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Assessment of nephron number and single-nephron glomerular filtration rate in a clinical setting

Abstract

Total nephron counts vary widely between individuals and may affect susceptibility to certain diseases, including hypertension and chronic kidney disease. Detailed analyses of whole kidneys collected from autopsy patients remain the only method for accurately counting nephrons in humans, with no equivalent option in living subjects. Current technological advances have enabled estimations of nephron numbers in vivo, particularly the use of total nephron number and whole-kidney glomerular filtration rate to estimate the mean single-nephron glomerular filtration rate. The use of this method would allow physicians to detect dynamic changes in filtration function at the single-nephron level rather than to simply count the number of nephrons that appear to be functioning. Currently available methods for estimating total nephron number in clinical practice have the potential to overcome limitations associated with autopsy analyses and may therefore pave the way for new therapeutic interventions and improved clinical outcomes.

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References

  1. 1.

    Hoy WE, Rees M, Kile E, Mathews JD, McCredie DA, Pugsley DJ, et al. Low birthweight and renal disease in Australian aborigines. Lancet. 1998;352:1826–7.

    CAS  PubMed  Article  Google Scholar 

  2. 2.

    Lackland DT, Bendall HE, Osmond C, Egan BM, Barker DJ. Low birth weights contribute to high rates of early-onset chronic renal failure in the Southeastern United States. Arch Intern Med. 2000;22, 160:1472–6.

    Article  Google Scholar 

  3. 3.

    White SL, Perkovic V, Cass A, Chang CL, Poulter NR, Spector T, et al. Is low birth weight an antecedent of CKD in later life? A systematic review of observational studies. Am J Kidney Dis. 2009;54:248–61.

    PubMed  Article  Google Scholar 

  4. 4.

    Nyengaard JR. Stereologic methods and their application in kidney research. J Am Soc Nephrol. 1999;10:1100–23.

    CAS  PubMed  Article  Google Scholar 

  5. 5.

    Bertram JF. Counting in the kidney. Kidney Int. 2001;59:792–6.

    CAS  PubMed  Article  Google Scholar 

  6. 6.

    Cullen-McEwen LA, Douglas-Denton RN, Bertram JF. Estimating total nephron number in the adult kidney using the physical disector/fractionator combination. Methods Mol Biol. 2012;886:333–50.

    CAS  PubMed  Article  Google Scholar 

  7. 7.

    Fogo A, Hawkins EP, Berry PL, Glick AD, Chiang ML, MacDonell RC Jr, et al. Glomerular hypertrophy in minimal change disease predicts subsequent progression to focal glomerular sclerosis. Kidney Int. 1990;38:115–23.

    CAS  PubMed  Article  Google Scholar 

  8. 8.

    Tóth T, Takebayashi S. Glomerular hypertrophy as a prognostic marker in childhood IgA nephropathy. Nephron. 1998;80:285–91.

    PubMed  Article  Google Scholar 

  9. 9.

    Lemley KV, Lafayette RA, Derby G, Blouch KL, Anderson L, Efron B, et al. Prediction of early progression in recently diagnosed IgA nephropathy. Nephrol Dial Transpl. 2008;23:213–22.

    CAS  Article  Google Scholar 

  10. 10.

    Hodgin JB, Rasoulpour M, Markowitz GS, D’Agati VD. Very low birth weight is a risk factor for secondary focal segmental glomerulosclerosis. Clin J Am Soc Nephrol. 2009;4:71–6.

    PubMed  PubMed Central  Article  Google Scholar 

  11. 11.

    Kataoka H, Ohara M, Honda K, Mochizuki T, Nitta K. Maximal glomerular diameter as a 10-year prognostic indicator for IgA nephropathy. Nephrol Dial Transpl. 2011;26:3937–43.

    Article  Google Scholar 

  12. 12.

    Tsuboi N, Kanzaki G, Koike K, Kawamura T, Ogura M, Yokoo T. Clinicopathological assessment of the nephron number. Clin Kidney J. 2014;7:107–14.

    PubMed  PubMed Central  Article  Google Scholar 

  13. 13.

    Hoy WE, Samuel T, Mott SA, Kincaid-Smith PS, Fogo AB, Dowling JP, et al. Renal biopsy findings among Indigenous Australians: a nationwide review. Kidney Int. 2012;82:1321–31.

    PubMed  Article  Google Scholar 

  14. 14.

    Tsuboi N, Utsunomiya Y, Koike K, Kanzaki G, Hirano K, Okonogi H, et al. Factors related to the glomerular size in renal biopsies of chronic kidney disease patients. Clin Nephrol. 2013;79:277–84.

    PubMed  Article  Google Scholar 

  15. 15.

    Zidar N, Cör A, Premru Srsen T, Stajer D. Is there an association between glomerular density and birth weight in healthy humans. Nephron. 1998;80:97–8.

