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.

  • Review Article
  • Published:

Hypertension-attributed nephropathy: what's in a name?

Nature Reviews Nephrology volume 12, pages 27–36 (2016)Cite this article

Subjects

Key Points

  • 'Hypertensive nephrosclerosis' is a non-specific clinical diagnosis applied to non-diabetic patients, often those with recent African ancestry, who present with chronic kidney disease, low-level proteinuria and elevated blood pressure

  • Poorly controlled mild-to-moderate hypertension can contribute to arteriolar nephrosclerosis, a vascular lesion in the preglomerular arterioles that leads to glomerular ischaemia

  • Non-diabetic aetiologies of end-stage renal disease (ESRD), including those typically ascribed to essential hypertension, lupus nephritis, focal segmental glomerulosclerosis or HIV-associated nephropathy, aggregate in African American families

  • Patients in such multiplex families who lack an obvious initiating cause of nephropathy are often labelled as having 'hypertensive nephrosclerosis' after a cursory evaluation

  • Genetic breakthroughs demonstrate that inherited forms of glomerulosclerosis can present in a similar fashion to arteriolar nephrosclerosis; these renal-limited disorders secondarily elevate blood pressure

  • The presence of two apolipoprotein L1 gene (APOL1) renal-risk variants is powerfully associated with approximately 70% of non-diabetic glomerulosclerosis and up to 40% of all cases of ESRD in African Americans

Abstract

Unrelated disease processes commonly occur in non-diabetic individuals with mild-to-moderate hypertension and low level or absent proteinuria who present with chronic kidney disease: primary glomerulosclerosis in those with recent African ancestry, and arteriolar nephrosclerosis with resultant glomerular ischaemia potentially related to hypertension and vascular disease risk factors in other cases. Unfortunately, nephrologists often indiscriminately apply a diagnosis of 'hypertensive nephrosclerosis' to patients in either scenario, which implies that the hypertension is causative of their renal disease. Although nephropathies that are associated with variants in the apolipoprotein L1 gene (APOL1) often cause secondarily elevated blood pressure, they belong to the spectrum of focal segmental glomerulosclerosis and are not initiated by systemic hypertension. Because genetic testing for APOL1 variants and other glomerulosclerosis-associated gene variants is available and can provide a precise definition of disease pathogenesis, we believe that the term 'hypertensive nephrosclerosis' should now be abandoned and replaced with either gene-based (for example, APOL1-associated) glomerulosclerosis or arteriolar nephrosclerosis. Precision medicine will be key to improving diagnostic accuracy in this field. Discrimination of these disparate disorders has the potential to eradicate primary forms of glomerulosclerosis that are associated with APOL1 renal-risk variants.

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

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

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

Figure 1: Schematic representation of vascular and glomerular lesions in hypertension-attributed nephropathy.
Figure 2: Histologic features of arteriolar nephrosclerosis.
Figure 3: Histologic features of APOL1-associated glomerulosclerosis.

Similar content being viewed by others

References

  1. Smith, S. R., Svetkey, L. P. & Dennis, V. W. Racial differences in the incidence and progression of renal diseases. Kidney Int. 40, 815–822 (1991).

    Article  CAS  PubMed  Google Scholar 

  2. Freedman, B. I., Iskandar, S. S. & Appel, R. G. The link between hypertension and nephrosclerosis. Am. J. Kidney Dis. 25, 207–221 (1995).

    Article  CAS  PubMed  Google Scholar 

  3. Freedman, B. I. & Murea, M. Target organ damage in African American hypertension: role of APOL1. Curr. Hypertens. Rep. 14, 21–28 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Kopp, J. B. Rethinking hypertensive kidney disease: arterionephrosclerosis as a genetic, metabolic, and inflammatory disorder. Curr. Opin. Nephrol. Hypertens. 22, 266–272 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Skorecki, K. L. & Wasser, W. G. Hypertension-misattributed kidney disease in African Americans. Kidney Int. 83, 6–9 (2013).

