Applied Renal Physiology in the PICU



The kidneys are central to numerous homeostatic mechanisms in the body. Responsible for solute and fluid handling, removal of waste products of nutrients, metabolism, detoxification, and excretion of drugs and metabolites, and regulation of vascular tone, the kidneys also elaborate many metabolites that act in local and distant fashion. The kidneys receive a high proportion of cardiac output per minute and have a high rate of oxygen consumption, evidence of the intensity of regulation that occurs in perpetuity. In this chapter, we will discuss renal physiology using the structure as background, function, and response to illness. Both hemodynamics and filtration will be described in detail. Relevant examples of how commonly encountered disease states affect kidney function will be discussed. Finally, the emerging paradigm of crosstalk between the kidneys and other vital organs will be broached. Critical illness carries dramatic consequence on kidney function and understanding the elements of how the kidneys regulate their own mechanics, and what happens when these compensatory mechanisms are overwhelmed, is essential to practitioners in the pediatric intensive care unit.


Renal hemodynamics Filtration Tubular reabsorption Tubuloglomerular feedback Endocrine kidney Kidney crosstalk 



Angiotensin converting enzyme inh


Anti-diuretic hormone


Anion exchanger


Angiotensin 2


Atrial natriuretic peptide




Angiotensin receptor blockers


Arginine vasopressin


Carbonic anhydrase




Calcium ATPase


Collecting duct




Distal convoluted tubule


Epithelial sodium channel


Glomerular basement membrane


Glomerular capillary perfusion


Glomerular filtration rate


Glucose transporter


Hydrogen ATPase




Hypoxia inducible factor


Juxtaglomerular apparatus




Loop of henle


Medullary collecting duct


Myogenic reflex




Sodium-potassium ATPase


Sodium chloride




Sodium hydrogen exchanger


Nitric oxide






Phospholipase C epsilon




Proximal tubule


Parathyroid hormone




Renal blood flow


Renal perfusion pressure


Oxygen consumption


Renal vascular resistance


Sodium-glucose transporters


Single nephron GFR


Severe sepsis associated AKI


Thick ascending limb


Thick ascending loop of henle


Tubuloglomerular feedback


Transient receptor potential


  1. 1.
    Carew RM, Wang B, Kantharidis P. The role of EMT in renal fibrosis. Cell Tissue Res. 2012;347(1):103–16.PubMedCrossRefGoogle Scholar
  2. 2.
    Hatch FE, Johnson JG. Intrarenal blood flow. Annu Rev Med. 1969;20:395–408.PubMedCrossRefGoogle Scholar
  3. 3.
    Grunfeld JP, et al. Intrarenal distribution of blood flow. Adv Nephrol Necker Hosp. 1971;1:125–43.PubMedGoogle Scholar
  4. 4.
    Rosenberger C, Rosen S, Heyman SN. Renal parenchymal oxygenation and hypoxia adaptation in acute kidney injury. Clin Exp Pharmacol Physiol. 2006;33(10):980–8.PubMedCrossRefGoogle Scholar
  5. 5.
    Heyman SN, Rosenberger C, Rosen S. Regional alterations in renal haemodynamics and oxygenation: a role in contrast medium-induced nephropathy. Nephrol Dial Transplant. 2005;20 Suppl 1:i6–11.PubMedCrossRefGoogle Scholar
  6. 6.
    Graves FT. The arterial anatomy of the kidney: the basis of surgical technique. Bristol: John Wright; 1971. p. xi. 101 p.Google Scholar
  7. 7.
    McCrory WW. Developmental nephrology. Cambridge: Harvard University Press; 1972. p. xii. 216 p.Google Scholar
  8. 8.
    Hunley TE, Kon V, Ichikawa I. Glomerular circulation and function. In: Harmon WE, Avner ED, Niaudet P, Yoshikawa N, editors. Pediatric nephrology. Heidelberg: Springer; 2009. p. 31.CrossRefGoogle Scholar
  9. 9.
    Visser MO, et al. Renal blood flow in neonates: quantification with color flow and pulsed Doppler US. Radiology. 1992;183(2):441–4.PubMedCrossRefGoogle Scholar
