Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Glomerular hyperfiltration: definitions, mechanisms and clinical implications

Nature Reviews Nephrology volume 8, pages 293–300 (2012)Cite this article

Subjects

Abstract

Glomerular hyperfiltration is a phenomenon that can occur in various clinical conditions including kidney disease. No single definition of glomerular hyperfiltration has been agreed upon, and the pathophysiological mechanisms, which are likely to vary with the underlying disease, are not well explored. Glomerular hyperfiltration can be caused by afferent arteriolar vasodilation as seen in patients with diabetes or after a high-protein meal, and/or by efferent arteriolar vasoconstriction owing to activation of the renin–angiotensin–aldosterone system, thus leading to glomerular hypertension. Glomerular hypertrophy and increased glomerular pressure might be both a cause and a consequence of renal injury; understanding the renal adaptations to injury is therefore important to prevent further damage. In this Review, we discuss the current concepts of glomerular hyperfiltration and the renal hemodynamic changes associated with this condition. A physiological state of glomerular hyperfiltration occurs during pregnancy and after consumption of high-protein meals. The various diseases that have been associated with glomerular hyperfiltration, either per nephron or per total kidney, include diabetes mellitus, polycystic kidney disease, secondary focal segmental glomerulosclerosis caused by a reduction in renal mass, sickle cell anemia, high altitude renal syndrome and obesity. A better understanding of the mechanisms involved in glomerular hyperfiltration could enable the development of new strategies to prevent progression of kidney disease.

Key Points

  • Glomerular hyperfiltration has been variably defined either as an abnormally high whole-kidney glomerular filtration rate (GFR), increased filtration fraction, or as increased filtration per nephron

  • An increased GFR occurs physiologically after consuming a high-protein meal and during pregnancy

  • Increased GFR can occur as an early manifestation of disease, for example in diabetes mellitus, but it remains to be proven whether glomerular hyperfiltration is a precursor of chronic kidney disease

  • Increased filtration per nephron occurs as an adaptive response to nephron loss, and leads to glomerular hypertension and subsequent glomerulosclerosis with progressive renal function decline

  • The mechanisms of glomerular hyperfiltration in disease conditions are variable and not entirely clear, although the renin–angiotensin–aldosterone system has been implicated as a contributing pathway

  • Longitudinal studies are needed to examine whether treatment of glomerular hyperfiltration will slow the progression of chronic kidney disease; this research requires uniform, pathophysiologically based definitions of glomerular hyperfiltration

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Learn more

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Mechanisms of glomerular hyperfiltration.

References

  1. Bergström, J., Ahlberg, M. & Alvestrand, A. Influence of protein intake on renal hemodynamics and plasma hormone concentrations in normal subjects. Acta Med. Scand. 217, 189–196 (1985).

    Article  PubMed  Google Scholar 

  2. Pecly, I. M., Genelhu, V. & Francischetti, E. A. Renal functional reserve in obesity hypertension. Int. J. Clin. Pract. 60, 1198–1203 (2006).

    Article  CAS  PubMed  Google Scholar 

  3. Bosch, J. P., Lauer, A. & Glabman, S. Short-term protein loading in assessment of patients with renal disease. Am. J. Med. 77, 873–879 (1984).

    Article  CAS  PubMed  Google Scholar 

  4. Brenner, B. M., Hostetter, T. H., Olson, J. L., Rennke, H. G. & Venkatachalam, M. A. The role of glomerular hyperfiltration in the initiation and progression of diabetic nephropathy. Acta Endocrinol. Suppl. (Copenh.) 242, 7–10 (1981).

    CAS  Google Scholar 

  5. Brenner, B. M., Lawler, E. V. & Mackenzie, H. S. The hyperfiltration theory: a paradigm shift in nephrology. Kidney Int. 49, 1774–1777 (1996).

    Article  CAS  PubMed  Google Scholar 

  6. Hostetter, T. H., Olson, J. L., Rennke, H. G., Venkatachalam, M. A. & Brenner, B. M. Hyperfiltration in remnant nephrons: a potentially adverse response to renal ablation. Am. J. Physiol. 241, F85–F93 (1981).

