and Complication Trial (DCCT) Research Group. The early worsening of diabetic retinopathy in the Diabetes Control and Complication Trial. Arch. Ophthalmol. 116, 874–886 (1998).

  64. Charpentier, G., Riveline, J. P. & Varroud-Vial, M. Management of drugs affecting blood glucose in diabetic patients with renal failure. Diabetes Metab. 26, 73–85 (2000).

    CAS  PubMed  Google Scholar 

  65. Reilly, J. B. & Berns, J. S. Selection and dosing of medications for management of diabetes in patients with advanced kidney disease. Semin. Dial. 23, 163–168 (2010).

    Article  PubMed  Google Scholar 

  66. McCaleb, M. L., Izzo, M. S. & Lockwood, D. H. Characterization and partial purification of a factor from uremic human serum that induces insulin resistance. J. Clin. Invest. 75, 391–396 (1985).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Ohkubo, Y. et al. Intensive insulin therapy prevents the progression of diabetic microvascular complications in Japanese patients with non-insulin-dependent diabetes mellitus: a randomized prospective 6-year study. Diabetes Res. Clin. Pract. 28, 103–117 (1995).

    Article  CAS  PubMed  Google Scholar 

  68. Mak, R. H. Impact of end-stage renal disease and dialysis on glycemic control. Semin. Dial. 13, 4–8 (2000).

    Article  CAS  PubMed  Google Scholar 

  69. Abe, M. et al. Disopyramide-induced hypoglycemia in a non-diabetic patient with hemodialysis: a case report and review of the literature. Clin. Nephrol. 76, 401–406 (2011).

    Article  CAS  PubMed  Google Scholar 

  70. Mak, R. H. Renal disease, insulin resistance and glucose intolerance. Diabetes Rev. 2, 19–28 (1994).

    Google Scholar 

  71. DeFronzo, R. A. et al. Insulin resistance in uremia. J. Clin. Invest. 67, 563–568 (1981).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Siew, E. D. & Ikizler, T. A. Insulin resistance and protein energy metabolism in patients with advanced chronic kidney disease. Semin. Dial. 23, 378–382 (2010).

    Article  PubMed  Google Scholar 

  73. Kim, J. C., Kalantar-Zadeh, K. & Kopple, J. D. Frailty and protein-energy wasting in elderly patients with end-stage kidney disease. J. Am. Soc. Nephrol. 24, 337–351 (2013).

    Article  PubMed  Google Scholar 

  74. Duranton, F. et al. Normal and pathologic concentrations of uremic toxins. J. Am. Soc. Nephrol. 23, 1258–1270 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Vanholder, R., Van Laecke, S. & Glorieux, G. What is new in uremic toxicity? Pediatr. Nephrol. 23, 1211–1221 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  76. Evenepoel, P., Meijers, B. K., Bammens, B. R. & Verbeke, K. Uremic toxins originating from colonic microbial metabolism. Kidney Int. Suppl. 114, S12–S19 (2009).

    Article  CAS  Google Scholar 

  77. Guarnieri, G. & Barazzoni, R. Fighting protein-energy wasting in chronic kidney disease: a challenge of complexity. J. Ren. Nutr. 21, 2–6 (2011).

    Article  PubMed  Google Scholar 

  78. Zoccali, C. et al. Adiponectin, metabolic risk factors, and cardiovascular events among patients with end-stage renal disease. J. Am. Soc. Nephrol. 13, 134–141 (2002).

    Article  CAS  PubMed  Google Scholar 

  79. Dzúric, R., Spustová, V. & Lajdová, I. Inhibition of glucose utilization is isolated rat soleus muscle by pseudouridine: Implications for renal failure. Nephron 65, 108–110 (1993).

    Article  Google Scholar 

  80. Eidmak, I. et al. Insulin resistance and hyperinsulinemia in mild to moderate progressive chronic renal failure and its association with aerobic work capacity. Diabetologia 38, 565–572 (1995).

    Article  Google Scholar 

  81. Goldberg, A., Hagberg, J., Delmez, J., Haynes, M. E. & Harter, H. R. The metabolic effects of exercise training in hemodialysis patients. Kidney Int. 18, 754–761 (1980).