  10. 10.
    Strickland AL, Kotchen TA. A study of the renin-aldosterone system in congenital adrenal hyperplasia. J Pediatr. 1972;81(5):962–9.PubMedCrossRefGoogle Scholar
  11. 11.
    Kotchen TA, et al. A study of the renin-angiotensin system in newborn infants. J Pediatr. 1972;80(6):938–46.PubMedCrossRefGoogle Scholar
  12. 12.
    Eliot RJ, et al. Plasma catecholamine concentrations in infants at birth and during the first 48 hours of life. J Pediatr. 1980;96(2):311–5.PubMedCrossRefGoogle Scholar
  13. 13.
    O’Rourke M. Mechanical principles in arterial disease. Hypertension. 1995;26(1):2–9.PubMedCrossRefGoogle Scholar
  14. 14.
    Fretschner M, et al. A narrow segment of the efferent arteriole controls efferent resistance in the hydronephrotic rat kidney. Kidney Int. 1990;37(5):1227–39.PubMedCrossRefGoogle Scholar
  15. 15.
    Casellas D, Navar LG. In vitro perfusion of juxtamedullary nephrons in rats. Am J Physiol. 1984;246(3 Pt 2):F349–58.PubMedGoogle Scholar
  16. 16.
    Imig JD, Roman RJ. Nitric oxide modulates vascular tone in preglomerular arterioles. Hypertension. 1992;19(6 Pt 2):770–4.PubMedCrossRefGoogle Scholar
  17. 17.
    Badr KF, Ichikawa I. Prerenal failure: a deleterious shift from renal compensation to decompensation. N Engl J Med. 1988;319(10):623–9.PubMedCrossRefGoogle Scholar
  18. 18.
    Helou CM, et al. Angiotensin receptor subtypes in thin and muscular juxtamedullary efferent arterioles of rat kidney. Am J Physiol Renal Physiol. 2003;285(3):F507–14.PubMedCrossRefGoogle Scholar
  19. 19.
    Yuan BH, Robinette JB, Conger JD. Effect of angiotensin II and norepinephrine on isolated rat afferent and efferent arterioles. Am J Physiol. 1990;258(3 Pt 2):F741–50.PubMedGoogle Scholar
  20. 20.
    Denton KM, et al. Morphometric analysis of the actions of angiotensin II on renal arterioles and glomeruli. Am J Physiol. 1992;262(3 Pt 2):F367–72.PubMedGoogle Scholar
  21. 21.
    Denton KM, et al. Effect of endothelin-1 on regional kidney blood flow and renal arteriole calibre in rabbits. Clin Exp Pharmacol Physiol. 2004;31(8):494–501.PubMedCrossRefGoogle Scholar
  22. 22.
    Kimura K, et al. Effects of atrial natriuretic peptide on renal arterioles: morphometric analysis using microvascular casts. Am J Physiol. 1990;259(6 Pt 2):F936–44.PubMedGoogle Scholar
  23. 23.
    Edwards RM, Trizna W, Kinter LB. Renal microvascular effects of vasopressin and vasopressin antagonists. Am J Physiol. 1989;256(2 Pt 2):F274–8.PubMedGoogle Scholar
  24. 24.
    Parekh N, et al. Nitric oxide modulates angiotensin II- and norepinephrine-dependent vasoconstriction in rat kidney. Am J Physiol. 1996;270(3 Pt 2):R630–5.PubMedGoogle Scholar
  25. 25.
    Parekh N, Zou AP. Role of prostaglandins in renal medullary circulation: response to different vasoconstrictors. Am J Physiol. 1996;271(3 Pt 2):F653–8.PubMedGoogle Scholar
  26. 26.
    Hayashi K, et al. Disparate effects of calcium antagonists on renal microcirculation. Hypertens Res. 1996;19(1):31–6.PubMedCrossRefGoogle Scholar
  27. 27.
    Kon V, Fogo A, Ichikawa I. Bradykinin causes selective efferent arteriolar dilation during angiotensin I converting enzyme inhibition. Kidney Int. 1993;44(3):545–50.PubMedCrossRefGoogle Scholar
  28. 28.
    Steinhausen M, et al. Responses of in vivo renal microvessels to dopamine. Kidney Int. 1986;30(3):361–70.PubMedCrossRefGoogle Scholar
  29. 29.
    Loutzenhiser R, Bidani A, Chilton L. Renal myogenic response: kinetic attributes and physiological role. Circ Res. 2002;90(12):1316–24.PubMedCrossRefGoogle Scholar
  30. 30.
    Schnermann J, Briggs JP. Tubuloglomerular feedback: mechanistic insights from gene-manipulated mice. Kidney Int. 2008;74(4):418–26.PubMedPubMedCentralCrossRefGoogle Scholar