    CAS  PubMed  Google Scholar 

  7. Hostetter, T. H., Troy, J. L. & Brenner, B. M. Glomerular hemodynamics in experimental diabetes mellitus. Kidney Int. 19, 410–415 (1981).

    Article  CAS  PubMed  Google Scholar 

  8. Brenner, B. M. Nephron adaptation to renal injury or ablation. Am. J. Physiol. 249, F324–F337 (1985).

    CAS  PubMed  Google Scholar 

  9. Anderson, S. & Brenner, B. M. The role of intraglomerular pressure in the initiation and progression of renal disease. J. Hypertens. Suppl. 4, S236–S238 (1986).

    Article  CAS  PubMed  Google Scholar 

  10. Neuringer, J. R. & Brenner, B. M. Glomerular hypertension: cause and consequence of renal injury. J. Hypertens. Suppl. 10, S91–S97 (1992).

    Article  CAS  PubMed  Google Scholar 

  11. Neuringer, J. R. & Brenner, B. M. Hemodynamic theory of progressive renal disease: a 10-year update in brief review. Am. J. Kidney Dis. 22, 98–104 (1993).

    Article  CAS  PubMed  Google Scholar 

  12. National Kidney Foundation. K/DOQI Clinical Practice Guidelines for Chronic Kidney Disease: Evaluation, classification, and stratification. Part 4. Definition and classification of stages of chronic kidney disease. Am. J. Kidney Dis. 39, S46–S75 (2002).

  13. Dahlquist, G., Stattin, E. L. & Rudberg, S. Urinary albumin excretion rate and glomerular filtration rate in the prediction of diabetic nephropathy; a long-term follow-up study of childhood onset type-1 diabetic patients. Nephrol. Dial. Transplant. 16, 1382–1386 (2001).

    Article  CAS  PubMed  Google Scholar 

  14. Amin, R. et al. The relationship between microalbuminuria and glomerular filtration rate in young type 1 diabetic subjects: The Oxford Regional Prospective Study. Kidney Int. 68, 1740–1749 (2005).

    Article  PubMed  Google Scholar 

  15. Chaiken, R. L. et al. Hyperfiltration in African-American patients with type 2 diabetes. Cross-sectional and longitudinal data. Diabetes Care 21, 2129–2134 (1998).

    Article  CAS  PubMed  Google Scholar 

  16. Hjorth, L., Wiebe, T. & Karpman, D. Hyperfiltration evaluated by glomerular filtration rate at diagnosis in children with cancer. Pediatr. Blood Cancer 56, 762–766 (2011).

    Article  PubMed  Google Scholar 

  17. Huang, S. H. et al. Hyperfiltration affects accuracy of creatinine eGFR measurement. Clin. J. Am. Soc. Nephrol. 6, 274–280 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  18. Stevens, L. A., Coresh, J., Greene, T. & Levey, A. S. Assessing kidney function—measured and estimated glomerular filtration rate. N. Engl. J. Med. 354, 2473–2483 (2006).

    CAS  Google Scholar 

  19. Cadnapaphornchai, M., Briner, V. & Schrier, R. W. in Renal and Electrolyte Disorders (ed. Schrier, R. W.) 539–579 (Lippincott Williams & Wilkins, Philadelphia, 2003).

    Google Scholar 

  20. Schrier, R. W. & Ohara, M. Dilemmas in human and rat pregnancy: proposed mechanisms relating to arterial vasodilation. J. Neuroendocrinol. 22, 400–406 (2010).

    Article  CAS  PubMed  Google Scholar 

  21. Schrier, R. W. Systemic arterial vasodilation, vasopressin, and vasopressinase in pregnancy. J. Am. Soc. Nephrol. 21, 570–572 (2010).

    Article  CAS  PubMed  Google Scholar 

  22. Chapman, A. B. et al. Temporal relationships between hormonal and hemodynamic changes in early human pregnancy. Kidney Int. 54, 2056–2063 (1998).

    Article  CAS  PubMed  Google Scholar 

  23. Conrad, K. P., Jeyabalan, A., Danielson, L. A., Kerchner, L. J. & Novak, J. Role of relaxin in maternal renal vasodilation of pregnancy. Ann. NY Acad. Sci. 1041, 147–154 (2005).