    CAS  PubMed  Article  Google Scholar 

  16. 16.

    Mañalich R, Reyes L, Herrera M, Melendi C, Fundora I. Relationship between weight at birth and the number and size of renal glomeruli in humans: a histomorphometric study. Kidney Int. 2000;58:770–3.

    PubMed  Article  Google Scholar 

  17. 17.

    Rule AD, Semret MH, Amer H, Cornell LD, Taler SJ, Lieske JC, et al. Association of kidney function and metabolic risk factors with density of glomeruli on renal biopsy samples from living donors. Mayo Clin Proc. 2011;86:282–90.

    PubMed  PubMed Central  Article  Google Scholar 

  18. 18.

    Tsuboi N, Kawamura T, Ishii T, Utsunomiya Y, Hosoya T. Changes in the glomerular density and size in serial renal biopsies during the progression of IgA nephropathy. Nephrol Dial Transpl. 2009;24:892–9.

    Article  Google Scholar 

  19. 19.

    Tsuboi N, Kawamura T, Koike K, Okonogi H, Hirano K, Hamaguchi A, et al. Glomerular density in renal biopsy specimens predicts the long-term prognosis of IgA nephropathy. Clin J Am Soc Nephrol. 2010;5:39–44.

    PubMed  PubMed Central  Article  Google Scholar 

  20. 20.

    Tsuboi N, Kawamura T, Miyazaki Y, Utsunomiya Y, Hosoya T. Low glomerular density is a risk factor for progression in idiopathic membranous nephropathy. Nephrol Dial Transpl. 2011;26:3555–60.

    Article  Google Scholar 

  21. 21.

    Koike K, Tsuboi N, Utsunomiya Y, Kawamura T, Hosoya T. Glomerular density-associated changes in clinicopathological features of minimal change nephrotic syndrome in adults. Am J Nephrol. 2011;34:542–8.

    PubMed  Article  Google Scholar 

  22. 22.

    Tsuboi N, Utsunomiya Y, Kanzaki G, Koike K, Ikegami M, Kawamura T, et al. Low glomerular density with glomerulomegaly in obesity-related glomerulopathy. Clin J Am Soc Nephrol. 2012;7:735–41.

    PubMed  Article  Google Scholar 

  23. 23.

    Kanzaki G, Tsuboi N, Utsunomiya Y, Ikegami M, Shimizu A, Hosoya T. Distribution of glomerular density in different cortical zones of the human kidney. Pathol Int. 2013;63:169–75.

    PubMed  Article  Google Scholar 

  24. 24.

    Haruhara K, Tsuboi N, Kanzaki G, Koike K, Suyama M, Shimizu A, et al. Glomerular density in biopsy-proven hypertensive nephrosclerosis. Am J Hypertens. 2015;28:1164–71.

    CAS  PubMed  Article  Google Scholar 

  25. 25.

    Koike K, Ikezumi Y, Tsuboi N, Kanzaki G, Haruhara K, Okabayashi Y, et al. Glomerular density and volume in renal biopsy specimens of children with proteinuria relative to preterm birth and gestational age. Clin J Am Soc Nephrol. 2017;12:585–90.

    PubMed  PubMed Central  Article  Google Scholar 

  26. 26.

    Hostetter TH, Olson JL, Rennke HG, Venkatachalam MA, Brenner BM. Hyperfiltration in remnant nephrons: a potentially adverse response to renal ablation. Am J Physiol. 1981;241:F85–93.

    CAS  PubMed  Google Scholar 

  27. 27.

    Brenner BM. Nephron adaptation to renal injury or ablation. Am J Physiol. 1985;249:F324–37.

    CAS  PubMed  Google Scholar 

  28. 28.

    Brenner BM, Lawler EV, Mackenzie HS. The hyperfiltration theory: a paradigm shift in nephrology. Kidney Int. 1996;49:1774–7.

    CAS  PubMed  Article  Google Scholar 

  29. 29.

    Luyckx VA, Brenner BM. The clinical importance of nephron mass. J Am Soc Nephrol. 2010;21:898–910.

    PubMed  Article  Google Scholar 

  30. 30.

    Fattah H, Layton A, Vallon V. How do kidneys adapt to a deficit or loss in nephron number? Physiology. 2019;34:189–97.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  31. 31.

    Denic A, Lieske JC, Chakkera HA, Poggio ED, Alexander MP, Singh P, et al. The substantial loss of nephrons in healthy human kidneys with aging. J Am Soc Nephrol. 2017;28:313–20.

    PubMed  Article  Google Scholar 

  32. 32.

    Denic A, Mathew J, Lerman LO, Lieske JC, Larson JJ, Alexander MP, et al. Single-nephron glomerular filtration rate in healthy adults. N. Engl J Med. 2017;376:2349–57.