  31. 31.
    DiBona GF, Kopp UC. Neural control of renal function. Physiol Rev. 1997;77(1):75–197.PubMedGoogle Scholar
  32. 32.
    Dzau VJ, et al. Prostaglandins in severe congestive heart failure. Relation to activation of the renin–angiotensin system and hyponatremia. N Engl J Med. 1984;310(6):347–52.PubMedCrossRefGoogle Scholar
  33. 33.
    De Nicola L, Blantz RC, Gabbai FB. Nitric oxide and angiotensin II. Glomerular and tubular interaction in the rat. J Clin Invest. 1992;89(4):1248–56.PubMedPubMedCentralCrossRefGoogle Scholar
  34. 34.
    Blantz RC. Pathophysiology of pre-renal azotemia. Kidney Int. 1998;53(2):512–23.PubMedCrossRefGoogle Scholar
  35. 35.
    Wan L, et al. Pathophysiology of septic acute kidney injury: what do we really know? Crit Care Med. 2008;36(4 Suppl):S198–203.PubMedCrossRefGoogle Scholar
  36. 36.
    Boffa JJ, Arendshorst WJ. Maintenance of renal vascular reactivity contributes to acute renal failure during endotoxemic shock. J Am Soc Nephrol. 2005;16(1):117–24.PubMedCrossRefGoogle Scholar
  37. 37.
    Gambaro G, Perazella MA. Adverse renal effects of anti-inflammatory agents: evaluation of selective and nonselective cyclooxygenase inhibitors. J Intern Med. 2003;253(6):643–52.PubMedCrossRefGoogle Scholar
  38. 38.
    Franklin SS, Smith RD. A comparison of enalapril plus hydrochlorothiazide with standard triple therapy in renovascular hypertension. Nephron. 1986;44 Suppl 1:73–82.PubMedGoogle Scholar
  39. 39.
    Okuyama H, et al. Effects of synchronous pulsatile extracorporeal membrane oxygenation in an endotoxin-induced shock model: an experimental study. Artif Organs. 1992;16(5):477–84.PubMedCrossRefGoogle Scholar
  40. 40.
    Roy BJ, Cornish JD, Clark RH. Venovenous extracorporeal membrane oxygenation affects renal function. Pediatrics. 1995;95(4):573–8.PubMedGoogle Scholar
  41. 41.
    Drenckhahn D, et al. Ultrastructural organization of contractile proteins in rat glomerular mesangial cells. Am J Pathol. 1990;137(6):1343–51.PubMedPubMedCentralGoogle Scholar
  42. 42.
    Ballermann BJ. Contribution of the endothelium to the glomerular permselectivity barrier in health and disease. Nephron Physiol. 2007;106(2):19–25.CrossRefGoogle Scholar
  43. 43.
    Miner JH, Sanes JR. Collagen IV alpha 3, alpha 4, and alpha 5 chains in rodent basal laminae: sequence, distribution, association with laminins, and developmental switches. J Cell Biol. 1994;127(3):879–91.PubMedCrossRefGoogle Scholar
  44. 44.
    Hassell JR, et al. Isolation of a heparan sulfate-containing proteoglycan from basement membrane. Proc Natl Acad Sci U S A. 1980;77(8):4494–8.PubMedPubMedCentralCrossRefGoogle Scholar
  45. 45.
    Groffen AJ, et al. Agrin is a major heparan sulfate proteoglycan in the human glomerular basement membrane. J Histochem Cytochem. 1998;46(1):19–27.PubMedCrossRefGoogle Scholar
  46. 46.
    Caulfield JP, Farquhar MG. Loss of anionic sites from the glomerular basement membrane in aminonucleoside nephrosis. Lab Invest. 1978;39(5):505–12.PubMedGoogle Scholar
  47. 47.
    Drumond MC, et al. Structural basis for reduced glomerular filtration capacity in nephrotic humans. J Clin Invest. 1994;94(3):1187–95.PubMedPubMedCentralCrossRefGoogle Scholar
  48. 48.
    Adler S. Integrin receptors in the glomerulus: potential role in glomerular injury. Am J Physiol. 1992;262(5 Pt 2):F697–704.PubMedGoogle Scholar
  49. 49.
    Regele HM, et al. Glomerular expression of dystroglycans is reduced in minimal change nephrosis but not in focal segmental glomerulosclerosis. J Am Soc Nephrol. 2000;11(3):403–12.PubMedGoogle Scholar
  50. 50.