    Article  CAS  PubMed  Google Scholar 

  24. Conrad, K. P. Mechanisms of renal vasodilation and hyperfiltration during pregnancy. J. Soc. Gynecol. Investig. 11, 438–448 (2004).

    Article  CAS  PubMed  Google Scholar 

  25. Cadnapaphornchai, M. A. et al. Chronic NOS inhibition reverses systemic vasodilation and glomerular hyperfiltration in pregnancy. Am. J. Physiol. Renal Physiol. 280, F592–F598 (2001).

    Article  CAS  PubMed  Google Scholar 

  26. Gumus, I. I. et al. Does glomerular hyperfiltration in pregnancy damage the kidney in women with more parities? Int. Urol. Nephrol. 41, 927–932 (2009).

    Article  PubMed  Google Scholar 

  27. Bank, N. Mechanisms of diabetic hyperfiltration. Kidney Int. 40, 792–807 (1991).

    Article  CAS  PubMed  Google Scholar 

  28. Levine, D. Z. Can rodent models of diabetic kidney disease clarify the significance of early hyperfiltration?: recognizing clinical and experimental uncertainties. Clin. Sci. (Lond.) 114, 109–118 (2008).

    Article  CAS  Google Scholar 

  29. Vora, J. P. et al. Renal hemodynamics in newly presenting non-insulin dependent diabetes mellitus. Kidney Int. 41, 829–835 (1992).

    Article  CAS  PubMed  Google Scholar 

  30. Nelson, R. G. et al. Development and progression of renal disease in Pima Indians with non-insulin-dependent diabetes mellitus. Diabetic Renal Disease Study Group. N. Engl. J. Med. 335, 1636–1642 (1996).

    Article  CAS  PubMed  Google Scholar 

  31. Keller, C. K., Bergis, K. H., Fliser, D. & Ritz, E. Renal findings in patients with short-term type 2 diabetes. J. Am. Soc. Nephrol. 7, 2627–2635 (1996).

    CAS  PubMed  Google Scholar 

  32. O'Bryan, G. T. & Hostetter, T. H. The renal hemodynamic basis of diabetic nephropathy. Semin. Nephrol. 17, 93–100 (1997).

    CAS  PubMed  Google Scholar 

  33. Zatz, R., Meyer, T. W., Rennke, H. G. & Brenner, B. M. Predominance of hemodynamic rather than metabolic factors in the pathogenesis of diabetic glomerulopathy. Proc. Natl Acad. Sci. USA 82, 5963–5967 (1985).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Hirschberg, R., Brunori, G., Kopple, J. D. & Guler, H. P. Effects of insulin-like growth factor I on renal function in normal men. Kidney Int. 43, 387–397 (1993).

    Article  CAS  PubMed  Google Scholar 

  35. Anderson, S. & Vora, J. P. Current concepts of renal hemodynamics in diabetes. J. Diabetes Complications 9, 304–307 (1995).

    Article  CAS  PubMed  Google Scholar 

  36. Sabbatini, M. et al. Early glycosylation products induce glomerular hyperfiltration in normal rats. Kidney Int. 42, 875–881 (1992).

    Article  CAS  PubMed  Google Scholar 

  37. Veelken, R. et al. Nitric oxide synthase isoforms and glomerular hyperfiltration in early diabetic nephropathy. J. Am. Soc. Nephrol. 11, 71–79 (2000).

    CAS  PubMed  Google Scholar 

  38. Kuno, Y., Iyoda, M., Shibata, T., Hirai, Y. & Akizawa, T. Sildenafil, a phosphodiesterase type 5 inhibitor, attenuates diabetic nephropathy in non-insulin-dependent Otsuka Long-Evans Tokushima Fatty rats. Br. J. Pharmacol. 162, 1389–1400 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Magee, G. M. et al. Is hyperfiltration associated with the future risk of developing diabetic nephropathy? A meta-analysis. Diabetologia 52, 691–697 (2009).