    PubMed  PubMed Central  Article  Google Scholar 

  33. 33.

    Denic A, Elsherbiny H, Rule AD. In-vivo techniques for determining nephron number. Curr Opin Nephrol Hypertens. 2019;28:545–51.

    PubMed  PubMed Central  Article  Google Scholar 

  34. 34.

    Nyengaard JR, Bendtsen TF. Glomerular number and size in relation to age, kidney weight, and body surface in normal man. Anat Rec. 1992;232:194–201.

    CAS  PubMed  Article  Google Scholar 

  35. 35.

    Hughson M, Farris AB 3rd, Douglas-Denton R, Hoy WE, Bertram JF. Glomerular number and size in autopsy kidneys: the relationship to birth weight. Kidney Int. 2003;63:2113–22.

    PubMed  Article  Google Scholar 

  36. 36.

    Keller G, Zimmer G, Mall G, Ritz E, Amann K. Nephron number in patients with primary hypertension. N. Engl J Med. 2003;348:101–8.

    PubMed  Article  Google Scholar 

  37. 37.

    Hughson MD, Douglas-Denton R, Bertram JF, Hoy WE. Hypertension, glomerular number, and birth weight in African Americans and white subjects in the southeastern United States. Kidney Int. 2006;69:671–8.

    CAS  PubMed  Article  Google Scholar 

  38. 38.

    Hoy WE, Hughson MD, Singh GR, Douglas-Denton R, Bertram JF. Reduced nephron number and glomerulomegaly in Australian Aborigines: a group at high risk for renal disease and hypertension. Kidney Int. 2006;70:104–10.

    CAS  PubMed  Article  Google Scholar 

  39. 39.

    McNamara BJ, Diouf B, Hughson MD, Douglas-Denton RN, Hoy WE, Bertram JF. Renal pathology, glomerular number and volume in a West African urban community. Nephrol Dial Transpl. 2008;23:2576–85.

    Article  Google Scholar 

  40. 40.

    Hughson MD, Gobe GC, Hoy WE, Manning RD Jr, Douglas-Denton R, Bertram JF. Associations of glomerular number and birth weight with clinicopathological features of African Americans and whites. Am J Kidney Dis. 2008;52:18–28.

    PubMed  Article  Google Scholar 

  41. 41.

    Hoy WE, Bertram JF, Denton RD, Zimanyi M, Samuel T, Hughson MD. Nephron number, glomerular volume, renal disease and hypertension. Curr Opin Nephrol Hypertens. 2008;17:258–65.

    PubMed  Article  Google Scholar 

  42. 42.

    Hughson MD, Puelles VG, Hoy WE, Douglas-Denton RN, Mott SA, Bertram JF. Hypertension, glomerular hypertrophy and nephrosclerosis: the effect of race. Nephrol Dial Transpl. 2014;29:1399–409.

    Article  Google Scholar 

  43. 43.

    Kanzaki G, Puelles VG, Cullen-McEwen LA, Hoy WE, Okabayashi Y, Tsuboi N, et al. New insights on glomerular hyperfiltration: a Japanese autopsy study. JCI Insight. 2017;2:e94334.

    PubMed Central  Article  PubMed  Google Scholar 

  44. 44.

    Kanzaki G, Tsuboi N, Shimizu A, Yokoo T. Human nephron number, hypertension, and renal pathology. Anat Rec (Hoboken). 2020;303:2537–43.

    CAS  Article  Google Scholar 

  45. 45.

    Gasser B, Mauss Y, Ghnassia JP, Favre R, Kohler M, Yu O, et al. A quantitative study of normal nephrogenesis in the human fetus: its implication in the natural history of kidney changes due to low obstructive uropathies. Fetal Diagn Ther. 1993;8:371–84.

    CAS  PubMed  Article  Google Scholar 

  46. 46.

    Hinchliffe SA, Sargent PH, Howard CV, Chan YF, van Velzen D. Human intrauterine renal growth expressed in absolute number of glomeruli assessed by the disector method and Cavalieri principle. Lab Invest. 1991;64:777–84.

    CAS  PubMed  Google Scholar 

  47. 47.

    Sutherland MR, Gubhaju L, Moore L, Kent AL, Dahlstrom JE, Horne RS, et al. Accelerated maturation and abnormal morphology in the preterm neonatal kidney. J Am Soc Nephrol. 2011;22:1365–74.

    PubMed  PubMed Central  Article  Google Scholar 

  48. 48.

    Schreuder MF, Nyengaard JR, Remmers F, van Wijk JA. Delemarre-van de Waal HA. Postnatal food restriction in the rat as a model for a low nephron endowment. Am J Physiol Ren Physiol. 2006;291:F1104–7.

    CAS  Article  Google Scholar 

  49. 49.