    Mundel P, et al. Synaptopodin: an actin-associated protein in telencephalic dendrites and renal podocytes. J Cell Biol. 1997;139(1):193–204.PubMedPubMedCentralCrossRefGoogle Scholar
  51. 51.
    Huber TB, et al. Bigenic mouse models of focal segmental glomerulosclerosis involving pairwise interaction of CD2AP, Fyn, and synaptopodin. J Clin Invest. 2006;116(5):1337–45.PubMedPubMedCentralCrossRefGoogle Scholar
  52. 52.
    Patrie KM, et al. The membrane-associated guanylate kinase protein MAGI-1 binds megalin and is present in glomerular podocytes. J Am Soc Nephrol. 2001;12(4):667–77.PubMedGoogle Scholar
  53. 53.
    Takeda T, et al. Expression of podocalyxin inhibits cell-cell adhesion and modifies junctional properties in Madin-Darby canine kidney cells. Mol Biol Cell. 2000;11(9):3219–32.PubMedPubMedCentralCrossRefGoogle Scholar
  54. 54.
    Sellin L, et al. NEPH1 defines a novel family of podocin interacting proteins. FASEB J. 2003;17(1):115–7.PubMedGoogle Scholar
  55. 55.
    Neal CR, et al. Glomerular filtration into the subpodocyte space is highly restricted under physiological perfusion conditions. Am J Physiol Renal Physiol. 2007;293(6):F1787–98.PubMedCrossRefGoogle Scholar
  56. 56.
    Deen WM, Lazzara MJ, Myers BD. Structural determinants of glomerular permeability. Am J Physiol Renal Physiol. 2001;281(4):F579–96.PubMedGoogle Scholar
  57. 57.
    Ohlson M, Sorensson J, Haraldsson B. A gel-membrane model of glomerular charge and size selectivity in series. Am J Physiol Renal Physiol. 2001;280(3):F396–405.PubMedGoogle Scholar
  58. 58.
    Deen WM, et al. Heteroporous model of glomerular size selectivity: application to normal and nephrotic humans. Am J Physiol. 1985;249(3 Pt 2):F374–89.PubMedGoogle Scholar
  59. 59.
    Herget-Rosenthal S, Bokenkamp A, Hofmann W. How to estimate GFR-serum creatinine, serum cystatin C or equations? Clin Biochem. 2007;40(3–4):153–61.PubMedCrossRefGoogle Scholar
  60. 60.
    Schwartz GJ, et al. New equations to estimate GFR in children with CKD. J Am Soc Nephrol. 2009;20(3):629–37.PubMedPubMedCentralCrossRefGoogle Scholar
  61. 61.
    Stevens LA, et al. Assessing kidney function–measured and estimated glomerular filtration rate. N Engl J Med. 2006;354(23):2473–83.PubMedCrossRefGoogle Scholar
  62. 62.
    Kim KE, et al. Creatinine clearance in renal disease. A reappraisal. Br Med J. 1969;4(5674):11–4.PubMedPubMedCentralCrossRefGoogle Scholar
  63. 63.
    Schwartz GJ, Work DF. Measurement and estimation of GFR in children and adolescents. Clin J Am Soc Nephrol. 2009;4(11):1832–43.PubMedCrossRefGoogle Scholar
  64. 64.
    Peti-Peterdi J, Bell PD. Cytosolic [Ca2+] signaling pathway in macula densa cells. Am J Physiol. 1999;277(3 Pt 2):F472–6.PubMedGoogle Scholar
  65. 65.
    Briggs JP, Schnermann JB. Whys and wherefores of juxtaglomerular apparatus function. Kidney Int. 1996;49(6):1724–6.PubMedCrossRefGoogle Scholar
  66. 66.
    Schnermann J, Briggs J. Role of the renin-angiotensin system in tubuloglomerular feedback. Fed Proc. 1986;45(5):1426–30.PubMedGoogle Scholar
  67. 67.
    Shemesh O, et al. Effect of colloid volume expansion on glomerular barrier size-selectivity in humans. Kidney Int. 1986;29(4):916–23.PubMedCrossRefGoogle Scholar
  68. 68.
    Kestila M, et al. Positionally cloned gene for a novel glomerular protein–nephrin–is mutated in congenital nephrotic syndrome. Mol Cell. 1998;1(4):575–82.PubMedCrossRefGoogle Scholar
  69. 69.
    Caridi G, et al. Infantile steroid-resistant nephrotic syndrome associated with double homozygous mutations of podocin. Am J Kidney Dis. 2004;43(4):727–32.PubMedCrossRefGoogle Scholar
  70. 70.
    Winn MP, et al. A mutation in the TRPC6 cation channel causes familial focal segmental glomerulosclerosis. Science. 2005;308(5729):1801–4.PubMedCrossRefGoogle Scholar