    Article  CAS  PubMed  Google Scholar 

  40. Vallon, V., Richter, K., Blantz, R. C., Thomson, S. & Osswald, H. Glomerular hyperfiltration in experimental diabetes mellitus: potential role of tubular reabsorption. J. Am. Soc. Nephrol. 10, 2569–2576 (1999).

    CAS  PubMed  Google Scholar 

  41. Thomson, S. C. et al. Ornithine decarboxylase, kidney size, and the tubular hypothesis of glomerular hyperfiltration in experimental diabetes. J. Clin. Invest. 107, 217–224 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Vervoort, G., Veldman, B., Berden, J. H., Smits, P. & Wetzels, J. F. Glomerular hyperfiltration in type 1 diabetes mellitus results from primary changes in proximal tubular sodium handling without changes in volume expansion. Eur. J. Clin. Invest. 35, 330–336 (2005).

    Article  CAS  PubMed  Google Scholar 

  43. Pruijm, M. et al. Glomerular hyperfiltration and increased proximal sodium reabsorption in subjects with type 2 diabetes or impaired fasting glucose in a population of the African region. Nephrol. Dial. Transplant. 25, 2225–2231 (2010).

    Article  CAS  PubMed  Google Scholar 

  44. Sällström, J. et al. Diabetes-induced hyperfiltration in adenosine A1-receptor deficient mice lacking the tubuloglomerular feedback mechanism. Acta Physiol. (Oxf.) 190, 253–259 (2007).

    Article  CAS  Google Scholar 

  45. Venezia, A. et al. Dietary sodium intake in a sample of adult male population in southern Italy: results of the Olivetti Heart Study. Eur. J. Clin. Nutr. 64, 518–524 (2010).

    Article  CAS  PubMed  Google Scholar 

  46. Chagnac, A. et al. Obesity-induced glomerular hyperfiltration: its involvement in the pathogenesis of tubular sodium reabsorption. Nephrol. Dial. Transplant. 23, 3946–3952 (2008).

    Article  CAS  PubMed  Google Scholar 

  47. Ficociello, L. H. et al. Renal hyperfiltration and the development of microalbuminuria in type 1 diabetes. Diabetes Care 32, 889–893 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Ecder, T., Fick-Brosnahan, G. M. & Schrier, R. W. in Diseases of the Kidney and Urinary Tract 8th edn (ed. Schrier, R. W.) 502–539 (Lippincott Williams & Wilkins, Philadelphia, 2007).

    Google Scholar 

  49. Franz, K. A. & Reubi, F. C. Rate of functional deterioration in polycystic kidney disease. Kidney Int. 23, 526–529 (1983).

    Article  CAS  PubMed  Google Scholar 

  50. Fick-Brosnahan, G. M., Belz, M. M., McFann, K. K., Johnson, A. M. & Schrier, R. W. Relationship between renal volume growth and renal function in autosomal dominant polycystic kidney disease: a longitudinal study. Am. J. Kidney Dis. 39, 1127–1134 (2002).

    Article  PubMed  Google Scholar 

  51. Grantham, J. J., Chapman, A. B. & Torres, V. E. Volume progression in autosomal dominant polycystic kidney disease: the major factor determining clinical outcomes. Clin. J. Am. Soc. Nephrol. 1, 148–157 (2006).

    Article  PubMed  Google Scholar 

  52. Meijer, E. et al. Early renal abnormalities in autosomal dominant polycystic kidney disease. Clin. J. Am. Soc. Nephrol. 5, 1091–1098 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Torres, V. E. et al. Magnetic resonance measurements of renal blood flow and disease progression in autosomal dominant polycystic kidney disease. Clin. J. Am. Soc. Nephrol. 2, 112–120 (2007).

    Article  PubMed  Google Scholar 

  54. Dimitrakov, D., Kumchev, E., Lyutakova, E. & Grigorov, L. Glomerular hyperfiltration and serum beta 2-microglobulin used as early markers in diagnosis of autosomal dominant polycystic kidney disease. Folia Med. (Plovdiv) 35, 59–62 (1993).