    Article  CAS  PubMed  Google Scholar 

  82. Mak, R. H. Correction of anemia by erythropoietin reverses insulin resistance and hyperinsulinemia in uremia. Am. J. Physiol. 270, F839–F844 (1996).

    CAS  PubMed  Google Scholar 

  83. Abe, M., Okada, K., Soma, M. & Matsumoto, K. Relationship between insulin resistance and erythropoietin responsiveness in hemodialysis patients. Clin. Nephrol. 75, 49–58 (2011).

    CAS  PubMed  Google Scholar 

  84. Fouque, D. et al. A proposed nomenclature and diagnostic criteria for protein-energy wasting in acute and chronic kidney disease. Kidney Int. 73, 391–398 (2007).

    Article  CAS  PubMed  Google Scholar 

  85. Stenvinkel, P., Heimburger, O., Lindholm, B., Kaysen, G. A. & Bergström, J. Are there two types of malnutrition in chronic renal failure? Evidence for relationship between malnutrition, inflammation and atherosclerosis (MIA syndrome). Nephrol. Dial. Transplant. 15, 953–960 (2000).

    Article  CAS  PubMed  Google Scholar 

  86. Kalantar-Zadeh, K., Block, G., McAllister, C. J., Humphreys, M. H. & Kopple, J. D. Appetite and inflammation, nutrition, anemia, and clinical outcome in hemodialysis patients. Am. J. Clin. Nutr. 80, 299–307 (2004).

    Article  CAS  PubMed  Google Scholar 

  87. Filho, R. P., Lindholm, B. & Stenvinkel, P. The malnutrition, inflammation, and atherosclerosis (MIA) syndrome—the heart of the matter. Nephrol. Dial. Transplant. 17, 28–31 (2002).

    Article  Google Scholar 

  88. Kalantar-Zadeh, K., Ikizler, A., Block, G., Avram, M. M. & Kopple, J. D. Malnutrition-inflammation complex syndrome in dialysis patients: causes and consequences. Am. J. Kidney Dis. 42, 864–881 (2003).

    Article  PubMed  Google Scholar 

  89. Shoji, T. et al. Additive impacts of diabetes and renal failure on carotid atherosclerosis. Atherosclerosis 153, 257–258 (2000).

    Article  CAS  PubMed  Google Scholar 

  90. Shinohara, K. et al. Insulin resistance as an independent predictor of cardiovascular mortality in patients with end-stage renal disease. J. Am. Soc. Nephrol. 13, 1894–1900 (2002).

    Article  PubMed  Google Scholar 

  91. Stenvinkel, P. et al. IL-10, IL-6, and TNF-α: central factors in the altered cytokine network of uremia—the good, the bad, and the ugly. Kidney Int. 67, 1216–1233 (2005).

    Article  CAS  PubMed  Google Scholar 

  92. Sande, F. M., Kooman, J. P. & Leunissen, K. M. The predictive value of C-reactive protein in end-stage renal disease: is it clinically significant? Blood Purif. 24, 335–341 (2006).

    Article  CAS  PubMed  Google Scholar 

  93. Zimmermann, J., Herrlinger, S., Pruy, A., Metzger, T. & Wanner, C. Inflammation enhances cardiovascular risk and mortality in hemodialysis patients. Kidney Int. 55, 648–658 (1999).

    Article  CAS  PubMed  Google Scholar 

  94. Abe, M. et al. Relationship between erythropoietin responsiveness, insulin resistance, and malnutrition-inflammation-atherosclerosis (MIA) syndrome in hemodialysis patients with diabetes. Int. J. Artif. Organs 34, 16–25 (2011).

    Article  CAS  PubMed  Google Scholar 

  95. Kopple, J. D. et al. OPPORTUNITY™: a large-scale randomized clinical trial of growth hormone in hemodialysis patients. Nephrol. Dial. Transplant. 26, 4095–4103 (2011).

    Article  CAS  PubMed  Google Scholar 

  96. Guebre-Egziabher, F. et al. Short-term administration of a combination of recombinant growth hormone and insulin-like growth factor-1 induces anabolism in maintenance hemodialysis. J. Clin. Endocrinol. Metab. 94, 2299–2305 (2009).