    Article  PubMed  Google Scholar 

  6. Meyrier, A. Nephrosclerosis: a term in quest of a disease. Nephron 129, 276–282 (2015).

    Article  CAS  PubMed  Google Scholar 

  7. Genovese, G. et al. Association of trypanolytic ApoL1 variants with kidney disease in African Americans. Science 329, 841–845 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Tzur, S. et al. Missense mutations in the APOL1 gene are highly associated with end stage kidney disease risk previously attributed to the MYH9 gene. Hum. Genet. 128, 345–350 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Freedman, B. I. et al. The apolipoprotein L1 (APOL1) gene and nondiabetic nephropathy in African Americans. J. Am. Soc. Nephrol. 21, 1422–1426 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Palmer, N. D. & Freedman, B. I. APOL1 and progression of nondiabetic nephropathy. J. Am. Soc. Nephrol. 24, 1344–1346 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Sadowski, C. E. et al. A single-gene cause in 29.5% of cases of steroid-resistant nephrotic syndrome. J. Am. Soc. Nephrol. 26, 1279–1289 (2015).

    Article  CAS  PubMed  Google Scholar 

  12. Rule, A. D. et al. The association between age and nephrosclerosis on renal biopsy among healthy adults. Ann. Intern. Med. 152, 561–567 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  13. Saran, R. et al. US Renal Data System 2014 Annual Data Report: epidemiology of kidney disease in the United States. Am. J. Kidney Dis. 66, S1–S306 (2015).

    Article  Google Scholar 

  14. Venkat-Raman, G. et al. New primary renal diagnosis codes for the ERA-EDTA. Nephrol. Dial. Transplant. 27, 4414–4419 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  15. Klag, M. J. et al. Blood pressure and end-stage renal disease in men. N. Engl. J. Med. 334, 13–18 (1996).

    Article  CAS  PubMed  Google Scholar 

  16. Castaneda, C. et al. Clinical decision support systems for improving diagnostic accuracy and achieving precision medicine. J. Clin. Bioinforma. 5, 4 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  17. Kiryluk, K. et al. Geographic differences in genetic susceptibility to IgA nephropathy: GWAS replication study and geospatial risk analysis. PLoS Genet. 8, e1002765 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Shaffer, J. R. et al. Genetic markers for ancestry are correlated with body composition traits in older African Americans. Osteoporos. Int. 18, 733–741 (2007).

    Article  CAS  PubMed  Google Scholar 

  19. Ochs-Balcom, H. M. et al. Association of DXA-derived bone mineral density and fat mass with African ancestry. J. Clin. Endocrinol. Metab. 98, E713–E717 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Powe, C. E. et al. Vitamin D-binding protein and vitamin D status of black Americans and white Americans. N. Engl. J. Med. 369, 1991–2000 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Wassel, C. L. et al. Genetic ancestry is associated with subclinical cardiovascular disease in African-Americans and Hispanics from the multi-ethnic study of atherosclerosis. Circ. Cardiovasc. Genet. 2, 629–636 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  22. Divers, J. et al. Admixture mapping of coronary artery calcified plaque in African Americans with type 2 diabetes mellitus. Circ. Cardiovasc. Genet. 6, 97–105 (2013).

    Article  CAS  PubMed  Google Scholar 

  23. Zarif, L. et al. Inaccuracy of clinical phenotyping parameters for hypertensive nephrosclerosis. Nephrol. Dial. Transplant. 15, 1801–1807 (2000).

    Article  CAS  PubMed  Google Scholar 

  24. Perneger, T. V., Whelton, P. K., Klag, M. J. & Rossiter, K. A. Diagnosis of hypertensive end-stage renal disease: effect of patient's race. Am. J. Epidemiol. 141, 10–15 (1995).

    Article  CAS  PubMed  Google Scholar 

  25. Kramer, H. J., Nguyen, Q. D., Curhan, G. & Hsu, C. Y. Renal insufficiency in the absence of albuminuria and retinopathy among adults with type 2 diabetes mellitus. JAMA 289, 3273–3277 (2003).

    Article  PubMed  Google Scholar 

  26. Mak, S. K. et al. Clinical predictors of non-diabetic renal disease in patients with non-insulin dependent diabetes mellitus. Nephrol. Dial. Transplant. 12, 2588–2591 (1997).