    Wlodek ME, Westcott K, Siebel AL, Owens JA, Moritz KM. Growth restriction before or after birth reduces nephron number and increases blood pressure in male rats. Kidney Int. 2008;74:187–95.

    PubMed  Article  Google Scholar 

  50. 50.

    Gubhaju L, Sutherland MR, Yoder BA, Zulli A, Bertram JF, Black MJ. Is nephrogenesis affected by preterm birth? Studies in a non-human primate model. Am J Physiol Ren Physiol. 2009;297:F1668–77.

    CAS  Article  Google Scholar 

  51. 51.

    Sutherland MR, Gubhaju L, Black MJ. Stereological assessment of renal development in a baboon model of preterm birth. Am J Nephrol. 2011;33:25–33.

    PubMed  Article  Google Scholar 

  52. 52.

    Benz K, Amann K. Maternal nutrition, low nephron number and arterial hypertension in later life. Biochim Biophys Acta. 2010;1802:1309–17.

    CAS  PubMed  Article  Google Scholar 

  53. 53.

    Langley-Evans SC, Langley-Evans AJ, Marchand MC. Nutritional programming of blood pressure and renal morphology. Arch Physiol Biochem. 2003;111:8–16.

    CAS  PubMed  Article  Google Scholar 

  54. 54.

    Regina S, Lucas R, Miraglia SM, Zaladek Gil F, Machado, Coimbra T. Intrauterine food restriction as a determinant of nephrosclerosis. Am J Kidney Dis. 2001;37:467–76.

    CAS  PubMed  Article  Google Scholar 

  55. 55.

    Woods LL, Weeks DA, Rasch R. Programming of adult blood pressure by maternal protein restriction: role of nephrogenesis. Kidney Int. 2004;65:1339–48.

    PubMed  Article  Google Scholar 

  56. 56.

    Almeida JR, Mandarim-de-Lacerda CA. Maternal gestational protein-calorie restriction decreases the number of glomeruli and causes glomerular hypertrophy in adult hypertensive rats. Am J Obstet Gynecol. 2005;192:945–51.

    PubMed  Article  Google Scholar 

  57. 57.

    Gilbert JS, Lang AL, Grant AR, Nijland MJ. Maternal nutrient restriction in sheep: hypertension and decreased nephron number in offspring at 9 months of age. J Physiol. 2005;15, 565:137–47.

    Article  CAS  Google Scholar 

  58. 58.

    Bhat PV, Manolescu DC. Role of vitamin A in determining nephron mass and possible relationship to hypertension. J Nutr. 2008;138:1407–10.

    CAS  PubMed  Article  Google Scholar 

  59. 59.

    Merlet-Bénichou C, Vilar J, Lelièvre-Pégorier M, Gilbert T. Role of retinoids in renal development: pathophysiological implication. Curr Opin Nephrol Hypertens. 1999;8:39–43.

    PubMed  Article  Google Scholar 

  60. 60.

    Maka N, Makrakis J, Parkington HC, Tare M, Morley R, Black MJ. Vitamin D deficiency during pregnancy and lactation stimulates nephrogenesis in rat offspring. Pediatr Nephrol. 2008;23:55–61.

    PubMed  Article  Google Scholar 

  61. 61.

    Koleganova N, Piecha G, Ritz E, Becker LE, Müller A, Weckbach M, et al. Both high and low maternal salt intake in pregnancy alter kidney development in the offspring. Am J Physiol Ren Physiol. 2011;301:F344–54.

    CAS  Article  Google Scholar 

  62. 62.

    Drake KA, Sauerbry MJ, Blohowiak SE, Repyak KS, Kling PJ. Iron deficiency and renal development in the newborn rat. Pediatr Res. 2009;66:619–24.

    CAS  PubMed  Article  Google Scholar 

  63. 63.

    Tomat AL, Inserra F, Veiras L, Vallone MC, Balaszczuk AM, Costa MA, et al. Moderate zinc restriction during fetal and postnatal growth of rats: effects on adult arterial blood pressure and kidney. Am J Physiol Regul Integr Comp Physiol. 2008;295:R543–9.

    CAS  PubMed  Article  Google Scholar 

  64. 64.

    Davis EM, Peck JD, Thompson D, Wild RA, Langlois P. Maternal diabetes and renal agenesis/dysgenesis. Birth Defects Res A Clin Mol Teratol. 2010;88:722–7.

    CAS  PubMed  Article  Google Scholar 

  65. 65.

    Tran S, Chen YW, Chenier I, Chan JS, Quaggin S, Hébert MJ, et al. Maternal diabetes modulates renal morphogenesis in offspring. J Am Soc Nephrol. 2008;19:943–52.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  66. 66.

    Gray SP, Kenna K, Bertram JF, et al. Repeated ethanol exposure during late gestation decreases nephron endowment in fetal sheep. Am J Physiol Regul Integr Comp Physiol. 2008;295:R568–74.