    Article  CAS  PubMed  Google Scholar 

  97. Macdonald, J. H. et al. Nandrolone decanoate as anabolic therapy in chronic kidney disease: a randomized phase II dose-finding study. Nephron Clin. Pract. 106, c125–c135 (2007).

    Article  CAS  PubMed  Google Scholar 

  98. Johansen, K. L., Mulligan, K. & Schambelan, M. Anabolic effects of nandrolone decanoate in patients receiving dialysis: a randomized controlled trial. JAMA 281, 1275–1281 (1999).

    Article  CAS  PubMed  Google Scholar 

  99. Dong, J. et al. The effect of resistance exercise to augment long-term benefits of intradialytic oral nutritional supplementation in chronic hemodialysis patients. J. Ren. Nutr. 21, 149–159 (2011).

    Article  PubMed  Google Scholar 

  100. Pupim, L. B., Flakoll, P. J., Levenhagen, D. K. & Ikizler, T. A. Exercise augments the acute anabolic effects of intradialytic parenteral nutrition in chronic hemodialysis patients. Am. J. Physiol. Endocrinol. Metab. 286, E589–E597 (2004).

    Article  CAS  PubMed  Google Scholar 

  101. Ikizler, T. A. et al. Prevention and treatment of protein energy wasting in chronic kidney disease patients: a consensus statement by the International Society of Renal Nutrition and Metabolism. Kidney Int. 84, 1096–1107 (2013).

    Article  CAS  PubMed  Google Scholar 

  102. Stubbs, J. R., Idiculla, A., Slusser, J., Menard, R. & Quarles, L. D. Cholecalciferol supplementation alters calcitriol-responsive monocyte proteins and decreases inflammatory cytokines in ESRD. J. Am. Soc. Nephrol. 21, 353–361 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Perkins, R. M. et al. Effect of pentoxifylline on GFR decline in CKD: a pilot, double-blind, randomized, placebo-controlled trial. Am. J. Kidney Dis. 53, 606–616 (2009).

    Article  CAS  PubMed  Google Scholar 

  104. Don, B. R. et al. The effect of etanercept on suppression of the systemic inflammatory response in chronic hemodialysis patients. Clin. Nephrol. 73, 431–438 (2010).

    Article  CAS  PubMed  Google Scholar 

  105. Hung, A. M., Ellis, C. D., Shintani, A., Booker, C. & Ikizler, T. A. IL-1β receptor antagonist reduces inflammation in hemodialysis patients. J. Am. Soc. Nephrol. 22, 437–442 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Ikizler, T. A. A patient with CKD and poor nutritional status. J. Am. Soc. Nephrol. 8, 2174–2182 (2013).

    Article  CAS  Google Scholar 

  107. Munoz Mendoza, J. et al. Fibroblast growth factor 23 and inflammation in CKD. Clin. J. Am. Soc. Nephrol. 7, 1155–1162 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Avram, M. M., Lipner, H. I., Sadiqali, R., Iancu, M. & Gan, A. C. Metabolic changes in diabetic uremic patients on hemodialysis. Trans. Am. Soc. Artif. Int. Organs 22, 412–419 (1976).

    CAS  Google Scholar 

  109. Abe, M., Kikuchi, F., Kaizu, K. & Matsumoto, K. The influence of hemodialysis membranes on the plasma insulin level of diabetic patients on maintenance hemodialysis. Clin. Nephrol. 69, 354–360 (2008).

    Article  CAS  PubMed  Google Scholar 

  110. Abe, M. et al. Comparison of the effects of polysulfone and polyester-polymer alloy dialyzers on glycemic control in diabetic patients undergoing hemodialysis. Clin. Nephrol. 71, 514–520 (2009).

    Article  CAS  PubMed  Google Scholar 

  111. Abe, M., Okada, K. & Matsumoto, K. Plasma insulin and C-peptide concentrations in diabetic patients undergoing hemodialysis: comparison with five types of high-flux dialyzer membranes. Diabetes Res. Clin. Pract. 82, e17–e19 (2008).

    Article  CAS  PubMed  Google Scholar 

  112. Abe, M. et al. Characterization of insulin adsorption behavior of dialyzer membranes used in hemodialysis. Artif. Organs 35, 398–403 (2011).