    Article  CAS  PubMed  Google Scholar 

  27. Freedman, B. I. et al. Differential effects of MYH9 and APOL1 risk variants on FRMD3 association with diabetic ESRD in African Americans. PLoS Genet. 7, e1002150 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Davids, M. R., Marais, N. & Jacobs, J. C. South African Renal Registry Annual Report 2012. South African Renal Society [online], (2014).

    Google Scholar 

  29. Seedat, Y. K. & Brewster, L. M. What role does African ancestry play in how hypertensive patients respond to certain antihypertensive drug therapy? Expert. Opin. Pharmacother. 15, 159–161 (2014).

    Article  CAS  PubMed  Google Scholar 

  30. Rostand, S. G., Brown, G., Kirk, K. A., Rutsky, E. A. & Dustan, H. P. Renal insufficiency in treated essential hypertension. N. Engl. J. Med. 320, 684–688 (1989).

    Article  CAS  PubMed  Google Scholar 

  31. Narvarte, J., Prive, M., Saba, S. R. & Ramirez, G. Proteinuria in hypertension. Am. J. Kidney Dis. 10, 408–416 (1987).

    Article  CAS  PubMed  Google Scholar 

  32. Mujais, S. K., Emmanouel, D. S., Kasinath, B. S. & Spargo, B. H. Marked proteinuria in hypertensive nephrosclerosis. Am. J. Nephrol. 5, 190–195 (1985).

    Article  CAS  PubMed  Google Scholar 

  33. Harvey, J. M. et al. Renal biopsy findings in hypertensive patients with proteinuria. Lancet 340, 1435–1436 (1992).

    Article  CAS  PubMed  Google Scholar 

  34. Freedman, B. I., Iskander, S. S., Buckalew, V. M. Jr, Burkart, J. M. & Appel, R. G. Renal biopsy findings in presumed hypertensive nephrosclerosis. Am. J. Nephrol. 14, 90–94 (1994).

    Article  CAS  PubMed  Google Scholar 

  35. Tracy, R. P. & Bovill, E. G. Thrombosis and cardiovascular risk in the elderly. Arch. Pathol. Lab. Med. 116, 1307–1312 (1992).

    CAS  PubMed  Google Scholar 

  36. Fogo, A. et al. Accuracy of the diagnosis of hypertensive nephrosclerosis in African Americans: a report from the African American Study of Kidney Disease (AASK) Trial. AASK Pilot Study Investigators. Kidney Int. 51, 244–252 (1997).

    Article  CAS  PubMed  Google Scholar 

  37. Harrison, D. G. et al. Inflammation, immunity, and hypertension. Hypertension 57, 132–140 (2011).

    Article  CAS  PubMed  Google Scholar 

  38. Marcantoni, C., Ma, L. J., Federspiel, C. & Fogo, A. B. Hypertensive nephrosclerosis in African Americans versus Caucasians. Kidney Int. 62, 172–180 (2002).

    Article  PubMed  Google Scholar 

  39. Larsen, C. P. et al. Histopathologic findings associated with APOL1 risk variants in chronic kidney disease. Mod. Pathol. 28, 95–102 (2014).

    Article  PubMed  Google Scholar 

  40. Hoy, W. E. et al. APOL1 risk alleles are associated with exaggerated age-related changes in glomerular number and volume in African-American adults: an autopsy study. J. Am. Soc. Nephrol. http://dx.doi.org/10.1681/ASN.2014080768 (2015).

  41. [No authors listed] The Australian therapeutic trial in mild hypertension: report by the Management Committee. Lancet 1, 1261–1267 (1980).

  42. Neaton, J. D., Kuller, L. H., Wentworth, D. & Borhani, N. O. Total and cardiovascular mortality in relation to cigarette smoking, serum cholesterol concentration, and diastolic blood pressure among black and white males followed up for five years. Am. Heart J. 108, 759–769 (1984).

    Article  CAS  PubMed  Google Scholar 

  43. Textor, S. C. & Lerman, L. Renovascular hypertension and ischemic nephropathy. Am. J. Hypertens. 23, 1159–1169 (2010).