    CAS  Google Scholar 

  55. Wong, H., Vivian, L., Weiler, G. & Filler, G. Patients with autosomal dominant polycystic kidney disease hyperfiltrate early in their disease. Am. J. Kidney Dis. 43, 624–628 (2004).

    Article  PubMed  Google Scholar 

  56. Helal, I. et al. Glomerular hyperfiltration and renal progression in children with autosomal dominant polycystic kidney disease. Clin. J. Am. Soc. Nephrol. 6, 2439–2443 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  57. Volpe, M. et al. The renin-angiotensin system as a risk factor and therapeutic target for cardiovascular and renal disease. J. Am. Soc. Nephrol. 13 (Suppl. 3), S173–S178 (2002).

    Article  CAS  PubMed  Google Scholar 

  58. Chapman, A. B., Johnson, A., Gabow, P. A. & Schrier, R. W. The renin-angiotensin-aldosterone system and autosomal dominant polycystic kidney disease. N. Engl. J. Med. 323, 1091–1096 (1990).

    Article  CAS  PubMed  Google Scholar 

  59. Loghman-Adham, M., Soto, C. E., Inagami, T. & Cassis, S. The intrarenal renin-angiotensin system in autosomal dominant polycystic kidney disease. Am. J. Physiol. Renal Physiol. 287, F775–F788 (2004).

    Article  CAS  PubMed  Google Scholar 

  60. Schrier, R. W. Renal volume, renin-angiotensin-aldosterone system, hypertension, and left ventricular hypertrophy in patients with autosomal dominant polycystic kidney disease. J. Am. Soc. Nephrol. 20, 1888–1893 (2009).

    Article  PubMed  Google Scholar 

  61. Santin, S. et al. Clinical utility of genetic testing in children and adults with steroid-resistant nephrotic syndrome. Clin. J. Am. Soc. Nephrol. 6, 1139–1148 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  62. Ingelfinger, J. R. MYO1E, focal segmental glomerulosclerosis, and the cytoskeleton. N. Engl. J. Med. 365, 368–369 (2011).

    Article  CAS  PubMed  Google Scholar 

  63. Rennke, H. G. & Klein, P. S. Pathogenesis and significance of nonprimary focal and segmental glomerulosclerosis. Am. J. Kidney Dis. 13, 443–456 (1989).

    Article  CAS  PubMed  Google Scholar 

  64. Praga, M. et al. Absence of hypoalbuminemia despite massive proteinuria in focal segmental glomerulosclerosis secondary to hyperfiltration. Am. J. Kidney Dis. 33, 52–58 (1999).

    Article  CAS  PubMed  Google Scholar 

  65. Darouich, S. et al. Clinicopathological characteristics of obesity-associated focal segmental glomerulosclerosis. Ultrastruct. Pathol. 35, 176–182 (2011).

    Article  PubMed  Google Scholar 

  66. Kambham, N., Markowitz, G. S., Valeri, A. M., Lin, J. & D'Agati, V. D. Obesity-related glomerulopathy: an emerging epidemic. Kidney Int. 59, 1498–1509 (2001).

    Article  CAS  PubMed  Google Scholar 

  67. Chen, H. M. et al. Podocyte lesions in patients with obesity-related glomerulopathy. Am. J. Kidney Dis. 48, 772–779 (2006).

    Article  PubMed  Google Scholar 

  68. Praga, M. et al. Influence of obesity on the appearance of proteinuria and renal insufficiency after unilateral nephrectomy. Kidney Int. 58, 2111–2118 (2000).

    Article  CAS  PubMed  Google Scholar 

  69. González, E. et al. Factors influencing the progression of renal damage in patients with unilateral renal agenesis and remnant kidney. Kidney Int. 68, 263–270 (2005).

    Article  PubMed  Google Scholar 

  70. Quinn, C. T. et al. for the Thalassemia Clinical Research Network. Renal dysfunction in patients with thalassaemia. Br. J. Haematol. 153, 111–117 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Schmitt, F. et al. Early glomerular dysfunction in patients with sickle cell anemia. Am. J. Kidney Dis. 32, 208–214 (1998).