    Article  PubMed  Google Scholar 

  113. Abe, M., Kaizu, K. & Matsumoto, K. Evaluation of the hemodialysis-induced changes in plasma glucose and insulin concentrations in diabetic patients: comparison between the hemodialysis and non-hemodialysis days. Ther. Apher. Dial. 11, 288–295 (2007).

    Article  CAS  PubMed  Google Scholar 

  114. Heller, S. R. & Cryer, P. E. Hypoinsulinaemia is not critical to glucose recovery from hypoglycemia in humans. Am. J. Physiol. 261, E41–E48 (1991).

    Article  CAS  PubMed  Google Scholar 

  115. Ganda, O. P., Aoki, T. T., Soeldner, J. S., Morrison, R. S. & Cahill, G. F. Jr. Hormone-fuel concentrations in anephric subjects. Effect of hemodialysis. J. Clin. Invest. 57, 1403–1411 (1976).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Sangill, M. & Pedersen, E. B. The effect of glucose added the dialysis fluid on blood pressure, blood glucose, and quality of life in hemodialysis patients: a placebo-controlled crossover study. Am. J. Kidney Dis. 47, 636–643 (2006).

    Article  CAS  PubMed  Google Scholar 

  117. Duong, U. et al. Glycemic control and survival in peritoneal dialysis patients with diabetes mellitus. Clin. J. Am. Soc. Nephrol. 6, 1041–1048 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Molnar, M. Z. et al. Association of pretransplant glycemic control with posttransplant outcomes in diabetic kidney transplant recipients. Diabetes Care 34, 2536–2541 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Hill, C. J. et al. Glycated hemoglobin and risk of death in diabetic patients treated with hemodialysis: a meta-analysis. Am. J. Kidney Dis. 63, 84–94 (2014).

    Article  CAS  PubMed  Google Scholar 

  120. Morioka, T. et al. Glycemic control is a predictor of survival for diabetic patients on hemodialysis. Diabetes Care 24, 909–913 (2001).

    Article  CAS  PubMed  Google Scholar 

  121. Oomichi, T. et al. Impact of glycemic control on survival of diabetic patients on chronic regular hemodialysis: a 7-year observational study. Diabetes Care 29, 1496–1500 (2006).

    Article  PubMed  Google Scholar 

  122. Hayashino, Y. et al. Diabetes, glycaemic control and mortality risk in patients on haemodialysis: the Japan Dialysis Outcomes and Practice Pattern Study. Diabetologia 50, 1170–1177 (2007).

    Article  CAS  PubMed  Google Scholar 

  123. Kim, Y. et al. Correlates of low hemoglobin A1c in maintenance hemodialysis patients. Int. Urol. Nephrol. 45, 1079–1090 (2013).

    Article  CAS  PubMed  Google Scholar 

  124. Drechsler, C., Krane, V., Ritz, E., März, W. & Wanner, C. Glycemic control and cardiovascular events in diabetic hemodialysis patients. Circulation 120, 2421–2428 (2009).

    Article  CAS  PubMed  Google Scholar 

  125. Ramirez, S. P. et al. Hemoglobin A1c levels and mortality in diabetic hemodialysis population: findings from the Dialysis Outcomes and Practice Patterns Study (DOPPS). Diabetes Care 35, 2527–2532 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Williams, M. E., Lacson, E. Jr, Wang, W., Lazarus, J. M. & Hakim, R. Glycemic control and extended hemodialysis survival in patients with diabetes mellirtus: comparative results of traditional and time-dependent Cox model analysis. Clin. J. Am. Soc. Nephrol. 5, 1595–1601 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  127. Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int. Suppl. 3, 1–150 (2013).

  128. Inaba, M. et al. Glycated albumin is a better glycemic indicator than glycated hemoglobin values in hemodialysis patients with diabetes: effect of anemia and erythropoietin injection. J. Am. Soc. Nephrol. 18, 896–903 (2007).

    Article  CAS  PubMed  Google Scholar 

  129. Abe, M. & Matsumoto, K. Glycated hemoglobin or glycated albumin for assessment of glycemic control in dialysis patients with diabetes? Nat. Clin. Pract. Nephrol. 4, 482–483 (2008).