    Article  CAS  PubMed  Google Scholar 

  44. Levey, A. S. et al. A new equation to estimate glomerular filtration rate. Ann. Intern. Med. 150, 604–612 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  45. Coresh, J., Astor, B. C., Greene, T., Eknoyan, G. & Levey, A. S. Prevalence of chronic kidney disease and decreased kidney function in the adult US population. Third National Health and Nutrition Examination Survey. Am. J. Kidney Dis. 41, 1–12 (2003).

    Article  PubMed  Google Scholar 

  46. Shulman, N. B. et al. Prognostic value of serum creatinine and effect of treatment of hypertension on renal function. Results from the hypertension detection and follow-up program. Hypertension 13, I80–I93 (1989).

    Article  CAS  PubMed  Google Scholar 

  47. Anyaegbu, E. I., Shaw, A. S., Hruska, K. A. & Jain, S. Clinical phenotype of APOL1 nephropathy in young relatives of patients with end-stage renal disease. Pediatr. Nephrol. 30, 983–989 (2015).

    Article  PubMed  Google Scholar 

  48. Ambrosius, W. T. et al. The design and rationale of a multicenter clinical trial comparing two strategies for control of systolic blood pressure: the Systolic Blood Pressure Intervention Trial (SPRINT). Clin. Trials 11, 532–546 (2014).

    Article  PubMed  Google Scholar 

  49. Wright, J. T. Jr et al. Effect of blood pressure lowering and antihypertensive drug class on progression of hypertensive kidney disease: results from the AASK trial. JAMA 288, 2421–2431 (2002).

    Article  CAS  PubMed  Google Scholar 

  50. Agodoa, L. Y. et al. Effect of ramipril vs amlodipine on renal outcomes in hypertensive nephrosclerosis: a randomized controlled trial. JAMA 285, 2719–2728 (2001).

    Article  CAS  PubMed  Google Scholar 

  51. Appel, L. J. et al. Intensive blood-pressure control in hypertensive chronic kidney disease. N. Engl. J Med 363, 918–929 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Kopp, J. B. et al. Clinical features and histology of apolipoprotein L1-associated nephropathy in the FSGS clinical trial. J. Am. Soc. Nephrol. 26, 1443–1448 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Alves, T. P. et al. Rate of ESRD exceeds mortality among African Americans with hypertensive nephrosclerosis. J. Am. Soc. Nephrol. 21, 1361–1369 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Lipkowitz, M. S. et al. Apolipoprotein L1 gene variants associate with hypertension-attributed nephropathy and the rate of kidney function decline in African Americans. Kidney Int. 83, 114–120 (2013).

    Article  CAS  PubMed  Google Scholar 

  55. Parsa, A. et al. APOL1 risk variants, race, and progression of chronic kidney disease. N. Engl. J. Med. 369, 2183–2196 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Manolio, T. A. et al. Finding the missing heritability of complex diseases. Nature 461, 747–753 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Gorski, M. et al. Genome-wide association study of kidney function decline in individuals of European descent. Kidney Int. 87, 1017–1029 (2015).

    Article  CAS  PubMed  Google Scholar 

  58. Okada, Y. et al. Meta-analysis identifies multiple loci associated with kidney function-related traits in East Asian populations. Nat. Genet. 44, 904–909 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Chasman, D. I. et al. Integration of genome-wide association studies with biological knowledge identifies six novel genes related to kidney function. Hum. Mol. Genet. 21, 5329–5343 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Pattaro, C. et al. Genome-wide association and functional follow-up reveals new loci for kidney function. PLoS Genet. 8, e1002584 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  61. Kottgen, A. et al. Multiple loci associated with indices of renal function and chronic kidney disease. Nat. Genet. 41, 712–717 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Kottgen, A. et al. New loci associated with kidney function and chronic kidney disease. Nat. Genet. 42, 376–384 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Chambers, J. C. et al. Genetic loci influencing kidney function and chronic kidney disease. Nat. Genet. 42, 373–375 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Basile, C. The long-term prognosis of acute kidney injury: acute renal failure as a cause of chronic kidney disease. J. Nephrol. 21, 657–662 (2008).