    CAS  PubMed  Article  Google Scholar 

  67. 67.

    Schreuder MF, Bueters RR, Huigen MC, Russel FG, Masereeuw R, van den Heuvel LP. Effect of drugs on renal development. Clin J Am Soc Nephrol. 2011;6:212–7.

    CAS  PubMed  Article  Google Scholar 

  68. 68.

    Singh RR, Cullen-McEwen LA, Kett MM, Boon WM, Dowling J, Bertram JF, et al. Prenatal corticosterone exposure results in altered AT1/AT2, nephron deficit and hypertension in the rat offspring. J Physiol. 2007;579:503–13.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  69. 69.

    Collins JW, Rankin KM, David RJ. Low birth weight across generations: the effect of economic environment. Matern Child Health J. 2011;15:438–45.

    PubMed  Article  Google Scholar 

  70. 70.

    Zhang Z, Quinlan J, Hoy W, Hughson MD, Lemire M, Hudson T, et al. A common RET variant is associated with reduced newborn kidney size and function. J Am Soc Nephrol. 2008;19:2027–34.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  71. 71.

    Quinlan J, Lemire M, Hudson T, Qu H, Benjamin A, Roy A, et al. A common variant of the PAX2 gene is associated with reduced newborn kidney size. J Am Soc Nephrol. 2007;18:1915–21.

    CAS  PubMed  Article  Google Scholar 

  72. 72.

    Barker DJ, Osmond C. Infant mortality, childhood nutrition, and ischaemic heart disease in England and Wales. Lancet. 1986;10, 1:1077–81.

    Article  Google Scholar 

  73. 73.

    Barker DJ, Osmond C, Golding J, Kuh D, Wadsworth ME. Growth in utero, blood pressure in childhood and adult life, and mortality from cardiovascular disease. BMJ. 1989;298:564–7.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  74. 74.

    Barker DJ. Adult consequences of fetal growth restriction. Clin Obstet Gynecol. 2006;49:270–83.

    PubMed  Article  Google Scholar 

  75. 75.

    Schreuder MF, Nauta J. Prenatal programming of nephron number and blood pressure. Kidney Int. 2007;72:265–8.

    CAS  PubMed  Article  Google Scholar 

  76. 76.

    Baum M. Role of the kidney in the prenatal and early postnatal programming of hypertension. Am J Physiol Ren Physiol. 2010;298:F235–47.

    CAS  Article  Google Scholar 

  77. 77.

    Ritz E, Amann K, Koleganova N, Benz K. Prenatal programming-effects on blood pressure and renal function. Nat Rev Nephrol. 2011;7:137–44.

    PubMed  Article  Google Scholar 

  78. 78.

    Abitbol CL, Rodriguez MM. The long-term renal and cardiovascular consequences of prematurity. Nat Rev Nephrol. 2012;8:265–74.

    CAS  PubMed  Article  Google Scholar 

  79. 79.

    Zandi-Nejad K, Luyckx VA, Brenner BM. Adult hypertension and kidney disease: the role of fetal programming. Hypertension. 2006;47:502–8.

    CAS  PubMed  Article  Google Scholar 

  80. 80.

    Blencowe H, Krasevec J, de Onis M, Black RE, An X, Stevens GA, et al. National, regional, and worldwide estimates of low birthweight in 2015, with trends from 2000: a systematic analysis. Lancet Glob Health. 2019;7:e849–60.

    PubMed  PubMed Central  Article  Google Scholar 

  81. 81.

    Ohmi H, Hirooka K, Hata A, Mochizuki Y. Recent trend of increase in proportion of low birthweight infants in Japan. Int J Epidemiol. 2001;30:1269–71.

    CAS  PubMed  Article  Google Scholar 

  82. 82.

    Luyckx VA, Bertram JF, Brenner BM, Fall C, Hoy WE, Ozanne SE, et al. Effect of fetal and child health on kidney development and long-term risk of hypertension and kidney disease. Lancet. 2013;382:273–83.

    PubMed  Article  Google Scholar 

  83. 83.

    McLachlan MS, Guthrie JC, Anderson CK, Fulker MJ. Vascular and glomerular changes in the ageing kidney. J Pathol. 1977;121:65–78.

    CAS  PubMed  Article  Google Scholar 

  84. 84.

    Rule AD, Amer H, Cornell LD, Taler SJ, Cosio FG, Kremers WK, et al. The association between age and nephrosclerosis on renal biopsy among healthy adults. Ann Intern Med. 2010;152:561–7.

    PubMed  PubMed Central  Article  Google Scholar 

  85. 85.

    Hommos MS, Glassock RJ, Rule AD. Structural and functional changes in human kidneys with healthy aging. J Am Soc Nephrol. 2017;28:2838–44.

    PubMed  PubMed Central  Article  Google Scholar 

  86. 86.

    Holscher CM, Haugen CE, Jackson KR, Garonzik Wang JM, Waldram MM, Bae S, et al. Self-reported incident hypertension and long-term kidney function in living kidney donors compared with healthy nondonors. Clin J Am Soc Nephrol. 2019;14:1493–9.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  87. 87.

    Carney EF. Glomerular filtration rate: CKD risk factors are associated with increased single-nephron GFR. Nat Rev Nephrol. 2017;13:443.

    PubMed  Article  Google Scholar 

  88. 88.

    Steiner RW. Increased single-nephron GFR in normal adults: too much of a good thing or maybe not? Am J Kidney Dis. 2018;71:312–4.

    PubMed  Article  Google Scholar 

  89. 89.

    Tonneijck L, Muskiet MH, Smits MM, van Bommel EJ, Heerspink HJ, van Raalte DH, et al. Glomerular hyperfiltration in diabetes: mechanisms, clinical significance, and treatment. J Am Soc Nephrol. 2017;28:1023–39.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  90. 90.

    Rosenberg AZ, Kopp JB. Focal segmental glomerulosclerosis. Clin J Am Soc Nephrol. 2017;12:502–17.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  91. 91.

    Melsom T, Stefansson V, Schei J, Solbu M, Jenssen T, Wilsgaard T, et al. Association of increasing GFR with change in albuminuria in the general population. Clin J Am Soc Nephrol. 2016;11:2186–94.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  92. 92.

    Ronco C, Rosner MH. Acute kidney injury and residual renal function. Crit Care. 2012;16:144.

    PubMed  PubMed Central  Article  Google Scholar 

  93. 93.

    Chawla LS, Ronco C. Renal stress testing in the assessment of kidney disease. Kidney Int Rep. 2016;1:57–63.

    PubMed  PubMed Central  Article  Google Scholar 

  94. 94.

    Wright FS, Giebisch G. Glomerular filtration in single nephrons. Kidney Int. 1972;1:201–9.

    CAS  PubMed  Article  Google Scholar 

  95. 95.

    Jamison RL. Micropuncture study of superficial and juxtamedullary nephrons in the rat. Am J Physiol. 1970;218:46–55.

    CAS  PubMed  Article  Google Scholar 

  96. 96.

    Shimamura T, Morrison AB. A progressive glomerulosclerosis occurring in partial five-sixths nephrectomized rats. Am J Pathol. 1975;79:95–106.

    CAS  PubMed  PubMed Central  Google Scholar 

  97. 97.

    Anderson S, Meyer TW, Rennke HG, Brenner BM. Control of glomerular hypertension limits glomerular injury in rats with reduced renal mass. J Clin Investig. 1985;76:612–9.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  98. 98.

    Anderson S, Rennke HG, Brenner BM. Therapeutic advantage of converting enzyme inhibitors in arresting progressive renal disease associated with systemic hypertension in the rat. J Clin Investig. 1986;77:1993–2000.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  99. 99.

    Blantz RC, Konnen KS, Tucker BJ. Angiotensin II effects upon the glomerular microcirculation and ultrafiltration coefficient of the rat. J Clin Investig. 1976;57:419–34.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  100. 100.

    Ichikawa I, Brenner BM. Importance of efferent arteriolar vascular tone in regulation of proximal tubule fluid reabsorption and glomerulotubular balance in the rat. J Clin Investig. 1980;65:1192–201.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  101. 101.

    Brenner BM, Bennett CM, Berliner RW. The relationship between glomerular filtration rate and sodium reabsorption by the proximal tubule of the rat nephron. J Clin Investig. 1968;47:1358–74.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  102. 102.

    Thomson SC, Deng A, Wead L, Richter K, Blantz RC, Vallon V. An unexpected role for angiotensin II in the link between dietary salt and proximal reabsorption. J Clin Investig. 2006;116:1110–6.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  103. 103.

    Thomson SC, Vallon V, Blantz RC. Resetting protects efficiency of tubuloglomerular feedback. Kidney Int Suppl. 1998;67:S65–S70.

    CAS  PubMed  Article  Google Scholar 

  104. 104.

    Blantz RC, Gabbai FB, Peterson OW, Thomson SC. Tubuloglomerular feedback activity after acute reductions in renal mass. Kidney Int Suppl. 1991;32:S102–5.

    CAS  PubMed  Google Scholar 

  105. 105.

    Brenner BM, Garcia DL, Anderson S. Glomeruli and blood pressure. Less of one, more the other? Am J Hypertens. 1988;1:335–47.

    CAS  PubMed  Article  Google Scholar 

  106. 106.

    Blantz RC, Gabbai FB. Glomerular hemodynamics in pathophysiologic conditions. Am J Hypertens. 1989;2:208S–212S.

    CAS  PubMed  Article  Google Scholar 

  107. 107.