    Article  CAS  PubMed  Google Scholar 

  130. Peacock, T. P. et al. Comparison of glycated albumin and hemoglobin A1c levels in diabetic subjects on hemodialysis. Kidney Int. 73, 1062–1068 (2008).

    Article  CAS  PubMed  Google Scholar 

  131. Nakao, T. et al. Influence of erythropoietin treatment on hemoglobin A1c levels in patients with chronic renal failure on hemodialysis. Intern. Med. 37, 826–830 (1998).

    Article  CAS  PubMed  Google Scholar 

  132. Fukuoka, K. et al. Glycated albumin levels predict long–term survival in diabetic patients undergoing haemodialysis. Nephrology (Carlton) 13, 278–283 (2008).

    Article  CAS  Google Scholar 

  133. Okada, T. et al. Association between markers of glycemic control, cardiovascular complications and survival in type 2 diabetic patients with end-stage renal disease. Intern. Med. 46, 807–814 (2007).

    Article  PubMed  Google Scholar 

  134. Inaba, M. et al. Impact of atherosclerosis on the relationship of glycemic control and mortality in diabetic patients on hemodialysis. Clin. Nephrol. 78, 273–280 (2012).

    Article  CAS  PubMed  Google Scholar 

  135. Isshiki, K. et al. Glycated albumin predicts the risk of mortality in type 2 diabetic patients on hemodialysis: evaluation of a target level for improving survival. Ther. Apher. Dial. 18, 434–442 (2014).

    Article  CAS  PubMed  Google Scholar 

  136. The Japanese Society for Dialysis Therapy [online], (2013).

  137. Mehrota, R., Kalantar-Zadeh, K. & Adler, S. Assessment of glycemic control in dialysis patients with diabetes: glycosylated hemoglobin or glycated albumin? Clin. J. Am. Soc. Nephrol. 6, 1520–1522 (2011).

    Article  CAS  Google Scholar 

  138. Parsons, F. M. & Stewart, W. K. in Replacement of Renal Function by Dialysis 2nd edn (eds Drukker, W., Parsons, F. M. & Maher, J.F.). 148–170 (Nijhoff Publishers, 1983).

    Book  Google Scholar 

  139. Sam, R. et al. Composition and clinical use of hemodialysates. Hemodial. Int. 10, 15–28 (2006).

    Article  PubMed  Google Scholar 

  140. Haviv, Y. S., Sharkia, M. & Safadi, R. Hypoglycemia in patients with renal failure. Ren. Fail. 22, 219–223 (2000).

    Article  CAS  PubMed  Google Scholar 

  141. Loipl, J., Scmekal, B. & Biesenbach, G. Long-term impact of chronic hemodialysis on glycemic control and serum lipids in insulin-treated type 2-diabetic patients. Ren. Fail. 27, 305–308 (2005).

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

K.K.Z.'s work is supported by research grants from the NIH/NIDDK (K24-DK091419 and R01-DK078106) and philanthropic grants from Harold Simmons, Louis Chang, and AVEO. The authors appreciate invaluable advice on this manuscript given by K. Kaizu (Abe Clinic and Nihon University School of Medicine, Japan).

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  1. Divisions of Nephrology, Department of Internal Medicine, Hypertension and Endocrinology, Nihon University School of Medicine, 30-1, Oyaguchi Kami-chou, Itabashi-ku, Tokyo, 173-8610, Japan

    Masanori Abe

  2. Division of Nephrology and Hypertension, Department of Medicine, University of California, Irvine, 101 The City Drive South, Orange, 92868, CA, USA

    Kamyar Kalantar-Zadeh

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  1. Masanori Abe
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M.A. researched the data for the article. Both authors contributed substantially to discussions of the content, wrote the article and reviewed and edited the manuscript before submission.

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Correspondence to Masanori Abe.

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M.A. declares no competing interests. K.K.Z. has received honoraria from Abbott, Abbvie, Amgen, Fresenius, Shire and Vifor.

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Abe, M., Kalantar-Zadeh, K. Haemodialysis-induced hypoglycaemia and glycaemic disarrays. Nat Rev Nephrol 11, 302–313 (2015). https://doi.org/10.1038/nrneph.2015.38

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