  71. 71.
    Weins A, et al. Mutational and biological analysis of alpha-actinin-4 in focal segmental glomerulosclerosis. J Am Soc Nephrol. 2005;16(12):3694–701.PubMedCrossRefGoogle Scholar
  72. 72.
    Hinkes B, et al. Positional cloning uncovers mutations in PLCE1 responsible for a nephrotic syndrome variant that may be reversible. Nat Genet. 2006;38(12):1397–405.PubMedCrossRefGoogle Scholar
  73. 73.
    O’Connor PM. Renal oxygen delivery: matching delivery to metabolic demand. Clin Exp Pharmacol Physiol. 2006;33(10):961–7.PubMedCrossRefGoogle Scholar
  74. 74.
    Kone BC. Metabolic basis of solute transport. In: Brenner BM, Rector FC, editors. Brenner and Rector’s the kidney, vol. 1. 8th ed. Philadelphia: Saunders Elsevier; 2008. p. 130.Google Scholar
  75. 75.
    Feraille E, Doucet A. Sodium-potassium-adenosinetriphosphatase-dependent sodium transport in the kidney: hormonal control. Physiol Rev. 2001;81(1):345–418.PubMedGoogle Scholar
  76. 76.
    Christov M, Alper SL. Tubular transport: core curriculum 2010. Am J Kidney Dis. 2010;56(6):1202–17.PubMedPubMedCentralCrossRefGoogle Scholar
  77. 77.
    Hughson M, et al. Glomerular number and size in autopsy kidneys: the relationship to birth weight. Kidney Int. 2003;63(6):2113–22.PubMedCrossRefGoogle Scholar
  78. 78.
    Wang T, et al. Role of NHE isoforms in mediating bicarbonate reabsorption along the nephron. Am J Physiol Renal Physiol. 2001;281(6):F1117–22.PubMedGoogle Scholar
  79. 79.
    Preisig PA, et al. Role of the Na+/H + antiporter in rat proximal tubule bicarbonate absorption. J Clin Invest. 1987;80(4):970–8.PubMedPubMedCentralCrossRefGoogle Scholar
  80. 80.
    Aalkjaer C, et al. Sodium coupled bicarbonate transporters in the kidney, an update. Acta Physiol Scand. 2004;181(4):505–12.PubMedCrossRefGoogle Scholar
  81. 81.
    Wang T, et al. Mechanisms of stimulation of proximal tubule chloride transport by formate and oxalate. Am J Physiol. 1996;271(2 Pt 2):F446–50.PubMedGoogle Scholar
  82. 82.
    Berry CA, Rector Jr FC. Mechanism of proximal NaCl reabsorption in the proximal tubule of the mammalian kidney. Semin Nephrol. 1991;11(2):86–97.PubMedGoogle Scholar
  83. 83.
    Rector Jr FC. Sodium, bicarbonate, and chloride absorption by the proximal tubule. Am J Physiol. 1983;244(5):F461–71.PubMedGoogle Scholar
  84. 84.
    Wright EM, Turk E. The sodium/glucose cotransport family SLC5. Pflugers Arch. 2004;447(5):510–8.PubMedCrossRefGoogle Scholar
  85. 85.
    Uldry M, Thorens B. The SLC2 family of facilitated hexose and polyol transporters. Pflugers Arch. 2004;447(5):480–9.PubMedCrossRefGoogle Scholar
  86. 86.
    Forster IC, et al. Proximal tubular handling of phosphate: a molecular perspective. Kidney Int. 2006;70(9):1548–59.PubMedCrossRefGoogle Scholar
  87. 87.
    Biber J, et al. Parathyroid hormone-mediated regulation of renal phosphate reabsorption. Nephrol Dial Transplant. 2000;15 Suppl 6:29–30.PubMedCrossRefGoogle Scholar
  88. 88.
    Gonska T, Hirsch JR, Schlatter E. Amino acid transport in the renal proximal tubule. Amino Acids. 2000;19(2):395–407.PubMedCrossRefGoogle Scholar
  89. 89.
    Christensen EI, Birn H. Megalin and cubilin: synergistic endocytic receptors in renal proximal tubule. Am J Physiol Renal Physiol. 2001;280(4):F562–73.PubMedGoogle Scholar
  90. 90.
    Lopez-Nieto CE, et al. Molecular cloning and characterization of NKT, a gene product related to the organic cation transporter family that is almost exclusively expressed in the kidney. J Biol Chem. 1997;272(10):6471–8.PubMedCrossRefGoogle Scholar
  91. 91.
    Sekine T, et al. Expression cloning and characterization of a novel multispecific organic anion transporter. J Biol Chem. 1997;272(30):18526–9.PubMedCrossRefGoogle Scholar
  92. 92.
    Wright SH, Dantzler WH. Molecular and cellular physiology of renal organic cation and anion transport. Physiol Rev. 2004;84(3):987–1049.PubMedCrossRefGoogle Scholar
  93. 93.
    Burckhardt G, Wolff NA. Structure of renal organic anion and cation transporters. Am J Physiol Renal Physiol. 2000;278(6):F853–66.PubMedGoogle Scholar
  94. 94.
    Enomoto A, Endou H. Roles of organic anion transporters (OATs) and a urate transporter (URAT1) in the pathophysiology of human disease. Clin Exp Nephrol. 2005;9(3):195–205.PubMedCrossRefGoogle Scholar
  95. 95.
    DiBona GF. Neural mechanisms in body fluid homeostasis. Fed Proc. 1986;45(13):2871–7.PubMedGoogle Scholar
  96. 96.
    Baum M, Quigley R. Inhibition of proximal convoluted tubule transport by dopamine. Kidney Int. 1998;54(5):1593–600.PubMedPubMedCentralCrossRefGoogle Scholar
  97. 97.
    Broer A, et al. The molecular basis of neutral aminoacidurias. Pflugers Arch. 2006;451(4):511–7.PubMedCrossRefGoogle Scholar
  98. 98.
    Goodyer P. The molecular basis of cystinuria. Nephron Exp Nephrol. 2004;98(2):e45–9.PubMedCrossRefGoogle Scholar
  99. 99.
    Schiavi SC, Moe OW. Phosphatonins: a new class of phosphate-regulating proteins. Curr Opin Nephrol Hypertens. 2002;11(4):423–30.PubMedCrossRefGoogle Scholar
  100. 100.
    Gottschalk CW, Mylle M. Micropuncture study of the mammalian urinary concentrating mechanism: evidence for the countercurrent hypothesis. Am J Physiol. 1959;196(4):927–36.PubMedGoogle Scholar
  101. 101.
    Sands JM, Layton HE. The physiology of urinary concentration: an update. Semin Nephrol. 2009;29(3):178–95.PubMedPubMedCentralCrossRefGoogle Scholar
  102. 102.
    Bray GA, Preston AS. Effect of urea on urine concentration in the rat. J Clin Invest. 1961;40:1952–60.PubMedPubMedCentralCrossRefGoogle Scholar
  103. 103.
    Zimmerhackl BL, Robertson CR, Jamison RL. The medullary microcirculation. Kidney Int. 1987;31(2):641–7.PubMedCrossRefGoogle Scholar
  104. 104.
    Pannabecker TL, et al. Role of three-dimensional architecture in the urine concentrating mechanism of the rat renal inner medulla. Am J Physiol Renal Physiol. 2008;295(5):F1271–85.PubMedPubMedCentralCrossRefGoogle Scholar
  105. 105.
    Capasso G, Unwin R, Giebisch G. Role of the loop of Henle in urinary acidification. Kidney Int Suppl. 1991;33:S33–5.PubMedGoogle Scholar
  106. 106.
    Capasso G, et al. Bicarbonate transport along the loop of Henle. I. Microperfusion studies of load and inhibitor sensitivity. J Clin Invest. 1991;88(2):430–7.PubMedPubMedCentralCrossRefGoogle Scholar
  107. 107.
    Karim Z, et al. Recent concepts concerning the renal handling of NH3/NH4+. J Nephrol. 2006;19 Suppl 9:S27–32.PubMedGoogle Scholar
  108. 108.
    Quamme GA, Dirks JH. The physiology of renal magnesium handling. Ren Physiol. 1986;9(5):257–69.PubMedGoogle Scholar
  109. 109.
    Sutton RA, Domrongkitchaiporn S. Abnormal renal magnesium handling. Miner Electrolyte Metab. 1993;19(4–5):232–40.PubMedGoogle Scholar
  110. 110.
    Taugner R, et al. Gap junctional coupling between the JGA and the glomerular tuft. Cell Tissue Res. 1978;186(2):279–85.PubMedCrossRefGoogle Scholar
  111. 111.
    Schnermann J. Juxtaglomerular cell complex in the regulation of renal salt excretion. Am J Physiol. 1998;274(2 Pt 2):R263–79.PubMedGoogle Scholar
  112. 112.
    Levens NR, Peach MJ, Carey RM. Role of the intrarenal renin-angiotensin system in the control of renal function. Circ Res. 1981;48(2):157–67.PubMedCrossRefGoogle Scholar
  113. 113.
    Good DW. Sodium-dependent bicarbonate absorption by cortical thick ascending limb of rat kidney. Am J Physiol. 1985;248(6 Pt 2):F821–9.PubMedGoogle Scholar
  114. 114.
    Amirlak I, Dawson KP. Bartter syndrome: an overview. QJM. 2000;93(4):207–15.PubMedCrossRefGoogle Scholar
  115. 115.
    de Groot T, Bindels RJ, Hoenderop JG. TRPV5: an ingeniously controlled calcium channel. Kidney Int. 2008;74(10):1241–6.PubMedCrossRefGoogle Scholar
  116. 116.
    Reilly RF, Ellison DH. Mammalian distal tubule: physiology, pathophysiology, and molecular anatomy. Physiol Rev. 2000;80(1):277–313.PubMedGoogle Scholar
  117. 117.
    Wang WH, Schwab A, Giebisch G. Regulation of small-conductance K + channel in apical membrane of rat cortical collecting tubule. Am J Physiol. 1990;259(3 Pt 2):F494–502.PubMedGoogle Scholar
  118. 118.
    Wade JB, et al. WNK1 kinase isoform switch regulates renal potassium excretion. Proc Natl Acad Sci U S A. 2006;103(22):8558–63.PubMedPubMedCentralCrossRefGoogle Scholar
  119. 119.
    Liu Z, Wang HR, Huang CL. Regulation of ROMK channel and K + homeostasis by kidney-specific WNK1 kinase. J Biol Chem. 2009;284(18):12198–206.PubMedPubMedCentralCrossRefGoogle Scholar
  120. 120.
    Lu Z, MacKinnon R. Electrostatic tuning of Mg2+ affinity in an inward-rectifier K + channel. Nature. 1994;371(6494):243–6.PubMedCrossRefGoogle Scholar
  121. 121.
    Sands JM, Knepper MA. Urea permeability of mammalian inner medullary collecting duct system and papillary surface epithelium. J Clin Invest. 1987;79(1):138–47.PubMedPubMedCentralCrossRefGoogle Scholar
  122. 122.
    Nielsen S, et al. Aquaporins in the kidney: from molecules to medicine. Physiol Rev. 2002;82(1):205–44.PubMedCrossRefGoogle Scholar
  123. 123.
    Wade JB, Stetson DL, Lewis SA. ADH action: evidence for a membrane shuttle mechanism. Ann N Y Acad Sci. 1981;372:106–17.PubMedCrossRefGoogle Scholar
  124. 124.
    Smith CP. Mammalian urea transporters. Exp Physiol. 2009;94(2):180–5.PubMedCrossRefGoogle Scholar
  125. 125.
    Teng-umnuay P, et al. Identification of distinct subpopulations of intercalated cells in the mouse collecting duct. J Am Soc Nephrol. 1996;7(2):260–74.PubMedGoogle Scholar
  126. 126.
    Schwartz GJ, Barasch J, Al-Awqati Q. Plasticity of functional epithelial polarity. Nature. 1985;318(6044):368–71.PubMedCrossRefGoogle Scholar
  127. 127.
    Al-Awqati Q. Plasticity in epithelial polarity of renal intercalated cells: targeting of the H(+)-ATPase and band 3. Am J Physiol. 1996;270(6 Pt 1):C1571–80.PubMedGoogle Scholar
  128. 128.
    Bonegio R, Lieberthal W. Role of apoptosis in the pathogenesis of acute renal failure. Curr Opin Nephrol Hypertens. 2002;11(3):301–8.PubMedCrossRefGoogle Scholar
  129. 129.
    Kellenberger S, Gautschi I, Schild L. Mutations in the epithelial Na + channel ENaC outer pore disrupt amiloride block by increasing its dissociation rate. Mol Pharmacol. 2003;64(4):848–56.PubMedCrossRefGoogle Scholar
  130. 130.
    Shimkets RA, et al. Liddle’s syndrome: heritable human hypertension caused by mutations in the beta subunit of the epithelial sodium channel. Cell. 1994;79(3):407–14.PubMedCrossRefGoogle Scholar
  131. 131.
    Chang SS, et al. Mutations in subunits of the epithelial sodium channel cause salt wasting with hyperkalaemic acidosis, pseudohypoaldosteronism type 1. Nat Genet. 1996;12(3):248–53.PubMedCrossRefGoogle Scholar
  132. 132.
    Huang CL, Kuo E. Mechanism of hypokalemia in magnesium deficiency. J Am Soc Nephrol. 2007;18(10):2649–52.PubMedCrossRefGoogle Scholar
  133. 133.
    Ko GJ, Rabb H, Hassoun HT. Kidney-lung crosstalk in the critically ill patient. Blood Purif. 2009;28(2):75–83.PubMedPubMedCentralCrossRefGoogle Scholar
  134. 134.
    Wang GL, et al. Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension. Proc Natl Acad Sci U S A. 1995;92(12):5510–4.PubMedPubMedCentralCrossRefGoogle Scholar
  135. 135.
    Arany Z, et al. An essential role for p300/CBP in the cellular response to hypoxia. Proc Natl Acad Sci U S A. 1996;93(23):12969–73.PubMedPubMedCentralCrossRefGoogle Scholar
  136. 136.
    Grigoryev DN, et al. The local and systemic inflammatory transcriptome after acute kidney injury. J Am Soc Nephrol. 2008;19(3):547–58.PubMedPubMedCentralCrossRefGoogle Scholar
  137. 137.
    Hoke TS, et al. Acute renal failure after bilateral nephrectomy is associated with cytokine-mediated pulmonary injury. J Am Soc Nephrol. 2007;18(1):155–64.PubMedCrossRefGoogle Scholar
  138. 138.
    Li X, et al. Organ crosstalk: the role of the kidney. Curr Opin Crit Care. 2009;15(6):481–7.PubMedCrossRefGoogle Scholar
  139. 139.
    Paladino JD, Hotchkiss JR, Rabb H. Acute kidney injury and lung dysfunction: a paradigm for remote organ effects of kidney disease? Microvasc Res. 2009;77(1):8–12.PubMedCrossRefGoogle Scholar
  140. 140.
    Liu M, et al. Acute kidney injury leads to inflammation and functional changes in the brain. J Am Soc Nephrol. 2008;19(7):1360–70.PubMedPubMedCentralCrossRefGoogle Scholar
  141. 141.
    Kelly KJ. Distant effects of experimental renal ischemia/reperfusion injury. J Am Soc Nephrol. 2003;14(6):1549–58.PubMedCrossRefGoogle Scholar
  142. 142.
    Shimozawa N, et al. Diagnosis of Zellweger syndrome by rectal biopsy: immunoblot of peroxisomal beta-oxidation enzyme and activity of dihydroxyacetone phosphate acyltransferase in rectal mucosa. Clin Chim Acta. 1988;175(3):345–7.PubMedCrossRefGoogle Scholar
  143. 143.
    Price JF, Goldstein SL. Cardiorenal syndrome in children with heart failure. Curr Heart Fail Rep. 2009;6(3):191–8.PubMedCrossRefGoogle Scholar
  144. 144.
    Price JF, et al. Worsening renal function in children hospitalized with decompensated heart failure: evidence for a pediatric cardiorenal syndrome? Pediatr Crit Care Med. 2008;9(3):279–84.PubMedCrossRefGoogle Scholar
  145. 145.
    Rabb H, et al. Acute renal failure leads to dysregulation of lung salt and water channels. Kidney Int. 2003;63(2):600–6.PubMedCrossRefGoogle Scholar
  146. 146.
    Basu RK, Wheeler D. Effects of ischemic acute kidney injury on lung water balance: nephrogenic pulmonary edema? Pulm Med. 2011;2011:414253.PubMedPubMedCentralCrossRefGoogle Scholar
  147. 147.
    Liu KD. Impact of acute kidney injury on lung injury. Am J Physiol Lung Cell Mol Physiol. 2009;296(1):L1–2.PubMedCrossRefGoogle Scholar
  148. 148.
    Singbartl K. Renal-pulmonary crosstalk. Contrib Nephrol. 2011;174:65–70.PubMedCrossRefGoogle Scholar
  149. 149.
    Schrier RW, Wang W. Acute renal failure and sepsis. N Engl J Med. 2004;351(2):159–69.PubMedCrossRefGoogle Scholar
  150. 150.
    Langenberg C, et al. Renal blood flow in experimental septic acute renal failure. Kidney Int. 2006;69(11):1996–2002.PubMedCrossRefGoogle Scholar
  151. 151.
    Guyton AC, Hall JE. Urine formation by the kidneys: I. Glomerular filtration, renal blood flow, and their control. In: Guyton AC, Hall JE, editors. Textbook of medical physiology. 11th ed. Philadelphia: Elsevier Saunders; 2011. p. 307–25.Google Scholar
  152. 152.
    Guyton AC, Hall JE. Regulation of extracellular fluid osmolarity and sodium concentration. In: Guyton AC, Hall JE, editors. Textbook of medical physiology. 11th ed. Philadelphia: Elsevier Saunders; 2011. p. 348–63.Google Scholar
  153. 153.
    Weichert J. Urinary system. On-line biological and bio-medical science encyclopedia. New York: McGraw-Hill Publishing; 2012.Google Scholar

Copyright information

© Springer-Verlag London 2014

Authors and Affiliations

  1. 1.Department of Pediatric Critical CareCincinnati Children’s Hospital and Medical CenterCincinnatiUSA
  2. 2.Pediatric Critical CareCincinnati Children’s Hospital and Medical CenterCincinnatiUSA

Personalised recommendations