    Article  CAS  PubMed  Google Scholar 

  72. Haymann, J. P. et al. Glomerular hyperfiltration in adult sickle cell anemia: a frequent hemolysis associated feature. Clin. J. Am. Soc. Nephrol. 5, 756–761 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Arestegui, A. H. et al. High altitude renal syndrome (HARS). J. Am. Soc. Nephrol. 22, 1963–1968 (2011).

    Article  CAS  PubMed  Google Scholar 

  74. Inatomi, J., Matsuoka, K., Fujimaru, R., Nakagawa, A. & Iijima, K. Mechanisms of development and progression of cyanotic nephropathy. Pediatr. Nephrol. 21, 1440–1445 (2006).

    Article  PubMed  Google Scholar 

  75. Henegar, J. R., Bigler, S. A., Henegar, L. K., Tyagi, S. C. & Hall, J. E. Functional and structural changes in the kidney in the early stages of obesity. J. Am. Soc. Nephrol. 12, 1211–1217 (2001).

    CAS  PubMed  Google Scholar 

  76. Ribstein, J., du Cailar, G. & Mimran, A. Combined renal effects of overweight and hypertension. Hypertension 26, 610–615 (1995).

    Article  CAS  PubMed  Google Scholar 

  77. Wuerzner, G. et al. Marked association between obesity and glomerular hyperfiltration: a cross-sectional study in an African population. Am. J. Kidney Dis. 56, 303–312 (2010).

    Article  PubMed  Google Scholar 

  78. Levey, A. S. & Kramer, H. Obesity, glomerular hyperfiltration, and the surface area correction. Am. J. Kidney Dis. 56, 255–258 (2010).

    Article  PubMed  Google Scholar 

  79. Goumenos, D. S. et al. Early histological changes in the kidney of people with morbid obesity. Nephrol. Dial. Transplant. 24, 3732–3738 (2009).

    Article  PubMed  Google Scholar 

  80. Bosma, R. J., van der Heide, J. J., Oosterop, E. J., de Jong, P. E. & Navis, G. Body mass index is associated with altered renal hemodynamics in non-obese healthy subjects. Kidney Int. 65, 259–265 (2004).

    Article  PubMed  Google Scholar 

  81. Tomaszewski, M. et al. Glomerular hyperfiltration: a new marker of metabolic risk. Kidney Int. 71, 816–821 (2007).

    Article  CAS  PubMed  Google Scholar 

  82. Serpa Neto, A. et al. Effect of weight loss after Roux-en-Y gastric bypass, on renal function and blood pressure in morbidly obese patients. J. Nephrol. 22, 637–646 (2009).

    CAS  PubMed  Google Scholar 

  83. Navarro-Díaz, M. et al. Effect of drastic weight loss after bariatric surgery on renal parameters in extremely obese patients: long-term follow-up. J. Am. Soc. Nephrol. 17, S213–S217 (2006).

    Article  PubMed  Google Scholar 

  84. Kinebuchi, S. et al. Short-term use of continuous positive airway pressure ameliorates glomerular hyperfiltration in patients with obstructive sleep apnea syndrome. Clin. Sci. (Lond.) 107, 317–322 (2004).

    Article  Google Scholar 

  85. Jennette, J. C., Charles, L. & Grubb, W. Glomerulomegaly and focal segmental glomerulosclerosis associated with obesity and sleep-apnea syndrome. Am. J. Kidney Dis. 10, 470–472 (1987).

    Article  CAS  PubMed  Google Scholar 

  86. Casserly, L. F. et al. Proteinuria in obstructive sleep apnea. Kidney Int. 60, 1484–1489 (2001).

    Article  CAS  PubMed  Google Scholar 

  87. Taal, M. W. & Brenner, B. M. Renoprotective benefits of RAS inhibition: from ACEI to angiotensin II antagonists. Kidney Int. 57, 1803–1817 (2000).

    Article  CAS  PubMed  Google Scholar 

  88. Cherney, D. Z. et al. Effect of direct renin inhibition on renal hemodynamic function, arterial stiffness, and endothelial function in humans with uncomplicated type 1 diabetes: a pilot study. Diabetes Care 33, 361–365 (2010).