    Hostetter TH, Troy JL, Brenner BM. Glomerular hemodynamics in experimental diabetes mellitus. Kidney Int. 1981;19:410–5.

    CAS  PubMed  Article  Google Scholar 

  108. 108.

    Bank N, Lahorra MA, Aynedjian HS, Schlondorff D. Vasoregulatory hormones and the hyperfiltration of diabetes. Am J Physiol. 1988;254:F202–9.

    CAS  PubMed  Google Scholar 

  109. 109.

    Pollock CA, Lawrence JR, Field MJ. Tubular sodium handling and tubuloglomerular feedback in experimental diabetes mellitus. Am J Physiol. 1991;260:F946–52.

    CAS  PubMed  Google Scholar 

  110. 110.

    Vallon V, Richter K, Blantz RC, Thomson S, Osswald H. Glomerular hyperfiltration in experimental diabetes mellitus: potential role of tubular reabsorption. J Am Soc Nephrol. 1999;10:2569–76.

    CAS  PubMed  Article  Google Scholar 

  111. 111.

    Bank N, Lahorra G, Aynedjian HS, Wilkes BM. Sodium restriction corrects hyperfiltration of diabetes. Am J Physiol. 1988;254:F668–76.

    CAS  PubMed  Google Scholar 

  112. 112.

    Vallon V, Thomson SC. The tubular hypothesis of nephron filtration and diabetic kidney disease. Nat Rev Nephrol. 2020;16:317–36.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  113. 113.

    Kidokoro K, Cherney DZI, Bozovic A, Nagasu H, Satoh M, Kanda E, et al. Evaluation of glomerular hemodynamic function by empagliflozin in diabetic mice using in vivo imaging. Circulation. 2019;140:303–15.

    CAS  PubMed  Article  Google Scholar 

  114. 114.

    Basgen JM, Steffes MW, Stillman AE, Mauer SM. Estimating glomerular number in situ using magnetic resonance imaging and biopsy. Kidney Int. 1994;45:1668–72.

    CAS  PubMed  Article  Google Scholar 

  115. 115.

    Fulladosa X, Moreso F, Narváez JA, Grinyó JM, Serón D. Estimation of total glomerular number in stable renal transplants. J Am Soc Nephrol. 2003;14:2662–8.

    PubMed  Article  Google Scholar 

  116. 116.

    Tan JC, Busque S, Workeneh B, Ho B, Derby G, Blouch KL, et al. Effects of aging on glomerular function and number in living kidney donors. Kidney Int. 2010;78:686–92.

    PubMed  PubMed Central  Article  Google Scholar 

  117. 117.

    Sasaki T, Tsuboi N, Kanzaki G, Haruhara K, Okabayashi Y, Koike K, et al. Biopsy-based estimation of total nephron number in Japanese living kidney donors. Clin Exp Nephrol. 2019;23:629–37.

    PubMed  Article  Google Scholar 

  118. 118.

    Sasaki T, Tsuboi N, Okabayashi Y, Haruhara K, Kanzaki G, Koike K, et al. Estimation of nephron number in living humans by combining unenhanced computed tomography with biopsy-based stereology. Sci Rep. 2019;9:14400.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  119. 119.

    Lenihan CR, Busque S, Derby G, Blouch K, Myers BD, Tan JC. Longitudinal study of living kidney donor glomerular dynamics after nephrectomy. J Clin Investig. 2015;125:1311–8.

    PubMed  PubMed Central  Article  Google Scholar 

  120. 120.

    Lenihan CR, Busque S, Derby G, Blouch K, Myers BD, Tan JC. The association of predonation hypertension with glomerular function and number in older living kidney donors. J Am Soc Nephrol. 2015;26:1261–7.

    PubMed  Article  Google Scholar 

  121. 121.

    D’Agati VD, Chagnac A, de Vries AP, Levi M, Porrini E, Herman-Edelstein M, et al. Obesity-related glomerulopathy: clinical and pathologic characteristics and pathogenesis. Nat Rev Nephrol. 2016;12:453–71.

    PubMed  Article  CAS  Google Scholar 

  122. 122.

    Chagnac A, Weinstein T, Herman M, Hirsh J, Gafter U, Ori Y. The effects of weight loss on renal function in patients with severe obesity. J Am Soc Nephrol. 2003;14:1480–6.

    PubMed  Article  Google Scholar 

  123. 123.

    Tsuboi N, Okabayashi Y, Shimizu A, Yokoo T. The renal pathology of obesity. Kidney Int Rep. 2017;2:251–60.

    PubMed  PubMed Central  Article  Google Scholar 

  124. 124.

    Okabayashi Y, Tsuboi N, Sasaki T, Haruhara T, Kanzaki G, Koike K, et al. Single-nephron glomerular filtration rate in patients with obesity-related glomerulopathy. Kidney Int Rep. 2020;5:1218–27.

    PubMed  PubMed Central  Article  Google Scholar 

  125. 125.

    Maas RJ, Deegens JK, Smeets B, Moeller MJ, Wetzels JF. Minimal change disease and idiopathic FSGS: manifestations of the same disease. Nat Rev Nephrol. 2016;1 2:768–76.

    Article  Google Scholar 

  126. 126.

    Sasaki T, Tsuboi T, Marumoto H, Okabayashi Y, Haruhara K, Kanzaki G, et al. Nephron number and time to remission in steroid-sensitive minimal change disease. Kidney Med. 2020;2:559–68.

    PubMed  PubMed Central  Article  Google Scholar 

  127. 127.

    Jamison RL. Evidence for functional intrarenal heterogeneity obtained by the micropuncture technique. Yale J Biol Med. 1972;45:254–62.

    CAS  PubMed  PubMed Central  Google Scholar 

  128. 128.

    Jamison RL. Intrarenal heterogeneity. The case for two functionally dissimilar populations of nephrons in the mammalian kidney. Am J Med. 1973;54:281–9.

    CAS  PubMed  Article  Google Scholar 

  129. 129.

    Ito S, Nagasawa T, Abe M, Mori T. Strain vessel hypothesis: a viewpoint for linkage of albuminuria and cerebro-cardiovascular risk. Hypertens Res. 2009;32:115–21.

    PubMed  Article  Google Scholar 

  130. 130.

    Samuel T, Hoy WE, Douglas-Denton R, Hughson MD, Bertram JF. Determinants of glomerular volume in different cortical zones of the human kidney. J Am Soc Nephrol. 2005;16:3102–9.

    PubMed  Article  Google Scholar 

  131. 131.

    Denic A, Ricaurte L, Lopez CL, Narasimhan R, Lerman LO, Lieske JC, et al. Glomerular volume and glomerulosclerosis at different depths within the human kidney. J Am Soc Nephrol. 2019;30:1471–80.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  132. 132.

    Okabayashi Y, Kanzaki G, Tsuboi N, Haruhara K, Koike K, Ikegami M et al. Heterogeneous distribution of glomerular size in adult kidneys with normal renal function. Pathol Int. 2018; https://doi.org/10.1111/pin.12681. e-pub ahead of print, 10 May, 2018.

  133. 133.

    Zhang X, Rule AD, McCulloch CE, Lieske JC, Ku E, Hsu CY. Tubular secretion of creatinine and kidney function: an observational study. BMC Nephrol. 2020;21:108.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  134. 134.

    Delanaye P, Jager KJ, Bökenkamp A, Christensson A, Dubourg L, Eriksen BO, et al. CKD: a call for an age-adapted definition. J Am Soc Nephrol. 2019;30:1785–805.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  135. 135.

    Venkatareddy M, Wang S, Yang Y, Patel S, Wickman L, Nishizono R, et al. Estimating podocyte number and density using a single histologic section. J Am Soc Nephrol. 2014;25:1118–29.

    PubMed  Article  Google Scholar 

  136. 136.

    Baldelomar EJ, Charlton JR, Beeman SC, Hann BD, Cullen-McEwen L, Pearl VM, et al. Phenotyping by magnetic resonance imaging nondestructively measures glomerular number and volume distribution in mice with and without nephron reduction. Kidney Int. 2016;89:498–505.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  137. 137.

    Baldelomar EJ, Charlton JR, Beeman SC, Bennett KM. Measuring rat kidney glomerular number and size in vivo with MRI. Am J Physiol Ren Physiol. 2018;314:F399–F406.

    Article  CAS  Google Scholar 

  138. 138.

    Charlton JR, Baldelomar EJ, deRonde KA, Cathro HP, Charlton NP, Criswell SJ, et al. Nephron loss detected by MRI following neonatal acute kidney injury in rabbits. Pediatr Res. 2020;87:1185–92.

    CAS  PubMed  Article  Google Scholar 

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Funding

This work was supported by a Japan Kidney Foundation research grant and JSPS KAKENHI grant numbers JP25461236 and JP16K0936 (to NT). Neither funding agency had a role in the research design.

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Conception and design: NT; paper drafting: NT. Each author contributed relevant intellectual content and ensured that questions pertaining to the accuracy or integrity of any portion of the work were appropriately investigated and resolved.

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Correspondence to Nobuo Tsuboi.

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Tsuboi, N., Sasaki, T., Okabayashi, Y. et al. Assessment of nephron number and single-nephron glomerular filtration rate in a clinical setting. Hypertens Res 44, 605–617 (2021). https://doi.org/10.1038/s41440-020-00612-y

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Keywords

  • Nephron number
  • Hypertension
  • CKD
  • Kidney biopsy
  • Kidney cortical volume
  • Single-nephron GFR

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