    PubMed  Google Scholar 

  65. Venkatachalam, M. A. et al. Acute kidney injury: a springboard for progression in chronic kidney disease. Am. J. Physiol. Renal Physiol. 298, F1078–F1094 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Newman, A. B. et al. Relationship between coronary artery calcification and other measures of subclinical cardiovascular disease in older adults. Arterioscler. Thromb. Vasc. Biol. 22, 1674–1679 (2002).

    Article  CAS  PubMed  Google Scholar 

  67. Bild, D. E. et al. Ethnic differences in coronary calcification: the Multi-Ethnic Study of Atherosclerosis (MESA). Circulation 111, 1313–1320 (2005).

    Article  PubMed  Google Scholar 

  68. Lee, T. C., O'Malley, P. G., Feuerstein, I. & Taylor, A. J. The prevalence and severity of coronary artery calcification on coronary artery computed tomography in black and white subjects. J. Am. Coll. Cardiol. 41, 39–44 (2003).

    Article  PubMed  Google Scholar 

  69. Freedman, B. I. et al. The impact of ethnicity and sex on subclinical cardiovascular disease: the Diabetes Heart Study. Diabetologia 48, 2511–2518 (2005).

    Article  CAS  PubMed  Google Scholar 

  70. Carnethon, M. R. et al. Racial/ethnic differences in subclinical atherosclerosis among adults with diabetes: the multiethnic study of atherosclerosis. Diabetes Care 28, 2768–2770 (2005).

    Article  PubMed  Google Scholar 

  71. Budoff, M. J. et al. Ethnic differences of the presence and severity of coronary atherosclerosis. Atherosclerosis 187, 343–350 (2006).

    Article  CAS  PubMed  Google Scholar 

  72. Keith, T. A. 3rd. Renovascular hypertension in black patients. Hypertension 4, 438–443 (1982).

    Article  PubMed  Google Scholar 

  73. Svetkey, L. P. et al. Similar prevalence of renovascular hypertension in selected blacks and whites. Hypertension 17, 678–683 (1991).

    Article  CAS  PubMed  Google Scholar 

  74. Simon, N., Franklin, S. S., Bleifer, K. H. & Maxwell, M. H. Clinical characteristics of renovascular hypertension. JAMA 220, 1209–1218 (1972).

    Article  CAS  PubMed  Google Scholar 

  75. Wheatley, K. et al. Revascularization versus medical therapy for renal-artery stenosis. N. Engl. J. Med. 361, 1953–1962 (2009).

    Article  PubMed  Google Scholar 

  76. Cooper, C. J. et al. Stenting and medical therapy for atherosclerotic renal-artery stenosis. N. Engl. J. Med. 370, 13–22 (2014).

    Article  CAS  PubMed  Google Scholar 

  77. Herrmann, S. M., Saad, A. & Textor, S. C. Management of atherosclerotic renovascular disease after Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL). Nephrol. Dial. Transplant. 30, 366–375 (2015).

    Article  CAS  PubMed  Google Scholar 

  78. Ferguson, R., Grim, C. E. & Opgenorth, T. J. A familial risk of chronic renal failure among blacks on dialysis? J. Clin. Epidemiol. 41, 1189–1196 (1988).

    Article  CAS  PubMed  Google Scholar 

  79. Freedman, B. I., Spray, B. J., Tuttle, A. B. & Buckalew, V. M. Jr. The familial risk of end-stage renal disease in African Americans. Am. J. Kidney Dis. 21, 387–393 (1993).

    Article  CAS  PubMed  Google Scholar 

  80. Freedman, B. I. et al. Familial clustering of end-stage renal disease in blacks with lupus nephritis. Am. J. Kidney Dis. 29, 729–732 (1997).

    Article  CAS  PubMed  Google Scholar 

  81. Freedman, B. I., Soucie, J. M., Stone, S. M. & Pegram, S. Familial clustering of end-stage renal disease in blacks with HIV-associated nephropathy. Am. J. Kidney Dis. 34, 254–258 (1999).

    Article  CAS  PubMed  Google Scholar 

  82. Freedman, B. I., Soucie, J. M. & McClellan, W. M. Family history of end-stage renal disease among incident dialysis patients. J. Am. Soc. Nephrol. 8, 1942–1945 (1997).

    CAS  PubMed  Google Scholar 

  83. Freedman, B. I. et al. Population-based screening for family history of end-stage renal disease among incident dialysis patients. Am. J. Nephrol. 25, 529–535 (2005).

    Article  PubMed  Google Scholar 

  84. Bergman, S., Key, B. O., Kirk, K. A., Warnock, D. G. & Rostant, S. G. Kidney disease in the first-degree relatives of African-Americans with hypertensive end-stage renal disease. Am. J. Kidney Dis. 27, 341–346 (1996).

    Article  CAS  PubMed  Google Scholar 

  85. Lei, H. H., Perneger, T. V., Klag, M. J., Whelton, P. K. & Coresh, J. Familial aggregation of renal disease in a population-based case-control study. J. Am. Soc. Nephrol. 9, 1270–1276 (1998).

    CAS  PubMed  Google Scholar 

  86. Bochud, M. et al. Heritability of renal function in hypertensive families of African descent in the Seychelles (Indian Ocean). Kidney Int. 67, 61–69 (2005).

    Article  PubMed  Google Scholar 

  87. Kopp, J. B. et al. APOL1 genetic variants in focal segmental glomerulosclerosis and HIV-associated nephropathy. J. Am. Soc. Nephrol. 22, 2129–2137 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Freedman, B. I. et al. End-stage renal disease in African Americans with lupus nephritis is associated with APOL1. Arthritis Rheumatol. 66, 390–396 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Kruzel-Davila, E., Wasser, W. G., Aviram, S. & Skorecki, K. APOL1 nephropathy: from gene to mechanisms of kidney injury. Nephrol. Dial. Transplant. http://dx.doi.org/10.1093/ndt/gfu391.

  90. Freedman, B. I. Renal microvascular susceptibility in African American pedigrees. Transplant Proc. 25, 2423–2425 (1993).

    CAS  PubMed  Google Scholar 

  91. Freedman, B. I. End-stage renal failure in African Americans: insights in kidney disease susceptibility. Nephrol. Dial. Transplant. 17, 198–200 (2002).

    Article  PubMed  Google Scholar 

  92. Scavini, M. et al. Kidney disease among the Zuni Indians: the Zuni Kidney Project. Kidney Int. 68, S126–S131 (2005).

    Article  Google Scholar 

  93. Hughson, M. D. et al. Mesangiopathic glomerulonephritis in Zuni (New Mexico) Indians. Arch. Pathol. Lab. Med. 113, 148–157 (1989).

    CAS  PubMed  Google Scholar 

  94. Qualheim, R. E., Rostand, S. G., Kirk, K. A., Rutsky, E. A. & Luke, R. G. Changing patterns of end-stage renal disease due to hypertension. Am. J. Kidney Dis. 18, 336–343 (1991).

    Article  CAS  PubMed  Google Scholar 

  95. Oliverio, M. I. et al. Reduced growth, abnormal kidney structure, and type 2 (AT2) angiotensin receptor-mediated blood pressure regulation in mice lacking both AT1A and AT1B receptors for angiotensin II. Proc. Natl Acad. Sci. USA 95, 15496–15501 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Freedman, B. I. & Skorecki, K. Gene–gene and gene–environment interactions in apolipoprotein L1 gene-associated nephropathy. Clin. J. Am. Soc. Nephrol. 9, 2006–2013 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Rosenberg, A. Z., Naicker, S., Winkler, C. A. & Kopp, J. B. HIV-associated nephropathies: epidemiology, pathology, mechanisms and treatment. Nat. Rev. Nephrol. 11, 150–160 (2015).

    Article  CAS  PubMed  Google Scholar 

  98. Ross, M. J. Advances in the pathogenesis of HIV-associated kidney diseases. Kidney Int. 86, 266–274 (2014).

    Article  CAS  PubMed  Google Scholar 

  99. Kasembeli, A. N. et al. APOL1 risk variants are strongly associated with HIV-associated nephropathy in black South Africans. J. Am. Soc. Nephrol. http://dx.doi.org/10.1681/ASN.2014050469.

  100. Jotwani, V. et al. APOL1 genotype and glomerular and tubular kidney injury in women with HIV. Am. J. Kidney Dis. 65, 889–898 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Estrella, M. M. et al. The association between APOL1 risk alleles and longitudinal kidney function differs by HIV viral suppression status. Clin. Infect. Dis. 60, 646–652 (2015).

    Article  CAS  PubMed  Google Scholar 

  102. Madhavan, S. M. et al. APOL1 localization in normal kidney and nondiabetic kidney disease. J. Am. Soc. Nephrol. 22, 2119–2128 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Ma, L. et al. Localization of APOL1 protein and mRNA in the human kidney: nondiseased tissue, primary cells, and immortalized cell lines. J. Am. Soc. Nephrol. 26, 339–348 (2015).

    Article  CAS  PubMed  Google Scholar 

  104. Bruggeman, L. A. et al. Plasma apolipoprotein L1 levels do not correlate with CKD. J. Am. Soc. Nephrol. 25, 634–644 (2014).

    Article  CAS  PubMed  Google Scholar 

  105. Reeves-Daniel, A. M. et al. The APOL1 gene and allograft survival after kidney transplantation. Am. J. Transplant. 11, 1025–1030 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Freedman, B. I. et al. Apolipoprotein L1 gene variants in deceased organ donors are associated with renal allograft failure. Am. J. Transplant. 15, 1615–1622 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Lee, B. T. et al. The APOL1 genotype of African American kidney transplant recipients does not impact 5-year allograft survival. Am. J. Transplant. 12, 1924–1928 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Nichols, B. et al. Innate immunity pathways regulate the nephropathy gene apolipoprotein L1. Kidney Int. 87, 332–342 (2015).

    Article  CAS  PubMed  Google Scholar 

  109. Genovese, G., Friedman, D. J. & Pollak, M. R. APOL1 variants and kidney disease in people of recent African ancestry. Nat. Rev. Nephrol. 9, 240–244 (2013).

    Article  CAS  PubMed  Google Scholar 

  110. Heneghan, J. F. et al. BH3 domain-independent apolipoprotein L1 toxicity rescued by BCL2 prosurvival proteins. Am. J. Physiol. Cell Physiol. 309, C332–C347 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Cheng, D. et al. Biogenesis and cytotoxicity of APOL1 renal risk variant proteins in hepatocytes and hepatoma cells. J. Lipid Res. 56, 1583–1593 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Khatua, A. K. et al. Exon 4-encoded sequence is a major determinant of cytotoxicity of apolipoprotein L1. Am. J. Physiol. Cell Physiol. 309, C22–C37 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Anderson, B. R. et al. In vivo modeling implicates APOL1 in nephropathy: evidence for dominant negative effects and epistasis under anemic stress. PLoS Genet. 11, e1005349 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Sampson, M. G. et al. Integrative genomics identifies novel associations with APOL1 risk genotypes in black NEPTUNE subjects. J. Am. Soc. Nephrol. http://dx.doi.org/10.1681/ASN.2014111131.

Download references

Acknowledgements

The authors thank Dr Todd W. Robinson, Wake Forest School of Medicine, NC, USA, for his expert review of this manuscript before submission. The authors' work described in this Review was supported by grants from the NIH (R01 DK070941, R01 DK084149 and R01 HL56266).

Author information

Authors and Affiliations

  1. Department of Internal Medicine, Section on Nephrology, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, 27157–1053, NC, USA

    Barry I. Freedman

  2. Department of Pathology, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, 27157–1053, NC, USA

    Arthur H. Cohen

Authors
  1. Barry I. Freedman
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Arthur H. Cohen
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

B.I.F. and A.H.C. contributed equally to researching the data, writing the article and reviewing and/or editing of the manuscript before submission.

Corresponding author

Correspondence to Barry I. Freedman.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

PowerPoint slides

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Freedman, B., Cohen, A. Hypertension-attributed nephropathy: what's in a name?. Nat Rev Nephrol 12, 27–36 (2016). https://doi.org/10.1038/nrneph.2015.172

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrneph.2015.172

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