    Article  CAS  PubMed  Google Scholar 

  89. van der Meer, I. M., Cravedi, P. & Remuzzi, G. The role of renin angiotensin system inhibition in kidney repair. Fibrogenesis Tissue Repair 3, 7 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Lewis, E. J., Hunsicker, L. G., Bain, R. P. & Rohde, R. D. for the Collaborative Study Group. The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. N. Engl. J. Med. 329, 1456–1462 (1993).

    Article  CAS  PubMed  Google Scholar 

  91. Bakris, G. L. Angiotensin-converting enzyme inhibitors and progression of diabetic nephropathy. Ann. Intern. Med. 118, 643–644 (1993).

    Article  CAS  PubMed  Google Scholar 

  92. Brenner, B. M. et al. for the RENAAL Study Investigators. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N. Engl. J. Med. 345, 861–869 (2001).

    Article  CAS  PubMed  Google Scholar 

  93. Nobakht, N., Kamgar, M., Rastogi, A. & Schrier, R. W. Limitations of angiotensin inhibition. Nat. Rev. Nephrol. 7, 356–359 (2011).

    Article  CAS  PubMed  Google Scholar 

  94. Nordquist, L., Lai, E. Y., Sjöquist, M., Patzak, A. & Persson, A. E. Proinsulin C-peptide constricts glomerular afferent arterioles in diabetic mice. A potential renoprotective mechanism. Am. J. Physiol. Regul. Integr. Comp. Physiol. 294, R836–R841 (2008).

    Article  CAS  PubMed  Google Scholar 

  95. Pistrosch, F. et al. Rosiglitazone improves glomerular hyperfiltration, renal endothelial dysfunction, and microalbuminuria of incipient diabetic nephropathy in patients. Diabetes 54, 2206–2211 (2005).

    Article  CAS  PubMed  Google Scholar 

  96. Luippold, G., Beilharz, M. & Mühlbauer, B. Chronic renal denervation prevents glomerular hyperfiltration in diabetic rats. Nephrol. Dial. Transplant. 19, 342–347 (2004).

    Article  Google Scholar 

  97. de Paula, R. B., da Silva, A. A. & Hall, J. E. Aldosterone antagonism attenuates obesity-induced hypertension and glomerular hyperfiltration. Hypertension 43, 41–47 (2004).

    Article  CAS  PubMed  Google Scholar 

  98. Ix, J. H. & Sharma, K. Mechanisms linking obesity, chronic kidney disease, and fatty liver disease: the roles of fetuin-A, adiponectin, and AMPK. J. Am. Soc. Nephrol. 21, 406–412 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

I. Helal has received an International Society of Nephrology funded fellowship and support from the Laboratory of Kidney Pathology, Charles Nicolle Hospital, Tunis, Tunisia (LR00SP01, H. B. Maiz). This research was supported by the Zell Family Foundation.

Author information

Authors and Affiliations

  1. Division of Renal Diseases and Hypertension, University of Colorado Denver, 12700 East 19th Avenue, Campus Box C281, Aurora, 80045, CO, USA

    Imed Helal, Godela M. Fick-Brosnahan, Berenice Reed-Gitomer & Robert W. Schrier

Authors
  1. Imed Helal
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Godela M. Fick-Brosnahan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Berenice Reed-Gitomer
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Robert W. Schrier
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

I. Helal and G. M. Fick-Brosnahan researched data to include in the manuscript. All authors contributed equally to discussion of content for the article. I. Helal, G. M. Fick-Brosnahan and R. W. Schrier wrote the manuscript and G. M. Fick-Brosnahan, B. Reed-Gitomer and R. W. Schrier reviewed and edited the manuscript before submission.

Corresponding author

Correspondence to Robert W. Schrier.

Ethics declarations

Competing interests

R. W. Schrier has received honoraria from Otsuka Pharmaceutical. The other authors declare no competing interests.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Helal, I., Fick-Brosnahan, G., Reed-Gitomer, B. et al. Glomerular hyperfiltration: definitions, mechanisms and clinical implications. Nat Rev Nephrol 8, 293–300 (2012). https://doi.org/10.1038/nrneph.2012.19

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrneph.2012.19

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing